Pubertal down-regulation of Tetraspanin 8 in testicular Sertoli cells is crucial for male fertility.
Abstract
The alarming decline in sperm count has become a global concern in the recent decades. The division and differentiation of male germ cells (Gc) into sperm are governed by Sertoli cells (Sc) upon their functional maturation during puberty. However, the roles of genes regulating pubertal maturation of Sc have not been fully determined. We have observed that Tetraspanin 8 (Tspan8) is down-regulated in Sc during puberty in rats. However, there has been no in vivo evidence for a causal link between the down-regulation of Tspan8 expression and the onset of spermatogenesis as yet. To investigate this, we generated a novel transgenic (Tg) rat, in which the natural down-regulation of Tspan8 was prevented specifically in Sc from puberty up to adulthood. Adult Tg male rats showed around 98% reduction in sperm count despite having a similar level of serum testosterone (T) as the controls. Functional maturation of Sc was impaired as indicated by elevated levels of Amh and low levels of Kitlg and Claudin11 transcripts. The integrity of the blood testis barrier was compromised due to poor expression of Gja1 and Gc apoptosis was discernible. This effect was due to a significant rise in both Mmp7 and phospho P38 MAPK in Tg rat testis. Taken tog...Continue Reading
References
USF1/2 transcription factor DNA-binding activity is induced during rat Sertoli cell differentiation.
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Apoptosis
Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis