Dehydroepiandrosterone stimulates inflammation and impairs ovarian functions of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is one of the most common causes of infertility in child-bearing-age women. It is characterized by ovulation dysfunction, polycystic ovaries, and hyperandrogenism. Inflammation is likely to be a crucial contributor to the pathogenesis of PCOS. However, the association between the inflammatory cytokines and the development of PCOS has not been reported. To explore the relationship between the inflammatory cytokines and PCOS, alterations of serum proteins in dehydroepiandrosterone (DHEA)-induced PCOS rats were screened by protein array, and the concentration of IFN-γ was further measured by using enzyme-linked immunosorbent assay (ELISA). DHEA-induced PCOS rats had a decreased level of IFN-γ compared with the control rats, which was restored partly in flutamide (an androgen receptor antagonist)-treated rats. Moreover, the level of IFN-γ in serum of patients with PCOS was also lower than that in healthy women. Using the ovarian granulosa cells (KGN), we demonstrated that DHEA downregulated the expression and secretion of IFN-γ in dose- and time-dependent manners, which could be restored to some extent by treating with flutamide. Furthermore, flutamide ameliorated the inhibitory effect on cell proliferation and promotive effect on cell apoptosis by DHEA. The results also revealed that IFN-γ promoted the proliferation but inhibited the apoptosis of KGN cells, which was suppressed by DHEA via activating the downstream PI3K/AKT signaling pathway. Taken together, these results showed that DHEA inhibited the proliferation and promoted the apoptosis of ovarian granulosa cells through downregulating the expression of IFN-γ which could be restored by flutamide, and IFN-γ may serve as a potential inflammatory biomarker for PCOS detection.

Baicalin promotes embryo adhesion and implantation by upregulating fucosyltransferase IV (FUT4) via Wnt/beta-catenin signaling pathway.

Glycosylation plays a significant role in determining the receptivity of the uterine endometrium to embryo. Fucosyltransferase IV (FUT4) is expressed stage-specifically in the uterine endometrium of mammalians, and considered as a marker of the endometrial receptivity. Baicalin, a monomer of flavonoids, is known to have functions in improving reproduction. However, the mechanism by which baicalin regulates the expression of FUT4 in embryo-endometrium adhesion remains unclear. Our results showed that baicalin significantly increased FUT4 mRNA and protein expression levels both in human endometrial cells and mouse endometrial tissue, and consistently elevated embryo adhesion rate during implantation in vitro and embryonic implantation competence in pregnant mouse. This study suggests that baicalin facilitates endometrial reproduction via elevating FUT4 expression through Wnt/ß-catenin signaling pathway.