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Mother’s Little Helper? The Placenta and Its Role in Intrauterine Maternal Investment in the Common Marmoset (Callithrix jacchus)

  • Julienne N. Rutherford
  • Suzette Tardif
Chapter
Part of the Developments in Primatology: Progress and Prospects book series (DIPR)

Abstract

Litter size variation within the Callitrichidae is the result of complex interactions among genetic and environmental factors, and occurs across many facets of the reproductive cycle, from ovulation number to intrauterine litter size reduction to neonate lactation competition. Selection appears to have acted upon the callitrichine ability to make “decisions” relative to maternal nutritional state and litter size in a way that has yielded a highly sensitive and plastic system. Natural variation in marmoset litter size, birth weights and placental weights, and maternal condition create an opportunity to test hypotheses related to intrauterine growth retardation and maternal investment. We present evidence suggesting that differences in fetal/placental weight ratios in marmosets represent distinct strategies of intrauterine resource solicitation by members of litters of different sizes as a result of prenatal parent-offspring conflict. Individual triplets are associated with a smaller share of the placenta by weight than are twins, suggesting a mechanism by which triplets increase placental efficiency in the face of finite maternal resources and uterine space constraints. Twin and triplet fetuses appear to pursue different intrauterine strategies for maximizing allocation of the maternal resources via the placenta. Since complete triplet litters are almost never successfully reared to weaning, maternal limitations of energy intake and investment in offspring from conception to weaning appear to be in conflict with the triplet strategy of optimizing the intrauterine environment through placental development and function.

Keywords

Litter Size Fetal Weight Common Marmoset Placental Weight Maternal Condition 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Resumen

El tamaño de la variación entre los Callitrichidae es el resultado de una compleja interacción entre factores genéticos y de medio ambiente, y parece ocurrir a lo largo de muchas facetas del ciclo reproductivo, desde el número de ovulación a la reducción del tamaño de la fuente intrauterina a la competencia lactante del recien nacido. La selección parece haber actuado sobre la habilidad de los calitricidos de tomar “decisiones” relacionadas con el estado nutricional maternal y el tamaño de las camada en una forma que ha producido un sistema altamente sensitivo y plástico. La variación del tamaño de las camadas marmoset, sus pesos al nacer y pesos de las placentas, junto a la condición materna crearon la oportunidad de poner a prueba la hipótesis relacionada con el retraso del crecimiento intrauterino y la inversión materna. Este estudio presenta evidencias que sugieren que las diferencias en los índices de peso fetal y de placenta entre los marmosets podrían representar distintas estrategias en los recursos de incitación intrauterina por miembros de camadas de diferentes tamaños; todo ello como resultado de conflicto prenatal entre padres y descendencia. Los individuos trillizos están asociados a mayor compartimiento de la placenta que los gemelos, sugiriendo un mecanismo en el cual los trillizos solicitan crecimiento placental compensatorio en cara a recursos maternales finitos. Los fetos gemelos y trillizos parecen seguir diferentes estrategias intrauterinas para maximizar para la repartición de la placenta. Desde que las camadas de trillizos son casi nunca exitosas en la crianza durante el destete, las limitaciones maternas de energia admitida y la inversión en las crias desde la concepcion hasta el destete parecen estar en conflicto con las estrategias de los trillizos de optimizar el medio ambiente intrauterino a través del crecimiento de la placenta.

Resumo

A variação entre tamanho da prole na família Callitrichidae é o resultado de situações complexas entre fatores genéticos e ambientais e parece ocorrer por meio de muitas facetas do ciclo reprodutivo, desde o número de ovulações até a redução do tamanho da prole intra-útero e a competição dos neonatos pela lactação. A seleção parece ter atuado sobre a habilidade dos calitriquídeos de tomar “decisões” relativas ao estado nutricional materno e tamanho da prole, que resultou na produção de um sistema altamente sensível e plástico. A variação natural no tamanho da prole em sagüi, do peso ao nascimento e do peso placentário e das condições maternas cria uma oportunidade para testar hipóteses relacionadas ao retardo no crescimento intra-uterino e ao investimento materno. Nós apresentamos evidências sugerindo que as diferenças na razão peso placentário/peso fetal em sagüi podem representar diferentes estratégias de solicitação de recursos intra-uterinos pelos membros das proles de diferentes tamanhos, resultante de um conflito pais-prole durante o período pré-natal. Tendo como base o peso, indivíduos de uma prole de triplos compartilham a placenta pelo peso mais do que os gêmeos sugerindo um mecanismo pelo qual os triplos requerem um crescimento compensatório da placenta em função dos recursos finitos da mãe. Fetos duplos e triplos parecem utilizar diferentes estratégias no útero da mãe para maximizar a alocação da placenta. Uma vez que as proles de triplos quase nunca são criadas com sucesso até o desmame, as limitações da mãe na ingestão de energia e investimento na prole, da concepção ao desmame, parece gerar um conflito com as estratégias de triplos de otimizar o ambiente intra-uterino por meio do crescimento placentário.

16.1 Introduction

When Trivers (1974) introduced the genetic explanation for parent–offspring conflict theory, he set in motion the dismantling of romantic notions of pregnancy as a time of unparalleled harmony and synchrony between the mother and fetus. There are real conflicts between the mother and fetus in terms of resource allocation throughout gestation. Since a fetus is more related to itself than to its mother or to nonmonozygous siblings, in the context of inclusive fitness it can be predicted to pursue a strategy of exploitation of maternal resources that may be at odds with the mother’s interest in long term reproductive investment (Haig 1993, 1996; Long 2005). If fetal demands outstrip maternal resources, fetal growth can be compromised due to maternal strategies of prenatal investment. Long term effects of this prenatal conflict may include the programming of the fetus for susceptibilities to adult onset of diseases such as diabetes, obesity, and cardiovascular disease (Leon et al. 1996; Barker 1998; Barker et al. 2002; Kuzawa and Adair 2003), and possibly even serious mental illness (Wahlbeck et al. 2001; Mittendorfer-Rutz et al. 2004).

The function and structure of the organ supporting pregnancy, the placenta, and its role as one of the unusual features of gestation in the Callitrichidae are often given only a cursory mention in most primate biology or anatomy texts (e.g., Ankel-Simons 2000). However, the study of the unique structure and function of the callitrichid placenta has the potential to yield tantalizing evidence regarding phylogeny, maternal investment, and the development of powerful models of fetal programming and parent–offspring conflict.

In this chapter, we provide an overview of marmoset placental structure and function, then describe relations among placental measures, litter size, fetal growth, and maternal condition. These findings are discussed in relation to theories regarding control of maternal investment. Mothers may need to make a series of physiological “decisions” that will have a negative impact on fetal growth. This negotiation of maternal investment in the current pregnancy can lead to disruption of normal placental development and consequential and/or concomitant disruption of fetal development.

Evidence suggests that the marmosets and tamarins have similar features of growth and development of the fetus and placenta, albeit with variations in event timing, but placental and fetal growth is most extensively studied in Callithrix jacchus (common marmosets) (Chambers and Hearn 1985; Merker et al. 1988; Rutherford and Tardif 2008, 2009). The Southwest National Primate Research Center (SNPRC) houses the largest known collection of common marmoset naturally-delivered term placentas and serves as the basis for our studies. The description and theoretical interpretation of placentation events and features derived from this and other studies of Callithrix should be viewed as relevant for tamarins as well. Because Callimico goeldii (the callimico) has singleton births and because not enough is known about the timing and nature of developmental events in this species, the description of fetal and placental weights and their relations as well as discussions about intrauterine resource allocation should be taken to apply primarily to twin-bearing marmosets and tamarins, despite the close evolutionary relationship between Callimico and Callithrix (see review by Cortés-Ortiz,  Chap. 1 this volume).

