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Aberrant H19 Expression Disrupts Ovarian Cyp17 and Testosterone Production and Is Associated with Polycystic Ovary Syndrome in Women.
Chen, Zhaojuan; Liu, Lan; Xi, Xia; Burn, Martina; Karakaya, Cengiz; Kallen, Amanda N.
Afiliación
  • Chen Z; Department of Gynecology, Beijing Haidian Hospital of Traditional Chinese Medicine, Beijing, China.
  • Liu L; Department of Obstetrics, Nanjing Maternity and Child Health Care Hospital, Women's Hospital of Nanjing Medical University, Nanjing, China.
  • Xi X; Peking University Shenzhen Hospital, Shenzhen, People's Republic of China.
  • Burn M; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar St, PO Box 208063, New Haven, CT, 06512, USA.
  • Karakaya C; Department of Medical Biochemistry, Gazi University School of Medicine, Ankara, Turkey.
  • Kallen AN; Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale University School of Medicine, 333 Cedar St, PO Box 208063, New Haven, CT, 06512, USA. amanda.kallen@yale.edu.
Reprod Sci ; 29(4): 1357-1367, 2022 04.
Article en En | MEDLINE | ID: mdl-34655046
ABSTRACT
As one of the most common endocrine disorders affecting women, polycystic ovary syndrome (PCOS) is associated with serious conditions including anovulation, endometrial cancer, infertility, hyperandrogenemia, and an increased risk for obesity and metabolic derangements. One contributing etiology to the pathophysiology of hyperandrogenemia associated with PCOS is an intrinsic alteration in ovarian steroidogenesis, leading to enhanced synthesis of androgens including testosterone. Studies have suggested that the increased testosterone synthesis seen in PCOS is driven in part by increased activity of CYP17A1, the rate-limiting enzyme for the formation of androgens in the gonads and adrenal cortex, which represents a critical factor driving enhanced testosterone secretion in PCOS. In this work, we evaluated the hypothesis that dysregulation of the noncoding RNA H19 results in aberrant CYP17 and testosterone production. To achieve this, we measured Cyp17 in ovarian tissues of H19 knockout mice, and quantified serum testosterone levels, in comparison with wild-type controls. We also evaluated circulating and ovarian H19 expression and correlated results with the presence or absence of PCOS in a group of women undergoing evaluation and treatment for infertility. We found that the loss of H19 in a mouse model results in decreased ovarian Cyp17, along with decreased serum testosterone in female mice. Moreover, utilizing serum samples and cumulus cells from women with PCOS, we showed that circulating and ovarian levels of H19 are increased in women with PCOS compared to controls. Findings from our multimodal experimental strategy, involving both a mouse model of dysregulated H19 expression and clinical serum and ovarian cellular samples from women with PCOS, suggest that the loss of H19 may disrupt androgen production via a Cyp17-mediated mechanism. Conversely, excess H19 may play a role in the pathogenesis of PCOS-associated hyperandrogenemia.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Síndrome del Ovario Poliquístico / Hiperandrogenismo / Infertilidad Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: Reprod Sci Asunto de la revista: MEDICINA REPRODUTIVA Año: 2022 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Síndrome del Ovario Poliquístico / Hiperandrogenismo / Infertilidad Tipo de estudio: Prognostic_studies / Risk_factors_studies Límite: Animals / Female / Humans Idioma: En Revista: Reprod Sci Asunto de la revista: MEDICINA REPRODUTIVA Año: 2022 Tipo del documento: Article País de afiliación: China