Does polycystic ovary syndrome begin before birth? A neurodevelopmental perspective

THE CONTEXT

Polycystic ovary syndrome (PCOS) is the most common hormonal disorder affecting female fertility, affecting between 10 and 15 percent of women worldwide. In addition to compromising fertility and increasing the risk of complications during pregnancy, PCOS is associated with potential health consequences for children exposed to it in utero.

Recent data suggest that the syndrome may have very early origins, beginning as early as fetal life. In some women with PCOS, high levels of androgens—particularly testosterone—are present during pregnancy. Although essential for normal development, these hormones can disrupt brain maturation when present in excess. Exposure to certain environmental endocrine disruptors, such as TBECH, could also replicate or amplify these effects.

To better understand these mechanisms, the research team is using innovative technology based on human brain organoids—or “mini-brains”—grown from stem cells. These models make it possible to safely and ethically study the impact of hormones and environmental contaminants on human brain development during pregnancy.

THE OBJECTIVES

The hypothesis is that prenatal exposure to high levels of androgens and the endocrine disruptor TBECH disrupts the neuroendocrine development of the hypothalamic arcuate nucleus (ARC), leading to changes comparable to those observed in PCOS.

The specific objectives are:

• To develop a human ARC organoid model and characterize the effects of androgen exposure on female neurodevelopment.
• To evaluate the impact of TBECH to determine whether it induces neuroendocrine changes similar to those associated with PCOS.

POTENTIAL IMPACT

This project addresses an emerging issue in maternal and pediatric health. By identifying the early brain mechanisms through which maternal hyperandrogenism and endocrine disruptors influence fetal brain development, this research will contribute to a better understanding of the origins of PCOS and its intergenerational effects.

The knowledge generated will make it possible to:

• better identify at-risk children from the earliest stages of life;
• support the development of early biomarkers of vulnerability;
• guide targeted clinical monitoring strategies;
• promote the implementation of preventive interventions before symptoms appear in adolescence or adulthood.

In the longer term, these advances could reduce the prevalence and socioeconomic burden associated with PCOS, while improving the reproductive, metabolic, and neurodevelopmental health of women and future generations.