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Sexual dimorphism in placental development and its contribution to health and diseases.

Abstract
According to the Developmental Origin of Health and Disease (DOHaD), intrauterine exposure to adverse environments can affect fetus and birth outcomes and lead to long-term disease susceptibility. Evidence has shown that neonatal outcomes and the timing and severity of adult diseases are sexually dimorphic. As the link between mother and fetus, the placenta is an essential regulator of fetal development programming. It is found that the physiological development trajectory of the placenta has sexual dimorphism. Furthermore, under pathological conditions, the placental function undergoes sex-specific adaptation to ensure fetal survival. Therefore, the placenta may be an important mediator of sexual dimorphism in neonatal outcomes and adult disease susceptibility. Few systematic reviews have been conducted on sexual dimorphism in placental development and its underlying mechanisms. In this review, sex chromosomes and sex hormones, as the main reasons for sexual differentiation of the placenta, will be discussed. Besides, in the etiology of fetal-originated adult diseases, overexposure to glucocorticoids is closely related to adverse neonatal outcomes and long-term disease susceptibility. Studies have found that prenatal glucocorticoid overexposure leads to sexually dimorphic expression of placental glucocorticoid receptor isoforms, resulting in different sensitivity of the placenta to glucocorticoids, and may further affect fetal development. The present review examines what is currently known about sex differences in placental development and the underlying regulatory mechanisms of this sex bias. This review highlights the importance of placental contributions to the origins of sexual dimorphism in health and diseases. It may help develop personalized diagnosis and treatment strategies for fetal development in pathological pregnancies.
AuthorsPengxia Yu, Yawen Chen, Caiyun Ge, Hui Wang
JournalCritical reviews in toxicology (Crit Rev Toxicol) Vol. 51 Issue 6 Pg. 555-570 (07 2021) ISSN: 1547-6898 [Electronic] England
PMID34666604 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)
Topics
  • Adult
  • Female
  • Fetal Development
  • Fetus
  • Humans
  • Infant, Newborn
  • Male
  • Placenta
  • Placentation
  • Pregnancy
  • Sex Characteristics

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