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Cited by 94Pregnancy and preeclampsia studiesReproductive System and PregnancyBirth, Development, and Health

Sex at the interface: the origin and impact of sex differences in the developing human placenta

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Braun, Amy E., Mitchel, Olivia R., Gonzalez, Tania L., Sun, Tianyanxin, Flowers, Amy E., Pisarska, Margareta D., Winn, Virginia D.·2022·Biology of Sex Differences
DOI 10.1186/s13293-022-00459-7PMC PMC9482177
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Abstract

The fetal placenta is a source of hormones and immune factors that play a vital role in maintaining pregnancy and facilitating fetal growth. Cells in this extraembryonic compartment match the chromosomal sex of the embryo itself. Sex differences have been observed in common gestational pathologies, highlighting the importance of maternal immune tolerance to the fetal compartment. Over the past decade, several studies examining placentas from term pregnancies have revealed widespread sex differences in hormone signaling, immune signaling, and metabolic functions. Given the rapid and dynamic development of the human placenta, sex differences that exist at term (37–42 weeks gestation) are unlikely to align precisely with those present at earlier stages when the fetal–maternal interface is being formed and the foundations of a healthy or diseased pregnancy are established. While fetal sex as a variable is often left unreported in studies performing transcriptomic profiling of the first-trimester human placenta, four recent studies have specifically examined fetal sex in early human placental development. In this review, we discuss the findings from these publications and consider the evidence for the genetic, hormonal, and immune mechanisms that are theorized to account for sex differences in early human placenta. We also highlight the cellular and molecular processes that are most likely to be impacted by fetal sex and the evolutionary pressures that may have given rise to these differences. With growing recognition of the fetal origins of health and disease, it is important to shed light on sex differences in early prenatal development, as these observations may unlock insight into the foundations of sex-biased pathologies that emerge later in life.

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  • Placental differences dependent on fetal sex are numerous, and there are many mechanisms that could be involved in explaining how fetuses of different sexes are affected differently by prenatal EDC exposure.

    “However, the placental differences dependent on fetal sex are numerous, and there are many mechanisms that could be involved in explaining how fetuses of different sexes are affected differently by prenatal EDC exposure (Braun et al., 2022).”

    From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Braun et al., 2022

    The Background sections “The dynamic placental transcriptome” and “How does sex manifest in the human placenta?” describe numerous fetal-sex-dependent placental differences and potential mechanisms involving gene expression and hormones (page numbers unavailable). The passages do not connect those mechanisms specifically to differing fetal effects of prenatal endocrine-disrupting chemical (EDC) exposure. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Throughout gestation placental function is influenced by fetal sex, resulting in sex-specific immunological and hormonal signaling, as well as sex-specific metabolism.

