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

Nat Commun. 2019 Oct 1;10(1):4456. doi: 10.1038/s41467-019-12406-z.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / metabolism
  • Angiogenic Proteins / metabolism
  • Animals
  • CD36 Antigens / metabolism
  • Cytoskeletal Proteins / metabolism
  • Epididymis
  • Female
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Models, Animal
  • Myoblasts, Skeletal
  • Nerve Tissue Proteins / metabolism
  • Neuropeptides / metabolism
  • Oocytes / metabolism*
  • Phagocytes / metabolism*
  • Phosphatidylserines / genetics
  • Phosphatidylserines / metabolism*
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism
  • Sperm-Ovum Interactions / physiology*
  • Spermatozoa / metabolism*
  • c-Mer Tyrosine Kinase / metabolism
  • rac1 GTP-Binding Protein / metabolism


  • Adaptor Proteins, Signal Transducing
  • Adgrb1 protein, mouse
  • Adgrb3 protein, mouse
  • Angiogenic Proteins
  • CD36 Antigens
  • Cd36 protein, mouse
  • Cytoskeletal Proteins
  • ELMO1 protein, mouse
  • Elmo2 protein, mouse
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Neuropeptides
  • Phosphatidylserines
  • Rac1 protein, mouse
  • Receptors, Cell Surface
  • TIM-4 protein, mouse
  • phosphatidylserine receptor
  • Mertk protein, mouse
  • c-Mer Tyrosine Kinase
  • rac1 GTP-Binding Protein