Journal of Zhejiang University-SCIENCE B

, Volume 16, Issue 6, pp 417–435 | Cite as

Within-litter variation in birth weight: impact of nutritional status in the sow

  • Tao-lin Yuan
  • Yu-hua Zhu
  • Meng Shi
  • Tian-tian Li
  • Na Li
  • Guo-yao Wu
  • Fuller W. Bazer
  • Jian-jun Zang
  • Feng-lai Wang
  • Jun-jun Wang


Accompanying the beneficial improvement in litter size from genetic selection for high-prolificacy sows, within-litter variation in birth weight has increased with detrimental effects on post-natal growth and survival due to an increase in the proportion of piglets with low birth-weight. Causes of within-litter variation in birth weight include breed characteristics that affect uterine space, ovulation rate, degree of maturation of oocytes, duration of time required for ovulation, interval between ovulation and fertilization, uterine capacity for implantation and placentation, size and efficiency of placental transport of nutrients, communication between conceptus/fetus and maternal systems, as well as nutritional status and environmental influences during gestation. Because these factors contribute to within-litter variation in birth weight, nutritional status of the sow to improve fetal-placental development must focus on the following three important stages in the reproductive cycle: pre-mating or weaning to estrus, early gestation and late gestation. The goal is to increase the homogeneity of development of oocytes and conceptuses, decrease variations in conceptus development during implantation and placentation, and improve birth weights of newborn piglets. Though some progress has been made in nutritional regulation of within-litter variation in the birth weight of piglets, additional studies, with a focus on and insights into molecular mechanisms of reproductive physiology from the aspects of maternal growth and offspring development, as well as their regulation by nutrients provided to the sow, are urgently needed.

Key words

Within-litter variation Pig Mortality Morbidity Growth Sow nutrition 



本综述旨在总结仔猪初生重窝内变异对仔猪健康、生长及生产管理造成的不利影响、形成因素、以及改善窝内变异的措施。在现代化高产母猪养殖中, 仔猪初生重窝内变异程度及低初生重猪的比例大幅增加, 导致新生期存活率、生长性能大大降低。初生重窝内变异的影响因素包括母猪排卵率、卵子质量、排卵持续时间、胚胎附植能力、子宫容积、胎盘体积和效率等; 品种差异对仔猪初生重的均匀度也有很大影响。在妊娠的三个关键阶段 (断奶-配种间隔期、妊娠早期和妊娠后期) 进行针对性的营养调控有望一定程度上提高窝内初生重均匀度。目前已被报道的包括: 在配种前母猪日粮中添加葡萄糖或者维生素A, 妊娠后期添加谷氨酰胺均可改善仔猪初生重均匀度, 精氨酸以及支链氨基酸也有提高仔猪初生重一致性的潜能。但总体而言, 目前相关研究相对较少、潜在的分子机制仍不明确, 需要大量深入的研究来加深对妊娠期母体与胎儿发育过程相关生物学事件、营养素作用机制的理解, 为制定出更加科学有效的母猪饲喂措施提供理论基础。


窝内变异 猪 死亡率 发病率 生长性能 母 猪营养 

Document code

CLC number


1 Introduction

Over the last few decades, selection for highly prolific sows has resulted in an increase in litter size (Quiniou et al., 2002); however, this is positively related to a substantial increase in pre- and post-natal mortality before weaning (Johnson et al., 1999) due to greater within-litter variation in birth weights characterized by a higher proportion of low-birth-weight piglets in the litter (Milligan et al., 2002a; Quesnel et al., 2008; Kapell et al., 2011). There is a tendency for the proportion of runt piglets to be higher in litters in which birth weights of piglets are highly variable (van der Lende and Dejager, 1991). While small piglets are at greater risk of death than their larger littermates (Winters et al., 1947; Sharpe, 1966; Quiniou et al., 2002), survival of all piglets increases when there is reduced variation in birth weights of piglets within a litter (van der Lende and Dejager, 1991). At the same time, heterogeneity in birth weights of piglets among and within litters increases management costs in modern all-in-all-out swine production systems (Quiniou et al., 2002). Though some highly related factors such as genetic merit, oocyte quality, uterine capacity, and placental efficiency have been documented, the underlying mechanisms responsible for the high variability in birth weights within litters are unclear.

The aim of this review is to summarize the negative effects resulting from within-litter variation in birth weights, causative factors, and possible strategies for improving overall survival of piglets in large litters.

2 Negative effects of within-litter variation in birth weight of piglets

2.1 Pre-weaning mortality

Pre-weaning mortality is the major problem associated with improving prolificacy of sows. Approximately 15%–20% of piglets born do not survive to weaning (Fahmy and Bernard, 1971; Quiniou et al., 2002), and low birth weight is a primary contributor to poor survival to weaning (Winters et al., 1947; Pomeroy, 1960; Sharpe, 1966; Fahmy and Bernard, 1971; Bereskin et al., 1973; Pettigrew et al., 1986). Pre-weaning survival of piglets lighter than 0.45 kg was significantly lower than that of piglets weighing 1.6 kg or more (18% vs. 97%) (Fahmy and Bernard, 1971). Further, there is considerable evidence that high variation in birth-weight distribution in litters negatively skews the distribution in birth weights with the majority of piglets having birth weights well below the mean birth weight of the litter (Milligan et al., 2002b). In fact, there is a linear relationship between piglet survival and coefficient of variation for within-litter birth weight, and a curvilinear relationship between average birth weight and mortality of piglets (Fahmy and Bernard, 1971). Although there is also a favorable correlation between pre-weaning survival and within-litter variation in birth weight from the genetic perspective (Knol et al., 2002; Kapell et al., 2011), it is worth emphasizing that the adverse effects of high variation in birth weight on piglet survival are mainly due to an increase in the proportion of small piglets (Milligan et al., 2002a) since normal variation in birth weight has little effect on piglet survival in healthy litters (Milligan et al., 2001).

2.1.1 Intra-uterine growth restriction and susceptibility to infection and disease

Low-birth-weight piglets in litters with high variation in birth weights experience intra-uterine growth restriction (IUGR), usually resulting in physiological dysfunctions and an increase in neonatal morbidity and mortality (Wootton et al., 1983; Aucott et al., 2004). In addition, IUGR neonates are more susceptible to infection or environmental changes due to an ineffective immune system (Cromi et al., 2009; Zhong et al., 2012), and IUGR animals have abnormal differences in size and histopathology of the thymus (Cromi et al., 2009). Consistently, overexpression of heat shock protein 70 (Hsp70) associated with impaired cellular immunity was observed in the intestine (Zhong et al., 2010) and liver (Li et al., 2012) of IUGR neonates, suggesting that immune function is altered widely in IUGR piglets. There is growing evidence that elevated Hsp70 reduces proliferation and impairs nuclear factor-kappa B (NF-κB) signaling for cell survival (Wei et al., 1995; Ran et al., 2004).

2.1.2 IUGR and hyperammonemia

Abnormal metabolism of ammonia must be taken into consideration as a cause for morbidity or mortality of small piglets (Wu G. et al., 2010). We detected an abnormally high activity of glutamate oxaloacetate transaminase in the liver of IUGR fetuses compared with normal fetuses at Day 110 of gestation, this enzyme being responsible for the generation of ammonia from glutamate (Liu et al., 2013). High levels of expression of glutamate dehydrogenase 1, coupled with reduced levels of carbomoyphosphate synthase 1 to degrade it, result in the accumulation of ammonia, which increases the risk of hyperammonemia in low-birth-weight piglets and low-birth-weight human infants (Batshaw and Brusilow, 1978). This condition severely threatens survival of the neonate. Moreover, IUGR fetuses both at Days 90 and 110 of gestation had higher concentrations of ammonia in umbilical vein plasma than normal fetuses (Lin et al., 2012), which may account for poor survival and development of IUGR fetuses. The rate of protein degradation in the IUGR fetus may be higher than that in the normal-weight fetus.

2.1.3 IUGR and insufficient colostrum intake

For low-birth-weight piglets, intake of colostrum is delayed and inadequate (Le Dividich et al., 1998; Quesnel et al., 2012), leading to a poor acquisition of passive immunity and a poor nutritional status, thereby increasing the incidence of death or poor growth performance of piglets during lactation (Rooke and Bland, 2002; Le Dividich et al., 2005). This is because colostrum is the most important source of highly digestible compounds for neonates, including glucose, fat, protein, immunoglobulins, hormones, and growth factors (Le Dividich et al., 2005) required to meet demands for energy of piglets and support maturation of the digestive and immune systems (Walzem et al., 2002; Politis and Chronopoulou, 2008). In addition, low-birth-weight neonates that have low energy reserves are at greater risk of being inadvertently crushed by the sow when she lies down (Fahmy and Bernard, 1971), as well as an inability to prevent chilling due to impaired thermogenic mechanisms (Le Dividich, 1999).

2.2 Pre-weaning growth performance

Differences in birth weights among piglets are also related to differences in pre-weaning growth performance within litters, which are mainly due to remarkable differences in both milk intake and efficiency of utilization of nutrients by littermates. Colostrum/milk intake is affected by both vitality of the piglet at birth and within-litter competition to access a teat as the teat order for suckling develops within the first 24 h after birth and is then maintained (McBride, 1963). Vigorous piglets prefer the anterior teats (Fraser et al., 1979; Thompson and Fraser, 1986), while small piglets are at a disadvantage in fighting to gain possession of these more productive anterior teats compared with their larger siblings since the teat order is a dominance hierarchy (Pond and Houpt, 1978; Auldist and King, 1995). However, per kg body weight, milk consumption does not appear to differ between IUGR and normal-weight piglets (Rezaei et al., 2011). Offspring that obtain milk from anterior and middle mammary glands (MGs) grow faster than those suckling posterior MG (Puppe and Tuchscherer, 1999; Kim et al., 2000). Besides the greater amount of colostrum and milk from anterior and middle MGs (Gill and Thomson, 1956), we reported that components in colostrum and milk secreted by anterior and posterior MGs are also distinctive (Wu W.Z. et al., 2010) in having proteins that are beneficial to passive immunity, intestinal development, and epithelial integrity; they include immunoglobulins and haptoglobin in colostrum and lactoferrin in milk from anterior MG, which are more abundant in anterior and middle MGs compared with posterior MG. In addition, piglet body weight and stimulation through suckling intensity to the MG strongly determine milk production (King et al., 1997).

The inefficient utilization of nutrient was reported for small piglets (Rezaei et al., 2011) owing to physiological immaturity at birth, especially severe dysfunction in several organs, including the intestine (Wang X.Q. et al., 2014b), liver (Liu et al., 2013), and skeletal muscle (Wang T. et al., 2013). Additionally, concentrations of key proteins involved in growth and development were reduced, while there was an abundance of proteins associated with oxidative stress, proteolysis, and ATP hydrolysis in the small intestine, liver, and muscle of low-birth-weight piglets (Wang et al., 2008). Impaired development and dysfunction of those organs and tissues that play vital roles in digestion, absorption, and metabolism of dietary nutrients (Jobgen et al., 2006) could permanently decrease post- natal growth performance and efficiency of nutrient utilization in piglets. There-fore, these overall capacity differences in intake and utilization efficiency of nutrients among piglets may partly explain why differences in body weight at birth are often maintained or even increase throughout the period of lactation.

2.3 Post-weaning growth and meat quality

In litters in which there is a high variability among piglets regarding birth weight, growth rates among those offspring are desynchronized. Litters with more variability in piglet weight at birth have more variable weaning weights (Thompson and Fraser, 1986; Milligan et al., 2001; 2002b), since birth weight, absolute body-weight gain during lactation and weight at weaning are highly correlated (Quiniou et al., 2002). As an unfavorable consequence, the time for pigs within a litter to achieve slaughter weight is variable, with an additional three weeks being required for small piglets to reach 25 kg compared with their heavier littermates (76 and 55 d, respectively) (Quiniou et al., 2002). These differences can result in an increase in feed and management costs for lighter pigs due to the longer time and increased feed required for them to reach the required minimum commercial slaughter weight.

The distribution of muscular fiber type for IUGR piglets is affected negatively (Widdowson, 1971; Wigmore and Stickland, 1983; Wu et al., 2006) as both secondary and total muscle fibers are reduced in number (Wigmore and Stickland, 1983; Wang T. et al., 2013) for small fetuses, which, in turn, adversely affects growth rate and post mortem quality of meat. The reduction in number of muscular fibers and the larger diameters for those fibers for IUGR piglets result in greater amounts of intramuscular lipids and decreased meat tenderness at slaughter (Gondret et al., 2005), leading to a decrease in meat quality and economic losses.

