Scientific studies on infertility in laboratory mice have shown that the absence of a certain transcription factor — p73 — leads to infertility in both male and female mice. In females, defective eggs are produced but the association between p73 and male infertility remained a mystery until recently. A new study indicates that the problem is a sperm support system that is in disarray.
Ute Moll led a team of researchers from Germany's University of Göttingen and Stony Brook University in New York. The researchers used male mice known to be p73 deficient.
Sperm production begins in multilayered tissue called epithelium that lines the seminiferous tubules of the testes. Developing sperm are nurtured along the way to maturity by Sertoli cells, which are described as "nurse" cells.
The Sertoli cells line the epithelium and tightly envelop sperm cells at every stage of development in pouch-like structures within the seminiferous tubules. When the testes of healthy mice are viewed with a microscope, the Sertoli cells are long, somewhat cylindrically shaped cells that line up side by side, resembling dominoes placed on end in an orderly row. The Sertoli cells are attached to the epithelium at one end and to the sperm-filled nursing pouch at the other end toward the middle of the tubule.
As sperm matures, the Sertoli cells divide the sperm cells according to stage of development and guide healthy, mature sperm cells away from the epithelium and toward the tubule surface, from where they will be released during ejaculation.
The Moll research team discovered that, when p73 is lacking, the Sertoli cells do not align properly. The microscopic view looks more like the row of dominoes after they've been toppled over. Without the guidance of the well-aligned nurse cells, sperm detaches from the epithelial wall prematurely and dies.
In addition, the sperm cells cannot stick to the Sertoli cells when p73 is deficient, a condition that leaves them vulnerable to toxins and circulating immune cells. In healthy testes, the Sertoli cells provide a blood-testis barrier that protects developing sperm cells from potential threats. The absence of p73 alters gene expression of proteins that regulate the adhesion between sperm and Sertoli cell.
Now that the issue of cell adhesion in infertile male mice has been discovered, Moll hopes to expand the study to include humans. If the lack of p73 in humans affects sperm development the way it does in mice, treatment options might someday be developed that can overcome this form of male infertility.
Source: Moll, Ute M, et al. "TAp73 is essential for germ cell adhesion and maturation in testis." JCB. The Rockefeller University Press. Mar 24, 2014. Web. Apr 6, 2014.