Department of Pharmacology, Basic Medical School of Wuhan University, Wuhan, China.
Department of Obstetrics and Gynaecology, Zhongnan Hospital of Wuhan University, Wuhan, China.
Crit Rev Toxicol. 2021 Jul;51(6):555-570. doi: 10.1080/10408444.2021.1977237. Epub 2021 Oct 19.
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.
根据健康与疾病的发育起源（DOHaD）理论，子宫内暴露于不利环境会影响胎儿和出生结局，并导致长期疾病易感性。有证据表明，新生儿结局和成年疾病的发生时间和严重程度存在性别差异。胎盘作为母婴之间的联系，是胎儿发育编程的重要调节者。研究发现，胎盘的生理发育轨迹存在性别二态性。此外，在病理条件下，胎盘功能会发生特定于性别的适应性变化，以确保胎儿存活。因此，胎盘可能是新生儿结局和成年疾病易感性性别差异的重要介导者。关于胎盘发育及其潜在机制的性别二态性，很少有系统的综述。在这篇综述中，将讨论胎盘性别分化的主要原因——性染色体和性激素。此外，在胎儿源性成年疾病的病因中，皮质醇过度暴露与不良新生儿结局和长期疾病易感性密切相关。研究发现，产前皮质醇过度暴露导致胎盘糖皮质激素受体同工型的性别二态性表达，使胎盘对皮质醇的敏感性不同，并可能进一步影响胎儿发育。本综述考察了胎盘发育中性别差异及其潜在调节机制的研究现状。这篇综述强调了胎盘对健康和疾病中性别二态性起源的重要贡献。它可能有助于为病理性妊娠中的胎儿发育制定个性化的诊断和治疗策略。
