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Phosphate, Calcium, and Vitamin D: Key Regulators of Fetal and Placental Development in Mammals

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Recent Advances in Animal Nutrition and Metabolism

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1354))

Abstract

Normal calcium and bone homeostasis in the adult is virtually fully explained by the interactions of several key regulatory hormones, including parathyroid hormone, 1,25 dihydroxy vitamin D3, fibroblast growth factor-23, calcitonin, and sex steroids (estradiol and testosterone). In utero, bone and mineral metabolism is regulated differently from the adult. During development, it is the placenta and not the fetal kidneys, intestines, or skeleton that is the primary source of minerals for the fetus. The placenta is able to meet the almost inexhaustible needs of the fetus for minerals by actively driving the transport of calcium and phosphorus from the maternal circulation to the growing fetus. These fundamentally important minerals are maintained in the fetal circulation at higher concentrations than those in maternal blood. Maintenance of these inordinately higher fetal levels is necessary for the developing skeleton to accrue sufficient minerals by term. Importantly, in livestock species, prenatal mineralization of the skeleton is crucial for the high levels of offspring activity soon after birth. Calcium is required for mineralization, as well as a plethora of other physiological functions. Placental calcium and phosphate transport are regulated by several mechanisms that are discussed in this review. It is clear that phosphate and calcium metabolism is intimately interrelated and, therefore, placental transport of these minerals cannot be considered in isolation.

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Abbreviations

1,25(OH)2D3:

1,25 Dihydroxyvitamin D3

ADAM:

A disintegrin and metalloprotease domain

cAMP:

Cyclic adenosine monophosphate

CTB:

Cytotrophoblasts

CYPs:

Cytochrome P450 mixed-function oxidases

E2:

Estradiol

ECM:

Extracellular Matrix

FGF:

Fibroblast growth factor

FGFR:

Fibroblast growth factor receptor

GE:

Glandular epithelium

IFNT:

Interferon tau

KL:

Klotho

LE:

Luminal epithelium

P21:

Cyclin-dependent kinase inhibitor

P4:

Progesterone

P53:

Tumor protein 53

PGR:

Progesterone receptor

PKC:

Protein kinase C

PMCA:

Plasma membrane Ca2+ATPase

PTH:

Parathyroid hormone

PTHR:

Parathyroid hormone receptor

PTHrP:

Parathyroid hormone-related protein

S100:

S100 calcium binding proteins

sFRP4:

Secreted frizzled-related protein 4

sGE:

Superficial glandular epithelium

SLC:

Solute carrier

SLC20:

Solute carrier family 20

SLC34:

Solute carrier family 34

SPP1:

Secreted phosphoprotein 1

STB:

Syncytiotrophoblast

STC:

Stanniocalcin

TRPV:

Transient receptor potential cation channel

VDR:

Vitamin D receptor

WNT:

Wingless-related integration site

References

  • Abbas SK, Care AD, Van Baelen H, Bouillon R (1987) Plasma vitamin D-binding protein and free 1,25-dihydroxyvitamin D3 index in pregnant ewes and their fetuses in the last month of gestation. J Endocrinol 115:7–12

    Article  PubMed  CAS  Google Scholar 

  • Abbas S, Pickard D, Rodda C, Heath J, Hammonds R, Wood W, Caple I, Martin T, Care A (1989) Stimulation of ovine placental calcium transport by purified natural and recombinant parathryoid hormone-related protein (PTHrP) preparations. Q J Exp Physiol 74:549–552

    Article  PubMed  CAS  Google Scholar 

  • Achkar M, Dodds L, Giguère Y, Forest JC, Armson BA, Woolcott C, Agellon S, Spencer A, Weiler HA (2015) Vitamin D status in early pregnancy and risk of preeclampsia. Am J Obstet Gynecol 212:e1–e7

    Article  Google Scholar 

  • Adams JS, Hewison M (2008) Unexpected actions of vitamin D: new perspectives on the regulation of innate and adaptive immunity. Nat Clin Pract Endocrinol Metab 4:80–90

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Aerssens J, Boonen S, Lowet G, Dequeker J (1998) Interspecies differences in bone composition, density, and quality: potential implications for in vivo bone reseach. Endocrinology 139:663–670

    Article  PubMed  CAS  Google Scholar 

  • Alimohamadi S, Esna-Ashari F, Rooy RSB (2020) Relationship of vitamin D serum level with intrauterine growth retardation in pregnant women. Int J Women’s Heal Reprod Sci 8:221–226

    Article  CAS  Google Scholar 

  • Allen WM, Sansom BF (1986) Parturient paresis (milk fever) and hypocalcemia (cows, ewes, and goats). In: Howard JL (ed) Current veterinary therapy: food animal practice, Philadelphia, vol 2, pp 311–320

    Google Scholar 

  • Allgrove J, Adami S, Manning RM, O’Riordan JL (1985) Cytochemical bioassay of parathyroid hormone in maternal and cord blood. Arch Dis Child 60:110–115

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • An B, Choi K, Kang SK, Hwang WS, Jeung E (2003) Novel Calbindin-D 9k protein as a useful biomarker for environmental estrogenic compounds in the uterus of immature rats. Reprod Toxicol 17:311–319

    Article  PubMed  CAS  Google Scholar 

  • Ardawi MSM, Nasrat HAN, Aqueel HSBA (1997) Calcium-regulating hormones and parathyroid hormone-related peptide in normal human pregnancy and postpartum: a longitudinal study. Eur J Endocrinol 137:402–409

    Article  PubMed  CAS  Google Scholar 

  • Arjmandi BH, Salih MA, Herbert DC, Sims SH, Kalu DN (1993) Evidence for estrogen receptor-linked calcium transport in the intestine. Bone Miner 21:63–74

    Article  PubMed  CAS  Google Scholar 

  • Baeke F, Takiishi T, Korf H, Gysemans C, Mathieu C (2010) Vitamin D: modulator of the immune system. Curr Opin Pharmacol 10:482–496

    Article  PubMed  CAS  Google Scholar 

  • Baker JR, Jeffery R, May RD, Mathies M, Spencer-Dene B, Poulsom R, Hogg N (2011) Distinct roles for S100a8 in early embryo development and in the maternal deciduum. Dev Dyn 240:2194–2203

    Article  PubMed  CAS  Google Scholar 

  • Banerjee A, Padh H, Nivsarkar M (2011) Hormonal crosstalk with calcium channel blocker during implantation. Syst Reprod Med 57:186–189

    Article  CAS  Google Scholar 

  • Barry JS, Anthony RV (2008) The pregnant sheep as a model for human pregnancy. Theriogenology 69:55–67

    Article  PubMed  CAS  Google Scholar 

  • Bazer FW, Spencer TE, Thatcher WW (2012) Growth and development of the ovine conceptus. J Anim Sci 90:159–170

    Article  PubMed  CAS  Google Scholar 

  • Belkacemi L, Gariépy G, Mounier C, Simoneau L, Lafond J (2004) Calbindin-D9k (CaBP9k) localization and levels of expression in trophoblast cells from human term placenta. Cell Tissue Res 315:107–117

    Article  PubMed  CAS  Google Scholar 

  • Bergada L, Pallares J, Arcidiacono M, Cardus A, Santacan M, Valls J, Cao G, Fernandez E, Dolcet X, Dusso A, Matias-Guiu X (2014) Role of local bioactivation of vitamin D by CYP27A1 and CYP2R1 in the control of cell growth in normal endometrium and endometrial carcinoma. Lab Invest 94:608–622

    Article  PubMed  CAS  Google Scholar 

  • Berndt T, Kumar R (2007) Phosphatonins and the regulation of phosphate homeostasis. Annu Rev Physiol 69:341–359

