Cutting-edge studies of the blood–testis barrier promise to help the Council develop novel male contraceptives.
The blood–testis barrier is a physical barrier separating the testes from the bloodstream. The barrier can be breached, however, by certain toxicants, such as PFOS (perfluorooctane sulfonate) and cadmium, that can cause male infertility. In addition, the barrier is crossed regularly by mature sperm cells during the final stage of spermatogenesis.
A better understanding of how cells cross this barrier could inform the development of novel male contraceptives, while also providing insights into the causes of unwanted male infertility.
The Council has published important findings in this field over the past decade that provide a solid basis for exploring the blood–testis barrier as a means of disrupting spermatogenesis. Unlike most blood–tissue barriers, the blood–testis barrier has been found to be made up of specialized, extremely tight junctions between Sertoli cells. The Council has identified a protein, focal adhesion kinase (FAK), that is the key regulator of the barrier’s opening and closing.
Further, the Council has discovered a peptide that regulates the expression of FAK, thereby compromising the integrity and function of the blood–testis barrier. Council researchers have produced this peptide in the lab and found that the administration of large quantities to rats causes the release of all sperm cells—mature and immature alike.
Additionally, recent studies from the laboratory have discovered there are two additional regulatory axes that modulate BTB remodeling to support the transport of preleptotene spermatocytes across the blood-testis barrier to support spermatogenesis. These axes are found between the blood-testis barrier and the basement membrane, involving fragments of collagen-α3 chain and also laminin-α2 chain, both are constituent components of the basement membrane. However, during spermatogenesis, these collagen and laminin chains are broken down to release the biologically active fragments to induce BTB remodeling to support spermatogenesis. These findings open new windows of opportunity to prepare novel male contraceptives and to better understand the biology of spermatogenesis.
The peptide discovered by the Population Council could potentially be used as a male contraceptive on its own. Additionally, it could serve to hold open the blood–testis barrier to allow more Adjudin to enter the testes, thus boosting Adjudin’s effectiveness at a lower dosage with potentially fewer side effects.