Prenatal Androgen Exposure and Transgenerational Susceptibility to Polycystic Ovary Syndrome
Open accessAbstract
How obesity and elevated androgen levels in women with polycystic ovary syndrome (PCOS) affect their offspring is unclear. In a Swedish nationwide register-based cohort and a clinical case-control study from Chile, we found that daughters of mothers with PCOS were more likely to be diagnosed with PCOS. Furthermore, female mice (F 0) with PCOS-like traits induced by late-gestation injection of dihydrotestosterone, with and without obesity, produced female F 1-F 3 offspring with PCOS-like reproductive and metabolic phenotypes. Sequencing of single metaphase II oocytes from F 1-F 3 offspring revealed common and unique altered gene expression across all generations. Notably, four genes were also differentially expressed in serum samples from daughters in the case-control study and unrelated women with PCOS. Our findings provide evidence of transgenerational effects in female offspring of mothers with PCOS and identify possible candidate genes for the prediction of a PCOS phenotype in future generations.
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Artemisinins ameliorate polycystic ovarian syndrome by mediating LONP1-CYP11A1 interaction
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Polycystic Ovary Syndrome: Pathophysiology and Therapeutic Opportunities
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Androgen excess: a hallmark of polycystic ovary syndrome
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Immunological and Metabolic Causes of Infertility in Polycystic Ovary Syndrome
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Signaling pathways and targeted therapeutic strategies for polycystic ovary syndrome
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Mitochondrial Dysfunction in PCOS: Insights into Reproductive Organ Pathophysiology
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Gut Microbiota as an Endocrine Organ: Unveiling Its Role in Human Physiology and Health
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Challenges in diagnosis and understanding of natural history of polycystic ovary syndrome
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Polycystic Ovary Syndrome: Challenges and Possible Solutions
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Abnormal GnRH pulsatility in polycystic ovary syndrome: Recent insights
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Prevalence, Phenotypes, and Comorbidities of Polycystic Ovary Syndrome Among Indian Women
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Probiotics and Polycystic Ovary Syndrome: A Perspective for Management in Adolescents with Obesity
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The evolutionary biology of endometriosis
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Epigenetic/circadian clocks and PCOS
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Criteria for Diagnosis of Polycystic Ovary Syndrome during Adolescence: Literature Review
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Polycystic ovary syndrome: A metabolic disorder with therapeutic opportunities
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The Goto-Kakizaki rat is a spontaneous prototypical rodent model of polycystic ovary syndrome
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Why are women with polycystic ovary syndrome obese?
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Rodent models in placental research. Implications for fetal origins of adult disease
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Hyperandrogenism and Polycystic ovary syndrome: Effects in pregnancy and offspring development
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Androgen signalling in the ovaries and endometrium
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Follicle stimulating hormone controls granulosa cell glutamine synthesis to regulate ovulation
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Epigenetic inheritance of PCOS by developmental programming and germline transmission
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Self-citationUpdate on Animal Models of Polycystic Ovary Syndrome
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Self-citationAndrogens Modulate the Immune Profile in a Mouse Model of Polycystic Ovary Syndrome
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Self-citationRoles of the Notch Signaling Pathway in Ovarian Functioning
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Decidualized endometrial stromal cells present with altered androgen response in PCOS
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The role of B cells in immune cell activation in polycystic ovary syndrome
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Self-citationThe role of the autonomic nervous system in polycystic ovary syndrome
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Pathogenesis of Reproductive and Metabolic PCOS Traits in a Mouse Model
Paris, V. R., Edwards, M. C., Aflatounian, A., Bertoldo, M. J., Ledger, W. J., Handelsman, D. J., Gilchrist, R. B., & Walters, K. A. (2021) · Journal of the Endocrine Society · doi:10.1210/jendso/bvab060 · Cited by 28 · see citing works
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Andræ, F., Abbott, D. H., Stridsklev, S., Schmedes, A., Odsæter, I. H., Vanky, E., & Salvesen, Ø. O. (2020) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/clinem/dgaa605 · Cited by 27 · see citing works
Maternal steroid levels and the autistic traits of the mother and infant
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Unravelling Polycystic Ovary Syndrome and Its Comorbidities
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Is there an association between prenatal testosterone and autistic traits in adolescents?
