Rhox5, also known as Pem, is a homeobox transcription factor encoded by the founding member of the Rhox gene cluster on the X chromosome. It is crucial for male reproduction, as it promotes germ-cell survival and sperm motility. Rhox5 functions in androgen-dependent pathways, being expressed in Sertoli cells of the testes and the caput region of the epididymis. Its regulation and function have significant implications for understanding spermatogenesis and male fertility [1].

Targeted deletion of Rhox5 in mice leads to male subfertility, marked by increased germ-cell apoptosis, decreased sperm count, and reduced sperm motility [1]. Microarray analyses of Rhox5-null mice identified a variety of genes regulated by Rhox5. For example, it negatively regulates Unc5c, a pro-apoptotic molecule, which supports the model that Rhox5 promotes germ-cell survival by down-regulating Unc5c [1,2]. Also, in the rodent epididymis, Rhox5 regulates the region-specific expression of its paralogs, with a targeted mutation of Rhox5 greatly diminishing the expression of several other family members in the caput region [3].

In conclusion, Rhox5 is essential for male reproductive processes, especially spermatogenesis and sperm function. The gene knockout mouse models have been instrumental in revealing its role in promoting germ-cell survival and regulating the expression of other genes involved in male reproduction. Understanding Rhox5 provides insights into the mechanisms underlying male subfertility and potentially offers new targets for therapeutic intervention in fertility-related diseases [1,2,3].

References:

1. Shanker, S, Hu, Z, Wilkinson, M F. 2008. Epigenetic regulation and downstream targets of the Rhox5 homeobox gene. In International journal of andrology, 31, 462-70. doi:10.1111/j.1365-2605.2008.00904.x. https://pubmed.ncbi.nlm.nih.gov/18637153/

2. Hu, Zhiying, Shanker, Sreenath, MacLean, James A, Ackerman, Susan L, Wilkinson, Miles F. 2007. The RHOX5 homeodomain protein mediates transcriptional repression of the netrin-1 receptor gene Unc5c. In The Journal of biological chemistry, 283, 3866-76. doi:. https://pubmed.ncbi.nlm.nih.gov/18077458/

3. MacLean, James A, Hayashi, Kanako, Turner, Terry T, Wilkinson, Miles F. 2012. The Rhox5 homeobox gene regulates the region-specific expression of its paralogs in the rodent epididymis. In Biology of reproduction, 86, 189. doi:10.1095/biolreprod.112.099184. https://pubmed.ncbi.nlm.nih.gov/22423045/

4. MacLean, James A, Wilkinson, Miles F. 2010. The Rhox genes. In Reproduction (Cambridge, England), 140, 195-213. doi:10.1530/REP-10-0100. https://pubmed.ncbi.nlm.nih.gov/20430877/

5. Hu, Zhiying, MacLean, James A, Bhardwaj, Anjana, Wilkinson, Miles F. . Regulation and function of the Rhox5 homeobox gene. In Annals of the New York Academy of Sciences, 1120, 72-83. doi:10.1196/annals.1411.011. https://pubmed.ncbi.nlm.nih.gov/18184911/