16.2 The Marmoset Placenta

16.2.1 The Marmoset Placenta in Comparative Context

The marmoset placenta, like that of most platyrrhines and many catarrhines regardless of litter size, is comprised of two separate placental discs (Fig. 16.1), whereas baboons, apes, and humans all have a single discoid placenta (Mossman 1987), except in the case of some multiple births (e.g., diamnionic/dizygotic twins with individual placentas). The presence of the relatively common bidiscoid placenta along with a simplex uterus and a single pair of pectorally located nipples is important evidence in the construction of mammalian phylogeny and the description of callitrichid twinning as a derived rather than a primitive condition (Ford 1980; Leutenegger 1980). The two discs of the callitrichine placenta fuse early in development and are connected by extensive vascular anastomoses, blood vessels that radiate from the umbilicus of each fetus out over the surface of the discs and traversing the placenta membranes, joining the discs to each fetus (Fig. 16.1; Wislocki 1932, 1939; Benirschke et al. 1962). Anastomotic placentas in human multiple pregnancy is a serious developmental abnormality that often underlies clinical presentations of twin-to-twin transfusion syndrome, a frequently fatal condition in which one twin receives an inordinate blood supply shunted from a “donor” twin frequently leading to the intrauterine demise of one or both twins (Benirschke 1995). This condition is not reported to occur in marmoset littermates. The extensive nature of the callitrichine placental anastomoses creates a more dispersed gradient for blood flow between the two discs, thus obviating the risk of a single vascular interconnection causing a unidirectional flow from one twin to the other. Haig (1999) suggests that the evolution of extensive placental anastomoses in marmosets may have occurred in response to the potentially lethal consequences of transfusion syndrome, and can thus be considered yet another component of the litter-bearing complex.
Fig. 16.1

Photo illustrating multiple (4) umbilical attachments to highly anastomosed bidiscoid placenta (photo by D. Layne Colòn)

The result of this shared placental circulation early in embryonic development is a “prenatal exchange of circulating hematopoietic tissue” (Benirschke et al. 1962, p 513). Marmosets and tamarins are thus hematopoietic chimeras, meaning that each individual is a composite of cells from multiple individuals, (Benirschke et al. 1962; Benirschke and Brownhill 1962; Gengozian et al. 1964), a phenomenon that is recognized as one of the unique aspects of marmoset biology (Haig 1999). Chimeric cells are found in the blood, bone marrow, and spleen in the form of the nucleated blood cells (e.g., lymphocytes). Chimerism has been demonstrated rarely in human twins (Benirschke and Brownhill 1962) and is not known to be a feature of normal fetal twin development in any species other than marmosets and tamarins. In cattle, when heterosexual twin pairs occur, shared placental circulation results in female exposure to male fetal androgenic steroids, leading to the masculinization of genitalia and gonads and ultimately causing sterility, i.e., “freemartinism” (Ono 1969). This does not occur in the marmoset, suggesting there is insensitivity to fetal androgens on the part of the female fetus. The absence of freemartinism in the marmoset has been interpreted as evidence that dizygotic twinning is a specialized trait in this primate group (Haig 1999).

Gengozian et al. (1980) rejected the idea that chimerism extended beyond blood cells to include the germ line. However, Ross and colleagues (Ross et al. 2007) have recently identified chimeric cells in a broad range of somatic tissues of Callithrix kuhlii, including the germ cells. If this observation bears out, the implication is that relatedness and inclusive fitness in this species is a far more complex phenomenon than has ever been considered among mammals. This would obviously have a significant impact on our understanding of marmoset reproductive biology and the evolution of twinning and cooperative infant care; this body of work is fascinating in its potential and further inquiry in the interest of substantiating these interesting results and their attendant theoretical ramifications is underway.

Some researchers have referred to individual placental discs as primary or secondary on the basis of weight (e.g., Merker et al. 1988). However, we discourage this usage as these appellations imply functional distinctions that are not likely to exist with any regularity. Underscoring the unity of function demonstrated by the two placental discs (beyond their highly anastomotic nature) is the random way in which multiple marmoset fetuses are attached to the discs. An early observation by Wislocki (1932) suggested that in a twin marmoset litter, the smaller of the two fetuses would be attached to the smaller of the two discs. However, the work of Wislocki (1939) revealed that patterns of placental attachment relate to blastocyst implantation, such that blastocysts that implant adjacent to each other on the same portion of the uterine wall (e.g., both on the ventral wall) share umbilical attachment to a single disc. In contrast, blastocysts implanting at points opposite each other (both the ventral and dorsal walls) will develop umbilical attachments separately (Fig. 16.2). A recent analysis of common marmoset placentas has shown that there is no significant difference in weight between the two discs (Rutherford 2007), confirming the finding of an earlier work by Chambers and Hearn (1985). Finally, of five triplet placentas for which individual disc weights and umbilical cord insertion number have been recorded at SNPRC, only one case had the greater number of cord insertions in the larger of the two discs (Rutherford, unpublished observations). These observations combined with demonstrations of microstructural identity between discs (Enders and Lopata 1999; Wynn et al. 1975) lead us to argue that the two placental discs are in effect a single functionally integrated organ supporting marmoset pregnancy, and analyses of function of an individual disc can be applied to interpretations of the function of the whole.
Fig. 16.2

Blastocyst implantation in the marmoset. Dashed circle illustrates region of eventual chorionic fusion and rupture, thus creating common exocoelomic cavity. (a) Blastocysts implant on opposing walls of the uterus. Each implantation site forms a separate placental disc and the developing embryos attach to their own disc. (b) The blastocysts implant side by side on the ventral wall and attach to a single disk. The star indicates the site of secondary disc formation at the abembryonic pole

16.2.2 Implantation and Early Placental Growth and Development

Like other anthropoid primate placentas (including those of humans), the marmoset placenta is hemochorial, meaning that a single chorionic layer separates the fetal and maternal circulations (Luckett 1974; see Fig. 16.3). At term, the hemochorial placental barrier consists primarily of one layer of trophoblast cells and the closely apposed endothelium of the fetal capillaries. These two cell layers share a fused basement membrane. Fetal tissues are directly nourished by the gas and nutrient content of maternal blood. This is the most intimate of placental arrangements (Mossman 1987) and may be related to the increased demand for gases and nutrients later in gestation due to primate brain growth. However, other mammals not noted for a primate-like fetal brain/body ratio also have hemochorial placentas (e.g., guinea pigs, rabbits), and some cetaceans, with brain/body ratios equal to or in excess of that of primates, have an epitheliochorial placenta (Haig 1993). This form introduces another barrier between maternal and fetal circulations, suggesting some effects of phylogenetic or perhaps even locomotor and mechanical constraints on placental development.
Fig. 16.3

The hemochorial placenta, separating the fetal and maternal circulations by three tissue layers: (1) Fetal capillary endothelium. (2) Villous mesoderm. (3) Trophoblast

The callitrichid placenta differs from other anthropoid placentas by taking on a trabecular arrangement of the tissue at the maternal–fetal interface. Whereas the tissue in contact with the maternal blood supply is ramified into small fingerlike-projections (i.e., villi) in the placentas of the old world monkeys, apes, and humans, the callitrichid placenta is finely layered in thin interconnected sheets called trabeculae, with only the regions closest to the maternal surface appearing as free villous structures. Although the cellular components of the chorion are the same in all anthropoid primates, this trabecular arrangement is a distinguishing feature of the callitrichid placenta. Benirschke (2002) describes the placenta of squirrel monkeys as having a trabecular/villous arrangement and Mossman (1987) describes the howler monkey placenta as trabecular (but see Benirschke 2002), suggesting the possibility that this structural feature of the placenta was shared by a common ancestor of the New World primates, but most extensively expressed by the marmosets and tamarins.

16.3 Litter Size Variation in Marmosets and Its Relation to Maternal Investment

Twinning in the marmosets and tamarins is one of a suite of derived traits including loss of the third molar, reduced complexity of the upper molars, clawlike nails, and allometric scaling of the eye, and are widely regarded as related to phyletic dwarfism, or a reduction in body size over evolutionary time (Ford 1980; Martin 1992). A variety of mechanisms for the evolution of twinning in the Callitrichidae have been proposed. These can broadly be divided into predation, ecological, and obstetric explanations, the tenets of which are not necessarily exclusive from one another. Eisenberg (1981) has argued that twinning is a response to increased predation pressures arising from decreased body size. Twinning would be favored if high infant mortality were common, and would co-evolve with behavioral strategies related to predation avoidance, such as increased intragroup cooperation (Caine 1993). The cryptic antipredation adaptations in these small-bodied primates suggest that cooperation, particularly with reference to infant care, is necessary; individuals carrying offspring must usually hide and remain still to avoid predation and such behavior would have a deleterious effect on foraging efficiency if infant care were restricted to only one individual (Tardif and Jaquish 1994). However, predation pressures and cooperation may be more relevant to the evolution of cooperative care of infants than to twinning per se. For example, Callimico exhibits a high degree of social cooperation and communal infant care that is decoupled from twinning (see Porter and Garber,  Chap. 4 this volume).

