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Cited by 43Ovarian function and disordersSexual Differentiation and DisordersReproductive Biology and Fertility

In utero Androgen Excess: A Developmental Commonality Preceding Polycystic Ovary Syndrome?

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Abbott, David H., Kraynak, Marissa, Dumesic, Daniel A., Levine, Jon E.·2019·Frontiers of Hormone Research
DOI 10.1159/000494899PMC PMC6954824
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Abstract

In utero androgen excess reliably induces polycystic ovary syndrome (PCOS)-like reproductive and metabolic traits in female monkeys, sheep, rats, and mice. In humans, however, substantial technical and ethical constraints on fetal sampling have curtailed safe, pathogenic exploration during gestation. Evidence consistent with in utero origins for PCOS in humans has thus been slow to amass, but the balance now leans toward developmental fetal origins. Given that PCOS is familial and highly heritable, difficulties encountered in discerning genetic contributions to PCOS pathogenesis are puzzling and, to date, accounts for <10% of PCOS presentations. Unaccounted heritability notwithstanding, molecular commonality in pathogenic mechanisms is emerging, suggested by co-occurrence at the same gene loci of (1) PCOS genetic variants (PCOS women), (2) epigenetic alterations in DNA methylation (PCOS women), and (3) bioinformatics, gene networks-identified, epigenetic alterations in DNA methylation (female rhesus monkeys exposed to testosterone (T) in utero). In addition, naturally occurring hyperandrogenism in female monkeys singles out individuals with PCOS-like reproductive and metabolic traits accompanied by somatic biomarkers of in utero T exposure. Such phenotypic and molecular convergence between highly related species suggests not only dual genetic and epigenetic contributions to a developmental origin of PCOS but also common molecular pathogenesis extending beyond humans.

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Crossref · 10.1159/000494899

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93 of 93 references verified0 citation errors · 0 not checkable

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  • Most of the animal and human research on the developmental origins of PCOS has focused on the role of prenatal androgen exposure.

    “Most of the animal and human research on the developmental origins of PCOS has focused on the role of prenatal androgen exposure.”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [46]

    The Introduction describes animal-model findings and accumulating human evidence on in utero androgen excess, and says the review focuses on that research. It does not establish that most animal and human research on the developmental origins of PCOS has focused on prenatal androgen exposure. Page numbers are unavailable in our copy. (LLM, conf=0.82)

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  • Experimental studies in primates, sheep, rats and mice show that PCOS-like syndromes can be induced by a range of treatments including androgens, anti-Mullerian hormone and letrozole.

    “Experimental studies in primates, sheep, rats and mice show that PCOS-like syndromes can be induced by a range of treatments including androgens, anti-Mullerian hormone and letrozole [19,44,46].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [46]

    The Introduction and animal-model sections report that in utero androgen exposure produces PCOS-like traits in monkeys, sheep, rats and mice. The human-studies section describes a mouse model in which maternal AMH may contribute to fetal androgen excess, but does not establish AMH-induced PCOS-like syndromes; the passages found do not address letrozole-induced models. This source therefore supports the androgen portion of the multi-cited sentence, not its full list of treatments. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Prenatal androgen exposure may play a role in the pathogenesis of PCOS-like syndromes in animal models.

    “Extensive experimental evidence suggests that prenatal androgen exposure may play a role in the pathogenesis of PCOS-like syndromes in animal models [19,44,45,46].”

    From Polycystic Ovary Syndrome: An Evolutionary Adaptation to Lifestyle and the Environment (2022) · cites this paper as [46]

  • Androgen exposure in utero is thought to be both a cause and a consequence of PCOS, impacting the transmission of the disease.

    “Therefore, androgen exposure in utero is thought to be both a cause and a consequence of PCOS, impacting the transmission of the disease [128].”

    From Developmental programming of offspring adipose tissue biology and obesity risk (2021) · cites this paper as [128]

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Research works printed but not linked: 2

  1. [9]Abbott DH, Dumesic DA, Eisner JR, Kemnitz JW, Goy RW. The prenatally androgenized female rhesus monkey as a model for polycystic ovarian syndrome In: Azziz R, Nestler JE and Dewailly D (eds). Androgen Excess Disorders in Women. Philadelphia, Lippencott-Raven Press, 1997, pp. 369– 382.
  2. [18]Moore AM, Campbell RE. Polycystic ovary syndrome: Understanding the role of the brain. Front Neuroendocrinol. 2017; 46: 1 28551304

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Authors
Abbott, D. H., Kraynak, M., Dumesic, D. A., & Levine, J. E.
Affiliations
  • University of Wisconsin System (US)
  • University of California, Los Angeles (US)
ORCID
Venue
Frontiers of Hormone Research
Publisher
S. Karger AG
Published
2019
Volume
53
Pages
1-17
ISSN
  • 0301-3073 (ISSN-L)
  • 1662-3762
DOI
10.1159/000494899
PMC
PMC6954824
OpenAlex
W2972730817
Cited by
42
References
93
Citations by year
2026: 7 · 2025: 3 · 2024: 3 · 2023: 7 · 2022: 4 · 2021: 8 · 2020: 9 · 2018: 1
FWCI
37.00
Type
book chapter
Language
en
Open access
Licence
Locations
  • Frontiers of hormone research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Institutes of Health (P51OD011106)
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD044405, P50HD071836, P50HD028934)
Topics
  • Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
  • Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
Keywords
polycystic ovary syndrome, developmental origins of health and disease, DNA methylation, epigenetics, hyperandrogenism, rhesus monkeys, heritability, gene networks, cross-species comparison
MeSH terms
Androgens, Animals, Female, Humans, Polycystic Ovary Syndrome, Pregnancy, Prenatal Exposure Delayed Effects, Hyperandrogenism

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