Homeobox genes and male reproductive development

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Abstract
Purpose: Homeobox genes encode transcription factors that dictate developmental events in philogenetically diverse organisms. In comparison to what is known about their role in embryogenesis, we know very little concerning homeobox gene function in neonates or adults. In this communication, we review studies that address the possible role of homebox genes in male reproductive development, a system active in neonate and adult animals. Methods: Studies have shown that many homeobox genes are expressed in germ cells of the testis, while less is known about the identity of homeobox genes expressed in somatic cells of the testis or epididymis. Hox homeobox genes display a pattern of expression in testis that is dependent on their paralogous and orthologous position within the Hox gene chromosome clusters. Other homeobox genes are expressed in the male reproductive system, including many POU and Prd/Pax homeobox gene family members. More recently, it has been shown that the orphan homeobox gene, Pem, originally isolated by subtraction hybridization on the basis of its differential expression in tumor cell lines, is selectively expressed in reproductive tissue. Alternatively spliced Pem transcripts accumulate in testis and epididymis that differ from those expressed in tumors and placenta. Pem transcripts accumulate postnatally in the epididymis in a developmentally regulated manner. Conclusions: The highly regulated pattern of expression exhibited by many homeobox genes in the male reproductive system suggests that homeobox transcription factors may dictate developmental events in this system. However, future studies are needed to determine the specific functional roles of homeobox genes in male reproductive development and spermatogenesis.