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Let's Talk about Placental Sex, Baby: Understanding Mechanisms That Drive Female- and Male-Specific Fetal Growth and Developmental Outcomes

Journal

Publisher

MDPI
DOI: 10.3390/ijms22126386

Keywords

placenta; fetal growth; sex differences; androgens; glucocorticoids; androgen receptor; glucocorticoid receptor; steroid hormone signaling; pregnancy; fetal development

Funding

  1. NHMRC [SRF APP1136100]
  2. ARC FF [FT170100431]
  3. MMRI-UQ
  4. Mater Foundation

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Males prioritize growth pathways to maximize reproductive success from infancy to adulthood, which may make them less adaptable to in-utero environment shifts. Females, on the other hand, are more adaptable to changes in utero environment but at the cost of growth, reducing the risk of certain poor outcomes.
It is well understood that sex differences exist between females and males even before they are born. These sex-dependent differences may contribute to altered growth and developmental outcomes for the fetus. Based on our initial observations in the human placenta, we hypothesised that the male prioritises growth pathways in order to maximise growth through to adulthood, thereby ensuring the greatest chance of reproductive success. However, this male-specific evolutionary advantage likely contributes to males being less adaptable to shifts in the in-utero environment, which then places them at a greater risk for intrauterine morbidities or mortality. Comparatively, females are more adaptable to changes in the in-utero environment at the cost of growth, which may reduce their risk of poor perinatal outcomes. The mechanisms that drive these sex-specific adaptations to a change in the in-utero environment remain unclear, but an increasing body of evidence within the field of developmental biology would suggest that alterations to placental function, as well as the feto-placental hormonal milieu, is an important contributing factor. Herein, we have addressed the current knowledge regarding sex-specific intrauterine growth differences and have examined how certain pregnancy complications may alter these female- and male-specific adaptations.

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