Aberrant activation of the Hedgehog signaling pathway in granulosa cells from patients with polycystic ovary syndrome

Objective The molecular mechanism that triggers polycystic ovary syndrome (PCOS) is mysterious. Abnormal development of ovarian granulosa cells(GCs) is one of the causes of PCOSMethods The study was carried out by using RNA-seq to detect the different gene expression levels in ovarian GCs between 3 patients with PCOS and 4 normal controls. To further verify the above results, GCs from 22 patients with PCOS and 21 controls with normal ovulation were collected to perform the RT-PCR analysisResults The results found Hedgehog signaling pathway(Hh) members, Ihh and Ptch2 were abnormally highly expressed in the PT. The qPCR results also indicated that the expression levels of other Hh signaling pathway downstream members, Ptch1, Gli1, and Gli2 in the PCOS group (PT) were significantly higher than those in the control group (NT). Besides, the expression of TNF-α mRNA in PCOS patients was higher than that in the control group. Finally, the Hh signaling pathway inhibitor, cyclopamine, can decrease the apoptosis of PCOS ovarian granulosa cellsConclusions These results suggest that abnormally activated Hh signaling pathway, especially Ihh signal, may have a profound influence on PCOS.