    Article  PubMed  CAS  Google Scholar 

  • Bikle D (2014) Vitamin D metabolism, mechanism of action, and clinical applications. Chem Biol 21:319–329

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Boass A, Garner SC, Schultz VL, Toverud SU (1997) Regulation of serum calcitriol by serum ionized calcium in rats during pregnancy and lactation. J Bone Miner Res 12:909–914

    Article  PubMed  CAS  Google Scholar 

  • Bodnar LM, Catov JM, Simhan HN, Holick MF, Powers RW, Roberts JM (2007) Maternal vitamin D deficiency increases the risk of preeclampsia. J Clin Endocrinol Metab 92:3517–3522

    Article  PubMed  CAS  Google Scholar 

  • Bon N, Frangi G, Sourice S, Guicheux J, Beck-cormier S, Beck L (2018) Phosphate-dependent FGF23 secretion is modulated by PiT2/Slc20a2. Mol Metab 11:197–204

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Bouillon R, Marcocci C, Carmeliet G, Bikle D, White JH, Dawson-hughes B, Lips P, Munns CF, Lazaretti-castro M, Giustina A, Bilezikian J (2019) Skeletal and extraskeletal actions of Vitamin D: current evidence and outstanding questions. Endocr Rev 40:1109–1151

    Article  PubMed  Google Scholar 

  • Bourdeau A, Manganella G, Thil-Trubert CL, Sachs C, Cournot G (1990) Bioactive parathyroid hormone in pregnant rats and fetuses. Am J Physiol 258:E549–E554

    PubMed  CAS  Google Scholar 

  • Bronner F (1989) Renal calcium transport: mechanisms and regulation-an overview. Am J Physiol 257:F707–F711

    PubMed  CAS  Google Scholar 

  • Brostrom MA, Brostrom CO (2003) Calcium dynamics and endoplasmic reticular function in the regulation of protein synthesis: implications for cell growth and adaptability. Cell Calcium 34:345–363

    Article  PubMed  CAS  Google Scholar 

  • Care AD (1991) The placental transfer of calcium. J Dev Physiol 15:253–257

    PubMed  CAS  Google Scholar 

  • Care AD, Caple IW, Singh R, Peddie M (1986) Studies on calcium homeostasis in the fetal Yucatan miniature pig. Lab Anim Sci 36:389–392

    PubMed  CAS  Google Scholar 

  • Carpenter TO, Ellis BK, Insogna KL, Philbrick WM, Sterpka J, Shimkets R (2005) Fibroblast growth factor 7: an inhibitor of phosphate transport derived from oncogenic osteomalacia-causing tumors. J Clin Endocrinol Metab 90:1012–1020

    Article  PubMed  CAS  Google Scholar 

  • Carter AM (2007) Animal models of human placentation—a review. Placenta 28:S41–S47

    Article  PubMed  Google Scholar 

  • Chang Q, Hoefs S, Van Der Kemp AW, Topala CN, Bindels RJ, Hoenderop JG (2005) Cell signalling: the β-glucuronidase klotho hydrolyzes and activates the TRPV5 channel. Science 310:490–493

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Spencer TE, Bazer FW (2000) Fibroblast growth factor-10: a stromal mediator of epithelial function in the ovine uterus. Biol Reprod 63:959–966

    Article  PubMed  CAS  Google Scholar 

  • Chen C, Podvin S, Gillespie E, Leeman SE, Abraham CR (2007) Insulin stimulates the cleavage and release of the extracellular domain of Klotho by ADAM10 and ADAM17. Proc Natl Acad Sci USA 104:19796–19801

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Chen YH, Fu L, Hao JH, Yu Z, Zhu P, Wang H, Xu YY, Zhang C, Tao FB, Xu DX (2015) Maternal vitamin D deficiency during pregnancy elevates the risks of small for gestational age and low birth weight infants in Chinese population. J Clin Endocrinol Metab 100:1912–1919

    Article  PubMed  CAS  Google Scholar 

  • Chhabra S, Singh A (2017) Role of calcium in hypertensive disorders of pregnancy current status of research a mini review. J Nutr Disord Ther 7:1–5

    Article  Google Scholar 

  • Chin KV, Cade C, Brostrom CO, Galuska EM, Brostrom MA (1987) Calcium-dependent regulation of protein synthesis at translational initiation in eukaryotic cells. J Biol Chem 262:16509–16514

    Article  PubMed  CAS  Google Scholar 

  • Choi KC, Jeung EB (2008) Molecular mechanism of regulation of the calcium-binding protein calbindin-D9k, and its physiological role(s) in mammals: a review of current research: molecular medicine. J Cell Mol Med 12:409–420

    Article  PubMed  CAS  Google Scholar 

  • Choi Y, Seo H, Kim M, Ka H (2009) Dynamic expression of calcium-regulatory molecules, TRPV6 and S100G, in the uterine endometrium during pregnancy in pigs. Biol Reprod 81:1122–1130

    Article  PubMed  CAS  Google Scholar 

  • Choi Y, Seo H, Shim J, Kim M, Ka H (2012) Regulation of S100G expression in the uterine endometrium during early pregnancy in pigs. Asian-Australasian J Anim Sci 25:44–51

    Article  CAS  Google Scholar 

  • Choi Y, Seo H, Shim J, Hyun S-H, Lee E, Ka H (2014a) Klotho: expression and regulation at the maternal-conceptus interface in pigs. J Anim Reprod Biotechnol 29:375–383

    Google Scholar 

  • Choi Y, Seo H, Shim J, Yoo I, Ka H (2014b) Calcium extrusion regulatory molecules: differential expression during pregnancy in the porcine uterus. Domest Anim Endocrinol 47:1–10

    Google Scholar 

  • Choi Y, Jang H, Seo H, Yoo I, Han J, Kim M, Lee S, Ka H (2019) Changes in calcium levels in the endometrium throughout pregnancy and the role of calcium on endometrial gene expression at the time of conceptus implantation in pigs. Mol Reprod Dev 86:883–895

    Article  PubMed  CAS  Google Scholar 

  • Collignon H, Davicco MJ, Barlet JP (1996) Calcitonin mRNA expression and plasma calciotropic hormones in fetal lambs. Domestric Anim Endocrinol 13:269–276

    Article  CAS  Google Scholar 

  • Comar CL (1956) Radiocalcium studies in pregnancy. Ann NY Acad Sci 64:281–298

    Article  CAS  Google Scholar 

  • Correia-Branco A, Rincon MP, Pereira LM, Wallingford MC (2020) Inorganic phosphate in the pathogenesis of pregnancy-related complications. Int J Mol Sci 21:1–11

    Article  Google Scholar 

  • Cross N, Hillman L, Allen S, Krause G, Vieira N (1995) Calcium homeostasis pregnancy, lactation, and bone metabolism during and postweaning: a longitudinal study. Am J Clin Nutr 61:514–523

    Article  PubMed  CAS  Google Scholar 

  • Darwish HM, DeLuca HF (1992) Identification of a 1,25-dihydroxyvitamin D3-response element in the 5′-flanking region of the rat calbindin D-9k gene. Proc Natl Acad Sci USA 89:603–607

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • DeGaris PJ, Lean IJ (2009) Milk fever in dairy cows: a review of pathophysiology and control principles. Vet J 176:58–69

    Article  Google Scholar 

  • Delivoria-Papadopoulos M, Battaglia FC, Bruns PD, Meschia G (1967) Total, protein-bound, and ultrafilterable calcium in maternal and fetal plasmas. Am J Physiol 213:363–366

