Klinefelter G R, Laskey J W, Perreault S D, Ferrell J, Jeffay S, Suarez J, Roberts N
United States Environmental Protection Agency, Developmental Toxicology Division, Research Triangle Park, North Carolina 27711.
J Androl. 1994 Jul-Aug;15(4):318-27.
Several decades ago it was reported that when adult male rats were exposed to a single injection of 50 mg/kg body weight ethane dimethanesulfonate (EDS) and mated with untreated females, average litter size was significantly reduced as early as 2 weeks later. Recently, we demonstrated that EDS exerts multiple effects in the epididymis of adult rats. Some of these effects were independent of reduced serum testosterone (T) levels. Later we found that EDS has direct effects on epididymal epithelial cells in vitro. Herein, we sought to determine whether EDS perturbs the fertilizing ability of cauda epididymal sperm. Four days after exposure to 50 mg/kg EDS, sperm from the proximal cauda epididymidis were inseminated into adult receptive females in utero; on the next day the percentage of fertilized eggs was determined. Exogenous T administration and castration were used to determine what role, if any, androgen deprivation and the testis had on the fertilizing ability of proximal cauda epididymal sperm. Sperm motion parameters, serum T, T in the caput/corpus epididymidis, and detergent-extracted sperm protein were evaluated and correlated with fertilizing ability. We found that both castration and EDS exposure significantly compromised the fertilizing ability of sperm in proximal cauda epididymidis 4 days after exposure. Exogenous T, sufficient to maintain serum T, completely restored the fertilizing ability of sperm following castration, but not after EDS exposure. Moreover, exogenous T failed to restore fertilizing ability when castrated animals were exposed to EDS. Thus, the effects that EDS exerts on sperm maturation in vivo are independent of the testis. Finally, the only endpoint that was well correlated with fertilizing ability was the relative amount of an acidic 18-kDa sperm protein.
几十年前有报道称，成年雄性大鼠单次注射50毫克/千克体重的乙烷二甲磺酸盐（EDS）并与未处理的雌性大鼠交配后，早在2周后平均窝仔数就显著减少。最近，我们证明EDS在成年大鼠附睾中发挥多种作用。其中一些作用独立于血清睾酮（T）水平的降低。后来我们发现EDS在体外对附睾上皮细胞有直接作用。在此，我们试图确定EDS是否会扰乱附睾尾精子的受精能力。在暴露于50毫克/千克EDS四天后，将来自附睾尾近端的精子经子宫内授精给成年可受孕雌性大鼠；次日测定受精卵的百分比。使用外源性睾酮给药和去势来确定雄激素剥夺和睾丸对附睾尾近端精子受精能力是否有作用以及有何作用。评估精子运动参数、血清T、附睾头/体部的T以及经去污剂处理的精子蛋白，并将其与受精能力进行关联。我们发现去势和暴露于EDS均在暴露四天后显著损害了附睾尾近端精子的受精能力。足以维持血清T水平的外源性T完全恢复了去势后精子的受精能力，但在暴露于EDS后却未能恢复。此外，当去势动物暴露于EDS时，外源性T未能恢复受精能力。因此，EDS在体内对精子成熟的作用独立于睾丸。最后，与受精能力相关性良好的唯一终点是一种酸性18 kDa精子蛋白的相对含量。
