CONTEXT: Preeclampsia is a major cause of maternal mortality and morbidity worldwide. Although there has been great progress in the understanding of preeclampsia, the exact cause for the disease development is still unclear. Recently, it showed that genetic deletion of ELABELA (ELA, also known as apela) could induce preeclampsia-like symptoms in mouse. However, the role of ELA in the disease development of preeclampsia remains elusive. OBJECTIVE: Measure the changes of ELA levels in maternal serum, urine and placenta from preeclamptic pregnancy and healthy pregnancy and evaluate the correlation between ELA level and the occurrence of preeclampsia. Meantime, investigate the effect of ELA on the migration and proliferation of human trophoblast cells. RESULTS: ELA level is significantly decreased in late-onset preeclampsia pregnancies compare to normal pregnancy. The mRNA and protein expression of ELA and apelin receptor (APLNR, or APJ) in late-onset preeclampsia placental tissues are also decreased. Furthermore, our in vitro study showed that addition of ELA significantly increased the invasion ability and proliferation of trophoblast cells, which was inhibited by the APJ specific antagonist-ML221. CONCLUSION: Our study identified ELA is significantly decreased in late-onset preeclampsia and thus it might play an important role in the pathogenesis of late-onset preeclampsia.

Sperm-oocyte membrane fusion is necessary for mammalian fertilization. The factors that determine the fusion of sperm with oocytes are largely unknown. So far, spermatozoon factor IZUMO1 and the IZUMO1 counter-receptor JUNO on the oocyte membrane has been identified as a protein requiring fusion. Some sperm membrane proteins such as FIMP, SPACA6 and TEME95, have been proved not to directly regulate fusion, but their knockout will affect the fusion process of sperm and oocytes. Here, we identified a novel gene C11orf94 encoding a testicular-specific small transmembrane protein that emerges in vertebrates likely acquired via horizontal gene transfer from bacteria and plays an indispensable role in sperm-oocyte binding. We demonstrated that the deletion of C11orf94 dramatically decreased male fertility in mice. Sperm from C11orf94-deficient mice could pass through the zona pellucida, but failed to bind to the oocyte membrane, thus accumulating in the perivitelline space. In consistence, when the sperm of C11orf94-deficient mice were microinjected into the oocyte cytoplasm, fertilized oocytes were obtained and developed normally to blastocysts. Proteomics analysis revealed that C11orf94 influenced the expression of multiple gene products known to be indispensable for sperm-oocyte binding and fusion, including IZUMO1, EQTN and CRISP1. Thus, our study indicated that C11ORF94 is a vertebrate- and testis-specific small transmembrane protein that plays a critical role in sperm binding to the oolemma.