3 Causes for within-litter variation in birth weight

Knowledge of the underlying mechanisms responsible for various distributions in birth weights of piglets within litters has important implications for the prevention of small neonates and is crucial for enhancing the efficiency of live-stock production and animal health. Growth and development of the fetus involve numerous complex biological events that can be influenced by genetics, epigenetics, maternal maturity, state of maternal nutrition, and environmental temperatures (Redmer et al., 2004). These factors affect implantation and placentation by the conceptus, angiogenesis within the uterus and placenta, utero-placental efficiency of transport of nutrients, and activities of fetal metabolic pathways (Bell and Ehrhardt, 2002; Fowden et al., 2005; Reynolds et al., 2006). All of those events may be influenced by breed characteristics that include maturity of ovulated oocytes, duration of ovulation, implantation and placentation capacity, available uterine space for implantation and placentation, size and efficiency of the placenta, as well as nutritional provision and environmental influences on the sow (Wu et al., 2006).

3.1 Duration of ovulation and oocyte maturation

The duration of ovulation, known as the time interval between ovulation of the first and the last follicle in a sow, and follicular diversity are believed to be associated with diversity in embryonic development during early pregnancy (Pope et al., 1990). Furthermore, the sequence of oocyte release during ovulation might contribute to differences in embryonic development with later-ovulated oocytes (42 h after human chorionic gonadotropin (hCG) injection) producing less-developed embryos at Day 4 of pregnancy, compared with earlier-ovulated oocytes (39 h after hCG injection); not surprisingly, the less-developed Day 4 embryos became the smaller blastocysts within a litter at Day 12 of gestation (Xie et al., 1990). In terms of hormone levels being key predictors of embryonic development, the more-developed blastocysts synthesize estradiol sooner than their contemporaries (Geisert et al., 1982a; Pope et al., 1988), while less-developed embryos at Day 12 of gestation contained less estradiol, less total protein, and less acid phosphatase activity (Xie et al., 1990), which might influence elongation and implantation of blastocysts. At the same time, the duration of ovulation in Meishan sows is 2 h versus 6 h for Large White sows, and this shorter interval was associated with less morphological variation and increased embryonic survival in litters of Meishan gilts (Bazer et al., 1988). Moreover, when later-ovulated follicles were removed, the diversity in embryonic morphology was reduced concomitantly, mainly through eliminating less-developed embryos (Pope et al., 1988). Further, duration of ovulation is related to the pattern of ovulation, since the distribution of follicular development and oocyte maturation are both skewed with a majority of mature follicles and oocytes (e.g. 70%) being ovulated during a short period of time and the rest (e.g. 30%) being ovulated during the following 2–6 h (Pope et al., 1990).

In contrast, Soede et al. (1992) concluded that embryonic diversity was not related to the duration of ovulation, at least up to 3 h, as they observed no significant differences in numbers of nuclei or numbers of cell cycles about 100 h after ovulation between Groups A and B (duration of ovulation was (1.8±0.6) and (4.6±1.7) h in Groups A and B, respectively). The reasons for these differences in results may include the maturation and quality of oocytes, as well as endocrine status of the sows. It is clear that embryonic diversity throughout at least the first 12 d of gestation is predetermined by factors that involve follicular development and oogenesis (Pope et al., 1990; Xie et al., 1990). Furthermore, oocyte maturation and quality can affect embryonic development and hormone secretion by the conceptus ultimately affecting the endocrine status of the uterus (Bazer et al., 2014). More studies are warranted to gain further insight into relationships between duration of ovulation and variations in embryonic development, although a body of evidence supports the view that the oocytes of later-ovulated follicles could be progenitors of small embryos.

3.2 Implantation capability of conceptuses and position within the uterus

The relationship between the fetal-placental growth and location within the uterus is evident. Pig fetuses from the ovarian end of the horn were approximately 10% heavier than those located at the middle or near end of the cervix (Waldorf et al., 1957; Perry and Rowell, 1969; Wise et al., 1997), and similar results have been described in rabbits (Rosahn and Greene, 1936). The effects of location within the uterine horn on fetal piglet weight are more notable during the last one-third of gestation when the demand for transfer of nutrients from the maternal system across the placenta to the fetus is greatest. Kim et al. (2013) concluded that fetal weight decreased linearly from the uterotubal junction to the cervix between Days 102 and 112 of gestation. It is postulated that vascular density within the placenta varies from uterine horn to cervix, that blood flow increases from the cervical to the oviductal end of each uterine horn in gilts during early pregnancy (Ford et al., 1982), and that implantation sites with less than three blood vessels were associated with poor development of the fetus which increased fetal weight variation within the litter. Moreover, it has been observed that there is considerable diversity in development of conceptuses prior to implantation within litters (Anderson, 1978; Geisert et al., 1982a), which may contribute to differences in timing and capacity to establish adequate surface area for implantation and placentation, since elongation of the conceptus during the peri-implantation period of pregnancy is critical to implantation and depends on the conceptus achieving a specific stage of differentiation and development (Anderson, 1978; Stroband and van der Lende, 1990; Blomberg et al., 2010).

3.3 Placental efficiency

Maternal nutrition during gestation, especially the amount of nutrients provided to each conceptus, has been regarded as a major cause for within-litter variation in birth weight of piglets currently born to sows. Fetuses acquire nutrients from the maternal system via the utero-placental circulation and umbilical vein throughout gestation (Kiserud and Acharya, 2004), and transfer of nutrients from mother to fetus is impaired in pregnancies with reduced blood flow in piglets which exhibit signs of IUGR (Reynolds et al., 2006; Kim et al., 2013). Furthermore, the composition of nutrients, gases, and other molecules in the umbilical vein blood is different between normal and IUGR fetuses. Previous results from our laboratory indicated lower circulating concentrations of glucose, amino acids of the arginine family, such as arginine and glutamine, and branched-chain amino acids (valine, leucine, and isoleucine), but increased concentrations of ammonia in umbilical vein plasma during late gestation in IUGR, compared with normal fetuses (Lin et al., 2012). It is clear that the transport of nutrients by the placenta of IUGR fetuses is altered and directly impairs fetal development (Wu et al., 2008).

3.4 Available uterine space

Increase in ovulation rates for gilts and sows during the past decades is a positive response to continuous selective breeding; however, as the number of conceptuses that survive during the post-implantation period greatly exceeds uterine capacity, there is a decrease of available uterine surface area for the development of each placenta. Therefore, there is a peak in post-implantation conceptus deaths between Days 30 and 50 of gestation when uterine surface area is insufficient (Knight et al., 1977; Vonnahme et al., 2002). As gestation progresses, the negative effects of limited uterine space on fetal development also increase (Vonnahme et al., 2002). The great within-litter variation in birth weight and increased proportion of small piglets born to the highly prolific sows as used today are likely related, in part, to intra-uterine crowding from at least the end of the first month of gestation (Foxcroft et al., 2006), especially when there are more than 14 fetuses present within the uterus (Webel and Dziuk, 1974). Moreover, intra-uterine crowding can alter the pattern of development of fetal muscle fibers in the immediate post-implantation period (Foxcroft et al., 2007), when mesenchymal stem cells of the embryo undergo differentiation for myogenesis, adipogenesis or mesenchymal cells (Cossu and Borello, 1999; Du et al., 2010). Detrimental effect of uterine crowding on fetal development (Town et al., 2004) is considered to be associated with insufficient development of placental vascularity (Argente et al., 2008), while a poor vascular supply and reduced uterine space limit development of offspring that thereby experience a deficit in nutrient availability before birth (Argente et al., 2006; Foxcroft et al., 2007). This subsequently increases within-litter variation in birth weight that is associated with greater post-natal death of piglets.

3.5 Breed characteristics

There is a body of evidence implying that genetic merit does exert considerable effects on litter homogeneity, as fetal genotype determines placental and endometrial vascularity during the last one-third of gestation (Biensen et al., 1998). Convincing data revealed that development of Meishan conceptuses was more uniform between Days 8 and 14 of gestation (Bazer et al., 1988), and within-litter variation in birth weight was lower in Meishan litters than in Large White litters (Lee and Haley, 1995). Differences in growth patterns for placentas and uterine capacity (Père and Etienne, 2000) between the two breeds can account for a large portion of the significant differences in birth-weight distribution. The Meishan placentas are smaller at farrowing (Wilson et al., 1998), while vascular density progressively increases between Days 90 and 110 of gestation with constant placental size. In contrast, Large White placental size progressively increased during late gestation, while vascular density remained constant (Biensen et al., 1998; Wilson et al., 1998). Hence, endometrial surface area per Meishan placenta decreased and competition among fetuses reduced simultaneously, which is associated with the high degree of uniformity in birth weight within litters of Meishan sows.

Within-litter variation in birth weight is also affected by parity, with older sows with greater parity often having less uniform litters as well as a higher proportion of low-birth-weight piglets (Damgaard et al., 2003; Quesnel et al., 2008; Wientjes et al., 2012). Pettigrew et al. (1986) also reported that birth weights of piglets from primiparous sows were more uniform. Litter size is positively correlated with parity, reaching the highest level between parities 3–5 (Dewey et al., 1995; Hughes, 1998). However, negative effects of parity on litter homogeneity may be related to its effects on litter size, which is positively related to within-litter variation in birth weight especially in litters with more than a total of 16 piglets born (Quiniou et al., 2002; Quesnel et al., 2008; 2014). An opposite view held by Pettigrew et al. (1986) is that the apparent increase in piglet birth weight standard deviation associated with increased litter size was far from enough to explain the impacts of parity on litter uniformity. Moreover, variation in birth weight is greater in older parity sows after correction for the total number of piglets born and excluding the effects of litter size (Wientjes et al., 2012). It has been postulated that the decrease in litter uniformity in older parity sows may result from deterioration in quality of follicles/oocytes with aging as reported for women (Broekmans et al., 2009), suggesting that litter uniformity in birth weight can also be affected solely by parity.

It follows that within-litter variation in birth weight is an integrated trait influenced by many factors. Additionally, these factors can interact with each other. Thus, studies focusing on within-litter variation in birth weight are in their infancy, and more studies are needed to clarify mechanisms and develop strategies to decrease IUGR in modern sows.

4 Strategies to decrease within-litter variation in birth weight

Pregnancy outcome is influenced by interactions between nutrition and genetics (Wu et al., 2006). For specific breeds in swine production, the sow’s nutrition is attracting the most research interest with a promise of decreasing within-litter variation in birth weight. Since there are three critical stages associated with conceptus/fetus survival and development throughout gestation, nutritional strategies that focus on pre-ovulation, peri-implantation and late gestation periods are expected to increase developmental homogeneity of oocytes and/or conceptuses, and decrease variations in the capability of conceptuses to undergo successful implantation and placentation, so that the birth weights of newborn piglets are more uniform. Improving litter uniformity is expected to increase the number of piglets born alive, as well as survival of piglets pre- and post-weaning and their growth performance after weaning.

4.1 Nutrition related to follicle/oocyte maturity

There is evidence that events during oogenesis influence survival and development of swine embryos (Pope et al., 1990), since oocyte maturity may be a determinant of uniformity in embryonic development, and subsequently, within-litter variation in birth weight (van der Lende et al., 1990). Therefore, nutritional strategies directed at sows prior to mating hold great promise to decrease within-litter variation in birth weight.

4.1.1 Energy intake

Energy intake should be regarded as the intake of lipids, carbohydrate, and amino acids in diets, as well as the ratios of these nutrients. Thus, knowledge of nutrient metabolism is essential to understand the utilization and function of dietary energy. Energy is critical for reproductive performance in swine. Sows fed low-energy diets during the weaning-to-estrus interval exhibit lower ovulation rates (Zak et al., 1997; van den Brand et al., 2000), smaller follicle size and fail to exhibit strong signs of estrous behavior (Prunier et al., 1993). However, modestly high-energy diets for sows pre-mating have positive impacts on embryonic survival (Ferguson et al., 2006) and litter homogeneity (Ashworth et al., 1999). Blastocysts recovered at Day 12 of gestation from gilts on a high level of feed intake pre-mating (3.5 kg/d) exhibited a lower within-litter standard deviation in blastocyst surface area, compared with blastocysts from gilts fed a maintenance diet pre-mating (1.15 kg/d), indicating that increasing pre-mating feed intake can reduce within-litter variability in blastocyst size at Day 12 of pregnancy (Ashworth et al., 1999). In addition, variation in body weight was less for sows fed 150 g/d dextrose-supplemented diets, compared with sows fed general diets during the weaning-to-estrus interval (van den Brand et al., 2006). Similar results were obtained in response to dietary supplementation with dextrose plus lactose from the last week of gestation until sows were inseminated (van den Brand et al., 2009).

4.1.2 Energy and insulin/IGF-1

Within-litter variation in birth weight reduced through dietary manipulation during the follicular phase of the estrous cycle (van den Brand et al., 2006; 2009) is likely due to improved follicle and oocyte development associated with changes in concentrations of metabolic hormones such as insulin-like growth factor-1 (IGF-1) and insulin (Yang et al., 2000; Ferguson et al., 2003). Development of follicles and oocytes is improved owing to higher concentrations of insulin (Matamoros et al., 1990; Tokach et al., 1992; van den Brand et al., 1998; 2000; Ziecik et al., 2002) or IGF-1 in plasma (Ferguson et al., 2003). The underlying mechanism by which insulin increases follicular development is possibly due to an increase in luteinizing hormone (LH) pulsatility (Cox et al., 1987) or LH production (Adashi et al., 1981), and a higher LH pulse frequency (van den Brand et al., 2000).