    “Throughout gestation placental function is influenced by fetal sex, resulting in sex-specific immunological and hormonal signaling, as well as sex-specific metabolism (Braun et al., 2022).”

    From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Braun et al., 2022

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  1. [1]Mittwoch U Blastocysts prepare for the race to be male Hum Reprod 1993 8 10 1550 1555 10.1093/oxfordjournals.humrep.a137889 8300805 · DOI
  2. [3]Clarke J Observations on some causes of the excess of the mortality of males above that of females Lond Med J. 1788 9 Pt 2 179 200 29139721 PMC5545249
  3. [4]Cooperstock M Campbell J Excess males in preterm birth: interactions with gestational age, race, and multiple birth Obstet Gynecol 1996 88 2 189 193 10.1016/0029-7844(96)00106-8 8692499 · DOI
  4. [5]Walker MG Fitzgerald B Keating S Ray JG Windrim R Kingdom JC Sex-specific basis of severe placental dysfunction leading to extreme preterm delivery Placenta 2012 33 7 568 571 10.1016/j.placenta.2012.03.011 22513321 · DOI
  5. [6]Challis J Newnham J Petraglia F Yeganegi M Bocking A Fetal sex and preterm birth Placenta 2013 34 2 95 99 10.1016/j.placenta.2012.11.007 23261268 · DOI
  6. [7]Di Renzo GC Rosati A Sarti RD Cruciani L Cutuli AM Does fetal sex affect pregnancy outcome Gend Med 2007 4 1 19 30 10.1016/S1550-8579(07)80004-0 17584623 · DOI
  7. [8]Hassold T, Quillen SD, Yamane JA (1993) Sex ratio in spontaneous abortions. Ann Hum Genet. 47(1):39–47. 6838169
  8. [9]Byrne J Warburton D Male excess among anatomically normal fetuses in spontaneous abortions Am J Med Genet 1987 26 3 605 611 10.1002/ajmg.1320260315 3565477 · DOI
  9. [10]Schalekamp-Timmermans S Arends LR Alsaker E Chappell L Hansson S Harsem NK Fetal sex-specific differences in gestational age at delivery in pre-eclampsia: a meta-analysis Int J Epidemiol 2017 46 2 632 642 27605586 PMC5837300
  10. [11]Melamed N Yogev Y Glezerman M Fetal gender and pregnancy outcome J Matern Fetal Neonatal Med 2010 23 4 338 344 10.3109/14767050903300969 20222831 · DOI
  11. [12]Mulla ZD Plavsic SK Ortiz M Nuwayhid BS Ananth CV Fetal sex pairing and adverse perinatal outcomes in twin gestations Ann Epidemiol 2013 23 1 7 12 10.1016/j.annepidem.2012.10.003 23137847 · DOI
  12. [13]Radulescu L Ferechide D Popa F The importance of fetal gender in intrauterine growth restriction J Med Life 2013 6 1 38 39 23599816 PMC3624643
  13. [14]Teixeira MP, Queiroga TP, Mesquita MD (2016) Frequency and risk factors for the birth of small-for-gestational-age newborns in a public maternity hospital. Einstein Sao Paulo. 14(3):317–23. PMC5234741 27759818
  14. [15]Inkster AM, Fernández-Boyano I, Robinson WP. Sex differences are here to stay: relevance to prenatal care. J Clin Med. 2021;10(13):3000. PMC8268816 34279482
  15. [16]Brown ZA Schalekamp-Timmermans S Tiemeier HW Hofman A Jaddoe VW Steegers EA Fetal sex specific differences in human placentation: a prospective cohort study Placenta 2014 35 6 359 364 10.1016/j.placenta.2014.03.014 24720894 · DOI
  16. [17]Alur P Sex differences in nutrition, growth, and metabolism in preterm infants Front Pediatr 2019 7 22 10.3389/fped.2019.00022 30792973 PMC6374621 · DOI
  17. [18]Broere-Brown ZA, Adank MC, Benschop L, Tielemans M, Muka T, Gonçalves R, et al. Fetal sex and maternal pregnancy outcomes: a systematic review and meta-analysis. Biol Sex Differ. 2020;11(1):26. PMC7216628 32393396
  18. [19]Aibar L Puertas A Valverde M Carrillo MP Montoya F Fetal sex and perinatal outcomes J Perinat Med 2012 40 3 271 276 10.1515/jpm-2011-0137 22505506 · DOI
  19. [20]Al-Qaraghouli M Fang YMV Effect of fetal sex on maternal and obstetric outcomes Front Pediatr 2017 5 144 10.3389/fped.2017.00144 28674684 PMC5476168 · DOI