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“[20] demonstrated a five-fold increase in risk of developing PCOS in mice born from mothers with PCOS.”
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Self-citationCandidate genes for polycystic ovary syndrome are regulated by TGFβ in the bovine foetal ovary
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Maternal genetic effect on apoptosis of ovarian granulosa cells induced by cadmium
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Self-citationUpdates on Molecular Targets and Epigenetic-Based Therapies for PCOS
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The Role of the Liver in the Pathophysiology of PCOS: A Literature Review
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Anti-Müllerian Hormone and Polycystic Ovary Syndrome in Women and Its Male Equivalent
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Dysregulated Liver Metabolism and Polycystic Ovarian Syndrome
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Variation among human populations in endometriosis and PCOS A test of the inverse comorbidity model
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Transgenerational Inheritance of Reproductive and Metabolic Phenotypes in PCOS Rats
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Self-citationInvestigating GABA Neuron–Specific Androgen Receptor Knockout in two Hyperandrogenic Models of PCOS
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Key glycometabolism during oocyte maturation and early embryonic development
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Pathology of hyperandrogenemia in the oocyte of polycystic ovary syndrome
Chappell, N. R., Gibbons, W. E., & Blesson, C. S. (2022) · Steroids · doi:10.1016/j.steroids.2022.108989 · Cited by 20 · see citing works
- Authors
- Risal, S., Pei, Y., Lu, H., Manti, M., Fornes, R., Pui, H.-P., Zhao, Z., Massart, J., Ohlsson, C., Lindgren, E., Crisosto, N., Maliqueo, M., Echiburú, B., Ladrón de Guevara, A., Sir-Petermann, T., Larsson, H., Rosenqvist, M. A., Cesta, C. E., Benrick, A., Deng, Q., & Stener-Victorin, E.
- Affiliations
- Karolinska Institutet (SE)
- Karolinska University Hospital (SE)
- University of Gothenburg (SE)
- University of Chile (CL)
- Örebro University (SE)
- University of Skövde (SE)
- Corresponding author
- Deng, Qiaolin
- ORCID
- Venue
- Nature Medicine
- Published
- 2019-12
- Volume
- 25
- Issue
- 12
- Pages
- 1894-1904
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- OpenAlex
- W2989769687
- Cited by
- 356
- References
- 73
- Citations by year
- 2026: 39 · 2025: 61 · 2024: 60 · 2023: 58 · 2022: 60 · 2021: 46 · 2020: 29 · 2019: 2
- FWCI
- 32.74
- Type
- journal article
- Language
- en
- Open access
- green
- zenodo.org
- Licence
- public-domain
- www.springer.com/tdm (tdm)
- www.springer.com/tdm (vor)
- Locations
- Nature Medicine (publishedVersion)
- PubMed (publishedVersion)
- Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, public-domain)
- DRYAD (public-domain)
- Funders
- Åke Wiberg Stiftelse
- Vetenskapsrådet (2014-02775, 2014-2870 QD, 2018-02435 ESV, 2018-02119 MR)
- Novo Nordisk Fonden (NNF14OC0010513, NNF18OC0033898, NNF13OC0005785, NNF18OC0033992, NNF19OC0056647)
- Novo Nordisk Foundation Center for Basic Metabolic Research (NNF19OC0056647, NNF16OC0020744, NNF17OC0026724, NNF18OC0033992)
- Fondo Nacional de Desarrollo Científico y Tecnológico (1181798 to MM)
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian function and disorders
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Keywords
- polycystic ovary syndrome, transgenerational effects, prenatal androgen exposure, dihydrotestosterone, maternal obesity, female offspring, oocyte gene expression, candidate genes, reproductive phenotypes, metabolic phenotypes, epigenetics
- MeSH terms
- Pregnancy in Obesity, Androgens, Animals, Female, Humans, Nuclear Family, Oocytes, Phenotype, Polycystic Ovary Syndrome, Pregnancy, Prenatal Exposure Delayed Effects, Cohort Studies, Gene Expression Regulation, Developmental, Mice, Single-Cell Analysis
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