4.1.3 Energy source

Effects of feeding level on reproductive performance depend on dietary energy. Follicle quality or oocyte maturation can be stimulated by carbohydrate-rich diets, but decreased by fat-rich diets (van den Brand et al., 2006), which can be explained partially by different ingredients in feed that affect different reproductive hormones (van den Brand et al., 2000). Feeding a carbohydrate-rich diet during and after lactation increases the pre-ovulatory LH peak and circulating concentrations of progesterone in comparison with feeding a fat-rich diet (Kemp et al., 1995). On the other hand, plasma insulin levels increase more rapidly in gilts fed dextrose than fat, which results in a significant difference in plasma insulin at 24 min after feeding (van den Brand et al., 1998). Furthermore, feeding a high fiber diet during the estrous cycle tends to increase embryonic survival and decrease the proportion of IUGR fetuses at Day (27±2) of gestation (Ferguson et al., 2006). This may be due to a longer time for energy or some fiber-related metabolites to enhance oocyte quality or follicular development.

4.1.4 Vitamin A/retinol

Vitamins function as micronutrients with extensive participation in metabolic processes. Alterations in dietary retinol could improve pregnancy outcome by decreasing both the incidence of low-birth-weight piglets and within-litter variation in birth weight (Whaley et al., 2000; Antipatis et al., 2008). Treatment of sows with vitamin A at weaning increased subsequent litter size through decreased embryonic mortality (Coffey and Britt, 1993) and synchronous development of embryos (Pope et al., 1990). Whaley et al. (2000) found that embryonic development was more advanced and more uniform when dietary supplementation with 1×106 IU vitamin A (retinyl palmitate) was provided from Day 15 after the second estrus until mating at the third estrus. Similarly, more embryos with greater uniformity were obtained at Day 11 of gestation from gilts treated with vitamin A before mating (Whaley et al., 1997). Positive effects of vitamin A are considered to be associated with enhanced maturation of oocytes (Robertson, 1997; Robertson et al., 1997) and, consequently, enhanced embryonic development (Besenfelder et al., 1996). Further, concentrations of progesterone, IGF-1, and prostaglandin F2-a (PGF2-a) in follicular fluid were greater in vitamin-A-treated than in control gilts. Effects of vitamin A on follicle maturation were suggested to be through an IGF-1 stimulatory mechanism, since IGF-1 produced by granulosa cells plays a key role in the resumption of oocyte meiosis (Hammond et al., 1991) and increases both proliferation and progesterone synthesis and secretion by granulosa cells (Giudice, 1992).

4.2 Nutrition related to the peri-implantation period of pregnancy

Maternal recognition of pregnancy and conceptus implantation are the most important biological events associated with the establishment of pregnancy (Perry et al., 1976). Estrogen secreted by pig conceptuses is the major signal for maternal recognition of pregnancy at approximately Day 11 of gestation (Dhindsa and Dziuk, 1968; Perry et al., 1973; Bazer and Thatcher, 1977; Flint et al., 1979), which coincides with the time of conceptus elongation (Heap et al., 1979; Geisert et al., 1982b). Moreover, the morphological transition of conceptuses from spherical to tubular and filamentous forms occurs between Days 10 and 12 (Geisert et al., 1982b; Bazer and Johnson, 2014).

Implantation is a gradual process starting as early as Day 13 when elongation of the conceptus is underway and is well advanced by Day 18 of gestation (Perry et al., 1976), which is a determinant for establishing sufficient uterine surface area for placentation and subsequent nutrient transport for piglet survival and development (Geisert et al., 2014; Bazer and Johnson, 2014). It should be emphasized that establishment of pregnancy (conceptus elongation and implantation) also involves maternal uterine proinflammatory and immune responses (Geisert et al., 2014), due to a number of cytokines released or stimulated by the elongating conceptuses, such as NF-κB (Hayden and Ghosh, 2012) and interleukin 1β (IL-1β) (Ross et al., 2003; Blomberg et al., 2005). In order to avoid rejection by the immune response, an increase in expression of both IL1B and estrogen by individual conceptuses counter-balances stimulation of the pro-inflammatory and immune response within the uterus (Geisert et al., 2014); thus elongating conceptus can attach across the uterine luminal epithelial surface successfully.

As stated above, elongation of pig conceptuses is triggered by the conceptus achieving a specific stage of differentiation and development within the uterus (Bazer et al., 2014). Thus, it is a maternal event and has never been achieved in vitro (Anderson, 1978; Stroband and van der Lende, 1990; Blomberg et al., 2010; Bazer, 2013). However, various stages of conceptus development (spherical, tubular and filamentous) can be observed prior to and during the time of trophoblast elongation within the same litter (Anderson, 1978; Geisert et al., 1982a), leading to remarkable differences in timing, position, and area of implantation, and, thereafter, various states of survival and development. It is worth noting that pre-implantation embryonic losses are considered to make up the largest proportion of prenatal losses in pigs (Wiseman et al., 1998), suggesting that this is a key period to regulate embryonic survival and development during the implantation window and to affect placentation.

4.2.1 L-Arginine

Dietary supplementation with 0.4% or 0.8% L-arginine between Days 14 and 25 of gestation increased number of viable fetuses per litter by 2 on Day 25 compared with a control group (Li et al., 2014). This positive result is consistent with the presence of unusually high concentrations of amino acids in the arginine family in porcine allantoic fluid at the stage of blastocyst expansion and implantation in vivo (Wu et al., 1996; Gao et al., 2012) and of an increase in endometrial angiogenesis between Days 13 and 18 of gestation (Keys et al., 1986). Furthermore, arginine stimulates the AKT1-mTOR/FRAP1-RPS6K-RPS6 cell signaling pathways to increase proliferation and migration of porcine (Kong et al., 2012) and ovine (Kim et al., 2011) trophectoderm cells during peri-implantation period. The positive impact of L-arginine supplementation during the peri-implantation period of pregnancy is due in part to the production of NO, since this is crucial for embryonic development and implantation (Maul et al., 2003; Wang X.Q. et al., 2014a). Putrescine, which is a product of arginine catabolism in maternal tissues (Wu et al., 2009), can also stimulate protein synthesis in porcine placental cells (Kong et al., 2014). Of note, dietary supplementation of 0.8% L-arginine between Day 0 and Day 25 of gestation reduced litter size, uterine weight, total number of fetuses, number of corpora lutea and total fetal weights significantly at Day 25 (Li et al., 2010). Even though there was increased vascularity of the uterus due to arginine supplementation, its administration too early (from onset of estrus) interfered with normal ovulation, which decreased production of progesterone and estrone (Li et al., 2010). From these aspects, dietary supplementation with L-arginine during the peri-implantation period is expected to promote survival and synchronize development of embryos within a litter.

4.2.2 Retinol/vitamin A

Providing a vitamin A-deficient diet for 100 d prior to mating and during the first month of pregnancy increased the uniformity of birth weights and showed a tendency to decrease the incidence of low-birth-weight piglets (Antipatis et al., 2008). Moreover, sows on vitamin A-deficient diets did not experience a reduction in fetal survival and growth at Day 30 of pregnancy (Ashworth and Antipatis, 1999), perhaps due to a compensatory increase in the abundance of retinol binding protein (RBP) (Antipatis et al., 2008). Since pig conceptuses secrete RBP prior to onset of elongation and throughout the peri-implantation period, RBP could be an important component of the uterine secretions for early embryonic development (Harney et al., 1990; Schweigert et al., 1999). Thus, elevated levels of RBP in gilts deficient in vitamin A can account for positive outcomes of piglets having low within-litter variation in birth weight.

It is well documented that progesterone is required to maintain pregnancy and circulating concentrations of progesterone can be modulated by feed intake. Sows receiving high ((2.8±0.02) kg/d) nutrient intake, compared with a low ((1.5±0.01) kg/d) nutrient intake, from Day 0 to Day 9 of pregnancy had higher embryonic survival at Day 10 of pregnancy ((92±3)% vs. (77±3)%) (Athorn et al., 2013), which may be due to higher concentrations of blood progesterone in response to adequate feed intake. Progesterone synthesis is likely to be impaired when dietary intake of nutrients (particularly amino acids) and energy is insufficient.

4.3 Nutrition related to fetal growth during late gestation

Approximately 90% of fetal growth occurs during the last one-third of pregnancy. This period of pregnancy is characterized by a high incidence of limitations on fetal development and increased within-litter variation in fetal weight. The weight variation among piglets in each litter increased from Day 45 to Day 60 of gestation (Kim et al., 2009). After implantation, the placenta is the only organ through which nutrients, waste and respiratory gases are exchanged between the sow and conceptus (Faber and Thornburg, 1983). The size and capacity of the placenta for nutrient transfer play key roles in determining the prenatal growth of the fetus and hence affect birth weight directly (Redmer et al., 2004). Placentation that occurs during early pregnancy is one of the most important developmental events (Boshier, 1969; King et al., 1982), since it is tightly associated with embryonic survival (Reynolds and Redmer, 2001). Extensive angiogenesis occurs in both the maternal uterus and fetal placenta during placentation, and umbilical blood flow increases during the same time (Reynolds et al., 1984; Reynolds and Redmer, 1992; 1995). It has been reported that early embryonic mortality increases as placental vascular development decreases (Meegdes et al., 1988; Reynolds and Redmer, 1995). Therefore, adequately balanced diets provided to sows and functional nutrients available for placental transport are two major factors affecting uniformity of piglets in a litter during late gestation. Supplementation of diets with functional amino acids (e.g. arginine and glutamine) holds great promise for preventing fetal growth restriction (Wu et al., 2013a; Lin et al., 2014).

4.3.1 L-Arginine/N-carbamyl-L-glutamate

Amino acids in the arginine family (arginine, glutamine, glutamate, proline, aspartate, asparagine, citrulline, and ornithine) have been studied extensively given their prominent effects in improving litter size (Greenberg et al., 1997; Hazeleger et al., 2007; Mateo et al., 2007; Gao et al., 2012; Li et al., 2014). At the same time, dietary supplementation with 25.5 g/d L-arginine from Day 77 of pregnancy until term reduced within-litter variation in birth weight of live-born piglets by 20.6% and 25.4% in arginine and control groups, respectively (Quesnel et al., 2014). Dietary supplementation with 0.1% N-carbamyl-L-glutamate (NCG) from Day 90 of gestation also increased litter size born alive and total litter weight for piglets born alive (Liu et al., 2012).

L-Arginine is an important precursor for the synthesis of NO and polyamines (Wu and Morris, 1998; Wu et al., 2007; Blachier et al., 2011), both of which play key roles in placental growth and angiogenesis (Wu et al., 2006). Similarly, NCG stimulates expression of vascular endothelial growth factor (Liu et al., 2012) associated with vasculogenesis and angiogenesis (Hanahan, 1997; Arroyo and Winn, 2008). Subsequently, NCG increases blood flow and placental efficiency (McCrabb and Harding, 1996; Gardner et al., 2001), as well as the provision of nutrients to fetuses. Therefore, nutrient partitioning among fetuses is less variable as is within-litter variation in birth weight of piglets. However, there are other reports that do not indicate positive effects of dietary supplementation with L-arginine during mid-gestation to term on within-litter uniformity (Mateo et al., 2007; Gao et al., 2012). These different findings may be explained by differences in the total amounts of dietary L-arginine and other amino acids consumed by gestating pigs (Wu et al., 2013b; 2013c).

As previously mentioned, either dextrose supplementation during the weaning-to-estrus interval or 1% L-arginine supplementation during the last one-third of gestation can reduce within-litter variation in birth weights (van den Brand et al., 2006; Quesnel et al., 2014). Unexpectedly, combined supplies of dextrose beginning one week before insemination and L-arginine during the last one-third of pregnancy in sow diets had no obvious beneficial effects on within-litter variation in birth weight, compared with control groups (Quesnel et al., 2014). This was postulated to be correlated with complex interactions between different nutrients. High levels of glucose can affect amino acid metabolism and, therefore, may not be beneficial for embryonic and fetal survival, growth, or development. Thus, consideration must be given to interactions among different nutrients when manipulating maternal diets during gestation.

4.3.2 Glutamine

As a member of the arginine family of amino acids, glutamine plays a key role in many metabolic processes, such as cell proliferation, differentiation, and embryonic development (Petters et al., 1990; Wu et al., 2011). Concentrations of glutamine are highest among amino acids in fetal tissues and maternal placenta (Self et al., 2004), and there are increased concentrations of glutamine in allantoic fluid in the second third of gestation (Wu et al., 1996), which highlights the importance of glutamine during that stage of rapid placental and fetal growth.