Leutenegger (1973, 1980) proposed the obstetric hypothesis, suggesting that twinning in the Callitrichidae evolved directly as a response to phyletic dwarfism. The ratio of fetal weight to maternal weight is high for small-bodied primates; Leutenegger (1973) suggested that this large fetal size makes delivery difficult and thus total fetal mass is divided across multiple fetuses to allow the mother to carry to term the maximum mass possible while limiting head circumference. Whereas stabilizing selection on the relation between fetal head circumference and the dimensions of the vaginal canal would constrain fetal size, particularly in small-bodied species that produce infants with relatively large brains, it is not clear how this relates to the number of fetuses produced per reproductive event (Goldizen 1990; Martin 1992). Small body size does not exhibit a default relation to twinning within all members of the Callitrichidae. Callimico goeldii exhibits adult weights similar to those found in the twin-bearing Callithrix (marmosets), Saguinus (tamarins), and Leontopithecus (lion tamarins), but produces a single infant. Birth weights for these single neonates are on average absolutely larger than, but relative to adult body weight and do not differ from those for callitrichine twins (Garber and Leigh 1997). Among other primates, the ratio of fetal weight to maternal weight is highest in two species of tarsiers (Tarsier bancanus and T. syrichta), higher than that seen in any of the callitrichid primates (Martin 1992). Martin (1992) points out that these primates would be expected to have difficulty during parturition and should produce smaller twins rather than a single large infant but this is not the case. Further, when marmosets do give birth to singletons, although birth weights tend to be higher (Chambers and Hearn 1985; Jaquish et al. 1995), they do not appear to be related to abnormal gestations and deliveries caused by high fetal weight and large head circumference. Such complications include dystocia, a condition in which delivery of the fetal shoulder is obstructed by the mother’s pubic symphysis. This situation is frequently exacerbated by abnormally large fetal size, which in humans is a frequent complication of gestational diabetes (Clausen et al. 2005). In marmosets, however, only a single case of dystocia has been reported in the literature (Lunn 1980) and is not known to be a sequelum of singleton deliveries. Indeed, dystocia leading to fetal and maternal death has been observed in a triplet pregnancy in which both maternal and fetal weights were abnormally high (Rutherford and Tardif, unpublished observations). In sum, marmosets happen to be small and happen to twin, but there is poor evidence indicating that the former causes the latter. Goldizen (1990) suggests there must be benefits of twinning other than constraining fetal size, because a more parsimonious solution would be to evolve a smaller single fetus.

It seems likely that twinning is related to a change in resource availability that supported an increase in maximum intrinsic rate of population growth (r max) in a way that is related to small body size, possibly as small-bodied marmosets and tamarins began to exploit an insectivorous/gummivorous ecological niche (Martin 1992). These resources are available in niches such as low shrubs and terminal branches that would be unable to support the body weight of larger primates (Eisenberg 1981). Further, exudates are a relatively stable resource in space and time. In a recent cladistic analysis of the Callitrichidae, Ah-King and Tullberg (2000) found that the appearance of twinning is linked to exudate feeding but not to reduction in body size. They point out that the callimico, which is similar in size to the other callitrichids but does not twin, also does not exploit plant gums as a food resource (Ah-King and Tullberg 2000). Exploitation of a temporally stable feeding niche unavailable to larger-bodied primates may have favored an increase in population growth. If the environment in which marmosets and tamarins evolved favored an increase in reproductive rate, a genetic or epigenetic trait for variable litter size could rapidly spread through time and be shaped by selection into a highly specialized system supported by changes in behavioral traits related to infant care.

Although marmosets and tamarins regularly produce twins, triplets are common in captivity, and quadruplets and even quintuplets have been observed (Rothe et al. 1992; Tardif et al. 2003; Rutherford and Tardif, unpublished observations), making it possible to investigate questions relating to litter size variation. Tardif and Jaquish (1997) found that ovulation number was related to body size, such that larger females had higher ovulation numbers, and that within females, individuals weighed more when ovulating 3–4 ova than when ovulating only 1–2. This finding suggests that potential reproductive output is sensitive to immediate energy availability. Sensitivity to environmental conditions in the form of current maternal energy supply may be one of the key determinants of reproductive output in marmosets. This interpretation is further supported by the low repeatability of both ovulation number (r = 0.081, Tardif and Jaquish 1997) and litter size (r = 0.128, Jaquish et al. 1991) within individual females, suggesting low heritability for these traits.

Litter size reduction throughout gestation is common (Jaquish et al. 1996; Windle et al. 1999). Jaquish et al. (1996) found that all singleton litters in a sample of pregnancies followed by serial ultrasonography started out as twin litters, and two cases in which triplet litters ultimately produced twins. Windle et al. (1999) have used both serial ultrasonography and hysterotomy to demonstrate litter size reduction during both early embryonic development and the later fetal period. At term, some littermates may be stillborn whereas other infants in the same litter are born healthy and survive to weaning. Postnatal mortality in one or more littermates with the survival of the rest is common as well, with triplets experiencing higher mortality rates than twins (Jaquish et al. 1991). There appear to be many points along the path from ovulation to weaning during which litter size in marmosets can be negotiated. This variability of reproductive output has likely been an important point of selection throughout the evolutionary history of the marmosets and tamarins (Tardif and Jaquish 1997). Callimicos, producing singletons but possibly having an earlier age of first reproduction than marmosets and tamarins (Martin 1992), may have exploited different pathways to respond to selective forces to optimize reproductive output.

16.4 The Model: Intrauterine Growth Retardation and Elevated Conflict Over Resource Allocation

16.4.1 Maternal Effects on Fetal, Postnatal, and Placental Growth

In marmosets, aspects of fetal and postnatal growth are related to maternal condition (e.g., weight and age) in complicated ways. Tardif and Jaquish (1994) found that larger females have higher ovulation numbers, and larger mothers have larger litters (Tardif and Jaquish 1994, 1997). Whereas birth weight is unrelated to maternal nonpregnant adult weight, it is related to maternal age, with older mothers having heavier offspring (Tardif and Bales 2004). Birth weight is also related to litter size, such that it decreases as litter size increases (Chambers and Hearn 1985). Since larger mothers have larger litters, fetal growth (as indicated by weight at birth) is a function, at least to some degree, of maternal weight.

Tardif and Bales (2004) also found that older mothers seemed able to support greater fetal long bone growth as reflected by knee-heel length, but only if they were also in the medium-to-high weight category. Low birth weight infants exhibited low initial postnatal weight gain (g/day). Being born to a low adult weight mother flattened but did not eliminate this effect, such that the difference in g/day between low and high birth weight infants was much greater in offspring of high weight mothers. High birth weight offspring of high weight mothers put on more weight per day than high birth weight offspring of low weight mothers, even when birth weights were the same. The significance of these relations is currently unclear, but underscores the complicated, multigenerational effects of birth weight on reproductive outcome and fetal development, and ultimately, the evolution of life histories (e.g., Kuzawa 2005).

Comparative and clinical studies suggest a role for maternal age and weight in placental development as well. Steven-Simons et al. (1995) found that placental weight in humans is significantly positively related to both prepregnant weight and to pregnant weight gain. Women starting pregnancy at higher weight produce heavier placentas. Taricco et al. (2003) reported that placental weights are increased in pregnancies complicated by gestational diabetes, a condition often associated with maternal obesity. Rahima and Bruce (1987) found that older rats have significantly heavier placentas compared to younger rats, even though fetal weights do not differ significantly.

16.4.2 The Fetal/Placental Weight Ratio and Intrauterine Conflict

Coall and Chisholm (2003), using parent–offspring conflict theory (Trivers 1974) as their foundation, predicted that if a mother attempts to restrict allocation of resources to her fetus, the fetus will respond by resisting that restriction. An increase in the number of fetuses may mimic this kind of restriction, particularly if not met by a concomitant increase in energy intake on the part of the mother. In the face of this potential shortfall, the triplet fetus may be capable of launching a resistant counterstrategy. Haig (1993) suggests that a fetus could respond to restriction of maternal resources by “increasing its absolute allocation to placental growth” (p 500). In effect, placental overgrowth should be solicited if an increase in the overall amount of placental tissue confers some in utero survival benefit to the fetus. This overgrowth would reduce the ratio of fetal to placental weight, (i.e., in this condition, one gram of placenta would produce fewer grams of fetus than in the “normal” state), providing a glimpse into the relative quality of the intrauterine environment. This ratio is known to be reduced in cases of intrauterine growth retardation in humans as a result of maternal hypoxia (Ali 1997), anemia (Howe 1994; Wheeler 1994), and famine (Lumey 1998), as well as in experimentally induced maternal nutritional restriction (rats: Langley-Evans et al. 1996; Doherty et al. 2003; sheep: Robinson et al. 1994). Maternal undernutrition can result from restriction of energy intake, but this restriction of energy available to fetal development could also lie at the interface of increased fetal demand as a function of litter size and relative per fetus resource allocation by the mother. In marmosets, mothers do not increase energy intake during gestation (Nievergelt and Martin 1999), so an additional fetus could represent restriction of resources available for fetal development, thus creating an environment of elevated conflict over maternal investment. Further, differences in maternal condition could relate to the quality of the intrauterine environment, mitigating or elevating conflict.

