Acrosome is a specialized organelle that covers the anterior part of the sperm nucleus and plays an essential role in the process of fertilization. The molecular mechanism underlying the biogenesis of this lysosome-related organelle (LRO) is still largely unknown. Here we show that germ cell specific Atg7 knockout mice were infertile due to defect in acrosome biogenesis and displayed a phenotype of human globozoospermia, and this reproductive defect was successfully rescued by intracytoplasmic sperm injections. Furthermore, we found that the depeletion of Atg7 in germ cells did not affect the early stages development of germ cells until round spermatids, but at later stages of spermatogenesis, the proacrosomal vesicles failed to fuse into a single acrosomal vesicle at Golgi-phase and finally resulted in irregular or nearly round-headed spermatozoa. We revealed that autophagic flux was disrupted in Atg7 depleted germ cells, and finally led to the failure of LC3 conjugation to Golgi apparatus-derived vesicles. In addition, we found that Atg7 partially regulates another globozoospermia-related protein PDZ- and coiled-coil motif-containing protein (GOPC), during acrosome biogenesis. Finally, we demonstrated that the injection of either autophagy or lysosome inhibitors into testis resulted in a similar phenotype to germ cell specific Atg7 knockout mice. Altogether, our results uncover a new role for Atg7 in the biogenesis of acrosome, and we provide evidences to support acrosomes autolysosome origination hypothesis.
02 Sep 2014 - 04 Sep 2014