  20. [21]Soncin F, Khater M, To C, Pizzo D, Farah O, Wakeland A, et al. Comparative analysis of mouse and human placentae across gestation reveals species-specific regulators of placental development. Development. 2018;145(2):156273. PMC5825847 29361559
  21. [22]Jauniaux E, Poston L, Burton GJ. Placental-related diseases of pregnancy: Involvement of oxidative stress and implications in human evolution. Hum Reprod Update. 2006;12(6):747–55. PMC1876942 16682385
  22. [23]Petropoulos S Edsgärd D Reinius B Deng Q Panula SP Codeluppi S Single-cell RNA-Seq reveals lineage and X chromosome dynamics in human preimplantation embryos Cell 2016 165 4 1012 1026 10.1016/j.cell.2016.03.023 27062923 PMC4868821 · DOI · Paper page
  23. [24]Sood R Zehnder JL Druzin ML Brown PO Gene expression patterns in human placenta Proc Natl Acad Sci USA 2006 103 14 5478 5483 10.1073/pnas.0508035103 16567644 PMC1414632 · DOI · Paper page
  24. [25]Osei-Kumah A Smith R Jurisica I Caniggia I Clifton VL Sex-specific differences in placental global gene expression in pregnancies complicated by asthma Placenta 2011 32 8 570 578 10.1016/j.placenta.2011.05.005 21641640 · DOI
  25. [26]Cvitic S Longtine MS Hackl H Wagner K Nelson MD Desoye G The human placental sexome differs between trophoblast epithelium and villous vessel endothelium PLoS ONE 2013 8 10 e79233 10.1371/journal.pone.0079233 24205377 PMC3812163 · DOI · Paper page
  26. [28]Sedlmeier EM Brunner S Much D Pagel P Ulbrich SE Meyer HH Human placental transcriptome shows sexually dimorphic gene expression and responsiveness to maternal dietary n-3 long-chain polyunsaturated fatty acid intervention during pregnancy BMC Genomics 2014 27 15 941 10.1186/1471-2164-15-941 PMC4232618 25348288 · DOI
  27. [29]Muralimanoharan S Maloyan A Myatt L Evidence of sexual dimorphism in the placental function with severe preeclampsia Placenta 2013 34 12 1183 1189 10.1016/j.placenta.2013.09.015 24140080 PMC3868439 · DOI
  28. [30]Yeganegi M Watson CS Martins A Kim SO Reid G Challis JR Effect of Lactobacillus rhamnosus GR-1 supernatant and fetal sex on lipopolysaccharide-induced cytokine and prostaglandin-regulating enzymes in human placental trophoblast cells: implications for treatment of bacterial vaginosis and prevention of preterm labor Am J Obstet Gynecol 2009 200 5 532.e1 8 10.1016/j.ajog.2008.12.032 19285652 · DOI
  29. [31]Winn VD Haimov-Kochman R Paquet AC Yang YJ Madhusudhan MS Gormley M Gene expression profiling of the human maternal-fetal interface reveals dramatic changes between midgestation and term Endocrinology 2007 148 3 1059 1079 10.1210/en.2006-0683 17170095 · DOI
  30. [32]Yong HEJ, Chan SY. Current approaches and developments in transcript profiling of the human placenta. Hum Reprod Update. 2020;26(6):799–840. PMC7600289 33043357
  31. [33]Gonzalez TL, Sun T, Koeppel AF, Lee B, Wang ET, Farber CR, et al. Sex differences in the late first trimester human placenta transcriptome. Biol Sex Differ. 2018;9(1):4. PMC5769539 29335024
  32. [34]Sun T, Gonzalez TL, Deng N, DiPentino R, Clark EL, Lee B, et al. Sexually Dimorphic Crosstalk at the Maternal-Fetal Interface. J Clin Endocrinol Metab. 2020;105(12):dgaa503. PMC7571453 32772088
  33. [35]Braun AE, Muench KL, Robinson BG, Wang A, Palmer TD, Winn VD. Examining Sex Differences in the Human Placental Transcriptome During the First Fetal Androgen Peak. Reprod Sci. 2021;28(3):801–18. 33150487
  34. [36]Flowers AE, Gonzalez TL, Joshi NV, Eisman LE, Clark EL, Buttle RA, et al. Sex differences in microRNA expression in first and third trimester human placenta†. Biol Reprod. 2022;106(3):551–67. PMC9077118 35040930