16.5 The Study: Assessing the Effects of Litter Size and Maternal Condition on Fetal and Placental Relations in the Marmoset

To test predictions of an intrauterine conflict model in marmosets, we first explored the hypothesis that triplet marmosets, experiencing potential restriction to maternal resources and at greater risk of mortality both pre- and postnatally, will be associated with a relatively larger share of the placenta than will twins (Rutherford and Tardif 2008). Those findings are summarized here. Second, we present our investigation of how maternal age, nonpregnant weight, pregnant weight gain, and maternal birth weight (“maternal condition”) are related to each other, and to placental weight, neonate weight, and fetal/placental weight ratios. We expect that the greatest conflict between mother and offspring over resource allocation would occur in triplet pregnancies carried by small females because this would seem to be a particularly energetically costly condition; therefore we predict that these pregnancies will be characterized by the lowest F/P ratios. No doubt, variance in intrauterine sibling competition for resources plays an important role in shaping this environment, but those interactions are not addressed here.

16.5.1 Methods

To determine the nature of litter size variation in the ability of the placenta to support fetal growth, we totaled birth weights within litters, for total litter weight, and divided this by the total placental weight. This is the fetal/placental weight (F/P) ratio. It should be stated that since these were weights taken at birth, the term “neonatal weight” is more accurate, but in the interest of nomenclature conventions within the literature, we will call it “fetal weight.” The ratio of fetal weight to placental weight is commonly termed placental efficiency since this relationship describes the amount of fetal mass supported by a unit of placental mass (e.g., Wilson et al. 1999; Wilson and Ford 2001; Mesa et al. 2003; Dwyer et al. 2005). Only pregnancies for which we had both placental and fetal weights were included in analyses of relations to the F/P ratio, yielding a sample of 28 pregnancies from 19 dams. A sample of 29 pregnancies from a total of 19 dams was included in the analyses of maternal birth weight and age. Nineteen pregnancies from a total of 13 dams were included in analyses of nonpregnant weight. Fifteen pregnancies from a total of 9 dams were used for analyses of pregnant weight gain. Because repeatability of ovulation number and litter size is low (Tardif and Jaquish 1997), each pregnancy is treated as an independent event.

To differentiate the effects of nonpregnant weight on placental and fetal growth regardless of litter size, we divided pregnancies into two categories: those produced by heavier-than-average females (> = 409.26 g; n = 8) and lighter-than-average females (<409.26 g, n = 12). To test the prediction that pregnancies of lighter mothers carrying triplets will be marked by significantly different ratios of fetal to placental ratios because of costs due to greater conflict over resources, we divided triplet pregnancies into two groups on the basis of the mean for nonpregnant weight: heavier (> = 429.64 g) and lighter (<429.64).

Data were analyzed to determine to what extent and in which direction twin and triplet pregnancies, as well as those of mothers of different weights, differed. All data were normally distributed and were analyzed using independent samples t-tests and Pearson’s correlations. ANCOVA was used to control the effects of placental weight when analyzing litter size patterns of difference in the fetal/placental weight ratio. Statistical analyses were performed using SPSS software, version 13.0.

16.5.2 Results

16.5.2.1 Litter Size and the Fetal/Placental Weight Ratio

Rutherford and Tardif (2008) conducted an analysis of differences in marmoset placental structure and function according to litter size and some of those results are summarized here. The means for individual fetal, total litter, placental weights, and the fetal/placental weight ratio are given in Table 16.1. Differences in placental and litter weights according to litter size are shown in Table 16.2. Individual triplets were smaller than twins (28.09 vs. 31.53 g, F = 0.794, df = 26, p = 0.044), but as a whole, triplet litters weighed significantly more (84.34 vs. 63.36 g, F = 0.4.128, df = 26, p < 0.001; Fig. 16.4). Despite striking differences in fetal and litter weights between the two litters, there was no significant difference in placental weight between twins and triplets (F = 0.016, df = 25, p = 0.283; Fig. 16.5). Placental weight and total litter weight were strongly correlated (r = 0.518, p = 0.007, not shown), but although triplet litters were significantly heavier than their twin counterparts, their placentas were not. As a consequence, the fetal/placental weight ratio was strongly correlated with placental weight in a negative direction (r = −0.700, p < 0.001). The fetal/placental weight ratio was unrelated to differences in total litter weight (r = 0.254, p = 0.221).
Fig. 16.4

Average fetal and total litter weights by litter size

Fig. 16.5

Placental weight by litter size

Table 16.1

Descriptive statistics for individual study components

 

n

Range

Minimum

Maximum

Mean

SD

Variance

Maternal variables

Maternal age

29

51

25

76

49.10

13.080

171.096

Maternal adult weight

19

170.00

337.00

507.00

409.263

52.976

2806.427

Maternal birth weight

29

13.00

25.00

38.00

30.345

3.446

11.877

Weight gained during pregnancy

15

123.00

45.00

168.00

92.467

31.904

1017.838

Placental weight

Placental weight

27

12.92

5.73

18.65

9.513

3.056

9.339

Fetal weights

Total litter weight

28

52.00

53.00

105.00

76.00

15.305

234.234

Average fetal weight

28

21.50

18.00

39.50

29.439

4.450

19.805

Fetal: placental weight ratio

(placental efficiency)

25

7.14:1

4.77:1

11.91:1

8.304:1

1.966

3.865

Table 16.2

Independent samples t-tests comparing placenta, fetal, and total litter weights between litter size categories

 

Twin litters

Triplet litters

n

Weight*

n

Weight*

Average fetal weight (g)

11

31.52 ± 3.64

17

28.09 ± 4.49**

Total litter weight (g)

11

63.36 ± 7.05

17

84.34 ± 13.44***

Placental weight (g)

10

8.68 ± 2.91

17

10.01 ± 3.12

*Weights are shown as the mean ± SD

**p < 0.05

***p < 0.01

Because placental weight strongly correlates with placental efficiency, an ANCOVA was performed to assess how much impact litter size has on differences in this variable once the effects of placental weight are accounted for. The grouping variable was litter size and placental weight was the covariate. Raw and estimated marginal means are presented in Table 16.3. The raw measures are labeled “Unadjusted Means.” The estimated marginal means are means that have been adjusted for the covariate and are labeled “Adjusted Means.” The triplet fetal/placental weight ratio was significantly higher than that for twins (adjusted marginal means: 9.04 g fetus/g placenta vs. 7.2 g fetus/g placenta), meaning that per gram, the triplet placenta supports more fetal growth than does the twin placenta, i.e., is relatively smaller than the twin placenta with respect to support of total fetal growth. This result is the opposite of that predicted by the overgrowth hypothesis. Triplet litters, although significantly heavier than twin litters, were associated with a decrease in placental mass relative to fetal mass.
Table 16.3

Analysis of covariance (ANCOVA) for Fetal/Placental weight ratio

 

Dependent variable = Fetal/Placental weight ratio (g fetus/g placenta)

MODEL

Independent variable=Litter size

GROUP

Unadjusted mean (SD)

N

Twin

7.765 (1.860)

10

Triplet

8.663 (2.014)

15

ANCOVA Results

Significance

Partial Eta Squared

Placental weight (covariate)

0.001*

0.392

  

95% Confidence interval

GROUP

Adjusted mean (SE)

Upper

Lower

Twin

7.203 (0.371)

6.434

7.972

Triplet

9.037 (0.300)

8.415

9.660

*Model significant at p<0.01

16.5.2.2 Relations between Maternal Condition and Litter and Fetal Characteristics

In the following sections, we present the results of our analyses of maternal condition and its relation to litter and placental characteristics. The average age for the mothers in this sample was 49.10 months, and mean adult weight was 409.26 g with an average weight gain during pregnancy of 92.47 g (Table 16.1).

Correlations among all maternal condition variables and between maternal condition and litter and placental weights are shown in Table 16.4. Weight gain during pregnancy was significantly correlated with litter weight (r = 0.838, p < 0.001). Maternal adult weight was significantly correlated both with total litter weight (r = 0.483, p = 0.042) and with weight gain during pregnancy (r = 0.522, p = 0.046), so that larger females produced heavier litters and gained more weight during pregnancy.
Table 16.4

Correlations among maternal variables and placental, fetal, and total litter weights

 

Placental weight

Total litter weight

Average fetal weight

Maternal age

Maternal adult weight

Maternal birth weight

Weight gained during pregnancy

Maternal

age

Pearson Corr.

