Advance-CTR

Advance RI-CTR Grant Resubmission Awards (Cohort 2)

"Genetics of Male Infertility"

Long-term male fertility is dependent on a highly regulated series of developmental events that begins with primordial germ cell (PGC) specification in early fetal development and ends with the exhaustion of an adult unipotent spermatogonial stem cell (SSC) population during old age.

While there is much known about PGC specification and identity and the postnatal development of SSCs in mice and men, a significant gap in knowledge exists about the molecular nature of the developmental transitions of prospermatogonia (proSPG) that bridge these more well characterized germ cell populations.

The ultimate success of the male germline is built upon by the intricate coordination of precise signaling and gene regulatory pathways that first occur during embryonic development. This study will dissect the TAF4b-dependent transcriptional and epigenetic regulation underlying proper development of embryonic prospermatogonia that give rise to spermatogonia, spermatogonial stem cells and ultimately all differentiated spermatozoa in the adult testis.

Dr. Freiman's study will identify novel genetic pathways and mechanisms by which mouse spermatogonia develop properly. Understanding this intricate genetic regulation will help improve the clinical diagnosis and treatment of infertility in men.