    Article  PubMed  CAS  Google Scholar 

  • Deol HK, Varghese R, Wagner GF, Dimattia GE (2000) Dynamic regulation of mouse ovarian stanniocalcin expression during gestation and lactation. Endocrinology 141:3412–3421

    Article  PubMed  CAS  Google Scholar 

  • Devaskar UP, Ho M, Devaskar SU, Tsang RC (1984) 25-hydroxy- and 1 alpha,25-dihydroxyvitamin D. Maternal-fetal relationship and the transfer of 1,25-dihydroxyvitamin D3 across the placenta in an ovine model. Dev Pharmacol Ther 7:213–220

    Article  PubMed  CAS  Google Scholar 

  • Dias RS, Kebreab E, Vitti DMSS, Roque AP, Bueno ICS, France J (2006) A revised model for studying phosphorus and calcium kinetics in growing sheep. J Anim Sci 84:2787–2794

    Article  PubMed  CAS  Google Scholar 

  • Díaz L, Noyola-martínez N, Barrera D, Hernández G, Avila E, Halhali A, Larrea F (2009) Calcitriol inhibits TNFa-induced inflammatory cytokines in human trophoblasts. J Reprod Immunol 81:17–24

    Article  PubMed  Google Scholar 

  • Dolegowska K, Marchelek-mysliwiec M, Nowosiad-magda M, Slawinski M, Dolegowska B (2019) FGF19 subfamily members: FGF19 and FGF21. J Physiol Biochem 75:229–240

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Donato R, Cannon BR, Sorci G, Riuzzi F, Hsu K, Weber DJ, Geczy CL (2013) Functions of S100 Proteins. Curr Mol Med 13:24–57

    Google Scholar 

  • Dubil EA, Magann EF (2013) Amniotic fluid as a vital sign for fetal wellbeing. Australas J Ultrasound Med 16:62–70

    Article  PubMed  PubMed Central  Google Scholar 

  • Ducusin RJT, Uzuka Y, Satoh E, Otani M, Nishimura M, Tanabe S, Sarashina T (2003) Effects of extracellular Ca2+ on phagocytosis and intracellular Ca2+ concentrations in polymorphonuclear leukocytes of postpartum dairy cows. Res Vet Sci 75:27–32

    Article  PubMed  CAS  Google Scholar 

  • 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 63:1092–1110

    Article  PubMed  CAS  Google Scholar 

  • Enders AC, Blankenship TN (1999) Comparative placental structure. Adv Drug Deliv Rev 38:3–15

    Article  PubMed  CAS  Google Scholar 

  • Enders AC, Carter AM (2004) What can comparative studies of placental structure tell us?—a review. Placenta 25:S3–S9

    Article  PubMed  CAS  Google Scholar 

  • Evans KN, Nguyen L, Chan J, Innes BA, Bulmer JN, Kilby MD, Hewison M (2006) Effects of 25-hydroxyvitamin D 3 and 1, 25-dihydroxyvitamin D 3 on cytokine production by human decidual cells. Biol Reprod 75:816–822

    Article  PubMed  CAS  Google Scholar 

  • Fleischman AR, Lerman S, Oakes GK, Epstein MF, Chez RA, Mintz DH (1975) Perinatal primate parathyroid hormone metabolism. Biol Neonate 21:40–49

    Article  Google Scholar 

  • Fotiou M, Michaelidou AM, Athanasiadis AP, Menexes G, Symeonidou M, Koulourida V, Ganidou M, Theodoridis TD, Tarlatzis BC (2015) Second trimester amniotic fluid glucose, uric acid, phosphate, potassium, and sodium concentrations in relation to maternal pre-pregnancy BMI and birth weight centiles. J Matern Neonatal Med 28:910–915

    Article  CAS  Google Scholar 

  • Fudge NJ, Kovacs CS (2010) Pregnancy up-regulates intestinal calcium absorption and skeletal mineralization independently of the vitamin D receptor. Endocrinology 151:886–895

    Article  PubMed  CAS  Google Scholar 

  • Fukino K, Suzuki T, Saito Y, Shindo T, Amaki T, Kurabayashi M, Nagai R (2002) Regulation of angiogenesis by the aging suppressor gene klotho. Biochem Biophys Res Commun 293:332–337

    Article  PubMed  CAS  Google Scholar 

  • Gao H, Wu G, Spencer TE, Johnson GA, Li X, Bazer FW (2009) Select nutrients in the ovine uterine lumen. I. Amino acids, glucose, and ions in uterine lumenal flushings of cyclic and pregnant ewes. Biol Reprod 80:86–93

    Article  PubMed  CAS  Google Scholar 

  • Garel JM (1972) Distribution of labeled parathyroid hormone in rat fetus. Horm Metab Res 4:131–132

    Article  PubMed  CAS  Google Scholar 

  • Geisert R, Thatcher W, Roberts R, Bazer F (1982) Establishment of pregnancy in the pig: III. Endometrial secretory response to estradiol administered on day 11 of the estrous cycle. Biol Reprod 27:957–965

    Article  PubMed  CAS  Google Scholar 

  • Gernand AD, Simhan HN, Caritis S, Bodnar LM (2014) Maternal vitamin D status and small-for-gestational-age offspring in women at high risk for preeclampsia. Obstet Gynecol 123:40–48

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Gillies BR, Ryna BA, Tonkin BA, Poulton IJ, Ma Y, Kirby BJ, St-Arnaud R, Sims NA, Kovacs CS (2018) Absence of calcitrol causes increased lactational bone loss and lower milk calcium but does not impair post-lactation bone recovery in Cyp27b1 null mice. J Bone Miner Res 33:16–26

    Article  PubMed  CAS  Google Scholar 

  • Givens MH, Macy IG (1933) Chemical composition of human fetus. J Biol Chem 102:7–17

    Article  CAS  Google Scholar 

  • Glancy B, Balaban RS (2012) Role of mitochondrial Ca2+ in the regulation of cellular energetics. Biochemistry 51:2959–2973

    Article  PubMed  CAS  Google Scholar 

  • Glazier JD, Sharpe PT, Atkinson DE, Thornburg KL, Edwards D, Boyd RDH, Sibley CP, Boyd RDH (1992) Gestational changes in Ca2+ transport across rat placenta and mRNA for calbinding K and Ca2+-ATPase. Am J Physiol 263:R930–R935

    PubMed  CAS  Google Scholar 

  • Grace ND, Watkinson JH, Martinson PL (1986) Accumulation of minerals by the foetus(es) and conceptus of single- and twin-bearing ewes. New Zeal J Agric Res 29:207–222

    Article  CAS  Google Scholar 

  • Grigsby PL (2016) Animal models to study placental development and function throughout normal and dysfunctional human pregnancy. Semin Reprod Med 34:11–16

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Günther T, Chen ZF, Kim J, Priemel M, Rueger JM, Amling M, Moseley JM, Martin TJ, Anderson DJ, Karsenty G (2000) Genetic ablation of parathyroid glands reveals another source of parathyroid hormone. Nature 406:199–203

    Article  PubMed  Google Scholar 

  • Habert R, Picon R (1984) Testosterone, dihydrotestosterone, and estradiol-17b levels in maternal and fetal plasma and in fetal testes in the rat. J Steroid Biochem 21:193–198

    Article  PubMed  CAS  Google Scholar 

  • Haddad JGJ, Boisseau V, Avioli LV (1971) Placental transfer of vitamin D3 and 25-hydroxycholecalciferol in the rat. J Lab Clin Med 77:908–915

    PubMed  CAS  Google Scholar 

  • Haussler MR, Whitfield GK, Kaneko I, Forster R, Saini R, Hsieh C, Haussler CA, Jurutka PW (2013) The role of Vitamin D in the FGF23, Klotho, and phosphate bone-kidney endocrine axis. Rev Endocr Metab Disord 13:57–69

    Article  Google Scholar 

  • Heaney RP, Skillman TG (1971) Calcium metabolism in normal human pregnancy. J Clin Endocrinol 33:661–670

    Article  CAS  Google Scholar 

  • Hermann A, Donato R, Weiger TM, Chazin WJ (2012) S100 calcium binding proteins and ion channels. Front Pharmacol 3:1–10

    Article  Google Scholar 

  • Hernando N, Wagner CA (2018) Mechanisms and regulation of intestinal phosphate absorption. Compr Physiol 8:1065–1090

    Article  PubMed  Google Scholar 

  • Hindson J, Winter A (2002) Appendix 3 nutrition. In: Manual of sheep diseases. Wiley-Blackwell Publisher, Hoboken, New Jersey, 304 pp.