0.209

0.028

0.445 (*)

 

–0.009

–0.381 (*)

–0.023

Sig. (2-tailed)

0.295

0.887

0.018

0.970

0.041

0.934

N

27

28

28

19

29

15

Maternal adult weight

Pearson Corr.

0.276

0.483 (*)

0.206

–0.009

 

0.480 (*)

0.522 (*)

Sig. (2-tailed)

0.268

0.042

0.412

0.970

0.038

0.046

N

18

18

18

19

19

15

Maternal birth weight

Pearson Corr.

–0.317

–0.146

–0.621 (**)

–0.381 (*)

0.480 (*)

 

0.329

Sig. (2-tailed)

0.107

0.459

0.000

0.041

0.038

0.231

N

27

28

28

29

19

15

Weight gained during pregnancy

Pearson Corr.

0.231

0.838 (**)

0.335

–0.023

0.522 (*)

0.329

 

Sig. (2-tailed)

0.427

0.000

0.223

0.934

0.046

0.231

N

14

15

15

15

15

15

*Correlation is significant at p < 0.05 level

**Correlation is significant at p < 0.01 level

Whereas there were strong relations between a) fetal and placental weights and b) maternal variables and fetal weights, there was no relation between placental weight and any maternal variable (Table 16.4). Neither age nor any aspect of maternal weight throughout her life history had any obvious bearing on placental weight.

In terms of differences between twins and triplets, neither maternal age nor birth weight differentiated the two litter categories (Table 16.5). However, maternal adult weight was significantly greater in mothers of triplets (Fig. 16.6), as was weight gain during pregnancy. Lighter-than-average mothers (<409.26 g) gave birth to both twin (n = 5) and triplet (n = 6) litters. In contrast, seven of the eight heavier-than-average mothers (∼409.26 g) gave birth only to triplet litters.
Fig. 16.6

Maternal nonpregnant adult weight by litter size

Table 16.5

Independent t-tests comparing maternal age and weights between litter size categories

 

Twin litters

Triplet litters

n

Weight*

n

Weight*

Maternal age (months)

11

53.36 ± 14.05

18

46.50 ± 12.12

Maternal adult (nonpregnant) weight (g)

6

376.67 ± 26.62

13

424.31 ± 56.02**

Maternal weight gained during pregnancy (g)

6

65.00 ± 16.15

9

110.78 ± 25.99***

Maternal birth weight (g)

11

29.00 ± 3.13

18

31.17 ± 3.45

*Values are shown as the mean ± SD

** p < 0.05

*** p < 0.01

In addition to producing primarily triplet litters, heavier mothers fall into two categories in terms of placental weight, those producing larger (>13 g, n = 2) or smaller (<9 g, n = 3) placentas (Fig. 16.7). Due to the small size of this sample, significance of this relation could not be assessed. However, it is interesting to note that large mothers with smaller placentas gave birth to neonates whose average weights fall within a range very close to the overall sample mean weight of 29.4 g. The average birth weights of those infants born to large mothers producing large placentas ranged from average (31.3 g) to very low (22.7 g).
Fig. 16.7

Relation between maternal weight and placental weight in heavier-than-average (∼424 g) mothers of triplets

16.5.2.3 Maternal Birth Weight

Maternal birth weight in this sample was significantly and positively related to nonpregnant adult weight (r = 0.480, p = 0.038). It was also significantly correlated with birth weight of the next generation, but this association was negative (r = −0.621, p < 0.001) (Table 16.4; Fig. 16.8). Maternal birth weight was not related to total litter weight (Table 16.4) or significantly different between twin and triplet litters (Table 16.5). Maternal birth weight was related to placental weight but not significantly (r = −0.317, p = 0.107), and there was no relation to total litter weight (r = −0.146, p = 0.459).
Fig. 16.8

Relation between maternal birth weight and offspring birth weight

16.5.2.4 Maternal Age

Maternal age was not related to placental weight, although it was significantly correlated with average neonate weight (r = 0.445, p = 0.018), such that older mothers have larger neonates (Table 16.4). Neither total litter weight nor litter size was related to age.

16.5.2.5 Maternal Variables and the Fetal/Placental Weight Ratio

As shown in Table 16.6, the fetal/placental weight ratio was significantly correlated with maternal weight gain during pregnancy (r = 0.702, p = 0.005), but unrelated to maternal adult weight (r = 0.170, p = 0.515). The fetal/placental ratio increased as maternal weight gain increased (Fig. 16.9). We found no differences in fetal/placental weight ratio between heavier and lighter mothers having triplet litters (Table 16.7).
Fig. 16.9

Relation between maternal weight gain and the fetal/placental weight ratio

Table 16.6

Correlations between the fetal/placental weight ratio and maternal variables

 

Maternal age

Maternal adult weight

Maternal birth weight

Weight gained during pregnancy

Fetal/placental weight ratio

(g fetus/g placenta)

Pearson correlation

–0.180

0.170

0.256

0.702 (*)

Sig. (2-tailed)

0.389

0.515

0.217

0.005

N

25

17

25

14

*Correlation is significant p < 0.01 level

Table 16.7

Independent samples t-test comparing the fetal/placental weight ratio from pregnancies produced by lighter- and heavier-than average mothers of triplets

 

Lighter mothers

(<424 g)

Heavier mothers

(±424 g)

n

Ratioa

n

Ratioa

Fetal/placental weight ratio

7

9.135:1 ± 1.060

4

8.485:1 ± 3.390b

a Ratios are shown as the mean ± SD

bns

16.6 Discussion

Several intriguing patterns relevant to models of maternal investment and intrauterine resource allocation emerge, creating a foundation for further model building and testing. The average nonpregnant weight for the mothers in this sample was 409.63 g, which is higher than that found in studies by Tardif and colleagues of the same colony (357.7 g, Tardif et al. 2001; 376.5 g, Tardif et al. 2002). The sample used in the current study is restricted to those females for whom pregnancy data included both fetal and placental weights. Placental collection is a relatively recent addition to colony protocol, and thus the maternal weights in the current study may be more representative of recent secular trends in adult weight. However, the pattern of relations among maternal weight variables and between maternal weight and fetal variables is consistent with previous reports. Total litter weight is associated with nonpregnant weight gain and with litter size. In other words, heavier mothers have larger litters of heavier infants. Also, older mothers have larger infants. These findings are similar to those of Tardif and colleagues (Tardif and Jaquish 1994, 1997; Tardif and Bales 2004).

Maternal birth weight was negatively related to neonate weight, and positively related, though nonsignificantly (p = 0.101) to litter size. This may be the result of a cascade of interrelated variables. The direction of these relations predicts the following: a female’s birth weight is positively related to her nonpregnant adult weight, and maternal nonpregnant weight is positively associated with litter size (e.g., small mothers have smaller litters), and litter size is negatively related to neonate size (e.g., small litters comprise relatively larger neonates, even when total litter weight is lower).

This is only one way in which a female born small could give birth, on average, to larger neonates. Tardif and Bales (2004) demonstrate that litter size is an important and sometimes confounding determinant of adult weight and so it is likely that the addition of maternal litter size and total litter weight into the analyses of reproductive outputs and outcomes will provide further nuance, and provoke more questions. In humans, heritability of birth weight is relatively high (i.e., 20–45% of variation in birth weight explained by genetic factors; Vlietinck et al. 1989; Clausson et al. 2000). In marmosets, litter size variation complicates the genetic components of this relation, suggesting a critical role for environmental effects in fetal development. These environmental effects are multi-level and multigenerational, encompassing the mother’s own fetal experience, resource availability prior to ovulation and during pregnancy, intrauterine competition between siblings, and the differential hormonal milieu associated with litter size variation.

Placental growth in marmosets seems not to be controlled by any variable relating to maternal adult weight. Whereas Steven-Simons et al. (1995) found that placental weight in humans was related to both nonpregnant weight and pregnant weight gain, we found no relation with either nonpregnant weight or weight gain. It appears that weight gain during marmoset pregnancy is a function entirely of litter size and total litter weight, not placental growth.

