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Cited by 114Gestational Diabetes Research and ManagementPancreatic function and diabetesPregnancy and preeclampsia studies

Placental endocrine activity: adaptation and disruption of maternal glucose metabolism in pregnancy and the influence of fetal sex

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Stern, Christina, Schwarz, Sarah, Moser, Gerit, Cvitic, Silvija, Jantscher-Krenn, Evelyn, Gauster, Martin, Hiden, Ursula·2021·International Journal of Molecular Sciences
DOI 10.3390/ijms222312722PMC PMC8657775
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Abstract

The placenta is an endocrine fetal organ, which secretes a plethora of steroid- and proteo-hormones, metabolic proteins, growth factors, and cytokines in order to adapt maternal physiology to pregnancy. Central to the growth of the fetus is the supply with nutrients, foremost with glucose. Therefore, during pregnancy, maternal insulin resistance arises, which elevates maternal blood glucose levels, and consequently ensures an adequate glucose supply for the developing fetus. At the same time, maternal β-cell mass and function increase to compensate for the higher insulin demand. These adaptations are also regulated by the endocrine function of the placenta. Excessive insulin resistance or the inability to increase insulin production accordingly disrupts physiological modulation of pregnancy mediated glucose metabolism and may cause maternal gestational diabetes (GDM). A growing body of evidence suggests that this adaptation of maternal glucose metabolism differs between pregnancies carrying a girl vs. pregnancies carrying a boy. Moreover, the risk of developing GDM differs depending on the sex of the fetus. Sex differences in placenta derived hormones and bioactive proteins, which adapt and modulate maternal glucose metabolism, are likely to contribute to this sexual dimorphism. This review provides an overview on the adaptation and maladaptation of maternal glucose metabolism by placenta-derived factors, and highlights sex differences in this regulatory network.

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  • Following birth, there is a precipitous decline in estrogen and progesterone levels, which increase during pregnancy.

    “Following birth, there is a precipitous decline in estrogen and progesterone levels, which increase during pregnancy.”

    From Understanding mothers’ lived experiences of postpartum depression: a qualitative phenomenological study (2025) · cites this paper as [2]

    Section 6.5 states that estrogen levels increase progressively toward term, and section 6.6 describes progressive secretion of progesterone into maternal circulation during pregnancy. Neither section states that estrogen and progesterone levels decline precipitously after birth; the post-delivery passage in section 1.2 concerns insulin sensitivity instead. Page numbers are not available in our copy. (LLM, conf=0.85)

    Experimental — accuracy not yet measured

  • PFASs can be transferred across the placenta.

    “Given that the human placenta may be a primary target of PFAS exposure in pregnant women and PFASs can be transferred across the placenta, further research is needed to reveal the role of PFASs in placental function and maternal-infant health during pregnancy (Appel et al., 2022; Stern et al., 2021).”

    From Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study (2023) · cites this paper as Stern et al., 2021

    Section 5 discusses placental release of hormones into maternal circulation, not transfer of PFASs across the placenta. Searches for PFASs, perfluoroalkyl substances, and placental transfer found no passage in our copy addressing the claim. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

  • The human placenta may be a primary target of PFAS exposure in pregnant women.

    “Given that the human placenta may be a primary target of PFAS exposure in pregnant women and PFASs can be transferred across the placenta, further research is needed to reveal the role of PFASs in placental function and maternal-infant health during pregnancy (Appel et al., 2022; Stern et al., 2021).”

    From Exposure to per- and polyfluoroalkyl substances in early pregnancy, risk of gestational diabetes mellitus, potential pathways, and influencing factors in pregnant women: A nested case-control study (2023) · cites this paper as Stern et al., 2021

    Section 7 says the placenta responds to maternal environmental stimuli, but does not identify PFAS as one of them. Searches for PFAS, perfluoroalkyl substances, and environmental pollutants found no passage addressing whether the placenta is a primary target of PFAS exposure. (LLM, conf=0.76)

    Experimental — accuracy not yet measured

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Cited by

Sorted by citations

Authors
Stern, C., Schwarz, S., Moser, G., Cvitic, S., Jantscher-Krenn, E., Gauster, M., & Hiden, U.
Affiliations
  • Medical University of Graz (AT)
  • Department of Obstetrics and Gynecology, Medical University of Graz, 8036 Graz, Austria
Corresponding author
  • Gauster, Martin
  • Hiden, Ursula
ORCID
Venue
International Journal of Molecular Sciences
Publisher
MDPI AG
Published
2021-11-24
Volume
22
Issue
23
Pages
12722
ISSN
1422-0067 (ISSN-L)
DOI
10.3390/ijms222312722
PMC
PMC8657775
OpenAlex
W3216461102
Cited by
114
References
3
Citations by year
2026: 33 · 2025: 26 · 2024: 27 · 2023: 23 · 2022: 5
FWCI
2.53
Type
journal article
Language
en
Open access
Licence
Locations
  • International Journal of Molecular Sciences (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • FWF Austrian Science Fund (Doc 31-B26, P33554)
  • Medical University of Graz (PhD program Inflammatory Disorders in Pregnancy, PhD program MolMed)
Topics
  • Health Sciences › Medicine › Obstetrics and Gynecology › Gestational Diabetes Research and Management
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Health Sciences › Medicine › Obstetrics and Gynecology › Pregnancy and preeclampsia studies
Keywords
placental endocrine function, maternal glucose metabolism, insulin resistance, gestational diabetes mellitus, fetal sex, sex differences, beta-cell function, pregnancy adaptation
MeSH terms
Adaptation, Physiological, Endocrine System, Female, Fetus, Glucose, Humans, Insulin, Insulin Resistance, Male, Placenta, Pregnancy, Sex Factors, Diabetes, Gestational

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