    Google Scholar 

  • Houtsmuller EJ, De Jong FH, Rowland DL, Slob AK (1995) Plasma testosterone in fetal rats and their mothers on day 19 of gestation. Physiol Behav 57:495–499

    Article  PubMed  CAS  Google Scholar 

  • Hu MC, Shi M, Moe OW (2019) Role of αKlotho and FGF23 in regulation of type II Na-dependent phosphate co-transporters. Pflugers Arch Eur J Physiol 471:99–108

    Article  CAS  Google Scholar 

  • Hunt JS (2006) Stranger in a strange land. Immunol Rev 213:36–47

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Husain S, Mughal M (1992) Mineral transport across the placenta. Arch Dis Child 67:874–878

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Iñiguez G, Gallardo P, Castro JJ, Gonzalez R, Garcia M, Kakarieka E, San Martin S, Johnson MC, Mericq V, Cassorla F (2019) Klotho gene and protein in human placentas according to birth weight and gestational age. Front Endocrinol (lausanne) 9:1–8

    Article  Google Scholar 

  • Inpanbutr N, Miller EK, Petroff BK, Iacopino AM (1994) CaBP(9K) levels during the luteal and follicular phases of the estrous cycle in the bovine uterus. Biol Reprod 50:561–571

    Article  PubMed  CAS  Google Scholar 

  • Ioannou C, Javaid MK, Mahon P, Yaqub MK, Harvey NC, Godfrey KM, Noble JA, Cooper C, Papageorghiou AT (2012) The effect of maternal vitamin D concentration on fetal bone. J Clin Endocrinol Metab 97:2070–2077

    Article  Google Scholar 

  • Islam MS (ed) (2011) Transient receptor potential channels. Adv Exp Med Biol 704:1–1095

    Google Scholar 

  • Jang H, Choi Y, Yoo I, Han J, Hong JS, Kim YY, Ka H (2017) Vitamin D-metabolic enzymes and related molecules: expression at the maternal-conceptus interface and the role of vitamin D in endometrial gene expression in pigs. PLoS ONE 12:1–20

    Article  Google Scholar 

  • Jeon US (2008) Kidney and calcium homeostasis. Electrolyte Blood Press 6:68–76

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Jones G, Prosser DE, Kaufmann M (2014) Cytochrome P450-mediated metabolism of vitamin D. J Lipid Res 55:13–31

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Karras SN, Fakhoury H, Muscogiuri G, Grant WB, van den Ouweland JM, Colao AM, Kotsa K (2016) Maternal vitamin D levels during pregnancy and neonatal health: evidence to date and clinical implications. Ther Adv Musculoskelet Dis 8:124–135

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kavsak P (2017) Textbook of clinical chemistry and molecular diagnostics, 6th ed. Elsevier, NewYork

    Google Scholar 

  • Kent G, Price R, Gutteridge D, Rosman K, Smith M, Allen J, Hickling C, Blakeman S (1991) The efficiency of intestinal calcium absorption is increased in late pregnancy but not in established lactation. Calcif Tissue Int Tissue 48:293–295

    Article  CAS  Google Scholar 

  • Khosla S, Johansen KL, Ory SJ, O’Brien PC, Kao PC (1990) Parathyroid hormone-related peptide in lactation and in umbilical cord blood. Mayo Clin Proc 65:1407–1414

    Article  Google Scholar 

  • Kim HJ, Lee GS, Ji YK, Choi KC, Jeung EB (2006) Differential expression of uterine calcium transporter 1 and plasma membrane Ca2+ ATPase 1b during rat estrous cycle. Am J Physiol 291:234–241

    Article  Google Scholar 

  • Kirby BJ, Ma Y, Martin HM, Favaro KLB, Karaplis AC, Kovacs CS (2013) Upregulation of calcitriol during pregnancy and skeletal recovery after lactation do not require parathyroid hormone. J Bone Miner Res 28:1987–2000

    Article  PubMed  CAS  Google Scholar 

  • Kovacs CS (2014) Bone development and mineral homeostasis in the fetus and neonate: roles of the calciotropic and phosphotropic hormones. Physiol Rev 94:1143–1218

    Article  PubMed  CAS  Google Scholar 

  • Kovacs CS (2015) Early human development calcium, phosphorus, and bone metabolism in the fetus and newborn. Early Hum Dev 91:623–628

    Article  PubMed  CAS  Google Scholar 

  • Kovacs CS (2016) Maternal mineral and bone metabolism during pregnancy, lactation, and post-weaning recovery. Physiol Rev 96:449–547

    Article  PubMed  CAS  Google Scholar 

  • Kovacs CS, Ralston SH (2015) Presentation and management of osteoporosis presenting in association with pregnancy or lactation. Osteoporos Int 26:2223–2241

    Article  PubMed  CAS  Google Scholar 

  • Kovacs CS, Lanske B, Hunzelman JL, Guo J, Karaplis AC, Kronenberg HM (1996) Parathyroid hormone-related peptide (PTHrP) regulates fetal-placental calcium transport through a receptor distinct from the PTH/PTHrP receptor. Proc Natl Acad Sci USA 93:15233–15238

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Kovacs CS, Chafe LL, Fudge NJ, Friel JK, Manley NR (2001a) PTH regulates fetal blood calcium and skeletal mineralization independently of PTHrP. Endocrinology 142:4983–4993

    Google Scholar 

  • Kovacs CS, Manley NR, Moseley JM, John Martin T, Kronenberg HM (2001b) Fetal parathyroids are not required to maintain placental calcium transport. J Clin Invest 107:1007–1015

    Google Scholar 

  • Kovacs CS, Woodland ML, Fudge NJ, Friel JK, Christopher S, Woodland ML, Fudge NJ (2005) The vitamin D receptor is not required for fetal mineral homeostasis or for the regulation of placental calcium transfer in mice. Am J Physiol 289:E133–E144

    CAS  Google Scholar 

  • Kubota M, Ohno J, Shiina Y, Suda T (1982) Vitamin D metabolism in pregnant rabbits: differences between the maternal and fetal response to administration of large amounts of vitamin D3. Endocrinology 110:1950–1956

    Article  PubMed  CAS  Google Scholar 

  • Kusaba T, Okigaki M, Matui A, Murakami M, Ishikawa K, Kimuraa T, Sonomura K, Adachi Y, Shibuya M, Shirayama T, Tanda S, Hatta T, Sasaki S, Mori Y, Matsubara H (2010) Klotho is associated with VEGF receptor-2 and the transient receptor potential canonical-1 Ca2+ channel to maintain endothelial integrity. Proc Natl Acad Sci USA 107:19308–19313

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lachenmaier-Currle U, Harmeyer J (1989) Placental transport of calcium and phosphorus in pigs. J Perinat Med 17:127–136