Within-litter variation in weight of piglets can also be reduced by dietary supplementation with glutamine (Wu et al., 2010). Sows fed a basal gestational diet supplemented with mixture of 8 g L-arginine and 12 g L-glutamine had reduced within-litter variation in birth weight either on the basis of total piglets or live-born piglets, and the pro-portion of runt piglets was decreased. It would be of interest to determine whether dietary supplementation with L-glutamate, which is the immediate precursor of L-glutamine (Rezaei et al., 2013b) and is another functional amino acid (Wu, 2010), can enhance fetal growth and reduce birth-weight variation among piglets.

4.3.3 Branched chain amino acids

Branched chain amino acids (BCAAs), including leucine, isoleucine, and valine, have received growing attention owing to their emerging functional importance (Lei et al., 2012; 2013). These amino acids are substrates for the synthesis of glutamate and arginine, and, therefore, alanine, citrulline, arginine, and proline in pigs (Rezaei et al., 2013a) and ruminant species (Wu et al., 2014). Data from our laboratories suggest that dietary supplementation with BCAAs throughout pregnancy can reverse IUGR in a rat model of malnutrition (Zheng et al., 2009). In litters derived from BCAA-supplemented gestating sows, weights of piglets and placentas increase by 18.4% and 18.0%, respectively, and litter size is also increased. Furthermore, BCAA treatment increased IGF-1 in embryonic liver, estrogen receptor-α and progesterone receptor in the uterus, and IGF-II in placentas, all of which are beneficial to survival and growth of the conceptus. There was also enhanced expression of two key enzymes (fructose-1,6-biphosphatase and phosphoenolpyruvate carboxykinase) involved in gluconeogenesis in embryonic livers. These positive findings indicate that BCAAs have important roles in enhancing positive pregnancy outcomes.

Fetal growth is affected by the nutritional, metabolic and endocrine status of the maternal system which is affected by dietary intake of nutrients (Lin et al., 2014). Moreover, nutrient requirements of sows are distinct at different stages of gestation (Kim et al., 2013). Therefore, more studies to gain insight into the molecular mechanism for the role of maternal nutrients on fetal programming are necessary for designing innovative nutrient-balanced gestational diets that enhance the homogeneity of birth weight of piglets.

4.4 Genetic selection

Litter size, directly related to productivity, has been considered as a key factor in genetic selection. As a result, the total number of piglets at birth has been significantly improved in past decades (Southwood and Kennedy, 1991; Estany and Sorensen, 1995). However, this practice has also increased the neonatal mortality of piglets owing to the increased percentage of low-birth-weight pigs (Lund et al., 2002). To avoid this situation, scientists have started to test whether litter size at Day 5 (LS5) after birth can be used to reduce the neonatal mortality while not decreasing the litter size at birth. Recent results from 42 807 Landrace and 33 225 Yorkshire sows showed a significant genetic and phenotypic improvement in the total number of piglets at birth and neonatal survival (Nielsen et al., 2013), as well as litter size at weaning (Su et al., 2007; EAAP, 2011) by using LS5 as an index of genetic selection. Therefore, this criterion has been extended for use in the Danish Landrace and Yorkshire breeding program since 2004 (Nielsen et al., 2013). At the same time, a maternal line selected on litter size at weaning in rabbits for 21 generations improved the number of progeny born alive and litter size at weaning, compared with selection on litter size at birth (García and Baselga, 2002), suggesting that it is effective in both promoting litter size at birth and survival rate during lactation (Savietto et al., 2014). Additionally, it is feasible to select for within-litter uniformity in birth weight (Damgaard et al., 2003; Kapell et al., 2011) to improve piglet survival (Canario et al., 2010). A selection experiment on within-litter birth-weight variation in rabbits yielded a favorable response and decreased pre-weaning morbidity (Garreau et al., 2004). Collectively, genetic selection by combining litter uniformity at birth, survival rate during lactation, and litter size at weaning holds a promise of improving pig productivity.

5 Summary and perspectives

Currently, special attention is given to within-litter variation in birth weight, as a distinct problem in modern highly prolific sows. Heterogeneity is a problem mainly for piglets with low birth weight that have suffered from IUGR (Foxcroft et al., 2006), which is associated with high pre-weaning mortality, variable weights at weaning, and poor growth performance post-weaning, resulting in lower production efficiency and economic losses. Furthermore, within-litter homogeneity in birth weight may also be related to a decrease in stillbirths (Damgaard et al., 2003; Canario et al., 2006). In this context, the development of strategies that reduce within-litter variation in birth weight or unfavorable traits that are negatively related to piglet survival is essential for sustaining the pig industry. Since the degree of heterogeneity within litters increases as a response to selection for litter size (Johnson et al., 1999), genetic selection on litter size should be accompanied by selection on piglet survival traits (losses from birth to weaning and the minimal birth weight in the litter, which are proposed as potential traits for a selection against piglet mortality) and birth-weight traits (Wolf et al., 2008). On the other hand, identifying the physiological and biochemical mechanisms responsible for variation in litter birth weight and optimizing maternal nutrition to support requirements for growth and development of conceptuses is essential. Research focused on regulation of litter homogeneity is in its infancy, and therefore, more researches are essential to better understand the cellular and molecular mechanisms by which certain nutrients regulate metabolic pathways and embryonic/fetal development. It should also be borne in mind that nutrient interactions (e.g. ratios of amino acids, carbohydrate, and fatty acids) affect within-litter variation in birth weight. Finally, gestating swine requires not only proteinogenic amino acids that cannot be synthesized in animal cells but also proteinogenic and possibly non-proteinogenic amino acids that can be synthesized in the body to support their maximum reproductive performance (Wang W.W. et al., 2013; Wu, 2014). These synthesizable, functional amino acids include L-arginine, L-glutamine, L-proline, and glycine (Wang W.W. et al., 2014; Wu, 2013) to improve anti-oxidative capacity, immunity, health, well-being, and tissue protein synthesis in gestating mammals (e.g. pigs).

Compliance with ethics guidelines

Tao-lin YUAN, Yu-hua ZHU, Meng SHI, Tian-tian LI, Na LI, Guo-yao WU, Fuller W. BAZER, Jian-jun ZANG, Feng-lai WANG, and Jun-jun WANG declare that they have no conflict of interest.

This article does not contain any studies with human or animal subjects performed by any of the authors.


