Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules

Desert hedgehog (Dhh) gene is required in the mouse testis for formation of adult-type Leydig cells and normal development of peritubular cells and seminiferous tubules
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DOI:
10.1095/biolreprod63.6.1825
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发表时间:
2000-12-01
影响因子:
3.6
通讯作者:
Russell, LD
Russell, LD
中科院分区:
生物学2区
文献类型:
--
作者:
Clark, AM;Garland, KK;Russell, LD

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对缺乏沙漠刺猬(Dhh)基因的成年和青春期前小鼠的睾丸进行了检查,以进一步描述Dhh在精子发生中的作用,因为在以前的报告中,Dhh缺失的雄性小鼠被证明是不育的。Dhh是由支持细胞表达的信号分子。其受体patched(Ptc)先前已定位于Leydig细胞,并且在本文中描述为也定位于管周细胞。观察到小鼠的两种表型:雄性化(7.5%的Dhh缺失雄性)和雌性化(92.5%),两者均显示出异常的管周组织和严重限制的精子发生。成年雌性化动物的睾丸缺乏成年型间质细胞,并在睾丸中显示出大量未分化的成纤维细胞,这些细胞产生丰富的胶原蛋白。通常存在于肌样细胞和支持细胞之间的基底层局灶性缺失。我们推测,异常的基膜有助于其他特征,如外索性腺细胞,非极性支持细胞,和吻合曲细精管。所描述的两种Dhh无效表型具有共同的管周细胞缺陷,这可能表明管周细胞在管状形态发育、间质细胞分化和精子发生的最终支持中的重要作用。
Testes from adult and prepubertal mice lacking the Desert hedgehog (Dhh) gene were examined in order tea describe further the role of Dhh in spermatogenesis because, in a previous report, Dhh-null male mice were shown to be sterile. Dhh is a signaling molecule expressed by Sertoli cells. Its receptor, patched (Ptc), has been previously localized to Leydig cells and is herein described as being localized also to peritubular cells. Two phenotypes of the mice were observed: masculinized (7.5 % of Dhh-null males) and feminized (92.5%), both of which displayed abnormal peritubular tissue and severely restricted spermatogenesis. Testes from adult feminized animals lacked adult-type Leydig cells and displayed numerous undifferentiated fibroblastic cells in the interstitium that produced abundant collagen. The basal lamina, normally present between the myoid cells and Sertoli cells, was focally absent. We speculate that the abnormal basal lamina contributed to other characteristics, such as extracordal gonocytes, apolar Sertoli cells, and anastomotic seminiferous tubules. The two Dhh-null phenotypes described have common peritubular cell defects that may be indicative of the essential role of peritubular cells in development of tubular morphology, the differentiation of Leydig cells, and the ultimate support of spermatogenesis.