We report that heavier marmoset mothers produce triplets much more frequently than twins. Tardif and Jaquish (1997) demonstrated that ovulation number is a function of body weight, such that large females produce the greatest number of ova per ovulatory event. This in turn is related to an increase in litter size, and the findings of this study, albeit involving a much smaller sample size, offer further support to an already well-supported phenomenon. Interestingly, the distribution of placental size in this group is strongly dichotomous. Heavier marmoset mothers produce either smaller or larger placental weights. The neonates associated with the larger placentas in the group (>9 g) were quite variable in birth weight. This variation may be the result of earlier litter-size reduction, a very common phenomenon in marmosets (Jaquish et al. 1996; Windle et al. 1999). In particular, the triplet litter that combined a very low average birth weight with a high nonpregnant weight and a heavy placenta may be indicative of a quadruplet litter that was reduced to triplets later in gestation. The range in birth weights may reflect the timing of this reduction, such that the heavier infants were a result of early litter size reduction and the lightest infants a result of litter reduction taking place sometime later.

In contrast to the findings by Rahima and Bruce (1987) in rats, we did not find any relation between maternal age and placental weight. They report that older mothers produce larger placentas, even when fetal weight is controlled for. This means that older rat mothers would have pregnancies with lower F/P ratios than younger mothers, and this suggests that maternal age, at least in rats, is associated with greater placental dysfunction as a result of increased conflict over resource allocation. This could be related to the very different life history of the rat, with a much faster developmental path to reproduction and senescence than the marmoset. Lurie et al. (1999) found a positive correlation between fetal/placental weight ratio and age in a study of 431 human females, suggesting the opposite effect. Young mothers (17–19 years) had the highest fetal/placental weight ratios and the lowest birth weight babies, indicating that this may be the greatest period of conflict over resource allocation and is likely related to the prolonged juvenile growth period that is the hallmark of human development. Maternal age in marmosets is not related to the fetal/placental weight ratio, an indication that age has no bearing on placental growth. It could also suggest that the range of ages of the females in this study was not large enough to capture differences related to elevated maternal age.

Our hypothesis that the fetal/placental weight ratio would be different in the pregnancies of lighter females carrying triplet litters was not supported. There was no difference within either twin or triplet litters between the fetal/placental weight ratio in pregnancies of lighter and heavier mothers. This may be related to the lack of a significant relation between placental weight and maternal weight. It could also signal that the burden of acquiring and maintaining access to placental tissue, and thus maternal resources, is on the fetus, and that the difference between gestating twins and triplets, at least in terms of investing in placental growth, is not particularly costly for the mother (Rutherford & Tardif 2008). Maternal condition does not appear to mitigate, nor directly elevate, allocation of placental tissue.

In marmosets, higher litter weight triplets are associated with a significantly smaller proportion of the total placental weight relative to fetal weight than are twins. Put another way, per gram, the triplet placenta supports more fetal growth than the twin placenta, suggesting some increase in placental efficiency. Therefore, if the triplet marmoset pregnancy represents a stressed, possibly nutrient-restricted state from the perspective of the individual fetus, the placenta is not responding by overgrowth as has been hypothesized by Haig (1993) and Coall and Chisholm (2003). Studies in mice have shown increases in active amino acid transport by placentas that have been restricted in growth due to the deletion of the gene coding for insulin-like growth hormone, a hormone produced by both the fetus and placenta that regulates placental growth (Constancia et al. 2002). In similar ways, triplets may in fact be engaging in strategies at the metabolic and cellular level that increase access to maternal resources, rather than strategies that increase overall placental growth.

Whereas triplet birth weight appears to be most limited late in gestation (Chambers and Hearn 1985), placental growth maxima may be determined earlier (Fig. 16.10). The maximum increase in placental weight is completed by day 90 (Chambers and Hearn 1985), a month earlier than the period of greatest increase in fetal growth, occurring between days 120–140 (Jaquish et al. 1995). Triplet fetuses experience growth restriction compared to twin trajectories relatively late in gestation, with the maximum difference between twin and triplets occurring around day 130 of a 143-day gestation (Chambers and Hearn 1985). Whereas overall placental size cannot be altered at this late point in development, the maturation of the placental trabeculae continues until term (Merker et al. 1988). Therefore, the stressed triplet pregnancy may be able to compensate for increasingly contested resources by expanding the tissue at the microscopic level of the maternal–fetal interface, or otherwise altering its function, thereby pursuing developmental pathways that increase efficiency at the cellular level, an outcome not captured by the fetal/placental weight ratio. In support of this hypothesis, we have recently shown that marmoset triplet placentas have an expanded microscopic surface area available for nutrient transport and endocrine signaling (Rutherford and Tardif 2009).
Fig. 16.10

Timeline of fetal and placental milestones during marmoset development

Compensatory growth of the placenta, like that described by Lumey (1998) in humans as being the result of famine experienced during early gestation and predicted by Haig (1993) to be evidence for conflict over resources, may not be an appropriate model for comparison to the triplet marmoset pregnancy. In the compensatory model, restriction of maternal energy intake early in gestation has an immediate and persistent effect on fetal and placental development because the pregnancy begins in a state of energetic burden to the mother. In contrast, a marmoset mother may not perceive the addition of a fetus early in gestation as an energetic burden. However, as fetal mass accrues and metabolic needs become more demanding, the fetuses in the triplet litter may experience a per capita restriction of maternal resources, compared to their twin counterparts. Restriction of resources available to the fetus on the part of the mother may be passive; Nievergelt and Martin (1999) report that marmoset females do not increase energy intake during pregnancy even when carrying triplet litters. This surprising finding suggests that from the mother’s perspective, gestating triplets is no more costly than gestating twins, or at least that her investment in the form of energy intake (not taking into account starting reserves in the form of body weight) is finite. However, the experience from the perspective of the fetus is much different. Postnatal survivorship for individual triplet neonates is much lower than that for twins, suggesting that in utero competition for resources is elevated. Fetal pathways (such as activation of placental hormonal signaling systems) that increase access or at least maintain normative planes of nutritional and metabolic support via the placenta to maintain pregnancy to term are separate from maternal patterns of pre- and postnatal energetic and behavioral investment. In this way, the relatively smaller, potentially more efficient triplet placenta represents an imperfect solution to the problem of offspring survival because it is at odds with the mother’s strategy of balancing resources she may prefer to invest in an optimal litter number of two, the lactation burden of her current offspring, and fat reserves that relate to ovulation number for future reproductive events. Understanding the range of adaptive pathways available to the placenta in the context of litter size variation will enhance our growing appreciation that the callitrichids as a group have evolved to exhibit great flexibility in reproductive output.

16.7 Conflicting Demands, Competing Strategies

Marmoset females have developed a variety of postnatal strategies for tailoring investment in their offspring according to litter size (Tardif et al. 2003). Marmoset mothers are limited to caring for two infants due to the number of nipples (Schultz 1948) and energetic constraints of lactation (Nievergelt and Martin 1999; Tardif et al. 2001). Mothers do not appear to increase their total behavioral investment in triplet litters versus twin litters in carrying or nursing bouts, but rather have finite time and energetic resources to devote to their offspring for which the offspring must actively compete (Tardif et al. 2002). Triplets do initiate infant-carrying bouts at a greater rate than twins do (Tardif et al. 2002), but these bouts are shorter in duration, and so are lactation bouts (Tardif et al. 2001), and are met with a higher degree of maternal harassment (Tardif et al. 2001). Fite et al. (2005a, b) have suggested that mothers will decrease caregiving efforts in the event of conception during intense lactation, further jeopardizing survival for triplets. An aggressive strategy to court mother’s time is no guarantee of garnering more resources, but because individual fitness costs for triplets are high, it is a strategy worth pursuing.

This strategy for acquiring allocation of maternal resources is one that begins early in gestation and differences in the relation between birth weight and placental weight in triplet and twin litters suggest triplets may employ strategies to maximize access to maternal resources in a way that is unavailable to them postnatally. We have shown that being a triplet is associated with relative placental undergrowth, but this leaves open the door on mechanisms that increase efficiency at the metabolic level. We have also demonstrated that maternal nonpregnant weight and birth weight interact with litter size in complicated ways to impact fetal growth and outcomes. Placental growth in marmosets appears to be under the control of the fetal soma, rather than maternal factors, and is potentially both responsive to and responsible for the growth of the individual fetus. These exciting findings are consistent with clinical models of intrauterine growth retardation and evolutionary predictions of parent–offspring conflict theory, and suggest that marmosets and the other callitrichids present unique opportunities to investigate the ways in which these processes interact in the intrauterine environment.

When there are finite resources to be devoted to fetal development, additional fetuses will strain availability. There are limits to maternal investment, and these limits are detrimental to individual marmoset triplets, whose most powerful ally in the tug-of-war over maternal resources is the placenta.

