Journal of Shandong University (Health Sciences) ›› 2021, Vol. 59 ›› Issue (6): 57-63.doi: 10.6040/j.issn.1671-7554.0.2021.0304

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Effects of WNT5A gene on insulin reactivity and insulin resistance in granulosa cells

NIU Qun, SHI Jingjing, FU Jiang   

  1. Center for Reproductive Medicine, Key Laboratory of Reproductive Endocrinology of Ministry of Education, ShandongKey Laboratory of Reproductive Medicine, National Research Center for Assisted Reproductive Technology and Reproductive Genetics, Shandong University, Jinan 250012, Shandong, China
  • Published:2021-06-10

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Abstract: Objective To explore the correlation between WNT5A gene overexpression and insulin resistance in granulosa cells. Methods Female Kunming mice aged 3 weeks(n=15)and 6 weeks(n=16)were selected. Expression of WNT5A in mice granulosa cells was detected with immunohistochemistry and real-time quantitative polymerase chain reaction(qRT-PCR). After human granulosa-like tumor cell line(KGN)were treated with Forskolin+pma to simulate luteinizing hormone(LH)peak for 24h, the effect of WNT5A on insulin reactivity was detected. After the KGN cells were transfected with p-EGFP-N1-WNT5A, the correlation between overexpression of WNT5A and insulin resistance was detected. Results Compared with preoestrus mice, oestrus mice (n=3, F=8.874, P=0.017)and postoestrus mice(n=3, F=8.874, P=0.001)had increased mRNA expression of WNT5A, and the protein expression of WNT5A increased in mature follicular granulosa cells. The expression of WNT5A in the granulosa cells of the ovulation-induced immature mice was also significantly increased(n=3, F=12.093, P=0.003). Ovulation induction inhibited insulin reactivity in KGN cells, which was improved by WNT5A. However, overexpression of WNT5A decreased insulin pathway responsiveness and lactate metabolism(n=3, F=15.281, P<0.001). Conclusion The expression of WNT5A benefits the insulin reactivity in granulosa cells during ovulation induction. However, when WNT5A is excessively elevated, such as in polycystic ovarian syndrome(PCOS), it may cause insulin resistance.

Key words: Granulosa cells, WNT5A gene, Overexpression, Insulin resistance

CLC Number: 

  • R715.9
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