| Abstract |
In many forms of sexual reproduction, only the most robust spermatozoa, which overcome multiple physiological challenges, reach the oocyte. However, the exact mechanisms of gamete recognition and fusion are unknown. In the present study, we demonstrated that with the onset of gamete recognition, oocyte microvilli form lamellipodium-like structures, activate actin polymerization, and subsequently engulf spermatozoa to initiate gamete fusion. Gamete fusion occurred via a phagocytosis-like process we termed "sperm engulfment activated by IZUMO1-JUNO linkage and gamete fusion-related factors" (SEAL). Gamete adhesion was strictly regulated by binding of sperm IZUMO1 to oocyte JUNO, while SEAL was primarily mediated by sperm DCST1/2, SPACA6, TMEM95, FIMP, and TMEM81, the essential factors for gamete fusion. Interestingly, JUNO was almost depleted from oocyte surfaces in the region where SEAL enveloped spermatozoa by microvilli without actin polymerization. SEAL formation was recapitulated using JUNO-expressing K562 lymphocytic cells rather than oocytes. Together, these findings suggest that dynamic rearrangement of membrane components facilitates SEAL prior to successful fertilization.
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