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 together, we demonstrated that the natural down-regulation of Tspan8 in Sc during puberty is a prerequisite for establishing male fertility. This study divulges one of the aetiologies of certain forms of idiopathic male infertility where somatic cell defect, but not hormonal deficiency, is responsible for impaired spermatogenesis.

中文翻译：

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睾丸支持细胞中 Tetraspanin 8 的青春期下调对男性生育能力至关重要。

近几十年来，精子数量惊人的下降已成为全球关注的问题。雄性生殖细胞 (Gc) 向精子的分裂和分化由支持细胞 (Sc) 在青春期功能成熟时控制。然而，调节 Sc 青春期成熟的基因的作用尚未完全确定。我们已经观察到 Tetraspanin 8 ( Tspan8 ) 在大鼠青春期期间在 Sc 中下调。然而，目前还没有体内证据表明 Tspan8 表达的下调与精子发生的发生之间存在因果关系。为了研究这一点，我们生成了一种新型转基因 (Tg) 大鼠，其中Tspan8的自然下调Sc 从青春期到成年期都被特别阻止。尽管血清睾酮 (T) 水平与对照组相似，但成年 Tg 雄性大鼠的精子数量减少了约 98%。正如Amh水平升高和Kitlg和 Claudin11 转录物水平低所表明的那样，Sc 的功能成熟受到损害。由于 Gja1 和 Gc 细胞凋亡的表达不佳，血液睾丸屏障的完整性受到损害。这种影响是由于Mmp7和磷酸 P ³⁸的显着增加Tg大鼠睾丸中的MAPK。总之，我们证明了青春期 Sc 中 Tspan8 的自然下调是建立男性生育能力的先决条件。这项研究揭示了某些形式的特发性男性不育症的病因之一，其中体细胞缺陷而非激素缺乏是导致精子发生受损的原因。