Mably T A, Bjerke D L, Moore R W, Gendron-Fitzpatrick A, Peterson R E
School of Pharmacy, University of Wisconsin, Madison 53706.
Toxicol Appl Pharmacol. 1992 May;114(1):118-26. doi: 10.1016/0041-008x(92)90103-y.
When administered in overtly toxic doses to postweanling male rats, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) produces adverse effects on the reproductive system including a decrease in spermatogenesis. Because the male reproductive system may be particularly susceptible to toxic insult during the perinatal period, the effects of in utero and lactational TCDD exposure on its development were examined. Male rats born to dams given TCDD (0.064, 0.16, 0.40, or 1.0 micrograms/kg, po) or vehicle on Day 15 of gestation were evaluated at various stages of development; effects on spermatogenesis and male reproductive capability are reported herein. Testis, epididymis, and cauda epididymis weights were decreased in a dose-related fashion at 32, 49, 63, and 120 days of age, that is, when males were at the juvenile, pubertal, postpubertal, and mature stages of sexual development, respectively. When measured on Days 49, 63, and 120, daily sperm production by the testis was reduced at the highest maternal TCDD dose to 57-74% of the control rate. Cauda epididymal sperm reserves in 63- and 120-day-old males were decreased to as low as 25 and 44%, respectively, of control values, although the motility and morphology of these sperm appeared to be unaffected. The magnitude of the effects described above tended to lessen with time; nevertheless, the decreases in epididymis and cauda epididymis weights, daily sperm production, and cauda epididymal sperm number were statistically significant at the lowest maternal dose tested (0.064 micrograms TCDD/kg) on Day 120 and at most earlier times. To determine if in utero and lactational TCDD exposure also affects male reproductive capability, rats were mated at approximately 70 and 120 days of age with control females. Little if any effect on fertility was seen, and the survival and growth of offspring was unaffected. These results are not inconsistent with the pronounced reductions in daily sperm production and cauda epididymal sperm reserves caused by perinatal TCDD exposure since rats produce and ejaculate far more sperm than are required for normal fertility. The TCDD-induced reduction in spermatogenesis cannot be accounted for by concurrent effects on plasma follicle-stimulating hormone or androgen concentrations or by undernutrition. To investigate the nature of the spermatogenic lesion, leptotene spermatocyte to Sertoli cell ratios were determined.(ABSTRACT TRUNCATED AT 400 WORDS)
当以明显有毒的剂量给断奶后的雄性大鼠用药时，2,3,7,8-四氯二苯并对二恶英（TCDD）会对生殖系统产生不良影响，包括精子发生减少。由于雄性生殖系统在围产期可能特别容易受到毒性损伤，因此研究了子宫内和哺乳期接触TCDD对其发育的影响。对妊娠第15天给予TCDD（0.064、0.16、0.40或1.0微克/千克，经口）或赋形剂的母鼠所生的雄性大鼠在不同发育阶段进行了评估；本文报告了对精子发生和雄性生殖能力的影响。在32、49、63和120日龄时，睾丸、附睾和附睾尾的重量呈剂量相关下降，也就是说，雄性分别处于性发育的幼年、青春期、青春期后和成熟阶段。在49、63和120日龄测量时，在母体TCDD最高剂量下，睾丸每日精子产量降至对照率的57 - 74%。63日龄和120日龄雄性大鼠附睾尾的精子储备分别降至对照值的低至25%和44%，尽管这些精子的活力和形态似乎未受影响。上述影响的程度往往随时间减轻；然而，在第120天以及大多数更早的时间，在测试的最低母体剂量（0.064微克TCDD/千克）下，附睾和附睾尾重量、每日精子产量以及附睾尾精子数量的减少具有统计学意义。为了确定子宫内和哺乳期接触TCDD是否也会影响雄性生殖能力，在大约70日龄和120日龄时将大鼠与对照雌性大鼠交配。几乎未观察到对生育力的影响，并且后代的存活和生长未受影响。这些结果与围产期接触TCDD导致的每日精子产量和附睾尾精子储备的显著减少并不矛盾，因为大鼠产生和射出的精子远远超过正常生育所需。TCDD诱导的精子发生减少不能用对血浆促卵泡激素或雄激素浓度的同时影响或营养不良来解释。为了研究精子发生损伤的性质，测定了细线期精母细胞与支持细胞的比例。（摘要截断于400字）
