Endometrial decidualization plays a pivotal role during early pregnancy. Compromised decidualization has been tightly associated with recurrent implantation failure (RIF). Primary cilium is an antenna-like sensory organelle and acts as a signaling nexus to mediate Hh, Wnt, TGFβ, BMP, FGF, and Notch signaling. However, whether primary cilium is involved in human decidualization is still unknown. In this study, we found that primary cilia are present in human endometrial stromal cells. The ciliogenesis and cilia length are increased by progesterone during in vitro and in vivo decidualization. Primary cilia are abnormal in the endometrium of RIF patients. Based on data from both assembly and disassembly of primary cilia, it has been determined that primary cilium is essential to human decidualization. Trichoplein (TCHP)-Aurora A signaling mediates cilia disassembly during human in vitro decidualization. Mechanistically, primary cilium modulates human decidualization through PTEN-PI3K-AKT-FOXO1 signaling. Our study highlights primary cilium as a novel decidualization-related signaling pathway.

Decidualization is essential to rodent and primate pregnancy. Senescence is increased during decidualization. Failure of senescence clearance during decidualization will cause pregnancy abnormality. Caveolin-1 is located in plasmalemmal caveolae and involved in senescence. However, whether caveolin-1 is involved in decidualization remains undefined. In this study, we examined the expression, regulation and function of Caveolin-1 during mouse early pregnancy and under mouse and human in vitro decidualization. From days 1 to 8 of pregnancy, Caveolin-1 signals are mainly located in endothelium and myometrium. Estrogen stimulates Caveolin-1 expression in endothelium. Deficiency of estrogen receptor α significantly promotes Caveolin-1 level in uterine stromal cells. Progesterone upregulates Caveolin-1 expression in luminal epithelium. During mouse in vitro decidualization, Caveolin-1 is significantly increased. However, Caveolin-1 is obviously decreased during human in vitro decidualization. Caveolin-1 overexpression and siRNA suppress and upregulate IGFBP1 expression under in vitro decidualization, respectively. Blastocysts-derived tumor necrosis factor α (TNFα) and human Chorionic Gonadotropin (hCG) regulate Caveolin-1 in mouse and human decidual cells, respectively. Caveolin-1 levels are also regulated by high glucose and insulin. In conclusion, a low level of Caveolin-1 should be beneficial for human decidualization.

Environmental exposure to cadmium (Cd) contributes to a decline in the quality of human semen. Although the testis is sensitive to Cd exposure, the mechanism underlying how cadmium affects the testis remains to be defined. In this study, male mice were treated with intraperitoneal injections of 0, 0.5, 1.5 and 2.5 mg CdCl₂/kg/day for 10 days, respectively. Both the testicular weight and the 3β-HSD activity of Leydig cells were significantly reduced with the administration of 2.5 mg CdCl₂/kg/day. The height of endothelial cells in the interstitial blood vessels significantly increased with the use of 2.5 mg CdCl₂/kg/day compared with the control. Western blot data showed that the protein levels of CD31, αSMA, caveolin and Ng2 increased with cadmium exposure, and this increase was particularly significant with the administration of 2.5 mg CdCl₂/kg/day. CD31, αSMA, caveolin and Ng2 are related to angiogenesis. Based on our data, cadmium exposure may stimulate the proliferation of the mural cells and endothelial cells of blood vessels, which may lead to abnormal function of the testis.