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二溴乙酸会影响雄性大鼠的生殖能力和精子质量。

Dibromoacetic acid affects reproductive competence and sperm quality in the male rat.

作者信息

Linder R E, Klinefelter G R, Strader L F, Narotsky M G, Suarez J D, Roberts N L, Perreault S D

机构信息

Health Effects Research Laboratory, United States Environmental Protection Agency, Research Triangle Park, North Carolina 27711, USA.

出版信息

Fundam Appl Toxicol. 1995 Nov;28(1):9-17. doi: 10.1006/faat.1995.1140.

Abstract

Recently, we demonstrated with short-duration tests that dibromoacetic acid (DBAA), a commonly occurring by-product of water disinfection, alters sperm morphology and motility in the male rat. These results suggested that the effects of DBAA on sperm quality were likely to compromise reproductive competence of the male rat early in subchronic exposure. The present studies were undertaken to investigate the dose response and time course of alterations in fertility and sperm quality. Proven breeder male rats were gavaged daily with 0, 2, 10, 50, or 250 mg DBAA/kg for up to 79 days; interim and terminal measurements of sperm quality and reproductive outcome were made. Because of the known neurotoxicity of the analogue, dichloroacetic acid, both natural breeding and artificial inseminations were evaluated in untreated females to distinguish between possible behavioral and spermatogenic effects. DBAA compromised male fertility during the second treatment week in naturally bred rats dosed with 250 mg/kg. The early antifertility effect appeared to be the result of behavioral changes since females artificially inseminated with sperm collected on Day 9 successfully produced offspring. However, sperm morphology and motility also were rapidly affected by DBAA treatment so that no offspring via natural insemination and only one litter via artificial insemination were produced subsequent to Day 15. Through 31 days, substantial effects on sperm motility, sperm morphology, and epididymal sperm numbers were observed, but there was no demonstrable effect on serum testosterone or sperm production. Because severe toxicity developed in the group given 250 mg/kg, exposure of these animals was prematurely terminated after 42 doses and their recovery was monitored through a 6-month posttreatment period; decreased testis weights and only limited recovery of reproductive performance were observed. Exposure to 50 mg/kg resulted in moderate changes in sperm morphology and motility and moderate decreases in epididymal sperm counts in rats dosed for 31 or 79 days. However, these males remained fertile, litter size was unaffected, and no paternally mediated developmental defects were noted in their offspring. No effects on sperm quality were detected at dosages of 2 or 10 mg/kg. However, compared to controls, naturally bred DBAA-treated rats tended to have fewer inseminations, fewer copulatory plugs, and fewer multiple litters, suggesting that DBAA may have altered mating behavior at dosages as low as 10 mg/kg.

摘要

最近,我们通过短期试验证明,二溴乙酸(DBAA)作为水消毒过程中常见的副产物,会改变雄性大鼠的精子形态和活力。这些结果表明,DBAA对精子质量的影响可能会在亚慢性暴露早期损害雄性大鼠的生殖能力。本研究旨在调查生育能力和精子质量改变的剂量反应及时间进程。将已证实具有繁殖能力的雄性大鼠每天灌胃给予0、2、10、50或250毫克DBAA/千克,持续79天;对精子质量和生殖结果进行中期和末期测量。由于已知类似物二氯乙酸具有神经毒性,因此对未处理的雌性大鼠进行了自然交配和人工授精评估,以区分可能的行为和生精效应。在给予250毫克/千克剂量的自然交配大鼠中,DBAA在第二个治疗周损害了雄性生育能力。早期抗生育作用似乎是行为改变的结果,因为用第9天采集的精子进行人工授精的雌性成功产下了后代。然而,DBAA处理也迅速影响了精子形态和活力,以至于在第15天后通过自然交配没有产生后代,通过人工授精只产生了一窝。在31天内,观察到对精子活力、精子形态和附睾精子数量有显著影响,但对血清睾酮或精子生成没有明显影响。由于给予250毫克/千克剂量的组出现了严重毒性,在给予42次剂量后提前终止了这些动物的暴露,并在治疗后6个月内监测它们的恢复情况;观察到睾丸重量下降,生殖性能仅有限恢复。给予50毫克/千克剂量导致给药31天或79天的大鼠精子形态和活力出现中度变化,附睾精子数量中度减少。然而,这些雄性仍具有生育能力,窝仔数未受影响,其后代未发现父系介导的发育缺陷。在2或10毫克/千克剂量下未检测到对精子质量的影响。然而,与对照组相比,经DBAA处理的自然交配大鼠往往交配次数更少、交配栓更少、多窝产仔更少,这表明DBAA可能在低至10毫克/千克的剂量下改变了交配行为。

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