Phosphatidylserine on viable sperm and phagocytic machinery in oocytes regulate mammalian fertilization

Claudia M. Rival, Wenhao Xu, Laura S. Shankman, Sho Morioka, Sanja Arandjelovic, Chang Sup Lee, Karen M. Wheeler, Ryan P. Smith, Lisa B. Haney, Brant E. Isakson, Scott Purcell, Jeffrey J. Lysiak () and Kodi S. Ravichandran ()
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Claudia M. Rival: University of Virginia
Wenhao Xu: University of Virginia
Laura S. Shankman: University of Virginia
Sho Morioka: University of Virginia
Sanja Arandjelovic: University of Virginia
Chang Sup Lee: University of Virginia
Karen M. Wheeler: University of Virginia
Ryan P. Smith: University of Virginia
Lisa B. Haney: University of Virginia
Brant E. Isakson: University of Virginia
Scott Purcell: Reproductive Medicine and Surgery Center of Virginia
Jeffrey J. Lysiak: University of Virginia
Kodi S. Ravichandran: University of Virginia

Nature Communications, 2019, vol. 10, issue 1, 1-13

Abstract: Abstract Fertilization is essential for species survival. Although Izumo1 and Juno are critical for initial interaction between gametes, additional molecules necessary for sperm:egg fusion on both the sperm and the oocyte remain to be defined. Here, we show that phosphatidylserine (PtdSer) is exposed on the head region of viable and motile sperm, with PtdSer exposure progressively increasing during sperm transit through the epididymis. Functionally, masking phosphatidylserine on sperm via three different approaches inhibits fertilization. On the oocyte, phosphatidylserine recognition receptors BAI1, CD36, Tim-4, and Mer-TK contribute to fertilization. Further, oocytes lacking the cytoplasmic ELMO1, or functional disruption of RAC1 (both of which signal downstream of BAI1/BAI3), also affect sperm entry into oocytes. Intriguingly, mammalian sperm could fuse with skeletal myoblasts, requiring PtdSer on sperm and BAI1/3, ELMO2, RAC1 in myoblasts. Collectively, these data identify phosphatidylserine on viable sperm and PtdSer recognition receptors on oocytes as key players in sperm:egg fusion.

Date: 2019
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DOI: 10.1038/s41467-019-12406-z

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