Abstract
Male infertility is a major and growing problem and, in most cases, the specific root cause is unknown. Here we show that the transcription factor SOX30 plays a critical role in mouse spermatogenesis. Sox30-null mice are healthy and females are fertile, but males are sterile. In the absence of Sox30 meiosis initiates normally in both sexes but, in males, germ cell development arrests during the post-meiotic round spermatid period. In the mutant testis, acrosome and axoneme development are aberrant, multinucleated germ cells (symplasts) form and round spermatids unable to process beyond step 3 of spermiogenesis. No elongated spermatids nor spermatozoa are produced. Thus, Sox30 represents a rare example of a gene for which loss of function results in a complete arrest of spermatogenesis at the onset of spermiogenesis. Our results suggest that SOX30 mutations may underlie some instances of unexplained non-obstructive azoospermia in humans.
Highlights
Spermatogenesis, the process whereby diploid spermatogonia differentiate into mature haploid spermatozoa, is highly complex and involves many precisely coordinated steps
Our findings demonstrate that the SOX family member SOX30 has an indispensable role in spermatogenesis, in mice
Staining of testis sections with periodic acid-Schiffs reagent (PAS) and further investigation with transmission electron microscopy (TEM) showed that the round spermatids fail to process beyond step 3 of spermiogenesis, a transition characterised by the attachment and flattening of the pro-acrosomal granule around the nucleus and the initiation of spermatid tail growth and attachment[22]
Summary
Spermatogenesis, the process whereby diploid spermatogonia differentiate into mature haploid spermatozoa, is highly complex and involves many precisely coordinated steps. During the post-meiotic developmental phase, known as spermiogenesis, round spermatids undergo a complicated restructuring program that includes compaction of DNA, ejection of cytoplasm and formation of the acrosome and flagellum[1,2]. Members of the SOX (Sry-related High Motility Group (HMG) box) gene family encode transcription factors that are highly conserved and are important for a range of developmental processes, including sex determination, neuronal development and regulation of stem cell pluripotency[9]. We describe the expression pattern of Sox[30] in mouse fetal ovary and pubertal testis demonstrating that, in both sexes, Sox[30] expression begins in germ cells shortly after expression of the pre-meiotic marker, Stra[8]. The clear-cut infertility phenotype we reveal, including a complete lack of elongated spermatids, demonstrates that this protein is essential for male fertility in mice
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