    Article  PubMed  CAS  Google Scholar 

  • Lachenmaier-Currle U, Breves G, Harmeyer J (1989) Role of 1,25-(OH)2D3 during pregnancy: studies with pigs suffering from pseudo-vitamin D-deficiency rickets, type 1. Q J Exp Physiol 74:875–881

    Article  PubMed  CAS  Google Scholar 

  • Lean IJ, Degaris PJ, Mcneil DM, Block E (2006) Hypocalcemia in dairy cows: meta-analysis and dietary cation anion difference theory revisited. J Dairy Sci 89:669–684

    Article  PubMed  CAS  Google Scholar 

  • Lederer E (2014) Renal phosphate transporters. Curr Opin Nephrol Hypertens 23:502–506

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Lee GS, Jeung EB (2007) Uterine TRPV6 expression during the estrous cycle and pregnancy in a mouse model. Am J Physiol 293:132–138

    Google Scholar 

  • Leiser R, Krebs C, Ebert B, Dantzer V (1997) Placental vascular corrosion cast studies: a comparison between ruminants and humans. Microsc Res Tech 38:76–87

    Article  PubMed  CAS  Google Scholar 

  • Lester GE, Gray TK, Lorenc RS (1978) Evidence for maternal and fetal differences in vitamin D metabolism. Proc Soc Exp Biol Med 159:303–307

    Article  PubMed  CAS  Google Scholar 

  • Li XY, Zheng SX, Wu G (2020) Amino acid metabolism in the kidneys: nutritional and physiological significance. Adv Exp Med Biol 1265:71–95

    Article  PubMed  CAS  Google Scholar 

  • Lim K, Lu TS, Molostvov G, Lee C, Lam FT, Zehnder D, Hsiao LL (2012) Vascular klotho deficiency potentiates the development of human artery calcification and mediates resistance to fibroblast growth factor 23. Circulation 125:2243–2255

    Article  PubMed  CAS  Google Scholar 

  • Lima MS, Kallfelz F, Krook L, Nathanielsz PW (1993) Humeral skeletal development and plasma constituent changes in fetuses of ewes maintained on a low calcium diet from 60 days of gestation. Calcif Tissue Int 52:283–290

    Article  PubMed  CAS  Google Scholar 

  • Liu N, Kaplan AT, Low J, Nguyen L, Liu GY, Equils O, Hewison M (2009) Vitamin D induces innate antibacterial responses in human trophoblasts via an intracrine pathway. Biol Reprod 80:398–406

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Liu NQ, Kaplan AT, Lagishetty V, Yuxin B, Ouyang Y, Simmons CF, Equils O, Hewison M (2011) Vitamin D and the regulation of placental inflammation. J Immunol 186:5974–5986

    Article  Google Scholar 

  • Liu XM, Ding GL, Jiang Y, Pan HJ, Zhang D, Wang TT, Zhang RJ, Shu J, Sheng JZ, Huang HF (2012) Down-regulation of S100A11, a calcium-binding protein, in human endometrium may cause reproductive failure. J Clin Endocrinol Metab 97:3672–3683

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Loichinger M, Towner D, Thompson K, Jun Ahn H, Bryant-Greenwood G (2016) Systemic and placental α-klotho: effects of preeclampsia in the last trimester of gestation. Placenta 41:53–61

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Loveridge N, Caple IW, Rodda C, Martin TJ, Care AD (1988) Further evidence for a parathryoid hormone-related protein in fetal parathyroid glands of sheep. Arthritis Rheum 73:781–784

    CAS  Google Scholar 

  • Lu M, Wagner GF, Renfro JL (1994) Stanniocalcin stimulates phosphate reabsorption by flounder renal proximal tubule in primary culture. Am J Physiol 267:R1356–R1362

    PubMed  CAS  Google Scholar 

  • Lyakhovich A, Aksenov N, Pennanen P, Miettinen S, Ahonen MH, Syvälä H, Ylikomi T, Tuohimaa P (2000) Vitamin D induced up-regulation of keratinocyte growth factor (FGF-7/KGF) in MCF-7 human breast cancer cells. Biochem Biophys Res Commun 273:675–680

    Article  PubMed  CAS  Google Scholar 

  • Ma R, Gu Y, Zhao S, Sun J, Groome LJ, Wang Y (2012) Expressions of vitamin D metabolic components VDBP, CYP2R1, CYP27B1, CYP24A1, and VDR in placentas from normal and preeclamptic pregnancies. Am J Physiol 303:E928–E935

    CAS  Google Scholar 

  • Ma Y, Samaraweera M, Cooke-hubley S, Kirby BJ, Karaplis AC, Lanske B, Kovacs CS (2014) Neither absence nor excess of FGF23 disturbs murine fetal-placental phosphorus homeostasis or prenatal. Endocrinology 155:1596–1605

    Article  PubMed  PubMed Central  Google Scholar 

  • MacIsaac RJ, Heath JA, Rodda CP, Moseley JM, Care AD, Martin TJ, Caple IW (1991) Role of the fetal parathyroid glands and parathyroid hormone-related protein in the regulation of placental transport of calcium, magnesium and inorganic phosphate. Reprod Fertil Dev 3:447–457

    Article  PubMed  CAS  Google Scholar 

  • Mahon P, Harvey N, Crozier S, Inskip H, Robinson S, Arden N, Swaminathan R, Cooper C, Godfrey K (2010) Low maternal vitamin D status and fetal bone development: cohort study. J Bone Miner Res 25:14–19

    Article  PubMed  CAS  Google Scholar 

  • Mayer GP, Ramberg CFJ, Kronfeld DS, Buckle RM, Sherwood LM, Aurbach GD, Potts JTJ (1969) Plasma parathyroid hormone concentration in hypocalcemic parturient cows. Am J Vet Res 30:1587–1597

    PubMed  CAS  Google Scholar 

  • Menon RK, Sperling MA (1998) Developmental endocrinology in the fetal-placental unit. In: Cowett RM (ed) Principles of perinatal-neonatal metabolism, 2nd edn. Springer, New York, pp 425–436

    Chapter  Google Scholar 

  • Miranda J, Romero R, Korzeniewski SJ, Schwartz AG, Chaemsaithong P, Stampalija T, Yeo L, Dong Z, Hassan SS, Chrousos GP, Gold P, Chaiworapongsa T (2014) The anti-aging factor α-klotho during human pregnancy and its expression in pregnancies complicated by small-for-gestational-age neonates and/or preeclampsia. J Matern Neonatal Med 27:449–457

    Article  CAS  Google Scholar 

  • Mitchell H, Hamilton T, Steggerda F, Bean H (1945) The chemical composition of the adult human body and its bearing on the biochemistry of growth. J Biol Chem 168:625–637

    Article  Google Scholar 

  • Montiel JF, Kaune H, Maliqueo M (2013) Maternal-fetal unit interactions and eutherian neocortical development and evolution. Front Neuroanat 7:1–14

    Article  Google Scholar 

  • Nabeshima YI, Imura H (2008) a-Klotho: a regulator that integrates calcium homeostasis. Am J Nephrol 28:455–464

    Article  PubMed  CAS  Google Scholar 

  • Nair RR, Khanna A, Singh K (2013) Role of inflammatory proteins S100A8 and S100A9 in pathophysiology of recurrent early pregnancy loss. Placenta 34:824–827

    Article  PubMed  CAS  Google Scholar 

  • Nie GY, Li Y, Wang J, Minoura H, Findlay JK, Salamonsen LA (2000) Complex regulation of calcium-binding protein D9k (calbindin-D(9k)) in the mouse uterus during early pregnancy and at the site of embryo implantation. Biol Reprod 62:27–36

