title: Prenatal androgen excess programs metabolic derangements in pubertal female rats.
abstract: Owing to the heterogeneity in the clinical symptoms of polycystic ovary syndrome (PCOS), the early pathophysiological mechanisms of PCOS remain unclear. Clinical, experimental, and genetic evidence supports an interaction between genetic susceptibility and the influence of maternal environment in the pathogenesis of PCOS. To determine whether prenatal androgen exposure induced PCOS-related metabolic derangements during pubertal development, we administrated 5α-dihydrotestosterone (DHT) in pregnant rats and observed their female offspring from postnatal 4 to 8 weeks. The prenatally androgenized (PNA) rats exhibited more numerous total follicles, cystic follicles, and atretic follicles than the controls. Fasting glucose, insulin, leptin levels, and homeostatic model assessment for insulin resistance were elevated in the PNA rats at the age of 5-8 weeks. Following intraperitoneal glucose tolerance tests, glucose and insulin levels did not differ between two groups; however, the PNA rats showed significantly higher 30- and 60-min glucose levels than the controls after insulin stimulation during 5-8 weeks. In addition, prenatal DHT treatment significantly decreased insulin-stimulated phosphorylation of AKT in the skeletal muscles of 6-week-old PNA rats. The abundance of IR substrate 1 (IRS1) and IRS2 was decreased in the skeletal muscles and liver after stimulation with insulin in the PNA group, whereas phosphorylation of insulin-signaling proteins was unaltered in the adipose tissue. These findings validate the contribution of prenatal androgen excess to metabolic derangements in pubertal female rats, and the impaired insulin signaling through IRS and AKT may result in the peripheral insulin resistance during pubertal development.
authors: State Key Laboratory of Reproductive Medicine, Clinical Center of Reproductive Medicine, First Affiliated Hospital, Nanjing Medical University, 300 Guangzhou Road, Nanjing 210029, China.
authors: Xiaonan
authors: X
authors: Yan
authors: Xiaonan
authors: X
authors: Dai
authors: Jing
authors: J
authors: Wang
authors: Nannan
authors: N
authors: Zhao
authors: Yugui
authors: Y
authors: Cui
authors: Jiayin
authors: J
authors: Liu
mesh_terms: D000728:Androgens / Q000009:adverse effects*; D000818:Animals; D013196:Dihydrotestosterone / Q000009:adverse effects; D005260:Female; D047109:Fetal Development / Q000187:drug effects*; D005496:Follicular Atresia / Q000187:drug effects; D018149:Glucose Intolerance / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects* / Q000378:metabolism; D010048:Ovarian Cysts / Q000139:chemically induced / Q000473:pathology; D006080:Ovarian Follicle / Q000187:drug effects / Q000473:pathology; D010766:Phosphorylation / Q000187:drug effects; D011085:Polycystic Ovary Syndrome / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000728:Androgens; D055504:Insulin Receptor Substrate Proteins; D013196:Dihydrotestosterone; C494920:Akt1 protein, rat; D051057:Proto-Oncogene Proteins c-akt