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Hyperandrogenic Milieu Dysregulates the Expression of Insulin Signaling Factors and Glucose Transporters in the Endometrium of Patients With Polycystic Ovary Syndrome

 Mee-Hwa Lee  ;  Jung-Ah Yoon  ;  Hye-Ryun Kim  ;  Yeon Sun Kim  ;  Sang Woo Lyu  ;  Byung Seok Lee  ;  Haengseok Song  ;  Dong Hee Choi 
 REPRODUCTIVE SCIENCES, Vol.27(8) : 1637-1647, 2020-08 
Journal Title
Issue Date
Androgens / adverse effects* ; Antigens, CD / metabolism ; Cells, Cultured ; Dihydrotestosterone / adverse effects* ; Endometrium / drug effects ; Endometrium / metabolism* ; Endometrium / pathology ; Female ; Glucose Transport Proteins, Facilitative / metabolism* ; Humans ; Insulin / adverse effects* ; Polycystic Ovary Syndrome / metabolism* ; Polycystic Ovary Syndrome / pathology ; Receptor, Insulin / metabolism ; Signal Transduction / drug effects ; Signal Transduction / physiology
androgen ; decidualization ; endometrium ; glucose transporter ; polycystic ovary syndrome
Purpose: Subfertility associated with polycystic ovary syndrome (PCOS) mainly originates from oligoovulation/anovulation. Although insulin resistance and androgen excess are known to cause PCOS-associated implantation failure, the consequences of PCOS on endometrial homeostasis and pathophysiology have not been comprehensively understood. In this study, we examined whether the pathophysiologic milieu of PCOS intrinsically affects expression profiles of genes related to insulin signaling and facilitative glucose transporters (GLUTs) in the human endometrium and/or during in vitro decidualization.

Study design: Seven healthy women with regular menstrual cycles and 13 patients with PCOS were recruited for this study. To mimic the hyperandrogenic or hyperinsulinemic milieu in the endometrium of patient with PCOS (PCOSE) in vitro, human endometrial stromal cells (hESCs) were treated with dihydrotestosterone (DHT) or insulin, respectively.

Results: In PCOSE, messenger RNA (mRNA) levels of insulin receptor (IR), IR substrate (IRS) 1, and IRS2 were significantly increased. Furthermore, GLUT1 and GLUT12 were aberrantly increased. Chronic exposure to insulin or DHT aberrantly increased IRS1/IRS2 phosphorylation and protein levels of GLUT1 and GLUT12 in hESCs, suggesting that not only hyperinsulinemic but also hyperandrogenic conditions affect insulin signaling and glucose metabolism. The mRNA microarrays demonstrated that DHT dysregulates various gene sets, including cell cycle and glucose metabolism, in hESCs. Furthermore, DHT suppressed the expression of GLUT1 and GLUT12 as well as decidualization markers, IGFBP1 and prolactin, during in vitro decidualization.

Conclusions: The hyperandrogenic milieu affects gene expression profiles, including gene sets associated with insulin signaling, cell cycle, glucose metabolism, and/or glucose transport, in human endometrium and during in vitro decidualization.
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1. College of Medicine (의과대학) > Dept. of Obstetrics and Gynecology (산부인과학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Pediatrics (소아과학교실) > 1. Journal Papers
Yonsei Authors
Shin, Jae Il(신재일) ORCID logo https://orcid.org/0000-0003-2326-1820
Lee, Byung Seok(이병석) ORCID logo https://orcid.org/0000-0001-6001-2079
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