Abstract
The dynamic process of spermatogenesis shows little variation between invertebrate models such as Drosophila, and vertebrate models such as mice and rats. In each case, germ stem cells undergo mitotic division to proliferate and then continue, via meiosis, through various stages of elongation and individualization from spermatogonia to spermatid to finally to form mature sperm. Mature sperm are then stored in the seminal vesicles for fertilization. Errors in any of these stages can lead to male infertility. Here, we identify that Drosophila Pif1A acts as a key regulator for sperm individualization. Loss of Pif1A leads to male sterility associated with irregular individualization complex and empty seminal vesicles without mature sperm. Pif1A is highly expressed in the testes of mated male adult flies and the Pif1A protein is expressed at a higher level in male than in female flies. Pif1A is homologous to mammalian coiled-coil domain-containing protein 157 (CCDC157), which is also enriched in the testes of humans and mice. Human CCDC157, with unknown function, was identified to be downregulated in men with idiopathic non-obstructive azoospermia (NOA). We map the function of Drosophila Pif1A during spermatogenesis, showing that Pif1A is essential for spermatide individualization and involved in the regulation of the lipid metabolism genes. Our findings might be applicable for studying the function of CCDC157 in spermatogenesis and other aspects of human male fertility.
Highlights
Spermatogenesis is a highly conserved process, not differing appreciably between any animal model, from Drosophila in insects to mice and rats in mammals[1]
We map the function of PFTAIRE interacting factor 1A (Pif1A) during Drosophila spermatogenesis, which might be informative for human coiled-coil domain-containing protein 157 (CCDC157)
Fertility test showed that WT females crossed with Pif1A1 or Pif1A1/DF males laid similar number of eggs as did those crossed with the WT males (Table S1), but the percentage of hatched embryos derived from Pif1A mutant males was zero (Fig. 1d)
Summary
Spermatogenesis is a highly conserved process, not differing appreciably between any animal model, from Drosophila in insects to mice and rats in mammals[1]. The combination of various genetic techniques applied to Drosophila, such as CRISPR/Cas[910] and the Gal4/ UAS transgenic system[11], have enabled the convenient mapping and prediction of functional genes which facilitate, for example, the identification of genes that might cause infertility due to deficiencies in a specific developmental stages or in certain type of cells. To gain insight into the molecular basis for male sterility, we made use of CRISPR/Cas[9] to produce mutations of the genes shown to be highly expressed in Drosophila testis. CCDC157 has been observed as highly expressed in the testes of humans and mice, and to be downregulated in men with idiopathic nonobstructive azoospermia (NOA)[13,14]. We map the function of Pif1A during Drosophila spermatogenesis, which might be informative for human CCDC157
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