UC San Diego

Androgens are a class of steroid hormones produced by men and women. Typically, men have ~10-fold higher levels of serum androgens than women, but elevated androgen production in women has undesirable effects. Hyperandrogenism is present in women with polycystic ovary syndrome (PCOS) and other conditions. Due to the correlation between hyperandrogenism and metabolic dysregulation in females, we used a hyperandrogenism mouse model to investigate when this metabolic dysregulation develops and whether gut microbiota transfer could alleviate this dysfunction. One model of hyperandrogenism in female mice is the 10-mm dihydrotestosterone (DHT) model, which has been reported to develop reproductive and metabolic dysfunction after 3 months of treatment. We were interested in understanding when this metabolic phenotype develops. Similar to a recently published study, we found that DHT treatment was sufficient to induce weight gain and insulin resistance after 8 weeks of treatment. Hyperandrogenism is associated with changes in the gut microbiome in humans and rodent models. In previous studies, modulation of the gut microbiome via fecal microbiome transplantation (FMT) or cohousing improved metabolic dysfunction in models of obesity and PCOS. We investigated if cohousing was effective in ameliorating the metabolic dysfunction induced in the DHT mouse model. We found that over 13 weeks, cohousing had a protective effect on the metabolic dysregulation observed in DHT-treated mice but did not eliminate the phenotype. These studies indicate that manipulation of gut microbiota with pre- or probiotics should be explored further as a treatment for PCOS.