Male infertility is an under-appreciated, yet highly relevant medical issue, affecting approximately 7% of men, in which most cases the aetiology is unknown. However, it is estimated that at least 50% of cases are contributed to by genetic abnormalities. With the advent of Assisted Reproductive Technologies, such as in-vitro fertilization, genetic mutations causing infertility are more likely to be passed on to future generations. Zinc is essential for the functioning of the male reproductive system, with studies showing a correlation between seminal plasma zinc and male infertility. However, this has not been investigated from a genetic standpoint.
In order to explore the relevance of Zinc metabolism to male fertility, we assembled a panel of Drosophila melanogaster lines containing genetic modifications in Zrt-, Irt-like Protein (ZIP) and Zinc Transporter (ZnT) genes, involved in zinc transport across cellular membranes. These fly lines were used to target ZIP and ZNT over expression and knockdown to either the somatic or the germline cell compartments of the developing male gonad, and male fertility was tested.
Preliminary data has shown that in the germline, manipulation of ZnT86D and ZIP71B caused partial or complete infertility. In the gonadal somatic cells, over-expression or knockdown of ZnT49B, fear-of-intimacy, catsup and ZIP89B also demonstrated sub-fertility or sterility. We are currently exploring the effect of these transgenes on the morphology of the larval gonad and adult testis.
This research demonstrates that multiple Zinc transporter genes are required for male fertility and that they function in both germline and somatic cells of the testis and further indicates the importance of Zinc and its transport in male fertility. Future work will aim to mutate the mouse orthologues of the genes of interest, in order to determine whether these infertility-causing mutations are conserved in a mammalian model.