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• W3200529327 abstract "One contributing factor to the pathophysiology of hyperandrogenemia associated with PCOS is an intrinsic alteration in ovarian steroidogenesis, leading to enhanced synthesis of androgens including testosterone (T). Increased activity of CYP17A1, the rate-limiting enzyme for the formation of androgens in the gonads, is thought to be a critical factor driving enhanced T secretion in PCOS. Given their diverse roles in biological process, interest has grown in the role of noncoding RNAs (ncRNAs) in the pathogenesis of PCOS. In this work, we evaluated the hypothesis that that dysregulation of the ncRNA H19 results in aberrant CYP17 and testosterone production and that H19 expression is altered in women with PCOS. To achieve this, we utilized a multimodal experimental strategy involving both a mouse model of dysregulated H19 expression as well as clinical samples from women with PCOS. To evaluate Cyp17 gene expression, ovarian tissue was collected from 8 week H19 knockout (H19KO) and WT female mice (5 per group), and RNA extraction and qRT-PCR were performed, and Western blot used to confirm gene expression. Serum steroid testosterone levels were also quantified. In order to identify correlations between circulating and ovarian H19 expression and PCOS, discarded blood samples were collected from 69 female patients undergoing evaluation for infertility at the Yale Fertility Center. These patients included controls (male/tubal infertility, n=19), and women hyperandrogenic PCOS by Rotterdam criteria (n=16). Concurrently, cumulus cells were collected at oocyte retrieval from women undergoing IVF-ICSI at Gazi University School of Medicine. Patients were stratified by diagnosis (PCOS, n=10; male/tubal infertility, n=29). qRT-PCR for H19 was performed as above. Cyp17α expression was decreased by 40% in ovaries of H19KO mice as compared with WT (p<0.05); Western blot for CYP17 confirmed these findings (p<0.01). Serum testosterone levels were lower in the estrus stage in female H19KO mice as compared to WT (20.66 ng/dL vs 33.42 ng/dL; p<0.01). Serum H19 expression was increased 2.5-fold in women with PCOS relative to non-PCOS controls (p<0.0005), and cumulus cell H19 expression was increased 2.8-fold in PCOS patients collected at the time of oocyte retrieval, compared to controls (p<0.05). In this study, we show that loss of H19 in a mouse model results in decreased ovarian Cyp17 and decreased serum testosterone in female mice. Moreover, we have provided a clinical correlation by utilizing serum samples and cumulus cells from women with PCOS, showing that in these women circulating and ovarian levels of H19 are increased as compared to controls." @default.
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• W3200529327 date "2021-09-01" @default.
• W3200529327 modified "2023-10-18" @default.
• W3200529327 title "ABERRANT H19 EXPRESSION DISRUPTS OVARIAN Cyp17 AND TESTOSTERONE PRODUCTION AND IS ASSOCIATED WITH POLYCYSTIC OVARY SYNDROME" @default.
• W3200529327 doi "https://doi.org/10.1016/j.fertnstert.2021.07.231" @default.
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