Abstract:

Objective: To examine the impact of prenatal intrauterine exposure to high anti-Müllerian hormone (AMH) and androgen on the gut microbiota in F1 offspring mice. Methods: Pregnant F0 dams were randomly allocated into three groups. To simulate altered prenatal hormonal environments, F0 dams received daily subcutaneous injections from embryonic day 16.5 to embryonic day 18.5 as follows: benzyl benzoate with sesame oil, benzyl benzoate with sesame oil and anti-Müllerian hormone (AMH), or benzyl benzoate with sesame oil and dihydrotestosterone. Their female F1 offspring were correspondingly designated as the control group (Con group), prenatal AMH group (PAMH group), and prenatal androgenized group (PNA group). Upon reaching adulthood, the estrous cycle of F1 female offsprings were monitored and assessed for regularity. Ovarian tissue and cecal contents were collected for histological evaluation and gut microbiota profiling via 16S amplicon sequencing. Results: Compared to the Con group, the PNA and PAMH groups exhibited disrupted estrous cyclicity and notable histological abnormalities in ovarian morphology, while F1 offspring mice showed significant alterations in gut microbial composition. Functional predictive analysis indicated that the differentially enriched microbial taxa were predominantly involved in immune regulation and metabolic pathways. Conclusions: Prenatal intrauterine exposure to high AMH and androgen reshaped the gut microbiota structure of F1 offspring mice, which may be associated with the immune system and metabolic pathways.

Key words: Polycystic ovary syndrome, Gastrointestinal microbiome, Androgens, Anti-müllerian hormone, Animal experimentation