    Article  PubMed  CAS  Google Scholar 

  • Noff D, Edelstein S (1978) Vitamin D and its hydroxylated metabolites in the rat. Placental and lacteal transport, subsequent metabolic pathways and tissue distribution. Horm Res 9:292–300

    Article  PubMed  CAS  Google Scholar 

  • Northrop G, Misenhimer HR, Becker FO (1977) Failure of parathyroid hormone to cross the nonhuman primate placenta. Am J Obstet Gynecol 129:449–453

    Article  PubMed  CAS  Google Scholar 

  • O’Brien KO, Li S, Cao C, Kent T, Young BV, Queenan RA, Pressman EK, Cooper EM (2014) Placental CYP27B1 and CYP24A1 expression in human placental tissue and their association with maternal and neonatal calcitropic hormones. Endocr Res 99:1348–1356

    Google Scholar 

  • Ohata Y, Arahori H, Namba N, Kitaoka T, Hirai H, Wada K, Nakayama M, Michigami T, Imura A, Nabeshima YI, Yamazaki Y, Ozono K (2011) Circulating levels of soluble α-klotho are markedly elevated in human umbilical cord blood. J Clin Endocrinol Metab 96:943–947

    Article  Google Scholar 

  • Okunade GW, Miller ML, Pyne GJ, Sutliff RL, O’Connor KT, Neumann JC, Andringa A, Miller DA, Prasad V, Doetschman T, Paul RJ, Shull GE (2004) Targeted ablation of plasma membrane Ca2+-ATPase (PMCA) 1 and 4 indicates a major housekeeping function for PMCA1 and a critical role in hyperactivated sperm motility and male fertility for PMCA4. J Biol Chem 279:33742–33750

    Article  PubMed  CAS  Google Scholar 

  • Passey RJ, Williams E, Lichanska AM, Wells C, Hu S, Geczy CL, Little MH, Hume DA (1999) A null mutation in the inflammation-associated S100 protein S100A8 causes early resorption of the mouse embryo. J Immunol 163:2209–2216

    PubMed  CAS  Google Scholar 

  • Paulson SK, DeLuca HF, Battaglia F (1987) Plasma levels of vitamin D metabolites in fetal and pregnant ewes. Proc Soc Exp Biol Med 185:267–271

    Article  PubMed  CAS  Google Scholar 

  • Paulson SK, Ford KK, Langman CB (1990) Pregnancy does not alter the metabolic clearance of 1,25-dihydroxyvitamin D in rats. Am J Physiol 258:E158–E162

    PubMed  CAS  Google Scholar 

  • Peacock M (2018) Hypoparathyroidism and the kidney. Endocrinol Metab Clin North Am 47:839–853

    Article  PubMed  Google Scholar 

  • Peacock M (2021) Phosphate metabolism in health and disease. Calcif Tissue Int 108:3–15

    Article  PubMed  CAS  Google Scholar 

  • Penido MGMG, Alon US (2012) Phosphate homeostasis and its role in bone health. Pediatr Nephrol 27:2039–2048

    Article  PubMed Central  Google Scholar 

  • Pike JW, Parker JB, Haussler MR, Boass A, Toverud SU (1979) Dynamic changes in circulating 1,25-dihydroxyvitamin D during reproduction in rats. Science 204:1427–1429

    Google Scholar 

  • Pizzagalli MD, Bensimon A, Superti-Furga G (2020) A guide to plasma membrane solute carrier proteins. FEBS J 1–52

    Google Scholar 

  • Poeter M, Radke S, Koese M, Hessner F, Hegemann A, Musiol A, Gerke V, Grewal T, Rescher U (2013) Disruption of the annexin A1/S100A11 complex increases the migration and clonogenic growth by dysregulating epithelial growth factor (EGF) signaling. Biochim Biophys Acta 1833:1700–1711

    Article  PubMed  CAS  Google Scholar 

  • Prasad V, Okunade G, Liu L, Paul RJ, Shull GE (2007) Distinct phenotypes among plasma membrane Ca2+-ATPase knockout mice. Ann NY Acad Sci 1099:276–286

    Article  PubMed  CAS  Google Scholar 

  • Qin LL, Lu FG, Yang SH, Xu HL, Luo BA (2016) Does maternal Vitamin D deficiency increase the risk of preterm birth: a meta-analysis of observational studies. Nutrients 8:1–10

    Article  Google Scholar 

  • Quarles LD (2008) Endocrine functions of bone in mineral metabolism regulation. J Clin Invest 118:3820–3828

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Reddy GS, Willis DM, Goltzman D, Guyda H, Solomon S, Philips DR, Bishop JE, Mayer E (1983) Regulation of vitamin D metabolism in normal human pregnancy. J Clin Endocrinol Metab 56:363–370

    Article  PubMed  CAS  Google Scholar 

  • Reyes FI, Winter JSD, Faiman C (1973) Studies on human sexual development. I. Fetal gonadal and adrenal sex steroids. J Clin Endocrinol Metab 37:74–78

    Article  PubMed  CAS  Google Scholar 

  • Risco C, Drost M, Thatcher WW, Savio J, Thatcher MJ (1994) Effects of calving-related disorders on prostaglandin, calcium, ovarian activity and uterine involution in postpartum dairy cows. Theriogenology 42:183–203

    Article  PubMed  CAS  Google Scholar 

  • Ritchie LD, Fung EB, Halloran BP, Turnlund JR, Van LMD, Cann CE, King JC (1998) A longitudinal study of calcium homeostasis during human pregnancy and lactation and after resumption of menses. Am J Clin Nutr 67:693–701

    Article  PubMed  CAS  Google Scholar 

  • Rodda CP, Kubota M, Heath JA, Ebeling PR, Moseley JM, Care AD, Caple IW, Martin TJ (1988) Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy. J Endocrinol 117:261–271

    Article  PubMed  CAS  Google Scholar 

  • Romero JJ, Liebig BE, Broeckling CD, Prenni JE, Hansen TR (2017) Pregnancy-induced changes in metabolome and proteome in ovine uterine flushings. Biol Reprod 97:273–287

    Article  PubMed  Google Scholar 

  • Ross R, Halbert K, Tsang RC (1989) Determination of the production and metabolic clearance rates of 1,25-dihydroxyvitamin D3 in the pregnant sheep and its chronically catheterized fetus by primed infusion technique. Pediatr Res 26:633–634

    Article  PubMed  CAS  Google Scholar 

  • Ryan BA, Kovacs CS (2021) Maternal and fetal vitamin D and their roles in mineral homeostasis and fetal bone development. J Endocrinol Invest 44:643–659

    Article  PubMed  CAS  Google Scholar 

  • Saito Y, Yamagishi T, Nakamura T, Ohyama Y, Aizawa H, Suga T, Matsumura Y, Masuda H, Kurabayashi M, Kuro-O M, Nabeshima YI, Nagai R (1998) Klotho protein protects against endothelial dysfunction. Biochem Biophys Res Commun 248:324–329

    Article  PubMed  CAS  Google Scholar 

  • Saki F, Sadeghian F, Kasaee SR, Koohpeyma F, Omrani GHR (2020) Effect of prolactin and estrogen on the serum level of 1,25-dihydroxy vitamin D and FGF23 in female rats. Arch Gynecol Obstet 302:265–271

    Article  PubMed  CAS  Google Scholar 

  • Santella L (1998) The role of calcium in the cell cycle: facts and hypotheses. Biochem Biophys Res Commun 244:317–324

    Article  PubMed  CAS  Google Scholar 

  • Schmid A, Walther B (2013) Natural vitamin D content in animal products. Adv Nutr 4:453–462