  1. Adashi, E.Y., Hsueh, A., Yen, S.,(1981) Insulin enhancementof luteinizing-hormone and follicle-stimulating-hormonerelease by cultured pituitary-cells. Endocrinology, 108(4):1441–1449. [doi:10.1210/endo-108-4-1441]PubMedCrossRefGoogle Scholar
  2. Anderson, L.L.,(1978) Growth, protein content and distributionof early pig embryos. Anat. Rec., 190(1):143–153.[doi:10.1002/ar.1091900112]Google Scholar
  3. Antipatis, C., Finch, A.M., Ashworth, C.J.,(2008) Effect ofcontrolled alterations in maternal dietary retinol on foetaland neonatal retinol status and pregnancy outcome in pigs. Livest. Sci., 118(3):247–254. [doi:10.1016/j.livsci.2008.01.026]CrossRefGoogle Scholar
  4. Argente, M.J., Santacreu, M.A., Climent, A., et al.,(2006)Influence of available uterine space per fetus on fetaldevelopment and prenatal survival in rabbits selected foruterine capacity. Livest. Sci., 102(1-2):83–91. [doi:10.1016/j.livprodsci.2005.11.022]CrossRefGoogle Scholar
  5. Argente, M.J., Santacreu, M.A., Climent, A., et al.,(2008)Effects of intrauterine crowding on available uterine space per fetus in rabbits. Livest. Sci., 114(2-3):211–219. [doi:10.1016/j.livsci.2007.05.008]CrossRefGoogle Scholar
  6. Arroyo, J.A., Winn, V.D.,(2008) Vasculogenesis and angiogenesisin the IUGR placenta. Semin. Perinatol., 32(3):172–177. [doi:10.1053/j.semperi.2008.02.006]PubMedCrossRefGoogle Scholar
  7. Ashworth, C.J., Antipatis, C.,(1999) Effects of pre- and postmatingnutrition on embryo survival in gilts. Reprod. Domest. Anim., 34(3-4):103–108. [doi:10.1111/j.1439-0531.1999.tb01226.x]CrossRefGoogle Scholar
  8. Ashworth, C.J., Beattie, L., Antipatis, C., et al.,(1999) Effectsof pre- and post-mating feed intake on blastocyst size,secretory function and glucose metabolism in Meishangilts. Reprod. Fert. Dev., 11(6):323–327. [doi:10.1071/RD99040]CrossRefGoogle Scholar
  9. Athorn, R.Z., Stott, P., Bouwman, E.G., et al.,(2013) Effect offeeding level on luteal function and progesterone concentrationin the vena cava during early pregnancy in gilts. Reprod. Fert. Dev., 25(3):531–538. [doi:10.1071/RD11295]CrossRefGoogle Scholar
  10. Aucott, S.W., Donohue, P.K., Northington, F.J.,(2004) Increasedmorbidity in severe early intrauterine growth restriction. J. Perinatol., 24(7):435–440. [doi:10.1038/]PubMedCrossRefGoogle Scholar
  11. Auldist, D.E., King, R.H.,(1995) Piglets’ role in determiningmilk production in the sow. In: Hennessy, D.P., Cranwell, P.D. (Eds.), Manipulating Pig Production V. AustralasianPig Science Association, Werribee, Australia, p.114–118.Google Scholar
  12. Batshaw, M.L., Brusilow, S.W.,(1978) Asymptomatic hyperammonemiain low-birth-weight infants. Pediatr. Res.,12(3):221–224. [doi:10.1203/00006450-197803000-00012]PubMedCrossRefGoogle Scholar
  13. Bazer, F.W.,(2013) Pregnancy recognition signaling mechanismsin ruminants and pigs. J. Anim. Sci. Biotech., 4(1):23. [doi:10.1186/2049-1891-4-23]Google Scholar
  14. Bazer, F.W., Thatcher, W.W.,(1977) Theory of maternal recognitionof pregnancy in swine based on estrogen controlledendocrine versus exocrine secretion of prostaglandin-f2aby uterine endometrium. Prostaglandins, 14(2):397–401.[doi:10.1016/0090-6980(77)90185-X]PubMedCrossRefGoogle Scholar
  15. Bazer, F.W., Johnson, G.A.,(2014) Pig blastocyst-uterineinteractions. Differentiation, 87(1-2):52–65. [doi:10.1016/j.diff.2013.11.005]PubMedCrossRefGoogle Scholar
  16. Bazer, F.W., Thatcher, W.W., Martinatbotte, F., et al.,(1988)Conceptus development in large white and prolific ChineseMeishan pigs. J. Reprod. Fert., 84(1):37–42. [doi:10.1530/jrf.0.0840037]CrossRefGoogle Scholar
  17. Bazer, F.W., Wu, G., Johnson, G.A., et al.,(2014) Environmentalfactors affecting pregnancy: endocrine disrupters,nutrients and metabolic pathways. Mol. Cell. Endocrinol., 398(1-2):53–68. [doi:10.1016/j.mce.2014.09.007]PubMedCrossRefGoogle Scholar
  18. Bell, A.W., Ehrhardt, R.A.,(2002) Regulation of placentalnutrient transport and implications for fetal growth. Nutr.Res. Rev., 15(2):211–230. [doi:10.1079/NRR200239]PubMedCrossRefGoogle Scholar
  19. Bereskin, B., Shelby, C.E., Cox, D.F.,(1973) Some factorsaffecting pig survival. J. Anim. Sci., 36(5):821–827.[doi:10.2134/jas1973.365821x]PubMedCrossRefGoogle Scholar
  20. Besenfelder, U., Solti, L., Seregi, J., et al.,(1996) Different roles for B-carotene and vitamin A in the reproduction onrabbits. Theriogenology, 45(8):1583–1591. [doi:10.1016/0093-691X(96)00127-6]CrossRefGoogle Scholar
  21. Biensen, N.J., Wilson, M.E., Ford, S.P.,(1998) The impact ofeither a Meishan or Yorkshire uterus on Meishan orYorkshire fetal and placental development to days 70, 90,and 110 of gestation. J. Anim. Sci., 76(8):2169–2176.PubMedCrossRefGoogle Scholar
  22. Blachier, F., Davila, A.M., Benamouzig, R., et al.,(2011) Channelling of arginine in NO and polyamine pathways incolonocytes and consequences. Front. Biosci. (LandmarkEd.), 16(1):1331–1343. [doi:10.2741/3792]CrossRefGoogle Scholar
  23. Blomberg, L.A., Long, E.L., Sonstegard, T.S., et al.,(2005) Serial analysis of gene expression during elongation of theperi-implantation porcine trophectoderm (conceptus). Physiol.Genomics, 20(2):188–194. [doi:10.1152/physiolgenomics.00157.2004]PubMedCrossRefGoogle Scholar
  24. Blomberg, L.A., Schreier, L., Li, R.W.,(2010) Characteristicsof peri-implantation porcine concepti population andmaternal milieu influence the transcriptome profile. Mol.Reprod. Dev., 77(11):978–989. [doi:10.1002/mrd.21253] 024.PubMedCrossRefGoogle Scholar
  25. Boshier, D.P.,(1969) A histological and histochemical examinationof implantation and early placentome formation insheep. J. Reprod. Fert., 19(1):51–61. [doi:10.1530/jrf.0.0190051]Google Scholar
  26. Broekmans, F.J., Soules, M.R., Fauser, B.C.,(2009) Ovarianaging: mechanisms and clinical consequences. Endocr.Rev., 30(5):465–493. [doi:10.1210/er.2009-0006]PubMedCrossRefGoogle Scholar
  27. Canario, L., Cantoni, E., Le Bihan, E., et al.,(2006) Betweenbreedvariability of stillbirth and its relationship with sowand piglet characteristics. J. Anim. Sci., 84(12):3185–3196.[doi:10.2527/jas.2005-775]PubMedCrossRefGoogle Scholar
  28. Canario, L., Lundgren, H., Haandlykken, M., et al.,(2010) Genetics of growth in piglets and the association withhomogeneity of body weight within litters. J. Anim. Sci.,88(4):1240–1247. [doi:10.2527/jas.2009-2056]PubMedCrossRefGoogle Scholar
  29. Coffey, M.T., Britt, J.H.,(1993) Enhancement of sow reproductive-performance by ß-carotene or vitamin-A. J. Anim.Sci., 71(5):1198–1202.PubMedCrossRefGoogle Scholar
  30. Cossu, G., Borello, U.,(1999) Wnt signaling and the activationof myogenesis in mammals. EMBO J., 18(24):6867–6872.[doi:10.1093/emboj/18.24.6867]PubMedPubMedCentralCrossRefGoogle Scholar
  31. Cox, N.M., Stuart, M.J., Althen, T.G., et al.,(1987) Enhancementof ovulation rate in gilts by increasing dietary energyand administering insulin during follicular-growth. J.Anim. Sci., 64(2):507–516. [doi:10.2134/jas1987.642507x]PubMedCrossRefGoogle Scholar
  32. Cromi, A., Ghezzi, F., Raffaelli, R., et al.,(2009) Ultrasonographicmeasurement of thymus size in IUGR fetuses:a marker of the fetal immunoendocrine response to malnutrition. Ultrasound Obst. Gyn., 33(4):421–426. [doi:10.1002/uog.6320]CrossRefGoogle Scholar
  33. Damgaard, L.H., Rydhmer, L., Lovendahl, P., et al.,(2003) Genetic parameters for within-litter variation in pigletbirth weight and change in within-litter variation duringsuckling. J. Anim. Sci., 81(3):604–610.PubMedCrossRefGoogle Scholar
  34. Dewey, C.E., Martin, S.W., Friendship, R.M., et al.,(1995) Associations between litter size and specific sow-levelmanagement factors in Ontario swine. Prev. Vet. Med., 23(1-2):101–110. [doi:10.1016/0167-5877(94)00427-K]CrossRefGoogle Scholar
  35. Dhindsa, D.S., Dziuk, P.J.,(1968) Influence of varying theproportion of uterus occupied by embryos on maintenanceof pregnancy in the pig. J. Anim. Sci., 27(3):668–672. [doi:10.2134/jas1968.273668x]PubMedCrossRefGoogle Scholar
  36. Du, M., Tong, J., Zhao, J., et al.,(2010) Fetal programming ofskeletal muscle development in ruminant animals. J.Anim. Sci., 88(13 Suppl.):E51-E60. [doi:10.2527/jas.2009-2311]Google Scholar
  37. EAAP,(2011) Book of Abstracts of the 62nd Annual Meetingof the European Association for Animal Production:Stavanger, Norway, Vol. 17, Wageningen Academic Pub.Google Scholar
  38. Estany, J., Sorensen, D.,(1995) Estimation of genetic-parametersfor litter size in Danish-Landrace and Yorkshire pigs. Anim. Sci., 60(2):315–324. [doi:10.1017/S1357729800008481]CrossRefGoogle Scholar
  39. Faber, J.J., Thornburg, K.L.,(1983) Placental Physiology.Structure and Function of Fetomaternal Exchange. RavenPress, New York, p.1–192.Google Scholar
  40. Fahmy, M.H., Bernard, C.,(1971) Cause of mortality inYorkshire pigs from birth to 20 weeks of age. Can. J.Anim. Sci., 51(2):351–359. [doi:10.4141/cjas71-048]CrossRefGoogle Scholar
  41. Ferguson, E.M., Ashworth, C.J., Edwards, S.A., et al.,(2003) Effect of different nutritional regimens before ovulationon plasma concentrations of metabolic and reproductivehormones and oocyte maturation in gilts. Reproduction,126(1):61–71. [doi:10.1530/rep.0.1260061]PubMedCrossRefGoogle Scholar
  42. Ferguson, E.M., Slevin, J., Edwards, S.A., et al.,(2006) Effectof alterations in the quantity and composition of thepre-mating diet on embryo survival and foetal growth inthe pig. Anim. Reprod. Sci., 96(1-2):89–103. [doi:10.1016/j.anireprosci.2005.11.007]PubMedCrossRefGoogle Scholar
  43. Flint, A., Burton, R.D., Gadsby, J.E., et al.,(1979) Blastocystoestrogen synthesis and the maternal recognition ofpregnancy. Ciba. Found. Symp., 64:209–238.Google Scholar
  44. Ford, S.P., Reynolds, L.P., Magness, R.R.,(1982) Blood flow tothe uterine and ovarian vascular beds of gilts during theestrous cycle or early pregnancy. Biol. Reprod., 27(4):878–885. [doi:10.1095/biolreprod27.4.878]PubMedCrossRefGoogle Scholar
  45. Fowden, A.L., Giussani, D.A., Forhead, A.J.,(2005) Endocrineand metabolic programming during intrauterine development. Early Hum. Dev., 81(9):723–734. [doi:10.1016/j.earlhumdev.2005.06.007]PubMedCrossRefGoogle Scholar
  46. Foxcroft, G.R., Dixon, W.T., Novak, S., et al.,(2006) Thebiological basis for prenatal programming of postnatalperformance in pigs. J. Anim. Sci., 84(13 Suppl.):E105-E112.Google Scholar
  47. Foxcroft, G.R., Vinsky, M.D., Paradis, F., et al.,(2007) Macroenvironmenteffects on oocytes and embryos in swine. Theriogenology, 68(Suppl. 1):S30-S39. [doi:10.1016/j.theriogenology.2007.04.032]Google Scholar
  48. Fraser, D., Thompson, B.K., Ferguson, D.K., et al.,(1979) The‘teat order’ of suckling pigs: 3. Relation to competitionwithin litters. J. Agric. Sci., 92(2):257–261. [doi:10.1017/S0021859600062742]CrossRefGoogle Scholar
  49. Gao, K., Jiang, Z., Lin, Y., et al.,(2012) Dietary L-argininesupplementation enhances placental growth and reproductiveperformance in sows. Amino Acids, 42(6):2207–2214. [doi:10.1007/s00726-011-0960-9]PubMedCrossRefGoogle Scholar
  50. García, M.L., Baselga, M.,(2002) Estimation of genetic responseto selection in litter size of rabbits using a cryopreservedcontrol population. Livest. Prod. Sci., 74(1):45–53. [doi:10.1016/S0301-6226(01)00280-9]CrossRefGoogle Scholar
  51. Gardner, D.S., Powlson, A.S., Giussani, D.A.,(2001) An in vivonitric oxide clamp to investigate the influence of nitricoxide on continuous umbilical blood flow during acutehypoxaemia in the sheep fetus. J. Physiol., 537(2):587–596. [doi:10.1111/j.1469-7793.2001.00587.x]PubMedPubMedCentralCrossRefGoogle Scholar