  35. [37]Lyon MF. Gene action in the X-chromosome of the mouse (Mus musculus L). Nature. 1961;190:372–3. 13764598
  36. [38]Barr ML Bertram EG A morphological distinction between neurones of the male and female, and the behaviour of the nucleolar satellite during accelerated nucleoprotein synthesis Nature 1949 163 4148 676 10.1038/163676a0 18120749 · DOI
  37. [39]Ellis N Goodfellow PN The mammalian pseudoautosomal region Trends Genet 1989 5 12 406 410 10.1016/0168-9525(89)90199-6 2696184 · DOI
  38. [40]Ciccodicola A D'Esposito M Esposito T Gianfrancesco F Migliaccio C Miano MG Differentially regulated and evolved genes in the fully sequenced Xq/Yq pseudoautosomal region Hum Mol Genet 2000 9 3 395 401 10.1093/hmg/9.3.395 10655549 · DOI
  39. [41]Tukiainen T, Villani AC, Yen A, Rivas MA, Marshall JL, Satija R, et al. Landscape of X chromosome inactivation across human tissues. Nature. 2017;550(7675):244–8. PMC5685192 29022598
  40. [42]Bondy CA Cheng C Monosomy for the X chromosome Chromosome Res 2009 17 5 649 658 10.1007/s10577-009-9052-z 19802705 · DOI
  41. [43]Raudsepp T Das PJ Avila F Chowdhary BP The pseudoautosomal region and sex chromosome aneuploidies in domestic species Sex Dev 2012 6 1–3 72 83 10.1159/000330627 21876343 · DOI
  42. [44]Saenger P Turner's syndrome N Engl J Med 1996 335 23 1749 1754 10.1056/NEJM199612053352307 8929268 · DOI
  43. [45]Cockwell A MacKenzie M Youings S Jacobs P A cytogenetic and molecular study of a series of 45, X fetuses and their parents J Med Genet 1991 28 3 151 155 10.1136/jmg.28.3.151 1675683 PMC1016795 · DOI
  44. [46]Ljunger E Cnattingius S Lundin C Annerén G Chromosomal anomalies in first-trimester miscarriages Acta Obstet Gynecol Scand 2005 84 11 1103 1107 10.1111/j.0001-6349.2005.00882.x 16232180 · DOI
  45. [47]Bermejo-Alvarez P Ramos-Ibeas P Gutierrez-Adan A Solving the "X" in embryos and stem cells Stem Cells Dev 2012 21 8 1215 1224 10.1089/scd.2011.0685 22309156 PMC3353759 · DOI
  46. [48]Takagi N Sasaki M Preferential inactivation of the paternally derived X chromosome in the extraembryonic membranes of the mouse Nature 1975 256 5519 640 642 10.1038/256640a0 1152998 · DOI
  47. [49]Huynh KD Lee JT Imprinted X inactivation in eutherians: a model of gametic execution and zygotic relaxation Curr Opin Cell Biol 2001 13 6 690 697 10.1016/S0955-0674(00)00272-6 11698184 · DOI
  48. [50]Huynh KD Lee JT X-chromosome inactivation: a hypothesis linking ontogeny and phylogeny Nat Rev Genet 2005 6 5 410 418 10.1038/nrg1604 15818384 · DOI
  49. [51]Migeon BR Do TT In search of nonrandom X inactivation: studies of the placenta from newborns heterozygous for glucose-6-phosphate dehydrogenase Basic Life Sci 1978 12 379 391 752327
  50. [52]Ropers HH Wolff G Hitzeroth HW Preferential X inactivation in human placenta membranes: is the paternal X inactive in early embryonic development of female mammals Hum Genet 1978 43 3 265 273 10.1007/BF00278833 700701 · DOI
  51. [53]Harrison KB Warburton D Preferential X-chromosome activity in human female placental tissues Cytogenet Cell Genet 1986 41 3 163 168 10.1159/000132221 3956266 · DOI
  52. [54]Moreira de Mello JC, de Araújo ES, Stabellini R, Fraga AM, de Souza JE, Sumita DR, et al. Random X inactivation and extensive mosaicism in human placenta revealed by analysis of allele-specific gene expression along the X chromosome. PLoS One. 2010;5(6):e10947. PMC2881032 20532033
  53. [55]Looijenga LH de Munnik H Oosterhuis JW A molecular model for the development of germ cell cancer Int J Cancer 1999 83 6 809 814 10.1002/(SICI)1097-0215(19991210)83:6<809::AID-IJC20>3.0.CO;2-0 10597200 · DOI