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Segawa H, Shiozaki Y, Kaneko I, Miyamoto KI (2015) The role of sodium-dependent phosphate transporter in phosphate homeostasis. J Nutr Sci Vitaminol (tokyo) 61:S119–S121

    Article  CAS  Google Scholar 

  • Seki K, Wada S, Nagata N, Nagata I (1994) Parathyroid hormone-related protein during pregnancy and the perinatal period. Gynecol Obstet Invest 37:83–86

    Article  PubMed  CAS  Google Scholar 

  • Shahbazi M, Jeddi-tehrani M, Zareie M, Salek-moghaddam A, Akhondi MM, Bahmanpoor M, Sadeghi MR, Zarnani AH (2011) Expression profiling of vitamin D receptor in placenta, decidua and ovary of pregnant mice. Placenta 32:657–664

    Article  PubMed  CAS  Google Scholar 

  • Shaikh A, Berndt T, Kumar R (2008) Regulation of phosphate homeostasis by the phosphatonins and other novel mediators. Pediatr Nephrol 23:1203–1210

    Article  PubMed  PubMed Central  Google Scholar 

  • Shibasaki Y, Etoh N, Hayasaka M, Takahashi MO, Kakitani M, Yamashita T, Tomizuka K, Hanaoka K (2009) Targeted deletion of the tybe IIb Na+-dependent Pi-co-transporter, NaPi-IIb, results in early embryonic lethality. Biochem Biophys Res Commun 381:482–486

    Google Scholar 

  • Simmonds CS, Kovacs CS (2010) Role of parathyroid hormone (PTH) and PTH-related protein (PTHrP) in regulating mineral homeostasis during fetal development. Crit Rev Eukaryot Gene Expr 20:235–273

    Article  PubMed  CAS  Google Scholar 

  • Simmonds CS, Karsenty G, Karaplis AC, Kovacs CS (2010) Parathyroid hormone regulates fetal-placental mineral homeostasis. J Bone Miner Res 25:594–605

    Article  PubMed  CAS  Google Scholar 

  • Sitara D, Razzaque MS, Hesse M, Yoganathan S, Taguchi T, Erben RG, Harald J, Lanske B (2004) Homozygous ablation of fibroblast growth factor-23 results in hyperphosphatemia and impaired skeletogenesis, and reverses hypophosphatemia in Phex- deficient mice. Matrix Biol 421–432

    Google Scholar 

  • Song G, Bazer FW, Wagner GF, Spencer TE (2006) Stanniocalcin (STC) in the endometrial glands of the ovine uterus: regulation by progesterone and placental hormones 1. Biol Reprod 74:913–922

    Article  PubMed  CAS  Google Scholar 

  • Song G, Dunlap KA, Kim J, Bailey DW, Spencer TE, Burghardt RC, Wagner GF, Johnson GA, Bazer FW (2009) Stanniocalcin 1. Is a luminal epithelial marker for implantation in pigs regulated by progesterone and estradiol. Endocrinology 150:936–945

    Article  PubMed  CAS  Google Scholar 

  • Stasko SE, DiMattia GE, Wagner GF (2001) Dynamic changes in stanniocalcin gene expression in the mouse uterus during early implantation. Mol Cell Endocrinol 174:145–149

    Article  PubMed  CAS  Google Scholar 

  • Stenhouse C, Halloran KM, Newton MG, Gaddy D, Suva LJ, Bazer FW (2021a) Novel mineral regulatory pathways in ovine pregnancy: II. Calcium binding proteins, calcium transporters, and vitamin D signaling. Biol Reprod 105:232–243

    Google Scholar 

  • Stenhouse C, Halloran KM, Newton MG, Gaddy D, Suva LJ, Bazer FW (2021b) Novel mineral regulatory pathways in ovine pregnancy: 1. Phosphate, klotho signaling, and sodium dependent phosphate transporters. Biol Reprod 104:1084–1096

    Google Scholar 

  • Strid H, Powell TL (2000) ATP-dependent Ca2+ transport is up-regulated during third trimester in human syncytiotrophoblast basal membranes. Pediatr Res 48:58–63

    Article  PubMed  CAS  Google Scholar 

  • Strott CA, Sundel H, Stahlman MT (1974) Maternal and fetal plasma progesterone, cortisol, testosterone and 17b-estradiol in preparturient sheep: response to fetal ACTH infusion. Endocrinology 95:1327–1339

    Article  PubMed  CAS  Google Scholar 

  • Stulc J, Stulcova B (1996) Placental transfer of phosphate in anaesthetized rats. Placenta 17:487–493

    Article  PubMed  CAS  Google Scholar 

  • Suva LJ, Winslow GA, Wettenhall RE, Hammonds RG, Moseley JM, Diefenbach-Jagger H, Rodda CP, Kemp BE, Rodriguez H, Chen EY (1987) A parathyroid hormone-related protein implicated in malignant hypercalcemia: cloning and expression. Science 237:893–896

    Article  PubMed  CAS  Google Scholar 

  • Suva LJ, Gaddy D, Perrien DS, Thomas RL, Findlay DM (2005) Regulation of bone mass by mechanical loading: microarchitecture and genetics. Curr Osteoporos Rep 3:46–51

    Article  PubMed  Google Scholar 

  • Suva L, Friedman P (2020) PTH and PTHrP actions on bone. In: Handbook of experimental pharmacology, vol 262. Springer, Berlin, pp 27–45

    Google Scholar 

  • Suzuki Y, Kovacs CS, Takanaga H, Peng J, Landowski CP, Hediger MA (2008) Calcium channel TRPV6 is involved in murine maternal-fetal calcium transport. J Bone Miner Res 23:1249–1256

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Swanson AM, David AL (2015) Animal models of fetal growth restriction: considerations for translational medicine. Placenta 36:623–630

    Article  PubMed  CAS  Google Scholar 

  • Tabatabaei S (2012) Gestational variations in the biochemical composition of the fetal fluids and maternal blood serum in goat. Comp Clin Path 21:1305–1312

    Article  CAS  Google Scholar 

  • Tamblyn JA, Hewison M, Wagner CL, Bulmer JN, Kilby MD (2015) Immunological role of vitamin D at the maternal—fetal interface. J Endocrinol 224:R107–R121

    Article  PubMed  CAS  Google Scholar 

  • Taylor-Miller T, Allgrove J (2021) Endocrine diseases of newborn: epidemiology, pathogenesis, therapeutic options, and outcome “Current Insights Into Disorders of Calcium and Phosphate in the Newborn.” Front Pediatr 9:1–8

    Article  Google Scholar 

  • Thomas ML, Anast CS, Forte LR (1981) Regulation of calcium homeostasis in the fetal and neonatal rat. Am J Physiol 240:E367–E372

    PubMed  CAS  Google Scholar 

  • Tuan RS, Bigioni N (1990) Ca-activated ATPase of the mouse chorioailantoic placenta: developmental expression, characterization and cytohistochemical localization. Development 110:505–513

    Article  PubMed  CAS  Google Scholar 

  • Tucci J, Russell A, Senior PV, Fernley R, Ferraro T, Beck F (1996) The expression of parathyroid hormone and parathyroid hormone-related protein in developing rat parathyroid glands. J Mol Endocrinol 17:149–157

    Article  PubMed  CAS  Google Scholar 

  • Verhaeghe J, Thomasset M, Brehier A, Assche FAV, Bouillon R (1988) 1,25(OH)2D3 and Ca-binding protein in fetal rats: relationship to maternal vitamin D status. Am J Physiol 254:E505–E512