  52. Garreau, H., Bolet, G., Hurtaud, J., et al.,(2004) Genetic homogenizationof a character. Preliminary results of acanalising selection on the birth weight of young rabbits. ITEA Prod. Anim., 100A(3):172–178 (in Spanish).Google Scholar
  53. Geisert, R.D., Renegar, R.H., Thatcher, W.W., et al., 1982a.Establishment of pregnancy in the pig: I. Interrelationshipsbetween preimplantation development of the pigblastocyst and uterine endometrial secretions. Biol. Reprod.,27(4):925–939. [doi:10.1095/biolreprod27.4.925]PubMedCrossRefGoogle Scholar
  54. Geisert, R.D., Brookbank, J.W., Roberts, R.M., et al., 1982b. Establishment of pregnancy in the pig: II. Cellular remodelingof the porcine blastocyst during elongation onDay 12 of pregnancy. Biol. Reprod., 27(4):941–955.[doi:10.1095/biolreprod27.4.941]PubMedCrossRefGoogle Scholar
  55. Geisert, R.D., Lucy, M.C., Whyte, J.J., et al.,(2014) Cytokinesfrom the pig conceptus: roles in conceptus developmentin pigs. J. Anim. Sci. Biotechnol., 5(1):51. [doi:10.1186/2049-1891-5-51]Google Scholar
  56. Gill, J.C., Thomson, W.,(1956) Observations on the behaviourof suckling pigs. Brit. J. Anim. Behav., 4(2):46–51.[doi:10.1016/S0950-5601(56)80022-1]CrossRefGoogle Scholar
  57. Giudice, L.C.,(1992) Insulin-like growth-factors and ovarianfollicular development. Endocr. Rev., 13(4):641–669.Google Scholar
  58. Gondret, F., Lefaucheur, L., Louveau, I., et al.,(2005) Thelong-term influences of birth weight on muscle characteristicsand eating meat quality in pigs individuallyreared and fed during fattening. Arch. Tierzucht., 48:68–73.Google Scholar
  59. Greenberg, S.S., Lancaster, J.R., Xie, J.M., et al.,(1997) Effectsof NO synthase inhibitors, arginine-deficient diet, andamiloride in pregnant rats. Am. J. Physiol., 273(3):R1031-R1045.Google Scholar
  60. Hammond, J.M., Mondschein, J.S., Samaras, S.E., et al.,(1991) The ovarian insulin-like growth-factors, a local amplificationmechanism for steroidogenesis and hormone action. J. Steroid Biochem. Mol. Biol., 40(1-3):411–416.[doi:10.1016/0960-0760(91)90209-N]PubMedCrossRefGoogle Scholar
  61. Hanahan, D.,(1997) Signaling vascular morphogenesis andmaintenance. Science, 277(5322):48–50. [doi:10.1126/science.277.5322.48]Google Scholar
  62. Harney, J.P., Mirando, M.A., Smith, L.C., et al.,(1990) Retinolbindingprotein—a major secretory product of the pigconceptus. Biol. Reprod., 42(3):523–532. [doi:10.1095/biolreprod42.3.523]PubMedCrossRefGoogle Scholar
  63. Hayden, M.S., Ghosh, S.,(2012) NF-B, the first quarter-century:remarkable progress and outstanding questions. GeneDev., 26(3):203–234. [doi:10.1101/gad.183434.111]Google Scholar
  64. Hazeleger, W., Ramaekers, P., Smits, C., et al.,(2007) Influenceof nutritional factors on placental growth and pigletimprinting. In: Wiseman, J., Varley, M.A., McOrist, S.(Eds.), Paradigms in Pig Science. Nottingham UniversityPress, Nottingham, p.309–327.Google Scholar
  65. Heap, R.B., Flint, A., Gadsby, J.E., et al.,(1979) Hormones, theearly embryo and the uterine environment. J. Reprod.Fert., 55(1):267–275. [doi:10.1530/jrf.0.0550267]CrossRefGoogle Scholar
  66. Hughes, P.E.,(1998) Effects of parity, season and boar contacton the reproductive performance of weaned sows. Livest.Prod. Sci., 54(2):151–157. [doi:10.1016/S0301-6226(97)00175-9]Google Scholar
  67. Jobgen, W.S., Fried, S.K., Fu, W.J., et al.,(2006) Regulatoryrole for the arginine-nitric oxide pathway in metabolismof energy substrates. J. Nutr. Biochem., 17(9):571–588.[doi:10.1016/j.jnutbio.2005.12.001]PubMedCrossRefGoogle Scholar
  68. Johnson, R.K., Nielsen, M.K., Casey, D.S.,(1999) Responses inovulation rate, embryonal survival, and litter traits inswine to 14 generations of selection to increase litter size. J. Anim. Sci., 77(3):541–557.PubMedCrossRefGoogle Scholar
  69. Kapell, D.N.R.G., Ashworth, C.J., Knap, P.W., et al.,(2011) Genetic parameters for piglet survival, litter size and birthweight or its variation within litter in sire and dam linesusing Bayesian analysis. Livest. Sci., 135(2-3):215–224.[doi:10.1016/j.livsci.2010.07.005]CrossRefGoogle Scholar
  70. Kemp, B., Soede, N.M., Helmond, F.A., et al.,(1995) Effects ofenergy source in the diet on reproductive hormones andinsulin during lactation and subsequent estrus in multiparoussows. J. Anim. Sci., 73(10):3022–3029.PubMedCrossRefGoogle Scholar
  71. Keys, J.L., King, G.J., Kennedy, T.G.,(1986) Increased uterinevascular-permeability at the time of embryonic attachmentin the pig. Biol. Reprod., 34(2):405–411. [doi:10.1095/biolreprod34.2.405]PubMedCrossRefGoogle Scholar
  72. Kim, J., Burghardt, R.C., Wu, G., et al.,(2011) Select nutrientsin the ovine uterine lumen. VII. Effects of arginine, leucine,glutamine, and glucose on trophectoderm cell signaling,proliferation, and migration. Biol. Reprod., 84(1):62–69. [doi:10.1095/biolreprod.110.085738]PubMedCrossRefGoogle Scholar
  73. Kim, S.W., Hurley, W.L., Han, I.K., et al.,(2000) Growth ofnursing pigs related to the characteristics of nursedmammary glands. J. Anim. Sci., 78(5):1313–1318.PubMedCrossRefGoogle Scholar
  74. Kim, S.W., Hurley, W.L., Wu, G., et al.,(2009) Ideal aminoacid balance for sows during gestation and lactation. J.Anim. Sci., 87(14 Suppl.):E123-E132. [doi:10.2527/jas.2008-1452]Google Scholar
  75. Kim, S.W., Weaver, A.C., Shen, Y.B., et al.,(2013) Improvingefficiency of sow productivity: nutrition and health. J.Anim. Sci. Biotechnol., 4(1):26. [doi:10.1186/2049-1891-4-26]PubMedPubMedCentralCrossRefGoogle Scholar
  76. King, G.J., Atkinson, B.A., Robertson, H.A.,(1982) Implantationand early placentation in domestic ungulates. J. Reprod.Fertil. Suppl., 31:17–30.PubMedGoogle Scholar
  77. King, R.H., Mullan, B.P., Dunshea, F.R., et al.,(1997) Theinfluence of piglet body weight on milk production ofsows. Livest. Prod. Sci., 47(2):169–174. [doi:10.1016/S0301-6226(96)01404-2]CrossRefGoogle Scholar
  78. Kiserud, T., Acharya, G.,(2004) The fetal circulation. PrenatalDiag., 24(13):1049–1059. [doi:10.1002/pd.1062]Google Scholar
  79. Knight, J.W., Bazer, F.W., Thatcher, W.W., et al.,(1977) Conceptus development in intact and unilaterallyhysterectomized-ovariectomized gilts: interrelations amonghormonal status, placental development, fetal fluids andfetal growth. J. Anim. Sci., 44(4):620–637. [doi:10.2134/jas1977.444620xPubMedCrossRefGoogle Scholar
  80. Knol, E.F., Leenhouwers, J.I., van der Lende, T.,(2002) Geneticaspects of piglet survival. Livest. Prod. Sci., 78(1):47–55. [doi:10.1016/S0301-6226(02)00184-7]CrossRefGoogle Scholar
  81. Kong, X.F., Tan, B.E., Yin, Y.L., et al.,(2012) L-Argininestimulates the mTOR signaling pathway and proteinsynthesis in porcine trophectoderm cells. J. Nutr. Biochem.,23(9):1178–1183. [doi:10.1016/j.jnutbio.2011.06.012]PubMedCrossRefGoogle Scholar
  82. Kong, X.F., Wang, X.Q., Yin, Y.L., et al.,(2014) Putrescinestimulates the mTOR signaling pathway and proteinsynthesis in porcine trophectoderm cells. Biol. Reprod., 91(5):106. [doi:10.1095/biolreprod.113.113977]PubMedCrossRefGoogle Scholar
  83. Le Dividich, J.,(1999) A review—neonatal and weaner pig:management to reduce variation. In: Manipulating PigProduction VII: Proceedings of the seventh biennialconference of the Australasian Pig Science Association(APSA). Adelaide, South Australia, p.135–155.Google Scholar
  84. Le Dividich, J., Noblet, J., Herpin, P., et al.,(1998) Thermoregulation.In: Wiseman, J., Varley, M.A., Chadwick, J.P. (Eds.), Progress in Pig Science. Nottingham UniversityPress, p.229–263.Google Scholar
  85. Le Dividich, J., Rooke, J.A., Herpin, P.,(2005) Nutritional andimmunological importance of colostrum for the new-bornpig. J. Agric. Sci., 143(6):469–485. [doi:10.1017/S0021859605005642]CrossRefGoogle Scholar
  86. Lee, G.J., Haley, C.S.,(1995) Comparative farrowing toweaning performance in Meishan and Large White pigsand their crosses. Anim. Sci., 60(2):269–280. [doi:10.1017/S1357729800008432]CrossRefGoogle Scholar
  87. Lei, J., Feng, D.Y., Zhang, Y.L., et al.,(2012) Nutritional andregulatory role of branched-chain amino acids in lactation. Front. Biosci. (Landmark Ed.), 17(7):2725–2739. [doi:10.2741/4082]CrossRefGoogle Scholar
  88. Lei, J., Feng, D.Y., Zhang, Y.L., et al.,(2013) Hormonal regulationof leucine catabolism in mammary epithelial cells. Amino Acids, 45(3):531–541. [doi:10.1007/s00726-012-1332-9]PubMedCrossRefGoogle Scholar
  89. Li, W., Zhong, X., Zhang, L., et al.,(2012) Heat shock protein70 expression is increased in the liver of neonatal intrauterinegrowth retardation piglets. Asian Australas. J. Anim.Sci., 25(8):1096–1101. [doi:10.5713/ajas.2012.12058]Google Scholar
  90. Li, X., Bazer, F.W., Johnson, G.A., et al.,(2010) Dietary supplementationwith 0.8% L-arginine between days 0 and 25of gestation reduces litter size in gilts. J. Nutr.,140(6):1111–1116. [doi:10.3945/jn.110.121350]PubMedCrossRefGoogle Scholar
  91. Li, X., Bazer, F.W., Johnson, G.A., et al.,(2014) Dietary supplementationwith L-arginine between days 14 and 25 ofgestation enhances embryonic development and survivalin gilts. Amino Acids, 46(2):375–384. [doi:10.1007/s00726-013-1626-6]PubMedCrossRefGoogle Scholar
  92. Lin, G., Liu, C., Feng, C., et al.,(2012) Metabolomic analysisreveals differences in umbilical vein plasma metabolitesbetween normal and growth-restricted fetal pigs duringlate gestation. J. Nutr., 142(6):990–998. [doi:10.3945/jn.111.153411]PubMedCrossRefGoogle Scholar
  93. Lin, G., Wang, X., Wu, G., et al.,(2014) Improving amino acidnutrition to prevent intrauterine growth restriction inmammals. Amino Acids, 46(7):1605–1623. [doi:10.1007/s00726-014-1725-z]PubMedCrossRefGoogle Scholar
  94. Liu, C., Lin, G., Wang, X., et al.,(2013) Intrauterine growthrestriction alters the hepatic proteome in fetal pigs. J. Nutr. Biochem., 24(6):954–959. [doi:10.1016/j.jnutbio.2012.06.016]PubMedCrossRefGoogle Scholar
  95. Liu, X.D., Wu, X., Yin, Y.L., et al.,(2012) Effects of dietaryL-arginine or N-carbamylglutamate supplementationduring late gestation of sows on the miR-15b/16,miR-221/222, VEGFA and eNOS expression in umbilicalvein. Amino Acids, 42(6):2111–2119. [doi:10.1007/s00726-011-0948-5]PubMedCrossRefGoogle Scholar
  96. Lund, M.S., Puonti, M., Rydhmer, L., et al.,(2002) Relationshipbetween litter size and perinatal and pre-weaningsurvival in pigs. Anim. Sci., 74(2):217–222.CrossRefGoogle Scholar
  97. Matamoros, I.A., Cox, N.M., Moore, A.B.,(1990) Exogenousinsulin and additional energy affect follicular distribution,follicular steroid concentrations, and granulosa-cell humanchorionic-gonadotropin binding in swine. Biol. Reprod., 43(1):1–7. [doi:10.1095/biolreprod43.1.1]PubMedCrossRefGoogle Scholar
  98. Mateo, R.D., Wu, G., Bazer, F.W., et al.,(2007) DietaryL-arginine supplementation enhances the reproductiveperformance of gilts. J. Nutr., 137(3):652–656.PubMedGoogle Scholar
  99. Maul, H., Longo, M., Saade, G.R., et al.,(2003) Nitric oxideand its role during pregnancy: from ovulation to delivery. Curr. Pharm. Design, 9(5):359–380. [doi:10.2174/1381612033391784]CrossRefGoogle Scholar
  100. McBride, G.,(1963) The “teat order” and communication inyour pigs. Anim. Behav., 11(1):53–56. [doi:10.1016/0003-3472(63)90008-3]Google Scholar
  101. McCrabb, G.J., Harding, R.,(1996) Role of nitric oxide in theregulation of cerebral blood flow in the ovine foetus. Clin. Exp. Pharmacol. Physiol., 23(10-11):855–860. [doi:10.1111/j.1440-1681.1996.tb01133.x]PubMedCrossRefGoogle Scholar
  102. Meegdes, B.H., Ingenhoes, R., Peeters, L.L., et al.,(1988) Earlypregnancy wastage: relationship between chorionic vascularizationand embryonic development. Fertil. Steril.,49(2):216–220.PubMedCrossRefGoogle Scholar
