Sertoli cells (SCs) are presumed to be the center of testis differentiation because they provide both structural support and biological regulation for spermatogenesis. Previous studies suggest that SCs control germ cell (GC) count and Leydig cell (LC) development in mouse testes. However, the regulatory role of SCs on peritubular myoid (PTM) cell fate in fetal testis has not been clearly reported. Here, we employed Amh-Cre; diphtheria toxin fragment A (DTA) mouse model to selectively ablate SCs from embryonic day (E) 14.5. Results found that SC ablation in the fetal stage caused the disruption of testis cords and the massive loss of GCs. Furthermore, the number of α-smooth muscle actin-labeled PTM cells was gradually decreased from E14.5 and almost lost at E18.5 in SC ablation testis. Interestingly, some Ki67 and 3β-HSD double-positive fetal LCs could be observed in Amh-Cre; DTA testes at E16.5 and E18.5. Consistent with this phenomenon, the messenger RNA levels of Hsd3b1, Cyp11a1, Lhr, Star and the protein levels of 3β-HSD and P450Scc were significantly elevated by SC ablation. SC ablation appears to induce ectopic proliferation of fetal LCs although the total LC number appeared reduced. Together, these findings bring us a better understanding of SCs' central role in fetal testis development.

中文翻译：

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使用细胞消融策略探索支持细胞在胎儿睾丸发育中的作用。

睾丸支持细胞（SCs）被认为是睾丸分化的中心，因为它们为精子发生提供结构支持和生物学调控。先前的研究表明，SC可控制小鼠睾丸中的生殖细胞（GC）计数和Leydig细胞（LC）发育。但是，SCs在胎儿睾丸中的肾小管周围肌样（PTM）细胞命运的调控作用尚未明确报道。在这里，我们雇用了Amh-Cre；白喉毒素片段A（DTA）小鼠模型可选择性消融来自胚胎形成天（E）14.5的SC。结果发现，在胎儿期进行SC消融会导致睾丸索的破裂和GC的大量丢失。此外，在SC消融睾丸中，α平滑肌肌动蛋白标记的PTM细胞的数量从E14.5逐渐减少，并在E18.5几乎消失。有趣的是 在Amh-Cre中可以观察到一些Ki67和3β-HSD双阳性胎儿LC。DTA睾丸位于E16.5和E18.5。与此现象一致，SC消融可显着提高Hsd3b1，Cyp11a1，Lhr，Star的信使RNA水平以及3β-HSD和P450Scc的蛋白水平。尽管总LC数似乎减少，但SC消融似乎可诱导胎儿LC的异位增殖。在一起，这些发现使我们更好地了解了SC在胎儿睾丸发育中的核心作用。