Klinefelter G R, Laskey J W, Kelce W R, Ferrell J, Roberts N L, Suarez J D, Slott V
United States Environmental Protection Agency, Developmental Toxicology Division, Health Effects Research Laboratory, Research Triangle Park, North Carolina 27711.
Biol Reprod. 1994 Jul;51(1):82-91. doi: 10.1095/biolreprod51.1.82.
Decades ago it was reported that when male rats were exposed to chloroethylmethanesulfonate (CEMS) for 5 days prior to weekly matings with untreated females, the second mating resulted in reduced litter size. Since fertility was not assessed at earlier time points, it was not possible to determine whether CEMS exerted any effects on sperm in the epididymis. In this study, we used a 4-day exposure and assessed multiple reproductive endpoints on Day 5 to characterize effects of CEMS exposure (6.25-25 mg/kg) on Leydig cells and the epididymis. Exposure to CEMS caused a dose-related decline in serum testosterone (T) levels. This occurred at a dose lower than that required to decrease T production in vitro by testicular parenchyma. The in vitro decline was not attributed to a decrease in maximal hCG-stimulated T production, but to a decrease in unstimulated T production. CEMS was 5-fold less sensitive than ethane dimethanesulfonate (EDS) in reducing maximal hCG-stimulated T production. To control for alterations in the epididymis resulting from decreased serum T alone, T was implanted in CEMS-treated animals to maintain serum T at a concentration similar to that found in normal rats. This exogenous T failed to prevent the CEMS-induced decrease in the weight of the caput/corpus epididymidis but did prevent the CEMS-induced decrease in seminal vesicle weight. Implantation of T failed to prevent the CEMS-induced reduction in sperm reserves in the cauda epididymidis, and it failed to prevent the CEMS-induced alterations in the histology of both the corpus and proximal cauda epididymidis. The height of the epithelium in both of these regions was increased, and clear cells disappeared from the proximal cauda epididymidis. These results demonstrate that CEMS might alter the ability of the Leydig cell to respond to LH stimulation in vivo, and that alterations in the structure and function of the epididymis occur even when the serum concentration of T is maintained.
几十年前有报道称，雄性大鼠在每周与未处理的雌性大鼠交配前5天暴露于氯乙基甲磺酸酯（CEMS），第二次交配时产仔数减少。由于未在更早的时间点评估生育力，因此无法确定CEMS是否对附睾中的精子产生任何影响。在本研究中，我们采用4天暴露，并在第5天评估多个生殖终点，以表征CEMS暴露（6.25 - 25 mg/kg）对睾丸间质细胞和附睾的影响。暴露于CEMS导致血清睾酮（T）水平呈剂量相关下降。这一现象发生的剂量低于睾丸实质在体外降低T产生所需的剂量。体外下降并非归因于最大hCG刺激的T产生减少，而是未刺激的T产生减少。在降低最大hCG刺激的T产生方面，CEMS的敏感性比乙烷二甲磺酸酯（EDS）低5倍。为了控制仅因血清T降低而导致的附睾改变，将T植入CEMS处理的动物体内，以使血清T维持在与正常大鼠相似的浓度。这种外源性T未能预防CEMS诱导的附睾头/体重量下降，但确实预防了CEMS诱导的精囊重量下降。植入T未能预防CEMS诱导的附睾尾精子储备减少，也未能预防CEMS诱导的附睾体和附睾尾近端组织学改变。这两个区域的上皮高度增加，附睾尾近端的透明细胞消失。这些结果表明，CEMS可能会改变睾丸间质细胞在体内对LH刺激的反应能力，并且即使维持血清T浓度，附睾的结构和功能仍会发生改变。
