PT  - JOURNAL ARTICLE
AU  - Sarah Herberg
AU  - Yoshitaka Fujihara
AU  - Andreas Blaha
AU  - Karin Panser
AU  - Kiyonori Kobayashi
AU  - Tamara Larasati
AU  - Maria Novatchkova
AU  - H. Christian Theußl
AU  - Olga Olszanska
AU  - Masahito Ikawa
AU  - Andrea Pauli
TI  - The sperm protein SPACA4 is required for efficient fertilization in mice
AID  - 10.1101/2021.05.02.442348
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.05.02.442348
4099  - http://biorxiv.org/content/early/2021/05/04/2021.05.02.442348.short
4100  - http://biorxiv.org/content/early/2021/05/04/2021.05.02.442348.full
AB  - Fertilization is the fundamental process that initiates the development of a new individual in all sexually reproducing species. Despite its importance, our understanding of the molecular players that govern mammalian sperm-egg interaction is incomplete, partly because many of the essential factors found in non-mammalian species do not have obvious mammalian homologs. We have recently identified the Ly6/uPAR protein Bouncer as a new, essential fertilization factor in zebrafish (Herberg et al., 2018). Here, we show that Bouncer’s homolog in mammals, SPACA4, is also required for efficient fertilization in mice. In contrast to fish, where Bouncer is expressed specifically in the egg, SPACA4 is expressed exclusively in the sperm. Male knockout mice are severely sub-fertile, and sperm lacking SPACA4 fail to fertilize wild-type eggs in vitro. Interestingly, removal of the zona pellucida rescues the fertilization defect of Spaca4-deficient sperm in vitro, indicating that SPACA4 is not required for the interaction of sperm and the oolemma but rather of sperm and zona pellucida. Our work identifies SPACA4 as an important sperm protein necessary for zona pellucida penetration during mammalian fertilization.Competing Interest StatementThe authors have declared no competing interest.