Notes

Acknowledgments

The authors would like to thank Donna Layne Colòn, L.A.T. for her ongoing excellent management of the SNPRC marmoset colony and her skillful execution of data collection and participation in research design. Our development of this research has benefited from conversations and correspondence with Christopher Kuzawa (Northwestern University) and David Haig (Harvard University). Comments from the editors of this volume, two anonymous reviewers, and Dr. Haig have greatly improved the final manuscript. Funding for SNPRC colony management and research has been provided by NIH grants R01-RR02022 and P51-RR1396 (SDT), and grants to JNR from the American Society of Primatologists, the Center for the Integrative Study of Animal Behavior (Indiana University) and the Indiana University Graduate School Grant-in-Aid of Doctoral Research program have funded the research on which this chapter is based.

References

  1. Ah-King M and Tullberg BS (2000) Phylogenetic analysis of twinning in Callitrichinae. Am J Primatol 51: 135–41Google Scholar
  2. Ali KMZ (1997) The association between spontaneous preterm birth and placental histology at high and low altitude areas of southern Saudi Arabia. Saudi Med J 18(4):349–352Google Scholar
  3. Ankel-Simons F (2000) Primate anatomy, 3rd edn. Academic Press, San DiegoGoogle Scholar
  4. Barker D (1998) In utero programming of chronic disease. Clin Sci 95:115–128CrossRefPubMedGoogle Scholar
  5. Barker D, Eriksson JG, Forsen T, Osmond C (2002) Fetal origins of adult disease: Strength of effects and biological basis. Int J Epidemiol 31:1235–1239CrossRefPubMedGoogle Scholar
  6. Benirschke K (1995) The biology of the twinning process: how placentation influences outcome. Semin Perinatol 19(5):342–350CrossRefPubMedGoogle Scholar
  7. Benirschke K (2002) Comparative placentation website. Download date: April 7, 2006. http://medicine.ucsd.edu/cpa/indxfs.html
  8. Benirschke K, Brownhill LM (1962) Further observations on marrow chimerism in marmosets. Cytogenetics 1:245–247CrossRefPubMedGoogle Scholar
  9. Benirschke K, Anderson JM, Brownhill LE (1962) Marrow chimerism in marmosets. Science 138:513–515CrossRefPubMedGoogle Scholar
  10. Caine N (1993) Flexibility and co-operation as unifying themes in Saguinus social organization and behaviour: The role of predation pressures. In: Rylands AB (ed) Marmosets and Tamarins: systematics, behaviour, and ecology. Oxford Science Publications, Oxford, pp 200–219Google Scholar
  11. Chambers PL, Hearn JP (1985) Embryonic, foetal and placental development in the common marmoset monkey (Callithrix jacchus). J Zool 207:545–561CrossRefGoogle Scholar
  12. Clausen T, Burksi TK, Oyen N, Godang K, Bollerslev J, Henriksen T (2005) Maternal anthropometric and metabolic factors in the first half of pregnancy and risk of neonatal macrosomia in term pregnancies: a prospective study. Eur J Endocrinol 153(6):887–894CrossRefPubMedGoogle Scholar
  13. Clausson B, Lichtenstien P, Cnattingius S (2000) Genetic influence on birth weight and gestational length determined by studies in offspring of twins. Br J Obstet Gynaecol 107(3):375–381Google Scholar
  14. Coall DA, Chisholm JS (2003) Evolutionary perspectives on pregnancy: maternal age at menarche and infant birth weight. Soc Sci Med 57:1771–1781CrossRefPubMedGoogle Scholar
  15. Constancia M, Hemberger M, Hughes J, Dean W, Ferguson-Smith A, Fundele R, Stewart F, Kelsey G, Fowden A, Sibley C, Reik W (2002) Placental-specific IGF-II is a major modulator of placental and fetal growth. Nature 417: 945–8CrossRefPubMedGoogle Scholar
  16. Cortés-Ortiz L (this volume) Molecular phylogenetics of the Callitrichidae with an emphasis on the marmosets and Callimico. In: Ford SM, Porter LM, Davis LC (eds) The smallest anthropoids: The marmoset/callimico radiation. Springer Press, New York, pp 3–24Google Scholar
  17. Dwyer CM, Calvert SK, Farish M, Donbavand J, Pickup HE (2005) Breed, litter and parity effects on placental weight and placentome number, and consequences for the neonatal behaviour of the lamb. Theriogenology 63: 1092–1110Google Scholar
  18. Eisenberg J (1981) The Mammalian radiations: An analysis of trends in evolution, adaptation, and behavior. Chicago, University of Chicago PressGoogle Scholar
  19. Enders AC, Lopata A (1999) Implantation in the marmoset monkey: Expansion of the early implantation site. Anat Rec 256:279–299CrossRefPubMedGoogle Scholar
  20. Fite JE, French JA, Patera KJ, Hopkins EC, Rukstalis M, Ross CN (2005a) Elevated urinary testosterone excretion and decreased maternal caregiving effort in marmosets when conception occurs during the period of infant dependence. Horm Behav 47:39–48CrossRefPubMedGoogle Scholar
  21. Fite JE, Patera KJ, French JA, Rukstalis M, Hopkins EC, Ross CN (2005b) Opportunistic mothers: Female marmosets (Callithrix kuhlii) reduce their investment in offspring when they have to, and when they can. J Hum Evol 49:122–142CrossRefPubMedGoogle Scholar
  22. Ford SM (1980) Marmosets and tamarins as phyletic dwarfs, and the place of the Callitrichidae in Platyrrhini. Primates 21(1):31–43CrossRefGoogle Scholar
  23. Garber PA, Leigh SR (1997) Ontogenetic variation in small-bodied New World primates: implications for patterns of reproduction and infant care. Folia Primatol 68:1–22CrossRefPubMedGoogle Scholar
  24. Gengozian N, Batson JS, Eide P (1964) Hematologic and cytogenetic evidence for hematopoietic chimerism in the marmoset Tamarinus nigricollis. Cytogenetics 10:384–393CrossRefPubMedGoogle Scholar
  25. Gengozian N, Brewen JG, Preston RJ, Batson JS (1980) Presumptive evidence for the absence of functional germ cell chimerism in the marmoset. J Med Primatol 9(1–2):9–27PubMedGoogle Scholar
  26. Goldizen AW (1990) A comparative perspective on evolution of tamarin and marmoset social systems. Int J Primatol 11: 63–83Google Scholar
  27. Haig D (1993) Genetic conflicts in human pregnancy. Q Rev Biol 68:495–532CrossRefPubMedGoogle Scholar
  28. Haig D (1996) Altercation of Generations: genetic conflicts of pregnancy. Am J Reprod Immunol 35:226–232PubMedGoogle Scholar
  29. Haig D (1999) What is a marmoset? Am J Primatol 49: 285–96Google Scholar
  30. Howe DT (1994) Maternal factors, fetal size, and placental ratio at 18 weeks: Their relationship to final size. In: Ward RHT, Smith SK, Donnai D (eds) Early fetal growth and development. Royal College of Obstetricians and Gynaecologists Press, London, pp 345–354Google Scholar
  31. Jaquish CE, Gage TB, Tardif SD (1991) Reproductive factors affecting survivorship in captive Callitrichidae. Am J Phys Anthropol 84:291–305CrossRefPubMedGoogle Scholar
  32. Jaquish CE, Toal RL, Tardif SD, Carson RL (1995) Use of ultrasound to monitor prenatal growth and development in the common marmoset (Callithrix jacchus). Am J Primatol 36:259–275CrossRefGoogle Scholar
  33. Jaquish CE, Tardif SD, Toal RL, Carson RL (1996) Patterns of prenatal survival in the common marmoset (Callithrix jacchus). J Med Primatol 25:57–63PubMedGoogle Scholar
  34. Kuzawa C (2005) Fetal origins of developmental plasticity: Are fetal cues reliable predictors of future nutritional environments? Am J Phys Anthropol 17:5–21Google Scholar
  35. Kuzawa C, Adair LS (2003) Lipid profiles in adolescent Filipinos: Relation to birth weight and maternal energy status during pregnancy. Am J Clin Nutr 77:960–966PubMedGoogle Scholar
  36. Langley-Evans SC, Phillips GJ, Benediktsson R, Gardner DS, Edwards CRW, Jackson AA, Seckl JR (1996) Protein intake in pregnancy, placental glucocorticoid metabolism and the programming of hypertension in the rat. Placenta 17:169–172CrossRefPubMedGoogle Scholar
