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Updated: Jul 16, 2026
A Hyperandrogenic Mouse Model to Study Polycystic Ovary Syndrome
Published on: October 2, 2018
Hypothalamic-pituitary-gonadal axis programming and disrupted ovarian-endocrine function in female offspring of the
Victoria N Bailey1, Kendall R Ball1, Kalynn E Grandberry1
1Department of Small Animal Clinical Sciences, Michigan State University College of Veterinary Medicine, East Lansing, Michigan, United States.
Insights
Children born after preeclampsia may face long-term reproductive issues. This study found that maternal high Anti-Mullerian hormone (AMH) in a mouse model contributes to offspring developing polycystic ovary syndrome (PCOS)-like conditions.
Area of Science:
- Reproductive Endocrinology
- Developmental Biology
- Maternal-Fetal Medicine
Background:
- Preeclampsia, a hypertensive disorder of pregnancy, predisposes offspring to long-term cardiometabolic and reproductive issues.
- Prenatal exposure to a dysregulated maternal endocrine environment is implicated in these offspring disorders.
- Previous studies identified abnormal pubertal development and hyperandrogenism in female offspring of the preeclamptic-like BPH/5 mouse model.
Purpose of the Study:
- To investigate the programming of the hypothalamic-pituitary-gonadal (HPG) axis in offspring of the BPH/5 mouse model.
- To characterize the hormonal profile of late-gestation BPH/5 dams.
- To elucidate the role of maternal endocrine disruption in offspring reproductive and metabolic phenotypes.
Main Methods:
- Assessed reproductive and metabolic phenotypes of BPH/5 and BPN/3 offspring from birth to adulthood (anogenital distance, pubertal onset, ovarian function, adiposity).
- Investigated maternal late-gestation circulating hormones and placental steroidogenic enzymes.
- Compared hormonal profiles and offspring development between the preeclamptic-like (BPH/5) and control (BPN/3) mouse lines.
Main Results:
- BPH/5 offspring exhibited longer anogenital distance, indicating increased prenatal androgen exposure.
- Female BPH/5 offspring showed precocious puberty, abnormal estrous cycles, increased visceral adiposity, and a polycystic ovary syndrome (PCOS)-like phenotype in adulthood.
- Late-gestation BPH/5 dams had significantly higher serum Anti-Mullerian hormone (AMH) concentrations compared to controls, while testosterone levels did not differ.
Conclusions:
- BPH/5 offspring recapitulate reproductive abnormalities observed in children born after preeclampsia, including PCOS-like characteristics.
- Maternal excess AMH during late gestation in the BPH/5 model is linked to abnormal fetal HPG axis programming and PCOS-like offspring phenotypes.
- This mouse model highlights the interplay between PCOS and preeclampsia, offering insights into shared endocrine disruption mechanisms.
Abstract:
Children born after preeclampsia, the leading hypertensive disorder of pregnancy, are predisposed to long-term cardiometabolic and reproductive disorders that are likely associated with prenatal exposure to a dysregulated maternal endocrine milieu. We have previously described abnormal pubertal development and hyperandrogenism in female offspring from the preeclamptic-like blood pressure high subline 5 (BPH/5) mouse, recapitulating patterns observed in adolescents born after preeclampsia. Herein, our objective was to elucidate BPH/5 offspring hypothalamic-pituitary-gonadal (HPG) axis programming and the associated hormonal profile of late-gestation BPH/5 dams. Reproductive and metabolic phenotypes of BPH/5 and blood pressure normal subline 3 (BPN/3) offspring were assessed from birth to adulthood, including anogenital distance, pubertal onset, ovarian function, and adiposity. Maternal late-gestation circulating hormones and placental steroidogenic enzymes were also investigated. Anogenital distance, indicative of prenatal androgen exposure, was longer in BPH/5 male and female offspring. BPH/5 female offspring exhibited precocious pubertal onset and, during adulthood, abnormal estrous cycles, increased visceral adiposity, increased serum anti-Mullerian hormone (AMH), and ovarian morphology consistent with a polycystic ovary syndrome (PCOS)-like phenotype. Serum testosterone did not differ between late-gestation BPH/5 and BPN/3 dams. Conversely, serum AMH concentrations were threefold higher in late-gestation BPH/5 dams, a maternal endocrine disruption previously linked to abnormal female fetus HPG axis programming and PCOS-like offspring phenotype. In conclusion, BPH/5 offspring recapitulate the aberrant reproductive phenotype seen in children born after preeclampsia and major PCOS-like characteristics. Furthermore, maternal AMH excess was identified in late-gestation BPH/5 females, highlighting this as a valuable model of the interplay between PCOS and preeclampsia.NEW & NOTEWORTHY This study explored hypothalamic-pituitary-gonadal (HPG) axis development in offspring from the preeclamptic-like BPH/5 mouse model. Female BPH/5 offspring exhibited precocious pubertal development, elevated AMH, abnormal estrous cycles, abnormal ovarian histomorphology, and increased visceral adiposity. Interestingly, male and female offspring had longer anogenital distance, indicative of prenatal androgen exposure. Late-gestation BPH/5 dams exhibited a threefold higher AMH concentration, elucidating a novel developmental link between preeclampsia, offspring HPG axis programming, and postnatal ovarian and endocrine dysfunction.
