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A Hyperandrogenic Mouse Model to Study Polycystic Ovary Syndrome
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FSHR antagonists can trigger a PCOS-like state.

Faiza Hanif Waghu1, Karishma Desai2, Sumana Srinivasan1

  • 1Department of Chemical Engineering, Indian Institute of Technology Bombay, Mumbai, India.

Systems Biology in Reproductive Medicine
|December 30, 2021
PubMed
Summary

Follicle-stimulating hormone receptor (FSHR) antagonists may induce a Polycystic Ovarian Syndrome (PCOS)-like state. This study validated the hypothesis using gene expression and theoretical simulations, revealing typical PCOS characteristics.

Keywords:
FSHR antagonismPCOSmathematical modelingmenstrual cyclesystems biology

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Area of Science:

  • Reproductive Endocrinology
  • Pharmacology
  • Genetics

Background:

  • Follicle-stimulating hormone receptor (FSHR) is a key target for fertility regulation agents.
  • FSHR antagonism can lead to subfertility or infertility.
  • Previous studies identified an FSHR antagonist peptide (FSHβ (89-97)) that induced PCOS-like symptoms.

Purpose of the Study:

  • To validate the hypothesis that FSHR antagonists can trigger a Polycystic Ovarian Syndrome (PCOS)-like state.
  • To investigate the molecular and physiological effects of FSHR antagonism in the context of PCOS.

Main Methods:

  • Quantitative real-time PCR (qRT-PCR) validation of gene expression in ovarian tissue samples.
  • Evaluation of genes known to be differentially expressed in PCOS.
  • Theoretical simulations using a human menstrual cycle model to assess FSHR antagonism effects.

Main Results:

  • Gene expression analysis showed patterns similar to the PCOS state.
  • Model simulations indicated increased testosterone levels and an elevated LH/FSH ratio.
  • Simulations also revealed stockpiling of secondary follicles, a hallmark of PCOS.

Conclusions:

  • FSHR antagonists show potential to induce a PCOS-like condition.
  • Findings are relevant for evaluating FSHR antagonists in fertility regulation and reproductive medicine.
  • Further research is warranted to understand the full implications of FSHR antagonism.