The role of androgen in regulating the expression of male phenotype, and the onset and maintenance of spermatogenesis has been well established through several studies. However, there persists uncertainty regarding the cell types mediating the androgen regulation of spermatogenesis. A recent study published in The FASEB Journal reports that androgen exerts its action via peritubular myoid (PTM) cells in order to regulate the normal spermatogenesis and male fertility. The study, claiming to provide the first direct evidence on the significance of stromal-epithelial interactions driven by androgen, holds great implications in developing strategies for male contraception, as well as treatment of male infertility.
Michelle Welsh, from the Medical Research Council Human Reproductive Sciences Unit, The Queen’s Medical Research Institute, Edinburgh, UK, and coworkers, conducted the study on peritubular myoid cell-specific androgen receptor-knockout (PTM-ARKO) mice. Although the researchers observed a gross reproductive development in the animal models, the PTM-ARKO male mice were infertile and azoospermic. Further analysis of the affected subjects showed a reduction in testicular weight beyond puberty, and an 86% decrease in the number of germ cells by adulthood when compared to wild-type littermates. The study ruled out the effect of decreased testosterone, luteinizing hormone, or follicle-stimulating hormone levels in contributing to the above changes.
The decline in the expression of androgen-dependent Sertoli cell (SC) genes, as well as the secretion of seminiferous tubule fluid indicated impaired functioning of SC in PTM-ARKO males. Based on the study findings, the researchers concluded that the action of androgen through PTM cells is crucial for the normal testicular functioning, spermatogenesis, and fertility.
PTM cells, the mesenchymal cells forming the outer lining of the seminiferous tubules, has been reported to play a substantial role in male fertility. Expressing a high percentage of androgen receptors (AR) from fetal life through adulthood, the cells regulate germ cell development based on androgen signaling. The peritubular myoid cells are also found to be significant in eliciting peristalsis-like movements and impulses in the tubules to facilitate the transport of sperm and fluid through the tubular lumen into the epididymis.
A previous study conducted by Zhang et al (Proceedings of the National Academy of Sciences, 2006) also proposed that the androgen receptors on the PTM cells are important in maintaining normal Sertoli cell function and peritubular myoid cell contractility.
Though substantial advancements have been made in the development and usage of various contraceptive options, almost half of the pregnancies are still considered as unwanted/unplanned. The discovery of newer methods for contraception, including delivery of oral and injectable agents, is predicted to revolutionize fertility management strategies. Further research and trials to clearly elucidate the androgen-based signaling pathways that regulate spermatogenesis will aid in expanding such possibilities.
References
1. Welsh M, Saunders PT, Atanassova N, Sharpe RM, Smith LB. Androgen action via testicular peritubular myoid cells is essential for male fertility. FASEB J. 2009 Dec;23(12):4218-30.
2. Zhang C, Yeh S, Chen Y-T. Oligozoospermia with normal fertility in male mice lacking the androgen receptor in testis peritubular myoid cells. Proc Natl Acad Sci U S A. 2006 Nov 21;103(47):17718–17723.