  54. [56]Phung TN, Olney KC, Silasi M, Perley L, O’Bryan J, Kliman HJ, Wilson MA. X chromosome inactivation in the human placenta is patchy and distinct from adult tissues. bioRxiv. 785105 PMC9194956 35712697
  55. [57]Marsh B, Blelloch R. Single nuclei RNA-seq of mouse placental labyrinth development. Elife. 20203;9:e60266. PMC7669270 33141023
  56. [58]Gong S, Sovio U, Aye IL, Gaccioli F, Dopierala J, Johnson MD, et al. Placental polyamine metabolism differs by fetal sex, fetal growth restriction, and preeclampsia. JCI Insight. 2018;3(13):120723. PMC6124516 29997303
  57. [59]Minks J Robinson WP Brown CJ A skewed view of X chromosome inactivation J Clin Investig 2008 118 1 20 23 10.1172/JCI34470 18097476 PMC2147673 · DOI
  58. [60]Wang P Zhang Y Wang BQ Li JL Wang YX Pan D Wu XB Fung WK Zhou JY A statistical measure for the skewness of X chromosome inactivation based on case-control design BMC Bioinformatics 2019 20 1 1 1 10.1186/s12859-018-2565-8 30616589 PMC6323862 · DOI
  59. [61]Balaton BP Cotton AM Brown CJ Derivation of consensus inactivation status for X-linked genes from genome-wide studies Biol Sex Differ 2015 6 35 10.1186/s13293-015-0053-7 26719789 PMC4696107 · DOI
  60. [62]Howerton CL Morgan CP Fischer DB Bale TL O-GlcNAc transferase (OGT) as a placental biomarker of maternal stress and reprogramming of CNS gene transcription in development Proc Natl Acad Sci USA 2013 110 13 5169 5174 10.1073/pnas.1300065110 23487789 PMC3612602 · DOI
  61. [63]Okae H, Toh H, Sato T, Hiura H, Takahashi S, Shirane K, et al. Derivation of human trophoblast stem cells. Cell Stem Cell. 2018;22(1):50–636. 29249463
  62. [64]Turco MY, Gardner L, Kay RG, Hamilton RS, Prater M, Hollinshead MS, et al. (2018) Trophoblast organoids as a model for maternal-fetal interactions during human placentation. Nature. 564(7735):263–7. PMC7220805 30487605
  63. [65]Haider S, Meinhardt G, Saleh L, Kunihs V, Gamperl M, Kaindl U, et al. Self-renewing trophoblast organoids recapitulate the developmental program of the early human placenta. Stem Cell Reports. 2018;11(2):537–51. PMC6092984 30078556
  64. [66]Meyfour A, Pooyan P, Pahlavan S, Rezaei-Tavirani M, Gourabi H, Baharvand H, et al. Chromosome-centric human proteome project allies with developmental biology: a case study of the role of Y chromosome genes in organ development. J Proteome Res. 2017;16(12):4259–72. 28914051
  65. [67]Holland OJ Linscheid C Hodes HC Nauser TL Gilliam M Stone P Minor histocompatibility antigens are expressed in syncytiotrophoblast and trophoblast debris: implications for maternal alloreactivity to the fetus Am J Pathol 2012 180 1 256 266 10.1016/j.ajpath.2011.09.021 22079431 PMC3338347 · DOI
  66. [68]Than NG Romero R Xu Y Erez O Xu Z Bhatti G Evolutionary origins of the placental expression of chromosome 19 cluster galectins and their complex dysregulation in preeclampsia Placenta 2014 35 11 855 865 10.1016/j.placenta.2014.07.015 25266889 PMC4203431 · DOI
  67. [69]Arthur HM Ure J Smith AJ Renforth G Wilson DI Torsney E Endoglin, an ancillary TGFbeta receptor, is required for extraembryonic angiogenesis and plays a key role in heart development Dev Biol 2000 217 1 42 53 10.1006/dbio.1999.9534 10625534 · DOI
  68. [70]Myatt L Muralimanoharan S Maloyan A Effect of preeclampsia on placental function: influence of sexual dimorphism, microRNA's and mitochondria Adv Exp Med Biol 2014 814 133 146 10.1007/978-1-4939-1031-1_12 25015807 · DOI
  69. [71]Jiang S Teague AM Tryggestad JB Aston CE Lyons T Chernausek SD Effects of maternal diabetes and fetal sex on human placenta mitochondrial biogenesis Placenta 2017 57 26 32 10.1016/j.placenta.2017.06.001 28864016 PMC5659203 · DOI
