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  2. GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway

GIMAP7 induces oxidative stress and apoptosis of ovarian granulosa cells in polycystic ovary syndrome by inhibiting sonic hedgehog signalling pathway

  • J Ovarian Res. 2022 Dec 30;15(1):141. doi: 10.1186/s13048-022-01092-z.
Anran Xu 1 Yuanyuan Fan 1 Song Liu 1 Lianbing Sheng 1 Yanyan Sun 1 Huijun Yang 2
Affiliations

Affiliations

  • 1 Center of Reproductive Medicine, Maternity and Child Health Care Hospital of Shandong Province/ Key Laboratory of Birth Regulation and Control Technology of the Health Commission of China, 238 Jiangshuiquan Road, Jinan, 250014, Shandong, People's Republic of China.
  • 2 Center of Reproductive Medicine, Maternity and Child Health Care Hospital of Shandong Province/ Key Laboratory of Birth Regulation and Control Technology of the Health Commission of China, 238 Jiangshuiquan Road, Jinan, 250014, Shandong, People's Republic of China. xarjlyy@163.com.
Abstract

Polycystic ovary syndrome (PCOS) is a gynaecological endocrine disease. The objective of the present study was to investigate the role of GTPase immunity-associated protein (GIMAP) 7 in PCOS. A PCOS rat model was established using dehydroepiandrosterone injection. The data showed that GIMAP7 was mainly located in granulosa cells and was abundantly expressed in the ovarian granulosa cells of PCOS rats. GIMAP7 silencing decreased blood glucose levels, HOMA-IR scores, and number of cystic follicles. In addition, GIMAP7 silencing corrected erratic oestrous cycles, inhibited Apoptosis and reduced c-caspase-3 protein expression in the ovarian tissues of PCOS rats. GIMAP7 silencing reduced malondialdehyde (MDA) but increased glutathione (GSH) and superoxide dismutase (SOD) levels in the serum and ovarian tissues of PCOS rats. The effects of GIMAP7 were further investigated in human ovarian granulosa KGN cells. GIMAP7 silencing increased the viability, promoted proliferation, and increased the percentage of S-phase KGN cells. The Apoptosis rate was significantly decreased by GIMAP7 silencing. GIMAP7 also inhibited oxidative stress in KGN cells, resulting in decreased levels of Reactive Oxygen Species (ROS) and MDA and increased levels of GSH and SOD. Notably, GIMAP7 inhibited the sonic Hedgehog (SHH) signalling pathway, and GIMAP7 silencing increased the expression of the SHH signalling pathway downstream genes SHH, Smo, and Gli1. Inhibition of the SHH signalling pathway using cyclopamine reduced the effect of GIMAP7 silencing on KGN cells. This study proved that GIMAP7 promotes oxidative stress and Apoptosis in ovarian granulosa cells in PCOS by inhibiting the SHH signalling pathway.

Keywords

GIMAP7; Oxidative stress; Polycystic ovary syndrome; Sonic hedgehog signalling pathway.

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