    PubMed  CAS  Google Scholar 

  • Voelkl J, Egli-Spichtig D, Alesutan I, Wagner CA (2021) Inflammation: a putative link between phosphate metabolism and cardiovascular disease. Clin Sci 135:201–227

    Article  CAS  Google Scholar 

  • Wagner GF (1994) The molecular biology of the corpuscles of stannius and regulation of stanniocalcin gene expression. Fish Physiol 13:273–306

    Article  CAS  Google Scholar 

  • Wagner GF, Jaworski E (1994) Calcium regulates stanniocalcin mRNA levels in primary cultured rainbow trout corpuscles of Stannius. Mol Cell Endocrinol 99:315–322

    Article  PubMed  CAS  Google Scholar 

  • Wagner GF, Hampong M, Park CM, Copp DH (1986) Purification, characterization, and bioassay of teleocalcin, glycoprotein from salmon corpuscles of stannius. Gen Comp Endocrinol 63:481–491

    Article  PubMed  CAS  Google Scholar 

  • Wallingford MC, Giachelli CM (2014) Loss of PiT-1 results in abnormal endocytosis in the yolk sac visceral endoderm. Mech Dev 133:189–202

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Wallingford M, Gammill H, Giachelli C (2016) SLC20A2 deficiency results in fetal growth restriction and placental calcification associated with thickened basement membranes and novel CD13 and lamininα1 expressing cells. Reprod Biol 16:13–26

    Article  PubMed  PubMed Central  Google Scholar 

  • Wang Y, Sun Z (2009) Current understanding of klotho. Ageing Res Rev 8:43–51

    Article  PubMed  Google Scholar 

  • Ward IL, Weisz J (1984) Differential effects of maternal stress of circulating levels of corticosterone, progesterone, and testosterone in male and female rat fetuses and their mothers. Endocrinology 114:1635–1644

    Article  PubMed  CAS  Google Scholar 

  • Widdowson EM (1962) Metabolic relationship of calcium, magnesium and phosphorus in the foetus and newly born. Voeding 23:62–71

    PubMed  CAS  Google Scholar 

  • Widdowson EM, McCance RA (1965) The metabolism of calcium, phosphorus, magnesium and strontium. Pediatr Clin North Am 12:595–614

    Article  PubMed  CAS  Google Scholar 

  • Wilson RL, Phillips JA, Bianco-Miotto T, McAninch D, Goh Z, Anderson PH, Roberts CT (2020) Reduced dietary calcium and vitamin D results in preterm birth and altered placental morphogenesis in mice during pregnancy. Reprod Sci 27:1330–1339

    Article  PubMed  CAS  Google Scholar 

  • Wu G (2018) Principles of animal nutrition. CRC Press, Boca Raton, FL

    Google Scholar 

  • Wu G (2021) Amino acids: biochemistry and nutrition. CRC Press, Boca Raton, FL

    Book  Google Scholar 

  • Wu G (2022) Nutrition and metabolism: Foundations for animal growth, development, reproduction, and health. Adv Exp Med Biol 1354:1–24

    Google Scholar 

  • Xia C, Braunstein Z, Toomey AC, Zhong J, Rao X (2018) S100 proteins as an important regulator of macrophage inflammation. Front Immunol 8:1–11

    Article  Google Scholar 

  • Xiao L, Yuan J, Song X, Li Y, Hu Z, Liu Y (2006) Expression and regulation of stanniocalcin 1 and 2 in rat uterus during embryo implantation and decidualization. Reproduction 131:1137–1149

    Article  PubMed  CAS  Google Scholar 

  • Yamamoto M, Clark JD, Pastor JV, Gurnani P, Nandi A, Kurosu H, Miyoshi M, Ogawa Y, Castrillon DH, Rosenblatt KP, Kuro-O M (2005) Regulation of oxidative stress by the anti-aging hormone klotho. J Biol Chem 280:38029–38034

    Article  PubMed  CAS  Google Scholar 

  • Yang H, Choi KC, Hyun SH, Jeung EB (2011) Coexpression and estrogen-mediated regulation of TRPV6 and PMCA1 in the human endometrium during the menstrual cycle. Mol Reprod Dev 78:274–282

    Article  PubMed  CAS  Google Scholar 

  • Yang H, Kim TH, Lee GS, Hong EJ, Jeung EB (2014) Comparing the expression patterns of placental magnesium/phosphorus-transporting channels between healthy and preeclamptic pregnancies. Mol Reprod Dev 81:851–860

    Article  PubMed  CAS  Google Scholar 

  • Yoshida T, Fujimori T, Nabeshima Y (2002) Mediation of unusually high concentrations of 1,25-Dihydroxyvitamin D in homozygous klotho mutant mice by increased expression of renal 1a-hydroxylase gene. Endocrinology 143:683–689

    Article  PubMed  CAS  Google Scholar 

  • Young BE, McNanley TJ, Cooper EM, McIntyre AW, Witter F, Harris ZL, O’Brien KO (2012) Maternal vitamin D status and calcium intake interact to affect fetal skeletal growth in utero in pregnant adolescents. Am J Clin Nutr 95:1103–1112

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  • Zeng S, Bick J, Ulbrich SE, Bauersachs S (2018) Cell type-specific analysis of transcriptome changes in the porcine endometrium on day 12 of pregnancy. BMC Genomics 19:1–19

    Article  Google Scholar 

  • Zeng S, Ulbrich SE, Bauersachs S (2019) Spatial organization of endometrial gene expression at the onset of embryo attachment in pigs. BMC Genomics 20:1–19

    Article  Google Scholar 

  • Zhang R, Lu Y, Ye L, Yuan B, Yu S, Qin C, Xie Y, Gao T, Drezner MK, Bonewald LF, Feng JQ (2011) Unique roles of phosphorus in endochondral bone formation and osteocyte maturation. J Bone Miner Res 26:1047–1056

    Article  PubMed  CAS  Google Scholar 

  • Zhou SS, Tao YH, Huang K, Zhu BB, Tao FB (2017) Vitamin D and risk of preterm birth: up-to-date meta-analysis of randomized controlled trials and observational studies. J Obstet Gynaecol Res 43:247–256

    Article  PubMed  CAS  Google Scholar 

  • Ziegler E, O’Donnell A, Nelson S, Fomon S (1976) Body composition of the reference fetus. Growth 40:329–341

    PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported, in part, by Texas A&M University Presidential Impact Fellow Funds (to FWB) and funds from Texas A&M AgriLife Research (to FWB and GW), and the National Institutes of Health # 1R21DE028076-01 (to DG).

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Authors and Affiliations

  1. Departments of Animal Science, Texas A&M University, College Station, TX, 77843, USA

    Claire Stenhouse & Guoyao Wu

  2. Veterinary Physiology and Pharmacology, Texas A&M University, College Station, TX, 77843, USA

    Larry J. Suva

  3. Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, 77843, USA

    Dana Gaddy

  4. Department of Animal Science, Kleberg Center, Texas A&M University, College Station, TX, 77843-2471, USA

    Fuller W. Bazer

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  1. Claire Stenhouse
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Correspondence to Fuller W. Bazer .

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  1. Department of Animal Science, Texas A&M University, College Station, TX, USA

    Guoyao Wu

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Stenhouse, C., Suva, L.J., Gaddy, D., Wu, G., Bazer, F.W. (2022). Phosphate, Calcium, and Vitamin D: Key Regulators of Fetal and Placental Development in Mammals. In: Wu, G. (eds) Recent Advances in Animal Nutrition and Metabolism. Advances in Experimental Medicine and Biology, vol 1354. Springer, Cham. https://doi.org/10.1007/978-3-030-85686-1_5

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