Lack of Acrosome Formation in Hrb-Deficient Mice

Abstract

The sperm acrosome is essential for sperm-egg fusion and is often defective in men with nonobstructive infertility. Here we report that male mice with a null mutation in Hrb are infertile and display round-headed spermatozoa that lack an acrosome. In wild-type spermatids, Hrb is associated with the cytosolic surface of proacrosomic transport vesicles that fuse to create a single large acrosomic vesicle at step 3 of spermiogenesis. Although proacrosomic vesicles form in spermatids that lack Hrb, the vesicles are unable to fuse, blocking acrosome development at step 2. We conclude that Hrb is required for docking and/or fusion of proacrosomic vesicles during acrosome biogenesis.

Atg7 is required for acrosome biogenesis during spermatogenesis in mice

“…Ten genes have been found to be associated with globozoospermia, including Csnk2a2 [30], Hrb [3], Gopc [19], Gba2 [31], Zpbp1 [32], Pick1 [11], Vps54 [27], Hsp90b1 [33], Spaca1 [34] and Dpy19l2 [35]. Among 25%.…”

“…Bar indicates 1 µm. them, Hrb [3], GOPC [19], PICK1 [11] and SPACA1 [34] control Golgi-derived vesicle fusion, which is necessary for acrosome formation. We found that GOPC partially colocalized with sp56 on the acrosome during spermatogenesis but failed to be recruited to the acrosome in Atg7-deficient spermatids, suggesting that Atg7 partially regulates GOPC and that both of them are involved in Golgi-derived vesicle fusion and transport to the preacrosome.…”

“…During the subsequent acrosome and maturation phases, the acrosome stops growing but changes its morphology. After a series of highly complex morphological changes, such as spermatid elongation and cytoplasm removal, spermiogenesis ends with the production of mature sperm [2,3]. Although the morphogenetic changes during acrosome biogenesis have been well-documented, the precise molecular mechanism underlying this process is still largely unknown.…”

“…The acrosome is regarded as a modified lysosome [4] or a novel lysosome-related organelle (LRO) [2,3]. However, the lysosome in mammalian cells is smaller than the acrosome.…”

Human male infertility and its genetic causes

“…A common region of homozygosity was identified that harbored the gene that encodes aurora kinase C ( AURKC ) at 19q13 in all of these men. It is known to be highly expressed in the testis34, 35 and is putatively involved in cytokinesis, mitosis, and meiosis 36, 37. A single nucleotide deletion (ca 144delC) was detected in the AURKC coding region in all of the patients who were analyzed 33.…”