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Cited by 158Birth, Development, and HealthPregnancy and preeclampsia studiesSexual Differentiation and Disorders

Let's talk about placental sex, baby: understanding mechanisms that drive female- and male-specific fetal growth and developmental outcomes

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Meakin, Ashley S., Cuffe, James S. M., Darby, Jack R. T., Morrison, Janna L., Clifton, Vicki L.·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms22126386PMC PMC8232290
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Abstract

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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  • The higher vulnerability in males and improved outcomes in females when the intrauterine milieu changes and becomes less hospitable is most likely explained by sex differences in fetal growth strategy and reserve capacity.

    “This most likely explains the higher vulnera­ bility in males and the improved outcomes in females seen when the intrauterine milieu changes and become less hospitable (Meakin et al., 2021; Teulings et al., 2020).”

    From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Meakin et al., 2021

  • Fetuses of different sexes respond differently to changes in the intrauterine milieu: male fetuses prioritize growth, whereas female fetuses show increased adaptability and higher reserve capacity.

    “In addition, fetuses of different sexes respond differently; while male fetuses prioritize growth, the females show increased adaptability and higher reserve capacity.”

    From Pregnancy-related maternal physiological adaptations and fetal chemical exposure (2023) · cites this paper as Meakin et al., 2021

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Cited by

Sorted by citations

Authors
Meakin, A. S., Cuffe, J. S. M., Darby, J. R. T., Morrison, J. L., & Clifton, V. L.
Affiliations
  • University of South Australia (AU)
  • The University of Queensland (AU)
Corresponding author
Clifton, Vicki L.
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-06-15
Volume
22
Issue
12
Pages
6386
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms22126386
PMC
PMC8232290
OpenAlex
W3172065230
Cited by
158
References
7
Citations by year
2026: 34 · 2025: 35 · 2024: 42 · 2023: 24 · 2022: 18 · 2021: 5
FWCI
5.52
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion, cc-by)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
  • UniSA Research Outputs Repository (University of South Australia) (submittedVersion, other-oa)
Funders
  • National Health and Medical Research Council (APP1136100)
  • Australian Research Council (FT170100431)
Topics
  • Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
Keywords
fetal growth, intrauterine environment, placental function, pregnancy complications, perinatal outcomes, fetal sex
MeSH terms
Androgens, Animals, Female, Glucocorticoids, Humans, Male, Placenta, Pregnancy, Sex Characteristics, Embryonic Development, Fetal Development

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