![TAF4b deficient mice (right) produce fewer undifferentiated germ cells (green) than mice with the intact gene (left). A scenario that leads to a decreased sustainability of sperm production. [Freiman lab/Brown University]](https://www.genengnews.com/wp-content/uploads/2018/08/87565_web4612143302.jpg "TAF4b deficient mice (right) produce fewer undifferentiated germ cells (green) than mice with the intact gene (left). A scenario that leads to a decreased sustainability of sperm production. [Freiman lab/Brown University]")
Researchers at Brown University have uncovered the molecular mechanisms that lead to the loss of sperm cells, which they believe could have a significant impact on men with a similar loss in fertility.
The Brown scientists discovered a mutation that leads to the lack of function in the gene coding for the TAF4b protein, causing a major deficiency in the number of spermatogonial stem cells (SSCs) at an early embryonic stage in male mice reproductive development. The loss of these stem cells impacts the sustainability of sperm production over the long term.
“What's fascinating about these mice is they can reproduce. Mice can usually reproduce until they are two years old, but these mice can only reproduce until they are four months old,” explained Richard Freiman, Ph.D., assistant professor of medical science at Brown University and senior author of the current study.
The results of this study were published recently in Stem Cells through an article entitled “TAF4b is required for mouse spermatogonial stem cell development”.
TAF4b is a component of the transcription factor complex TFIID, which is required for the maintenance of spermatogenesis in mice. Dr. Freiman’s team was able to examine mice with and without the TAF4b gene to determine its effects on gonadal cell development. In mice with intact TAF4b, germ cell progenitors in male embryos were able to proliferate normally, developing the proper infrastructure for SSCs to develop. Conversely, the loss of TAF4b led to fewer progenitor cells and ultimately less SSCs.
Interestingly, a previous study reported that four Turkish brothers, who carried a mutation in the TAF4b gene, had extremely low sperm counts and that the mutation was in the same region as Dr. Freiman and his team created in the mice.
“The human implications are very exciting,” Dr. Freiman stated. “It is possible that those men, as teenagers, were able to make functional sperm. This is why fundamental knowledge is so important. If we understand the process, we might be able to do something we couldn't do before.”
While the Brown team agrees that more research into these developmental pathways is required, they believe that if the TAF4b mutation functions in humans similarly to what they observed in mice, than detecting the mutation early in adolescence could allow physicians to freeze sperm supplies for patient use later in life.
“Developmental processes that occur in embryogenesis really have a profound effect on the ability of adult organ systems to function properly. This may be an example where a deficit during embryogenesis may preclude the ability of these mice to reproduce as adults,” Dr. Freiman concluded.