  103. Milligan, B.N., Fraser, D., Kramer, D.L.,(2001) Birth weightvariation in the domestic pig: effects on offspring survival,weight gain and suckling behaviour. Appl. Anim. Behav. Sci., 73(3):179–191. [doi:10.1016/S0168-1591(01)00136-8]PubMedCrossRefGoogle Scholar
  104. Milligan, B.N., Dewey, C.E., de Grau, A.F., 2002a. Neonatalpigletweight variation and its relation to pre-weaningmortality and weight gain on commercial farms. Prev. Vet.Med., 56(2):119–127. [doi:10.1016/S0167-5877(02)00157-5]PubMedCrossRefGoogle Scholar
  105. Milligan, B.N., Fraser, D., Kramer, D.L., 2002b. Within-litterbirth weight variation in the domestic pig and its relationto pre-weaning survival, weight gain, and variation inweaning weights. Livest. Prod. Sci., 76(1-2):181-191.[doi:10.1016/S0301-6226(02)00012-X]Google Scholar
  106. Nielsen, B., Su, G., Lund, M.S., et al.,(2013) Selection forincreased number of piglets at d 5 after farrowing hasincreased litter size and reduced piglet mortality. J. Anim.Sci., 91(6):2575–2582. [doi:10.2527/jas.2012-5990]PubMedCrossRefGoogle Scholar
  107. Père, M.C., Etienne, M.,(2000) Uterine blood flow in sows:effects of pregnancy stage and litter size. Reprod. Nutr.Dev., 40(4):369–382. [doi:10.1051/rnd:2000105]PubMedCrossRefGoogle Scholar
  108. Perry, J.S., Rowell, J.G.,(1969) Variation in foetal weight andvascular supply along the uterine horn of the pig. J. Reprod.Fertil., 19(3):527–534. [doi:10.1530/jrf.0.0190527]PubMedCrossRefGoogle Scholar
  109. Perry, J.S., Heap, R.B., Amoroso, E.C.,(1973) Steroid hormoneproduction by pig blastocysts. Nature, 245(5419):45–47.[doi:10.1038/245045a0]PubMedCrossRefGoogle Scholar
  110. Perry, J.S., Heap, R.B., Burton, R.D., et al.,(1976) Endocrinologyof the blastocyst and its role in the establishmentof pregnancy. J. Reprod. Fertil. Suppl., (25):85–104.Google Scholar
  111. Petters, R.M., Johnson, B.H., Reed, M.L., et al.,(1990) Glucose,glutamine and inorganic-phosphate in early developmentof the pig embryo in vitro. J. Reprod. Fertil., 89(1):269–275. [doi:10.1530/jrf.0.0890269]PubMedCrossRefGoogle Scholar
  112. Pettigrew, J.E., Cornelius, S.G., Moser, R.L., et al.,(1986) Effects of oral doses of corn oil and other factors onpreweaning survival and growth of pigs. J. Anim. Sci.,62(3):601–612.PubMedCrossRefGoogle Scholar
  113. Politis, I., Chronopoulou, R.,(2008) Milk peptides and immuneresponse in the neonate. In: Bösze, Z. (Ed.), BioactiveComponents of Milk. Advances in Experimental Medicineand Biology. Vol. 606, Springer New York,p.253–269. [doi:10.1007/978-0-387-74087-4_10]Google Scholar
  114. Pomeroy, R.W.,(1960) Infertility and neonatal mortality in thesow. I. Lifetime performance and reasons for disposal ofsows. J. Agric. Sci., 54(1):1–17. [doi:10.1017/S0021859600021432]Google Scholar
  115. Pond, W.G., Houpt, K.A.,(1978) The Biology of the Pig.Comstock Pub. Associates, p.371.Google Scholar
  116. Pope, W.F., Wilde, M.H., Xie, S.,(1988) Effect of electrocauteryof nonovulated day 1 follicles on subsequent morphologicalvariation among day 11 porcine embryos. Biol.Reprod., 39(4):882–887. [doi:10.1095/biolreprod39.4.882]PubMedCrossRefGoogle Scholar
  117. Pope, W.F., Xie, S., Broermann, D.M., et al.,(1990) Causes andconsequences of early embryonic diversity in pigs. J.Reprod. Fertil. Suppl., 40:251-260.Google Scholar
  118. Prunier, A., Dourmad, J.Y., Etienne, M.,(1993) Feeding level,metabolic parameters and reproductive-performance ofprimiparous sows. Livest. Prod. Sci., 37(1-2):185-196.[doi:10.1016/0301-6226(93)90071-O]Google Scholar
  119. Puppe, B., Tuchscherer, A.,(1999) Developmental and territorialaspects of suckling behaviour in the domestic pig (Susscrofa f. domestica). J. Zool., 249(3):307–313. [doi:10.1111/j.1469-7998.1999.tb00767.x]CrossRefGoogle Scholar
  120. Quesnel, H., Brossard, L., Valancogne, A., et al.,(2008) Influence of some sow characteristics on within-littervariation of piglet birth weight. Animal, 2(12):1842.[doi:10.1017/S175173110800308X]PubMedCrossRefGoogle Scholar
  121. Quesnel, H., Farmer, C., Devillers, N.,(2012) Colostrum intake:influence on piglet performance and factors of variation. Livest. Sci., 146(2-3):105–114. [doi:10.1016/j.livsci.2012.03.010]CrossRefGoogle Scholar
  122. Quesnel, H., Quiniou, N., Roy, H., et al.,(2014) Supplyingdextrose before insemination and L-arginine during thelast third of pregnancy in sow diets: effects on withinlittervariation of piglet birth weight. J. Anim. Sci.,92(4):1445–1450. [doi:10.2527/jas.2013-6701]PubMedCrossRefGoogle Scholar
  123. Quiniou, N., Dagorna, J., Gaudre, D.,(2002) Variation of pigletsbirth weight and consequences on subsequent performance.Livest. Prod. Sci., 78(1):63–70. [doi:10.1016/S0301-6226(02)00181-1]CrossRefGoogle Scholar
  124. Ran, R., Lu, A., Zhang, L., et al.,(2004) Hsp70 promotesTNF-mediated apoptosis by binding IKK? and impairingNF-?B survival signaling. Genes Dev., 18(12):1466–1481.[doi:10.1101/gad.1188204]PubMedPubMedCentralCrossRefGoogle Scholar
  125. Redmer, D.A., Wallace, J.M., Reynolds, L.P.,(2004) Effect ofnutrient intake during pregnancy on fetal and placentalgrowth and vascular development. Domest. Anim. Endocrinol.,27(3):199–217. [doi:10.1016/j.domaniend.2004.06.006]PubMedCrossRefGoogle Scholar
  126. Reynolds, L.P., Redmer, D.A.,(1992) Growth and microvasculardevelopment of the uterus during early pregnancy inewes. Biol. Reprod., 47(5):698–708. [doi:10.1095/biolreprod47.5.698]PubMedCrossRefGoogle Scholar
  127. Reynolds, L.P., Redmer, D.A.,(1995) Utero-placental vasculardevelopment and placental function. J. Anim. Sci., 73(6):1839–1851.PubMedCrossRefGoogle Scholar
  128. Reynolds, L.P., Redmer, D.A.,(2001) Angiogenesis in theplacenta. Biol. Reprod., 64(4):1033–1040. [doi:10.1095/biolreprod64.4.1033]PubMedCrossRefGoogle Scholar
  129. Reynolds, L.P., Magness, R.R., Ford, S.P.,(1984) Uterineblood flow during early pregnancy in ewes: interactionbetween the conceptus and the ovary bearing the corpusluteum. J. Anim. Sci., 58(2):423–429.PubMedCrossRefGoogle Scholar
  130. Reynolds, L.P., Caton, J.S., Redmer, D.A., et al.,(2006) Evidencefor altered placental blood flow and vascularity incompromised pregnancies. J. Physiol., 572(1):51–58.[doi:10.1113/jphysiol.2005.104430]PubMedPubMedCentralCrossRefGoogle Scholar
  131. Rezaei, R., Knabe, D.A., Li, X., et al.,(2011) Enhanced efficiencyof milk utilization for growth in surviving lowbirth-weight piglets. J. Anim. Sci. Biotechnol., 2(2):73–83.Google Scholar
  132. Rezaei, R., Wang, W.W., Wu, Z.L., et al., 2013a. Biochemicaland physiological bases for utilization of dietary aminoacids by young pigs. J. Anim. Sci. Biotechnol., 4(1):7.[doi:10.1186/2049-1891-4-7]Google Scholar
  133. Rezaei, R., Knabe, D.A., Tekwe, C.D., et al., 2013b. Dietary supplementation with monosodium glutamate is safe andimproves growth performance in postweaning pigs. Amino Acids, 44(3):911–923. [doi:10.1007/s00726-012-1420-x]PubMedCrossRefGoogle Scholar
  134. Robertson, J.A.,(1997) Investigations of the action of vitaminA and ß carotene on reproductive performance in pigs. PhD Thesis, Victoria University of Technology, Australia.Google Scholar
  135. Robertson, J.A., Towstoless, M.K., Ott, T.L., et al.,(1997) Effect of retinol palmitate on ovarian follicle size andfollicular hormone concentration in the gilt. Biol. Reprod., 56(1):452.Google Scholar
  136. Rooke, J.A., Bland, I.M.,(2002) The acquisition of passiveimmunity in the new-born piglet. Livest. Prod. Sci., 78(1):13–23. [doi:10.1016/S0301-6226(02)00182-3]CrossRefGoogle Scholar
  137. Rosahn, P.D., Greene, H.S.N.,(1936) The influence of intrauterinefactors on the fetal weight of rabbits. J. Exp. Med.,63(6):901–921. [doi:10.1084/jem.63.6.901]PubMedPubMedCentralCrossRefGoogle Scholar
  138. Ross, J.W., Ashworth, M.D., Hurst, A.G., et al.,(2003) Analysisand characterization of differential gene expressionduring rapid trophoblastic elongation in the pig usingsuppression subtractive hybridization. Reprod. Biol. Endocrinol., 1(1):23. [doi:10.1186/1477-7827-1-23]Google Scholar
  139. Savietto, D., Cervera, C., Rodenas, L., et al.,(2014) Differentresource allocation strategies result from selection forlitter size at weaning in rabbit does. Animal, 8(4):618–628.[doi:10.1017/S1751731113002437]PubMedCrossRefGoogle Scholar
  140. Schweigert, F.J., Bonitz, K., Siegling, C., et al.,(1999) Distributionof vitamin A, retinol-binding protein, cellular retinoicacid-binding protein I, and retinoid X receptor ß inthe porcine uterus during early gestation. Biol. Reprod.,61(4):906–911. [doi:10.1095/biolreprod61.4.906]PubMedCrossRefGoogle Scholar
  141. Self, J.T., Spencer, T.E., Johnson, G.A., et al.,(2004) Glutaminesynthesis in the developing porcine placenta. Biol.Reprod., 70(5):1444–1451. [doi:10.1095/biolreprod.103.025486]PubMedCrossRefGoogle Scholar
  142. Sharpe, H.B.,(1966) Pre-weaning mortality in a herd of Large White pigs. Brit. Vet. J., 122(3):99–111.Google Scholar
  143. Soede, N.M., Noordhuizen, J.P.T.M., Kemp, B.,(1992) Theduration of ovation in pigs, studied by transrectal ultrasonography,is not related to early embryonic diversity. Theriogenology, 38(4):653–666. [doi:10.1016/0093-691X(92)90028-P]PubMedCrossRefGoogle Scholar
  144. Southwood, O.I., Kennedy, B.W.,(1991) Genetic and environmentaltrends for litter size in swine. J. Anim. Sci., 69(8):3177–3182.PubMedCrossRefGoogle Scholar
  145. Stroband, H.W., van der Lende, T., (1990) Embryonic anduterine development during early pregnancy in pigs. J.Reprod. Fertil. Suppl., 40:261–277.PubMedGoogle Scholar
  146. Su, G., Lund, M.S., Sorensen, D.,(2007) Selection for litter sizeat day five to improve litter size at weaning and pigletsurvival rate. J. Anim. Sci., 85(6):1385–1392. [doi:10.2527/jas.2006-631]PubMedCrossRefGoogle Scholar
  147. Thompson, B.K., Fraser, D.,(1986) Variation in piglet weights:development of within litter variation over a 5-week lactationand effect of farrowing crate design. Can. J. Anim. Sci., 66(2):361–372. [doi:10.4141/cjas86-037]CrossRefGoogle Scholar
  148. Tokach, M.D., Pettigrew, J.E., Dial, G.D., et al.,(1992) Characterizationof luteinizing-hormone secretion in the primiparous,lactating sow-relationship to blood metabolitesand return-to-estrus interval. J. Anim. Sci., 70(7):2195–2201.PubMedCrossRefGoogle Scholar
  149. Town, S.C., Putman, C.T., Turchinsky, N.J., et al.,(2004) Number of conceptuses in utero affects porcine fetalmuscle development. Reproduction, 128(4):443–454. [doi:10.1530/rep.1.00069]PubMedCrossRefGoogle Scholar
  150. van den Brand, H., Soede, N.M., Schrama, J.W., et al.,(1998) Effects of dietary energy source on plasma glucose andinsulin concentration in gilts. J. Anim. Physiol. An. N., 79(1-5):27–32. [doi:10.1111/j.1439-0396.1998.tb00626.x]CrossRefGoogle Scholar
  151. van den Brand, H., Dieleman, S.J., Soede, N.M., et al.,(2000) Dietary energy source at two feeding levels during lactationof primiparous sows: I. Effects on glucose, insulin,and luteinizing hormone and on follicle development,weaning-to-estrus interval, and ovulation rate. J. Anim.Sci., 78(2):396–404.PubMedCrossRefGoogle Scholar
  152. van den Brand, H., Soede, N.M., Kemp, B.,(2006) Supplementationof dextrose to the diet during the weaning toestrus interval affects subsequent variation in within-litterpiglet birth weight. Anim. Reprod. Sci., 91(3-4):353–358.[doi:10.1016/j.anireprosci.2005.04.009]PubMedCrossRefGoogle Scholar
