Rijntjes Eddy, van Kesteren-Buiting Anita, Keijer Jaap, Teerds Katja J
Department of Animal Sciences, Human & Animal Physiology Group, Wageningen University, Wageningen, The Netherlands.
Int J Androl. 2010 Feb;33(1):e123-31. doi: 10.1111/j.1365-2605.2009.00955.x. Epub 2009 Mar 18.
Chronic prenatally induced dietary hypothyroidism delays adult-type Leydig cell development, but does not block this process. Using a chemical model to induce hypothyroidism, it was suggested that development of a new population of Leydig cells was completely inhibited following the addition of the cytotoxic compound ethane-1,2-dimethyl sulphonate (EDS). In this study, we used a dietary approach to induce hypothyroidism and reinvestigated the regeneration of the Leydig cell population following EDS administration. Eighty-four day old euthyroid and chronically hypothyroid rats received an injection of EDS and were killed directly before or at regular intervals up to 77 days after EDS. In some control and hypothyroid animals, the first progenitor-type Leydig cells were observed at day 12 after EDS. At day 16, Leydig cell progenitors were present in all rats. The percentage of proliferating Leydig cells peaked in the euthyroid animals at day 21 after EDS. In the hypothyroid testis such a peak was not observed, although the percentage of proliferating regenerating Leydig cells was significantly higher from days 35 to 56 compared with the controls. This suggested that the wave of Leydig cell proliferation was delayed in the hypothyroid animals as compared with the euthyroid controls. On the day of EDS injection, the Leydig/Sertoli cell ratio was 37% lower in the hypothyroid rats compared with the controls. The Leydig/Sertoli cell ratio remained lower in the EDS-treated hypothyroid animals compared with the controls at all time points investigated. At day 77 after EDS, the Leydig cell population had returned to its pre-treatment size in both groups. Plasma testosterone production was reduced to below detectable levels immediately after EDS injection, and started to increase again on day 16, reaching pre-treatment values on day 21 in both groups. Taken together, severely reduced thyroid hormone levels did not block the regeneration of the adult-type Leydig cell population following EDS, as has been suggested previously.
孕期慢性诱导的饮食性甲状腺功能减退会延迟成年型睾丸间质细胞的发育，但不会阻断这一过程。使用化学模型诱导甲状腺功能减退时，有人提出添加细胞毒性化合物乙烷-1,2-二甲磺酸酯（EDS）后，新的睾丸间质细胞群体的发育会被完全抑制。在本研究中，我们采用饮食方法诱导甲状腺功能减退，并重新研究了给予EDS后睾丸间质细胞群体的再生情况。84日龄的甲状腺功能正常和慢性甲状腺功能减退的大鼠接受了EDS注射，并在注射前或注射后定期处死，直至注射后77天。在一些对照和甲状腺功能减退的动物中，在注射EDS后第12天观察到第一批祖细胞型睾丸间质细胞。在第16天，所有大鼠中都存在睾丸间质细胞祖细胞。增殖的睾丸间质细胞百分比在甲状腺功能正常的动物中于注射EDS后第21天达到峰值。在甲状腺功能减退的睾丸中未观察到这样的峰值，尽管从第35天到第56天，增殖的再生睾丸间质细胞百分比与对照组相比显著更高。这表明与甲状腺功能正常的对照组相比，甲状腺功能减退的动物中睾丸间质细胞增殖的浪潮有所延迟。在注射EDS当天，甲状腺功能减退的大鼠中睾丸间质细胞/支持细胞的比例比对照组低37%。在所有研究的时间点，与对照组相比，接受EDS治疗的甲状腺功能减退动物中睾丸间质细胞/支持细胞的比例仍然较低。在注射EDS后第77天，两组中的睾丸间质细胞群体均恢复到治疗前的大小。注射EDS后，血浆睾酮水平立即降至可检测水平以下，并在第16天开始再次升高，两组均在第21天达到治疗前值。综上所述，严重降低的甲状腺激素水平并没有像之前所认为的那样阻断给予EDS后成年型睾丸间质细胞群体的再生。
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