ADAM20 Participates Modestly to Fertilization as Its Absence Leads to In Vitro Hypofertility in Mouse.

A mutation of the ADAM20 gene was described in an infertile patient whose spermatozoa were observed accumulating in the perivitelline space of oocytes. To decipher its role in the fertilization process, we produced a mouse model knock-out (KO) for the Adam20 gene. Surprisingly, Adam20-KO males showed an in vivo fertility similar to their wild-type littermates and had normal sperm counts and morphology. However, they presented a reduced fertility in in vitro fertilization assays. To explore the hypothesis that the two flanking genes Adam25 and Adam39 could compensate the lack of Adam20 given their very high homology, we produced a triple KO deleting these three neighbor genes simultaneously. The phenotype was strictly identical to that of the single gene deletion. Therefore, ADAM20, ADAM25, and ADAM39 are not essential proteins for fertilization in mice but they seem to participate modestly to the process. Adam20-KO males are fertile in vivo but have a reduced fertility in vitro. Males deleted for three neighbor and very homologous genes (Adam20, Adam25, and Adam39) have the same phenotype as the simple Adam20-KO. These genes are dispensable for normal fertility but contribute modestly to fertilization.