  153. van den Brand, H., van Enckevort, L.C.M., van der Hoeven, E.M., et al.,(2009) Effects of dextrose plus lactose in thesows diet on subsequent reproductive performance andwithin litter birth weight variation. Reprod. Domest. Anim., 44(6):884–888. [doi:10.1111/j.1439-0531.2008.01106.x]PubMedCrossRefGoogle Scholar
  154. van der Lende, T., Dejager, D.,(1991) Death risk andpreweaning growth-rate of piglets in relation to thewithin-litter weight distribution at birth. Livest. Prod. Sci.,28(1):73–84. [doi:10.1016/0301-6226(91)90056-V]CrossRefGoogle Scholar
  155. van der Lende, T., Hazeleger, W., Dejager, D.,(1990) Weightdistribution within litters at the early fetal stage and atbirth in relation to embryonic mortality in the pig. Livest. Prod. Sci., 26(1):53–65. [doi:10.1016/0301-6226(90)90055-B]CrossRefGoogle Scholar
  156. Vonnahme, K.A., Wilson, M.E., Foxcroft, G.R., et al.,(2002) Impacts on conceptus survival in a commercial swineherd. J. Anim. Sci., 80(3):553–559.PubMedCrossRefGoogle Scholar
  157. Waldorf, D.P., Foote, W.C., Sele, H.L., et al.,(1957) Factoryaffecting fetal pig weight late in gestation. J. Anim. Sci.,4(16):976–985. [doi:10.2134/jas1957.164976x]CrossRefGoogle Scholar
  158. Walzem, R.L., Dillard, C.J., German, J.B.,(2002) Whey components:millennia of evolution create functionalities formammalian nutrition: what we know and what we may beoverlooking. Crit. Rev. Food Sci. Nutr., 42(4):353–375.[doi:10.1080/10408690290825574]PubMedCrossRefGoogle Scholar
  159. Wang, J., Chen, L., Li, D., et al.,(2008) Intrauterine growthrestriction affects the proteomes of the small intestine,liver, and skeletal muscle in newborn pigs. J. Nutr.,138(1):60–66.PubMedGoogle Scholar
  160. Wang, T., Liu, C., Feng, C., et al.,(2013) IUGR alters musclefiber development and proteome in fetal pigs. Front Biosci. (Landmark Ed.), 18(2):598–607. [doi:10.2741/4123]CrossRefGoogle Scholar
  161. Wang, W.W., Wu, Z.L., Dai, Z.L., et al.,(2013) Glycine metabolismin animals and humans: implications for nutritionand health. Amino Acids, 45(3):463–477. [doi:10.1007/s00726-013-1493-1]PubMedCrossRefGoogle Scholar
  162. Wang, W.W., Wu, Z.L., Lin, G., et al.,(2014) Glycine stimulatesprotein synthesis and inhibits oxidative stress in pigsmall-intestinal epithelial cells. J. Nutr., 144(10):1540–1548. [doi:10.3945/jn.114.194001]PubMedCrossRefGoogle Scholar
  163. Wang, X.Q., Frank, J.W., Xu, J., et al., 2014a. Functional roleof arginine during the peri-implantation period of pregnancy.II. Consequences of loss of function of nitric oxidesynthase NOS3 mRNA in ovine conceptus trophectoderm. Biol. Reprod., 91(3):59. [doi:10.1095/biolreprod.114.121202]PubMedCrossRefGoogle Scholar
  164. Wang, X.Q., Lin, G., Liu, C., et al., 2014b. Temporal proteomicanalysis reveals defects in small-intestinal developmentof porcine fetuses with intrauterine growth restriction. J. Nutr. Biochem., 25(7):785–795. [doi:10.1016/j.jnutbio.2014.03.008]PubMedCrossRefGoogle Scholar
  165. Webel, S.K., Dziuk, P.J.,(1974) Effect of stage of gestation anduterine space on prenatal survival in pig. J. Anim. Sci.,38(5):960–963. [doi:10.2134/jas1974.385960x]PubMedCrossRefGoogle Scholar
  166. Wei, Y.Q., Zhao, X., Kariya, Y., et al.,(1995) Inhibition ofproliferation and induction of apoptosis by abrogation ofheat-shock protein (HSP) 70 expression in tumor cells. Cancer Immunol. Immunother., 40(2):73–78. [doi:10.1007/BF01520287]PubMedCrossRefGoogle Scholar
  167. Whaley, S.L., Hedgpeth, V.S., Britt, J.H.,(1997) Evidence thatinjection of vitamin A before mating may improve embryosurvival in gilts fed normal or high-energy diets. J.Anim. Sci., 75(4):1071–1077.PubMedCrossRefGoogle Scholar
  168. Whaley, S.L., Hedgpeth, V.S., Farin, C.E., et al.,(2000) Influence of vitamin A injection before mating on oocytedevelopment, follicular hormones, and ovulation in giltsfed high-energy diets. J. Anim. Sci., 78(6):1598–1607.PubMedCrossRefGoogle Scholar
  169. Widdowson, E.M.,(1971) Intrauterine growth retardation in pig.I. Organ size and cellular development at birth and aftergrowth to maturity. Neonatology, 19(4-6):329–340.[doi:10.1159/000240427]Google Scholar
  170. Wientjes, J.G.M., Soede, N.M., van der Peet-Schwering, C.M.C., et al.,(2012) Piglet uniformity and mortality inlarge organic litters: effects of parity and pre-mating dietcomposition. Livest. Sci., 144(3):218–229. [doi:10.1016/j.livsci.2011.11.018]CrossRefGoogle Scholar
  171. Wigmore, P., Stickland, N.C.,(1983) Muscle development inlarge and small pig fetuses. J. Anat., 137(Pt 2):235–245.PubMedPubMedCentralGoogle Scholar
  172. Wilson, M.E., Biensen, N.J., Youngs, C.R., et al.,(1998) Development of Meishan and Yorkshire littermate conceptusesin either a Meishan or Yorkshire uterine environmentto day 90 of gestation and to term. Biol. Reprod.,58(4):905–910. [doi:10.1095/biolreprod58.4.905]PubMedCrossRefGoogle Scholar
  173. Winters, L.M., Cummings, J.N., Stewart, H.A.,(1947) A studyof factors affecting survival from birth to weaning andtotal weaning weight of the litter in swine. J. Anim. Sci.,6(3):288–296. [doi:10.2134/jas1947.63288x]PubMedCrossRefGoogle Scholar
  174. Wise, T., Roberts, A.J., Christenson, R.K.,(1997) Relationshipsof light and heavy fetuses to uterine position, placentalweight, gestational age, and fetal cholesterol concentrations. J. Anim. Sci., 75(8):2197–2207.PubMedCrossRefGoogle Scholar
  175. Wiseman, J., Varley, M.A., Chadwick, J.P.,(1998)Progress in Pig Science. Nottingham University Press.Google Scholar
  176. Wolf, J., Zakova, E., Groeneveld, E.,(2008) Within-litter variationof birth weight in hyperprolific Czech Large Whitesows and its relation to litter size traits, stillborn pigletsand losses until weaning. Livest. Sci., 115(2-3):195–205.[doi:10.1016/j.livsci.2007.07.009]CrossRefGoogle Scholar
  177. Wootton, R., Flecknell, P.A., Royston, J.P., et al.,(1983) Intrauterine growth-retardation detected in several speciesby non-normal birth-weight distributions. J. Reprod. Fertil., 69(2):659–663. [doi:10.1530/jrf.0.0690659]PubMedCrossRefGoogle Scholar
  178. Wu, G.,(2010) Functional amino acids in growth, reproductionand health. Adv. Nutr., 1(1):31–37. [doi:10.3945/an.110.1008]Google Scholar
  179. Wu, G.,(2013) Functional amino acids in nutrition and health. Amino Acids, 45(3):407–411. [doi:10.1007/s00726-013-1500-6]Google Scholar
  180. Wu, G.,(2014) Dietary requirements of synthesizable aminoacids by animals: a paradigm shift in protein nutrition. J. Anim. Sci. Biotechnol., 5(1):34. [doi:10.1186/2049-1891-5-34]Google Scholar
  181. Wu, G., Morris, S.M.,(1998) Arginine metabolism: nitric oxideand beyond. Biochem. J., 336(1):1–17.PubMedPubMedCentralCrossRefGoogle Scholar
  182. Wu, G., Bazer, F.W., Tuo, W.B., et al.,(1996) Unusual abundanceof arginine and ornithine in porcine allantoic fluid. Biol. Reprod., 54(6):1261–1265.PubMedCrossRefGoogle Scholar
  183. Wu, G., Bazer, F.W., Wallace, J.M., et al.,(2006) Board-invitedreview: intrauterine growth retardation: implications forthe animal sciences. J. Anim. Sci., 84(9):2316–2337. [doi:10.2527/jas.2006-156]PubMedCrossRefGoogle Scholar
  184. Wu, G., Bazer, F.W., Davis, T.A., et al.,(2007) Important rolesfor the arginine family of amino acids in swine nutritionand production. Livest. Sci., 112(1-2):8–22. [doi:10.1016/j.livsci.2007.07.003]CrossRefGoogle Scholar
  185. Wu, G., Bazer, F.W., Datta, S., et al.,(2008) Proline metabolismin the conceptus: implications for fetal growth anddevelopment. Amino Acids, 35(4):691–702. [doi:10.1007/s00726-008-0052-7]PubMedCrossRefGoogle Scholar
  186. Wu, G., Bazer, F.W., Davis, T.A., et al.,(2009) Arginine metabolismand nutrition in growth, health and disease. Amino Acids, 37(1):153–168. [doi:10.1007/s00726-008-0210-y]PubMedCrossRefGoogle Scholar
  187. Wu, G., Bazer, F.W., Burghardt, R.C., et al.,(2010) Impacts ofamino acid nutrition on pregnancy outcome in pigs:mechanisms and implications for swine production. J.Anim. Sci., 88(13 Suppl.):E195-E204. [doi:10.2527/jas.2009-2446]Google Scholar
  188. Wu, G., Bazer, F.W., Johnson, G.A., et al.,(2011) TriennialGrowth Symposium: important roles for L-glutamine inswine nutrition and production. J. Anim. Sci., 89(7):2017–2030. [doi:10.2527/jas.2010-3614]PubMedCrossRefGoogle Scholar
  189. Wu, G., Wu, Z.L., Dai, Z.L., et al., 2013a. Dietary requirementsof “nutritionally nonessential amino acids” byanimals and humans. Amino Acids, 44(4):1107–1113.[doi:10.1007/s00726-012-1444-2]PubMedCrossRefGoogle Scholar
  190. Wu, G., Bazer, F.W., Satterfield, M.C., et al., 2013b. Impactsof arginine nutrition on embryonic and fetal developmentin mammals. Amino Acids, 45(2):241–256. [doi:10.1007/s00726-013-1515-z]PubMedCrossRefGoogle Scholar
  191. Wu, G., Bazer, F.W., Johnson, G.A., et al., 2013c. Maternaland fetal amino acid metabolism in gestating sows. Soc.Reprod. Fertil. Suppl., 68:185–198.Google Scholar
  192. Wu, G., Bazer, F.W., Dai, Z., et al.,(2014) Amino acid nutritionin animals: protein synthesis and beyond. Annu. Rev.Anim. Biosci., 2(1):387–417. [doi:10.1146/annurev-animal-022513-114113]PubMedCrossRefGoogle Scholar
  193. Wu, W.Z., Wang, X.Q., Wu, G.Y., et al.,(2010) Differentialcomposition of proteomes in sow colostrum and milkfrom anterior and posterior mammary glands. J. Anim.Sci., 88(8):2657–2664. [doi:10.2527/jas.2010-2972]PubMedCrossRefGoogle Scholar
  194. Xie, S., Broermann, D.M., Nephew, K.P., et al.,(1990) Ovulationand early embryogenesis in swine. Biol. Reprod.,43(2):236–240. [doi:10.1095/biolreprod43.2.236]PubMedCrossRefGoogle Scholar
  195. Yang, H., Foxcroft, G.R., Pettigrew, J.E., et al.,(2000) Impactof dietary lysine intake during lactation on follicular developmentand oocyte maturation after weaning in primiparoussows. J. Anim. Sci., 78(4):993–1000.PubMedCrossRefGoogle Scholar
  196. Zak, L.J., Cosgrove, J.R., Aherne, F.X., et al.,(1997) Pattern offeed intake and associated metabolic and endocrinechanges differentially affect postweaning fertility in primiparouslactating sows. J. Anim. Sci., 75(1):208–216.PubMedCrossRefGoogle Scholar
  197. Zheng, C., Huang, C., Cao, Y., et al.,(2009) Branched-chainamino acids reverse the growth of intrauterine growthretardation rats in a malnutrition model. Asian Australas. J. Anim. Sci., 22(11):1495–1503. [doi:10.5713/ajas.2009.90127]CrossRefGoogle Scholar
  198. Zhong, X., Wang, T., Zhang, X., et al.,(2010) Heat shock protein 70 is upregulated in the intestine of intrauterine growth retardation piglets. Cell Stress Chaperones, 15(3):335–342. [doi:10.1007/s12192-00-0148-3]PubMedCrossRefGoogle Scholar
  199. Zhong, X., Li, W., Huang, X., et al.,(2012) Impairment of cellular immunity is associated with overexpression of heat shock protein 70 in neonatal pigs with intrauterine growth retardation. Cell Stress Chaperones, 17(4):495–505. [doi:10.1007/s12192-012-0326-6]PubMedPubMedCentralCrossRefGoogle Scholar
  200. Ziecik, A.J., Kapelanski, W., Zaleska, M., et al.,(2002) Effect of diet composition and frequency of feeding on postprandial insulin level and ovarian follicular development in prepubertal pigs. J. Anim. Feed Sci., 11(3):471–483.CrossRefGoogle Scholar

Copyright information

© Zhejiang University and Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Tao-lin Yuan
    • 1
  • Yu-hua Zhu
    • 1
  • Meng Shi
    • 1
  • Tian-tian Li
    • 1
  • Na Li
    • 1
  • Guo-yao Wu
    • 2
  • Fuller W. Bazer
    • 2
  • Jian-jun Zang
    • 1
  • Feng-lai Wang
    • 1
  • Jun-jun Wang
    • 1
  1. 1.State Key Laboratory of Animal Nutrition, College of Animal Science and TechnologyChina Agricultural UniversityBeijingChina
  2. 2.Department of Animal Science, Texas A&M UniversityCollege StationTexasUSA

Personalised recommendations