ena-STUDY-UNIVERSITY OF CALIFORNIA - SAN DIEGO-01-03-2019-19:35:34:064-36
Letrozole Treatment of Pubertal Female Mice Results in Activational Effects on Reproduction, Metabolism and the Gut Microbiome
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women that is comprised of two out of the following three features: hyperandrogenism, oligo- or amenorrhea, or polycystic ovaries. Women with PCOS are at risk for infertility, pregnancy complications, type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease. Many rodent models have been used to study PCOS including those that model exposure to excess androgens. Androgens have been shown to exert permanent (organizational) effects during prenatal or early post-natal development, but it remains unclear whether hyperandrogenism results in organizational or activational effects during puberty. We recently developed a letrozole-induced PCOS mouse model that recapitulates both reproductive and metabolic phenotypes of PCOS. In this study, we investigated whether letrozole treatment of pubertal female mice exerts organizational or activational effects by testing whether discontinuation of letrozole resulted in transient or permanent effects on host physiology and the gut microbiome. Two months after letrozole removal, we observed normalization of reproductive and metabolic parameters, as well as diversity and composition of the gut microbiome, indicating that letrozole treatment of female mice during puberty resulted in predominantly transient, activational effects. These results suggest that studies utilizing pubertal or adult hyperandrogenic models should determine whether excess androgens result in organizational or activational effects in their specific model in order for the appropriate experimental design to be employed.
Polycystic ovary syndrome (PCOS) is a common endocrine disorder in reproductive-aged women that is comprised of two out of the following three features: hyperandrogenism, oligo- or amenorrhea, or polycystic ovaries. Women with PCOS are at risk for infertility, pregnancy complications, type 2 diabetes, cardiovascular disease and non-alcoholic fatty liver disease. Many rodent models have been used to study PCOS including those that model exposure to excess androgens. Androgens have been shown to exert permanent (organizational) effects during prenatal or early post-natal development, but it remains unclear whether hyperandrogenism results in organizational or activational effects during puberty. We recently developed a letrozole-induced PCOS mouse model that recapitulates both reproductive and metabolic phenotypes of PCOS. In this study, we investigated whether letrozole treatment of pubertal female mice exerts organizational or activational effects by testing whether discontinuation of letrozole resulted in transient or permanent effects on host physiology and the gut microbiome. Two months after letrozole removal, we observed normalization of reproductive and metabolic parameters, as well as diversity and composition of the gut microbiome, indicating that letrozole treatment of female mice during puberty resulted in predominantly transient, activational effects. These results suggest that studies utilizing pubertal or adult hyperandrogenic models should determine whether excess androgens result in organizational or activational effects in their specific model in order for the appropriate experimental design to be employed.