Thepot, D. | Search bioRxiv

bioRxiv2023

Sixteen oogenesin genes are dispensable for fertilityWhat is the significance of the dispensability of genes expressed in germ-cell?

Gene knockout experiments have shown that many genes are dispensable for a given biological function. The Oogenesin/Pramel family contains almost 85 paralogs, about thirty of which are specific to female (as well as male for some of them) germ cells. In this paper, we show that the deletion of a block of around 1Mb containing sixteen paralogous genes of the Oogenesin/Pramel family specific to germ cells, including Oogenesin-2, -3 and -4, has no consequences on fertility or prolificacy in mouse both sexes. The dispensability of these genes is probably due to the compensation by the other germ-cell specific paralogs.

molecular biology↗

bioRxiv2023

DMRT1 is a Testis Determining Gene in Rabbits and is Also Essential for Female Fertility

DMRT1 is the testis-determining factor in several species of vertebrates, but its involvement in mammalian testes differentiation, where SRY is the testis-determining gene, remains ambiguous. So far, DMRT1 loss of function has been described in two mammalian species and induces different phenotypes: disorders of sex development (46, XY DSD) in men and male infertility in mice. We thus abolished DMRT1 expression by CRISPR/Cas9 in a third species of mammal, the rabbit. First, we observed that gonads from XY DMRT1-/- rabbit fetuses differentiated like ovaries, highlighting that DMRT1 is involved in testis determination. In addition to SRY, DMRT1 is required in the supporting cells to increase the expression of the SOX9 gene, which heads the testicular genetic cascade. Second, we highlighted another function of DMRT1 in the germline since XX and XY DMRT1-/- ovaries did not undergo meiosis and folliculogenesis. XX DMRT1-/- adult females were sterile, showing that DMRT1 is also crucial for female fertility. To conclude, these phenotypes indicate an evolutionary continuum between non-mammalian vertebrates such as birds and non-rodent mammals. Furthermore, our data support the potential involvement of DMRT1 mutations in different human pathologies, such as 46, XY DSD as well as male and female infertility.

developmental biology↗