  37. Leon DA, Koupilova I, Lithell HO, Berglund L, Mohsen R, Vagero D, Lithell U-B, McKeigue PM (1996) Failure to realize growth potential in utero and adult obesity in relation to blood pressure in 50 year old Swedish men. Br J Med 312:401–416Google Scholar
  38. Leutenegger W (1973) Maternal-fetal weight relations in Primates. Folia Primatol 20:280–293CrossRefPubMedGoogle Scholar
  39. Leutenegger W (1980) Monogamy in Callitrichids: A consequence of phyletic dwarfism? Int J Primatol 1(1):95–98CrossRefGoogle Scholar
  40. Long TA (2005) The influence of mating system on the intensity of parent-offspring conflict in primates. J Evol Biol 18:509–515CrossRefPubMedGoogle Scholar
  41. Luckett WP (1974) Comparative development and evolution of the placenta in primates. In: Luckett WP (ed) Contributions to primatology, vol. 3: Reproductive biology of the primates. S Karger, Basel, pp 142–234Google Scholar
  42. Lumey LH (1998) Compensatory placental growth after restricted maternal nutrition. Placenta 19:105–111CrossRefPubMedGoogle Scholar
  43. Lunn SF (1980) A case of placenta praevia in a common marmoset (Callithrix jacchus). Vet Rec 106:414CrossRefPubMedGoogle Scholar
  44. Lurie S, Feinstein M, Mamet Y (1999) Human fetal-placental weight ratio in normal singleton near-term pregnancies. Gynecol Obstet Invest 48(3):155–157CrossRefPubMedGoogle Scholar
  45. Martin RD (1992) Goeldi and the dwarfs: The evolutionary biology of the small New World monkeys. J Hum Evol 22:367–393CrossRefGoogle Scholar
  46. Mesa H, Safranski TJ, Johnson RK, and Lamberson WR (2003) Correlated response in placental efficiency in swine selected for an index of components of litter size. J Anim Sci 81: 74–79Google Scholar
  47. Merker H-J, Bremer D, Csato W, Heger W, Gossrau R (1988) Development of the marmoset placenta. In: Neubert D, Merker H-J, Hendrickx A (eds) Non-human primates – developmental biology and toxicology. Ueberreuter Wissenschaft, Berlin, pp 245–272Google Scholar
  48. Mittendorfer-Rutz E, Rassmussen F, Wasserman D (2004) Restricted fetal growth and adverse maternal psychosocial and socioeconomic conditions as risk factors for suicidal behaviour of offspring: a cohort study. Lancet 364(9440):1102–1104CrossRefGoogle Scholar
  49. Mossman HW (1987) Vertebrate fetal membranes. MacMillan, HoundmillsGoogle Scholar
  50. Nievergelt C, Martin RD (1999) Energy intake during reproduction in captive common marmosets (Callithrix jacchus). Physiol Behav 65(4/5):849–854PubMedGoogle Scholar
  51. Ono S (1967) The problem of the bovine freemartin. J Reprod Fert 7(Suppl):53–61Google Scholar
  52. Porter L, Garber PA (this volume) Social behavior of callimicos: Mating strategies and infant care. In: Ford SM, Porter LM, Davis LC (eds) The smallest anthropoids: The marmoset/callimico radiation. Springer Press, New York, pp 87–101Google Scholar
  53. Rahima A, Bruce NW (1987) Fetal and placental growth in young, primiparous and old, multiparous rats. Exp Gerontol 22:257–261CrossRefPubMedGoogle Scholar
  54. Robinson JS, Owens JA, DeBarro T, Lok F, Chidzanja S (1994) Maternal nutrition and fetal growth. In: Ward RHT, Smith SK, Donnai D (eds) Early fetal growth and development. Royal College of Obstetricians and Gynaecologists Press, London, pp 317–328Google Scholar
  55. Ross CN, French JA, Orti G (2007) Germ-line chimerism and paternal care in marmosets (Callithrix kuhlii). Proc Natl Acad Sci USA 104(15):6278–6282CrossRefPubMedGoogle Scholar
  56. Rothe H, Darms K, Koenig A (1992) Sex ratio and mortality in a laboratory colony of the common marmoset (Callithrix jacchus). Lab Animal 26(2):88–99CrossRefGoogle Scholar
  57. Rutherford JN (2007) Litter size effects on placental structure and function in common marmoset monkeys (Callithrix jacchus): implications for intrauterine resource allocation strategies. Unpublished doctoral Dissertation, Indiana UniversitGoogle Scholar
  58. Schultz AH (1948) The number of young at birth and the number of nipples in primates. Am J Phys Anthropol 6(1):1–23CrossRefPubMedGoogle Scholar
  59. Steven-Simons C, Metlay L, McAnarney E (1995) Maternal prepregnant weight and pregnant weight gain: relation to placental microstructure and morphometric oxygen diffusion capacity. Am J Perinatol 12(6):407–412CrossRefGoogle Scholar
  60. Tardif SD, Bales K (2004) Relations among birth condition, maternal condition, and postnatal growth in captive common marmoset monkeys (Callithrix jacchus). Am J Primatol 62:83–94CrossRefPubMedGoogle Scholar
  61. Tardif SD, Jaquish CE (1994) The common marmoset as a model for nutritional impacts upon reproduction. Ann NY Acad Sci 709:214–215CrossRefPubMedGoogle Scholar
  62. Tardif SD, Jaquish CE (1997) Number of ovulations in the marmoset monkey (Callithrix jacchus): Relation to body weight, age and repeatability. Am J Primatol 42:323–329CrossRefPubMedGoogle Scholar
  63. Tardif SD, Power M, Oftedal O, Power R, Layne DG (2001) Lactation, maternal behavior and infant growth in common marmoset monkeys (Callithrix jacchus): Effects of maternal size and litter size. Behav Ecol Sociobiol 51:17–25CrossRefGoogle Scholar
  64. Tardif SD, Layne DG, Smucny DA (2002) Can marmoset mothers count to three? Ethology 108:825–836CrossRefGoogle Scholar
  65. Tardif SD, Smucny DA, Abbott DH, Mansfield K, Schultz-Darken N, Yamomato ME (2003) Reproduction in captive common marmosets (Callithrix jacchus). Comp Med 53(4):364–368PubMedGoogle Scholar
  66. Taricco E, Radaelli MS, Nobile de Santis MS, Cetin I (2003) Foetal and placental weights in relation to maternal characteristics in gestational diabetes. Placenta 24:343–347CrossRefPubMedGoogle Scholar
  67. Trivers RL (1974) Parent-offspring conflict. Am Zool 14:249–264Google Scholar
  68. Vlietinck R, Derom R, Neale MC, Maes H, van Loon H, Derom C, Thiery M (1989) Genetic and environmental variation in the birth weight of twins. Behav Genet 19(1):151–161CrossRefPubMedGoogle Scholar
  69. Wahlbeck K, Forsen T, Osmond C, Barker DJ, Eriksson JG (2001) Association of schizophrenia with low maternal body mass index, small size at birth, and thinness during childhood. Arch Gen Psychiatry 58(1):48–52CrossRefPubMedGoogle Scholar
  70. Wheeler T (1994) Influences of the maternal environment on placental growth and function. In: Ward RHT, Smith SK, Donnai D (eds) Early fetal growth and development. Royal College of Obstetricians and Gynaecologists Press, London, pp 257–265Google Scholar
  71. Wilson ME, Biensen NJ, Ford SP (1999) Insight into the control of litter size in pigs, using placental efficiency as a selection tool. J Anim Sci 77:1654–1658Google Scholar
  72. Wilson ME and Ford SP (2001) Comparative aspects of placental efficiency. Reproduction Suppl 58: 223–32Google Scholar
  73. Windle CP, Baker HF, Ridley RM, Oerke A-K, Martin RD (1999) Unrearable litters and prenatal reduction of litter size in the common marmoset (Callithrix jacchus). J Med Primatol 28:73–83PubMedGoogle Scholar
  74. Wislocki GB (1932) Placentation in the marmoset (Oedipomidas geoffroyi), with remarks on twinning in monkeys. Anat Rec 52(4):381–399CrossRefGoogle Scholar
  75. Wislocki GB (1939) Observations on twinning in marmosets. Am J Anat 64:445–483CrossRefGoogle Scholar
  76. Wynn RM, Richards SC, Harris J (1975) Electron microscopy of the placenta and related structures of the marmoset. Am J Obstet Gynecol 122(1):60–69Google Scholar

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© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of Oral Biology, College of DentistryUniversity of Illinois at ChicagoChicagoUSA

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