  70. [72]Sedlmeier EM Meyer DM Stecher L Sailer M Daniel H Hauner H Fetal sex modulates placental microRNA expression, potential microRNA–mRNA interactions, and levels of amino acid transporter expression and substrates: INFAT study subpopulation analysis of n-3 LCPUFA intervention during pregnancy and associations with offspring body composition BMC Mol Cell Biol 2021 22 1 15 10.1186/s12860-021-00345-x 33657992 PMC7931339 · DOI
  71. [73]Roberts OL Holmes K Müller J Cross DA Cross MJ ERK5 and the regulation of endothelial cell function Biochem Soc Trans 2009 37 Pt 6 1254 1259 10.1042/BST0371254 19909257 · DOI
  72. [74]Roberts OL Holmes K Müller J Cross DA Cross MJ ERK5 is required for VEGF-mediated survival and tubular morphogenesis of primary human microvascular endothelial cells J Cell Sci 2010 123 Pt 18 3189 3200 10.1242/jcs.072801 20736307 · DOI
  73. [76]Balogh A Pozsgay J Matkó J Placental protein 13 (PP13/galectin-13) undergoes lipid raft-associated subcellular redistribution in the syncytiotrophoblast in preterm preeclampsia and HELLP syndrome Am J Obstet Gynecol 2011 205 2 156.e1 156.14 10.1016/j.ajog.2011.03.023 PMC3527099 21596368 · DOI
  74. [77]Nielsen HS Secondary recurrent miscarriage and H-Y immunity Hum Reprod Update 2011 17 4 558 574 10.1093/humupd/dmr005 21482560 · DOI
  75. [78]Vokalova L Balogh A Toth E Van Breda SV Schäfer G Hoesli I Placental protein 13 (Galectin-13) polarizes neutrophils toward an immune regulatory phenotype Front Immunol 2020 11 145 10.3389/fimmu.2020.00145 32117288 PMC7028707 · DOI
  76. [79]Del Prete A Martínez-Muñoz L Mazzon C Toffali L Sozio F Za L The atypical receptor CCRL2 is required for CXCR2-dependent neutrophil recruitment and tissue damage Blood 2017 130 10 1223 1234 10.1182/blood-2017-04-777680 28743719 · DOI
  77. [80]Amsalem H Kwan M Hazan A Zhang J Jones RL Whittle W Identification of a novel neutrophil population: proangiogenic granulocytes in second-trimester human decidua J Immunol 2014 193 6 3070 3079 10.4049/jimmunol.1303117 25135830 · DOI
  78. [81]Bongen E Lucian H Khatri A Fragiadakis GK Bjornson ZB Nolan GP Sex differences in the blood transcriptome identify robust changes in immune cell proportions with aging and influenza infection Cell Rep 2019 29 7 1961 1973e4 10.1016/j.celrep.2019.10.019 31722210 PMC6856718 · DOI
  79. [82]Meakin AS Cuffe JSM Darby JRT Morrison JL Clifton VL Let's talk about placental sex, baby: understanding mechanisms that drive female- and male-specific fetal growth and developmental outcomes Int J Mol Sci 2021 22 12 6386 10.3390/ijms22126386 34203717 PMC8232290 · DOI · Paper page
  80. [83]Pasqualini JR, Chetrite GS. The formation and transformation of hormones in maternal, placental and fetal compartments: biological implications. Hormone Mol Biol Clin Investig 2016;27. 27567599
  81. [84]Connan-Perrot S Léger T Lelandais P Desdoits-Lethimonier C David A Fowler PA Six decades of research on human fetal gonadal steroids IJMS 2021 22 6681 10.3390/ijms22136681 34206462 PMC8268622 · DOI
  82. [85]Geyer J Bakhaus K Bernhardt R Blaschka C Dezhkam Y Fietz D The role of sulfated steroid hormones in reproductive processes J Steroid Biochem Mol Biol 2017 172 207 221 10.1016/j.jsbmb.2016.07.002 27392637 · DOI
  83. [86]Lanciotti L Cofini M Leonardi A Penta L Esposito S Up-to-date review about minipuberty and overview on hypothalamic–pituitary–gonadal axis activation in fetal and neonatal life Front Endocrinol (Lausanne) 2018 9 410 10.3389/fendo.2018.00410 30093882 PMC6070773 · DOI · Paper page
  84. [87]Conte FA, Grumbach MM. Chapter 14. Disorders of Sex Determination and Differentiation. In: Gardner DG, Shoback D. eds. Greenspan’s Basic & Clinical Endocrinology, 9e. McGraw Hill; 2011. Accessed May 19, 2022.
