TY - JOUR
T1 - Phosphatidylserine on viable sperm and phagocytic machinery in oocytes regulate mammalian fertilization
AU - Rival, Claudia M.
AU - Xu, Wenhao
AU - Shankman, Laura S.
AU - Morioka, Sho
AU - Arandjelovic, Sanja
AU - Lee, Chang Sup
AU - Wheeler, Karen M.
AU - Smith, Ryan P.
AU - Haney, Lisa B.
AU - Isakson, Brant E.
AU - Purcell, Scott
AU - Lysiak, Jeffrey J.
AU - Ravichandran, Kodi S.
N1 - Funding Information:
We thank members of the Ravichandran laboratory for discussions and critical reading of manuscript; Virginia Rubianes and Sheri VanHoose (Histology Core, UVa) and Pat Pramoonjago (Biorepository and Tissue Research Facility, UVa). We also acknowledge the early discussions on this topic with Dr. John Herr that provided some of the inputs. This work is supported by grants to K.S.R. from the NIGMS (GM064709), the Center for Cell Signaling at the University of Virginia, and the Odysseus I award from the FWO (Belgium). Additional support was provided via the T32HL007284 and a fellowship from the American Cancer Society (L.S.S.). S.M. is supported by grants from the Mishima-Kaiun Memorial Foundation and The Kanae Foundation for the Promotion of Medical Science. This project has also received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation programme (grant agreement No. 835243).
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85072848268&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-12406-z
DO - 10.1038/s41467-019-12406-z
M3 - Article
C2 - 31575859
AN - SCOPUS:85072848268
SN - 2041-1723
VL - 10
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 4456
ER -