PPAR-gamma agonist pioglitazone improves endometrial receptivity, reverses endometrial barrier disruption and promotes ovarian function in thin endometrium rats via modulation PPAR-γ/Wnt5/β-catenin pathway.

Thin endometrium (TE) is a common reproductive endocrine disorder, PPAR-γ has been reported to regulate cell proliferation and crosstalk with the Wnt5/β-catenin pathway. However, whether PPAR-γ promotes endometrial epithelial cell proliferation and acts through the Wnt5/β-catenin pathway has not been explored. A rat model of endometrial thinning was established and administered for 15 days, and the morphology of the uterus and ovaries was observed by HE staining. Serum sex hormone levels were measured by enzyme-linked immunosorbent assay (ELISA). The morphology of endometrial surface was observed by electron microscopy. Immunohistochemistry was used to detect the expression of endometrial receptivity, endometrial barrier and ovarian function proteins. Activation of PPAR-γ/Wnt5/β-catenin pathway was analyzed by molecular docking and Western blotting. The results showed that PIO improved endometrial morphology, endometrial thickness, gland number and expression of endometrial tolerance-related proteins, and promoted the repair of endometrial barrier in TE rats. Serum hormone levels, mature follicle and corpus luteum numbers were increased, indicating improved ovarian function. PIO downregulated the Wnt5/β-catenin signaling pathway and increased the expression of ovarian endocrine-related proteins, as shown by western blot analysis. Our findings revealed that thr PPAR-γ agonist pioglitazone inhibited the Wnt5/β-catenin pathway by up-regulating the expression of PPAR-γ and promoted the proliferation of epithelial cells and the repair of the endometrial barrier, which played a role in protecting ovarian function while treating TE.