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

Author

Listed:
  • Claudia M. Rival

    (University of Virginia
    University of Virginia
    University of Virginia)

  • Wenhao Xu

    (University of Virginia)

  • Laura S. Shankman

    (University of Virginia
    University of Virginia)

  • Sho Morioka

    (University of Virginia
    University of Virginia)

  • Sanja Arandjelovic

    (University of Virginia
    University of Virginia)

  • Chang Sup Lee

    (University of Virginia
    University of Virginia
    Gyeongsang National University)

  • Karen M. Wheeler

    (University of Virginia)

  • Ryan P. Smith

    (University of Virginia)

  • Lisa B. Haney

    (University of Virginia
    University of Virginia)

  • Brant E. Isakson

    (University of Virginia)

  • Scott Purcell

    (Reproductive Medicine and Surgery Center of Virginia)

  • Jeffrey J. Lysiak

    (University of Virginia
    University of Virginia)

  • Kodi S. Ravichandran

    (University of Virginia
    University of Virginia
    Department of Biomedical Molecular Biology, Ghent University, and the UGent-VIB Center for Inflammation Research)

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.

Suggested Citation

  • 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. L, 2019. "Phosphatidylserine on viable sperm and phagocytic machinery in oocytes regulate mammalian fertilization," Nature Communications, Nature, vol. 10(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12406-z
    DOI: 10.1038/s41467-019-12406-z
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