  85. [88]Institute of Medicine (US) Committee on Understanding the Biology of Sex and Gender Differences, Wizemann TM, Pardue ML, eds. Exploring the Biological Contributions to Human Health: Does Sex Matter? Washington (DC): National Academies Press (US); 2001. 25057540
  86. [89]O'Shaughnessy PJ Antignac JP Le Bizec B Morvan ML Svechnikov K Söder O Alternative (backdoor) androgen production and masculinization in the human fetus PLoS Biol 2019 17 2 3000002 10.1371/journal.pbio.3000002 PMC6375548 30763313 · DOI · Paper page
  87. [90]Sathishkumar K Balakrishnan M Chinnathambi V Chauhan M Hankins GD Yallampalli C Fetal sex-related dysregulation in testosterone production and their receptor expression in the human placenta with preeclampsia J Perinatol 2012 32 5 328 335 10.1038/jp.2011.101 21904298 PMC3712643 · DOI
  88. [91]Steier JA Bergsjø PB Myking OL Disappearance of human chorionic gonadotropin after cesarean section with regard to fetal sex Acta Obstet Gynecol Scand 2002 81 5 403 10.1034/j.1600-0412.2002.810505.x 12027812 · DOI
  89. [92]Uhlén M Fagerberg L Hallström BM Lindskog C Oksvold P Mardinoglu A Sivertsson Å Kampf C Sjöstedt E Asplund A Olsson I Tissue-based map of the human proteome Science 2015 347 6220 1260419 10.1126/science.1260419 25613900 · DOI · Paper page
  90. [93]Reyes FI Boroditsky RS Winter JS Faiman C Studies on human sexual development. II. Fetal and maternal serum gonadotropin and sex steroid concentrations J Clin Endocrinol Metab 1974 38 4 612 617 10.1210/jcem-38-4-612 4856555 · DOI
  91. [94]Hayder H O'Brien J Nadeem U Peng C MicroRNAs: crucial regulators of placental development Reproduction 2018 155 6 R259 R271 10.1530/REP-17-0603 29615475 · DOI
  92. [96]Sharma S Eghbali M Influence of sex differences on microRNA gene regulation in disease Biol Sex Differ 2014 5 1 1 8 10.1186/2042-6410-5-3 24484532 PMC3912347 · DOI
  93. [97]Guo S Huang S Jiang X Hu H Han D Moreno CS Variation of microRNA expression in the human placenta driven by population identity and sex of the newborn BMC Genomics 2021 22 1 286 10.1186/s12864-021-07542-0 33879051 PMC8059241 · DOI
  94. [98]Di Palo A Siniscalchi C Salerno M Russo A Gravholt CH Potenza N What microRNAs could tell us about the human X chromosome Cell Mol Life Sci 2020 77 20 4069 4080 10.1007/s00018-020-03526-7 32356180 PMC7854456 · DOI
  95. [99]Morales-Prieto DM Ospina-Prieto S Chaiwangyen W Schoenleben M Markert UR Pregnancy-associated miRNA-clusters J Reprod Immunol 2013 97 1 51 61 10.1016/j.jri.2012.11.001 23432872 · DOI
  96. [100]Larsen SO Wøjdemann KR Shalmi AC Sundberg K Christiansen M Tabor A Gender impact on first trimester markers in Down syndrome screening Prenat Diagn 2002 22 13 1207 1208 10.1002/pd.493 12478634 · DOI
  97. [101]Yaron Y Ochshorn Y Heifetz S Lehavi O Sapir Y Orr-Urtreger A First trimester maternal serum free human chorionic gonadotropin as a predictor of adverse pregnancy outcome Fetal Diagn Ther 2002 17 6 352 356 10.1159/000065384 12393965 · DOI
  98. [102]Adibi JJ Lee MK Naimi AI Barrett E Nguyen RH Sathyanarayana S Human chorionic gonadotropin partially mediates phthalate association with male and female anogenital distance J Clin Endocrinol Metab 2015 100 9 E1216 E1224 10.1210/jc.2015-2370 26200238 PMC4570159 · DOI
  99. [103]Steier JA Myking OL Bergsjø PB Correlation between fetal sex and human chorionic gonadotropin in peripheral maternal blood and amniotic fluid in second and third trimester normal pregnancies Acta Obstet Gynecol Scand 1999 78 5 367 371 10326878
