A breakthrough mouse model —generated by Phenomics Australia’s Monash Genome Modification Platform node— reveals how inhibins finely balance fertility and pregnancy, offering new insights for improving reproductive health and IVF outcomes.
Women’s Health Week is held during the first week of September annually, it is a national campaign dedicated to the health and wellbeing of all women, girls and gender-diverse people.
Reproductive health research is crucial to improving outcomes for women experiencing infertility, pregnancy complications or menopause-related conditions. Understanding the hormonal mechanisms that regulate ovarian function is essential for improving outcomes in both natural conception and assisted reproductive technologies such as IVF.
A collaboration between Monash University and the University of Queensland has been advancing our understanding of the molecular mechanisms of key hormones involved in pregnancy, including inhibin A/B and the follicle-stimulating hormone (FSH). This study, published in Endocrinology, has shed new light on this issue by creating a new mouse model with an inactivating mutation in the Inha gene (the equivalent of a human mutation at R232A). This model allowed researchers to directly test what happens when inhibins — hormones that normally restrain follicle-stimulating hormone (FSH) — are disrupted.
FSH plays a key role in ovarian follicle development, stimulating their growth and maturation. Because of this, ovarian stimulation via administration of FSH to women with infertility is part of the primary therapeutic intervention used in assisted reproductive technology. In this study, the Female InhaR233A/R233A mutant mice (those with inhibin inactivation), generated by Phenomics Australia’s Monash Genome Modification Platform node (MGMP), showed markedly elevated FSH levels, leading to enhanced follicle development, up to 4x higher ovulation rates, and significantly enlarged ovaries. However, these changes came at a cost: despite enhanced folliculogenesis and ovulation rates, pregnancies were marked by significant pregnancy loss and premature infertility. It is worth noting that this study also found that partial loss of inhibin function appears to enhance fertility without the same negative impacts, suggesting a dose-dependent role of inhibin in reproductive success.
Dr Alexander Combes, Phenomics Australia Scientific Director, head of the MGMP platform said “This study utilises precision gene editing to isolate inhibin function from confounding effects, revealing novel roles in pregnancy establishment, maintenance, and ovarian function.”
This new model of inhibin loss-of-function is a valuable research tool for uncovering the physiological activities of inhibin A and B, highlighting the critical role of inhibins in the establishment and maintenance of pregnancy. By revealing the dual role of inhibins in both enhancing fertility and safeguarding pregnancy, this study opens the door to improving fertility treatments and reducing the burden of pregnancy loss.
Phenomics Australia provides a national centre of expertise and service provision to deploy a more comprehensive and sophisticated range of in vitro Genome Engineering and Disease Modelling capabilities to understand the functional consequences of DNA sequence variation in the human genome for health and disease while maintaining the expertise for in vivo disease modelling and genome engineering. To meet the high demand for adaptable and scalable disease-modelling platforms for improved diagnosis, Precision Medicine for genetic disorders, and therapeutic development by both academia and the biopharmaceutical industry, Phenomics Australia offers In Vitro services through a collaborative consortium of ten laboratories and facilities across Australia, operating at ANU (ANU Centre for Therapeutic Discovery), Perkins (Translational Cancer Research Program in Oncology), Monash (Monash Organoid Program & Monash Genome Modification Platform), MCRI (iPSC derivation & Gene Editing Facility), Peter Mac (Victorian Centre for Functional Genomics), UMelb (Centre for Stem Cell Systems & Stem Cell Disease Modelling Laboratory), UQ (In vitro Genome Engineering and Disease Modelling Service), and VCCRI (Stem Cell Production Facility iPSC Reprogramming Service)
