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Publication
Letrozole treatment of pubertal female mice results in activational effects on
reproduction, metabolism and the gut microbiome.
Authors Arroyo P, Ho BS, Sau L, Kelley ST, Thackray VG
Submitted By Submitted Externally on 11/24/2019
Status Published
Journal PLoS ONE
Year 2019
Date Published
Volume : Pages 14 : e0223274
PubMed Reference 31568518
Abstract 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. In
addition to infertility, many women with PCOS have metabolic dysregulation that
increases the risk of developing type 2 diabetes, hypertension, and
non-alcoholic fatty liver disease. Changes in the gut microbiome are associated
with PCOS and gut microbes may be involved in the pathology of this disorder.
Since PCOS often manifests in the early reproductive years, puberty is
considered to be a critical time period for the development of PCOS. Exposure to
sex steroid hormones during development results in permanent, organizational
effects, while activational effects are transient and require the continued
presence of the hormone. Androgens exert organizational effects during prenatal
or early post-natal development, but it is unclear whether androgen excess
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 on host physiology and the gut microbiome. Two months after
letrozole removal, we observed recovery 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 activational effects. These results suggest that if exposure to
excess androgens during puberty leads to the development of PCOS, reduction of
androgen levels during this time may improve reproductive and metabolic
phenotypes in women with PCOS. These results also imply that continuous
letrozole exposure is required to model PCOS in pubertal female mice since
letrozole exerts activational rather than organizational effects during puberty.




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