  100. [104]Steier JA Bergsjø PB Thorsen T Myking OL Human chorionic gonadotropin in maternal serum in relation to fetal gender and utero-placental blood flow Acta Obstet Gynecol Scand 2004 83 2 170 174 10.1111/j.0001-6349.2004.00407.x 14756735 · DOI
  101. [105]Gol M Altunyurt S Cimrin D Guclu S Bagci M Demir N Different maternal serum hCG levels in pregnant women with female and male fetuses: does fetal hypophyseal–adrenal–gonadal axis play a role J Perinat Med 2004 32 4 342 345 10.1515/JPM.2004.064 15346821 · DOI
  102. [106]Xiong F Sun Q Li GG Chen PL Yao ZH Wan CY Initial serum HCG levels are higher in pregnant women with a male fetus after fresh or frozen single blastocyst transfer: a retrospective cohort study Taiwan J Obstet Gynecol 2019 58 6 833 839 10.1016/j.tjog.2019.09.019 31759537 · DOI
  103. [107]Hang Lam Y Hoi Yin Tang M The effect of fetal gender on second-trimester maternal serum inhibin—a concentration Prenat Diagn 2001 21 8 662 664 10.1002/pd.120 11536266 · DOI
  104. [108]Braun AE Carpentier PA Babineau BA Narayan AR Kielhold ML Moon HM "Females Are Not Just 'Protected' Males": sex-specific vulnerabilities in placenta and brain after prenatal immune disruption eNeuro. 2019 6 6 ENEURO.0358-19.2019 10.1523/ENEURO.0358-19.2019 31611335 PMC6838689 · DOI
  105. [109]Samura O Update on noninvasive prenatal testing: a review based on current worldwide research J Obstet Gynaecol Res 2020 46 8 1246 1254 10.1111/jog.14268 32558079 · DOI
  106. [110]Ngo TTM Moufarrej MN Rasmussen MH Camunas-Soler J Pan W Okamoto J Noninvasive blood tests for fetal development predict gestational age and preterm delivery Science 2018 360 6393 1133 1136 10.1126/science.aar3819 29880692 PMC7734383 · DOI
  107. [111]Trivers RL Willard DE Natural selection of parental ability to vary the sex ratio of offspring Science 1973 179 4068 90 92 10.1126/science.179.4068.90 4682135 · DOI
  108. [112]Clifton VL Review: sex and the human placenta: mediating differential strategies of fetal growth and survival Placenta 2010 31 Suppl S33 S39 10.1016/j.placenta.2009.11.010 20004469 · DOI · Paper page
  109. [113]Eriksson JG Kajantie E Osmond C Thornburg K Barker DJ Boys live dangerously in the womb Am J Hum Biol 2010 22 3 330 335 10.1002/ajhb.20995 19844898 PMC3923652 · DOI · Paper page

Cited by

Sorted by citations

Authors
Braun, A. E., Mitchel, O. R., Gonzalez, T. L., Sun, T., Flowers, A. E., Pisarska, M. D., & Winn, V. D.
Affiliations
  • Stanford Medicine (US)
  • Cedars-Sinai Medical Center (US)
Corresponding author
Braun, Amy E.
ORCID
Venue
Biology of Sex Differences
Publisher
Springer Science and Business Media LLC
Published
2022-09-16
Volume
13
Issue
1
Pages
50-50
ISSN
2042-6410 (ISSN-L)
DOI
10.1186/s13293-022-00459-7
PMC
PMC9482177
OpenAlex
W4295997725
Cited by
94
References
4
Citations by year
2026: 27 · 2025: 29 · 2024: 24 · 2023: 14
FWCI
3.47
Type
journal article
Language
en
Open access
Licence
Locations
  • Biology of Sex Differences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Immunology and Microbiology › Immunology › Reproductive System and Pregnancy
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
Keywords
sex differences, human placenta, placental development, fetal sex, first trimester placenta, maternal-fetal interface, maternal-fetal immune tolerance, placental hormones, placental metabolism, evolutionary pressure
MeSH terms
Female, Gestational Age, Hormones, Humans, Male, Placenta, Pregnancy, Sex Characteristics, Fetal Development

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