Population Council Research that makes a difference

Spermatogenesis is an intriguing but complicated biological process. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli–germ cell communication, and junction dynamics. As part of spermatogenesis, developing germ cells must translocate across the blood–testis barrier (BTB) as well as traverse the seminiferous epithelium during their development. Without this timely movement of developing germ cells across the BTB, spermatogenesis will be disrupted, leading to infertility. While the concept of the BTB has been known for more than a century and its significance to spermatogenesis discerned for more than five decades, its regulation has remained largely unknown.

The tight junctions, anchoring junctions (known as basal ectoplasmic specialization), and desmosome-gap junctions between Sertoli cells, which make up the BTB, play a major role in keeping the developing spermatozoa and immune system separate. During spermatogenesis, such as meiosis, many sperm-specific antigens, which are highly immunogenic to the host immune system, express themselves transiently. To avoid the production of antisperm antibodies, autoantigenic germ cells must be sequestered from the immune system by the BTB. In addition, other immunosuppressive mechanisms are necessary to suppress antigenic responses behind the BTB, such as via secretions from Sertoli cells (e.g., growth factors, bioactive peptides, and lipids).

The Council has published important findings in this field over the last decade that provide a solid basis for this expanded line of research. Council researchers have used in vitro and in vivo models for studying tight junction dynamics and their regulation, which has revealed many targets that can be tackled to compromise the BTB function and to perturb spermatogenesis, forming the basis of new approaches for male contraceptive development. The Council is investigating the role of focal adhesion kinase (FAK), specifically, in regulating the timely "opening" and "closing" of the BTB.