Insulin Reduces Reaction of Follicular Granulosa Cell to FSH Stimulation in Obesity-Related Infertility Women during IVF.

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Insulin Reduces Reaction of Follicular Granulosa Cell to FSH Stimulation in Obesity-Related Infertility Women during IVF.

J Clin Endocrinol Metab. 2018 Nov 21;:

Authors: Xu P, Huang BY, Zhan JH, Liu MT, Fu Y, Su YQ, Sun QY, Wang WH, Chen DJ, Liu JQ

Abstract
Context: Obese women usually need larger doses of FSH for ovarian stimulation, resulting in poor outcomes; however, the mechanism is still unclear.
Objective: To investigate the molecular regulation of FSH receptor (FSHR) expression associated with obesity.
Design: Case-control study to improve IVF outcomes.
Patients: Eighty-two obese and 457 overweight women undergoing IVF and 1,790 age-matched controls with normal weight from our reproductive medicine center.
Intervention: No special.
Main Outcome Measures: FSHR expression was decreased in parallel with BMI, while the oestradiol (E2) level on the hCG trigger day was significantly lower.
Results: FSHR expression in hGCs, both mRNA (P = 0.02) and protein (P = 0.001) levels, was decreased in overweight/obese women. Both insulin (P < 0.001) and glucose (P = 0.0017) levels were positively correlated with BMI in fasting blood and follicle fluids(FF) but not with FF leptin level. Treated KGN cells with insulin, E2 production was compromised, the level of p-Akt2 decreased while p-GSK3 increased, similar changes in hGCs from obese women. Stimulated hGCs from obese women with CP21, an inhibitor of GSK3β, resulting in upregulated β-catenin activation and increased FSHR expression. CP21 also increased the expression of IRS-1 and PI3K as well as the p-Akt2.
Conclusions: Obesity was associated with reduced FSHR expression and E2 production in IVF women, caused by dysfunctional insulin pathway. Decreased FSHR expression in hGCs from obese women and insulin-treated KGN could be rescued by inhibition of GSK3β, which might be a potential target for improving the impaired FSH response in obese women.

PMID: 30476103 [PubMed - as supplied by publisher]

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