Primary cilia abnormalities participate in the occurrence of spontaneous abortion through TGF-ß/SMAD2/3 signaling pathway.

Spontaneous abortion is the most common complication in early pregnancy, the exact etiology of most cases cannot be determined. Emerging studies suggest that mutations in ciliary genes may be associated with progression of pregnancy loss. However, the involvement of primary cilia on spontaneous abortion and the underlying molecular mechanisms remains poorly understood. We observed the number and length of primary cilia were significantly decreased in decidua of spontaneous abortion in human and lipopolysaccharide (LPS)-induced abortion mice model, accompanied with increased expression of proinflammatory cytokines interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α. The length of primary cilia in human endometrial stromal cell (hESC) was significantly shortened after TNF-α treatment. Knocking down intraflagellar transport 88 (IFT88), involved in cilia formation and maintenance, promoted the expression of TNF-α. There was a reverse regulatory relationship between cilia shortening and TNF-α expression. Further research found that shortened cilia impair decidualization in hESC through transforming growth factor (TGF)-ß/SMAD2/3 signaling. Primary cilia were impaired in decidua tissue of spontaneous abortion, which might be mainly caused by inflammatory injury. Primary cilia abnormalities resulted in dysregulation of TGF-ß/SMAD2/3 signaling transduction and decidualization impairment, which led to spontaneous abortion.

Oxidative damage contributes to bisphenol S-induced development block at 2-cell stage preimplantation embryos in mice through inhibiting of embryonic genome activation.

Although bisphenol S (BPS), as a bisphenol A (BPA) substitute, has been widely used in the commodity, it is embryotoxic in recent experiments. Nowadays, it remains unclear how BPS affects preimplantation embryos. Here, my team investigated the effects of BPS on preimplantation embryos and the possible molecular mechanisms in mice. The results showed that 10-6 mol/L BPS exposure delayed the blastocysts stage, and exposure to 10-4 mol/L BPS induced 2-cell block in mice preimplantation embryos. A significant increase in reactive oxygen species (ROS) level and antioxidant enzyme genes Sod1, Gpx1, Gpx6, and Prdx2 expression were shown, but the level of apoptosis was normal in 2-cell blocked embryos. Further experiments demonstrated that embryonic genome activation (EGA) specific genes Hsp70.1 and Hsc70 were significantly decreased, which implied that ROS and EGA activation have the potential to block 2-cell development. Antioxidant enzymes, including superoxide dismutase (SOD), coenzyme Q10 (CoQ10), and folic acid (FA) were used to further explore the roles of ROS and EGA in 2-cell block. Only 1200 U/mL SOD was found to alleviate the phenomenon of 2-cell block, reduce oxidative damage, and restore the expression of EGA-specific genes Hsp70.1 and Hsc70. Conclusively, this study demonstrates for the first time that BPS can induce 2-cell block, which is mainly mediated by ROS aggregation and results in the failure of EGA activation.