Foradori Chad D, Sawhney Coder Prägati, Tisdel Merrill, Yi Kun Don, Simpkins James W, Handa Robert J, Breckenridge Charles B
Department of Anatomy, Physiology and Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, Alabama.
Birth Defects Res B Dev Reprod Toxicol. 2014 Jun;101(3):262-75. doi: 10.1002/bdrb.21109. Epub 2014 May 15.
Atrazine (ATR) blunts the hormone-induced luteinizing hormone (LH) surge, when administered by gavage (50-100 mg/kg/day for 4 days), in ovariectomized rats. In this study, we determined if comparable doses delivered either by gavage (bolus dose) or distributed in diet would reduce the LH surge and subsequently affect fertility in the intact female rat. ATR was administered daily to intact female Sprague-Dawley (SD) or Long Evans (LE) rats by gavage (0, 0.75 1.5, 3, 6, 10, 12, 50, or 100 mg/kg/day) or diet (0, 30, 100, 160, 500, 660, or 1460 ppm) during one complete 4-day estrous cycle, starting on day of estrus. Estrous status, corpora lutea, ova, and LH plasma concentrations were evaluated. A second cohort of animals was mated on the fourth treatment day. Fertility metrics were assessed on gestational day 20. A higher portion of LE rats had asynchronous estrous cycles when compared to SD rats both during pretreatment and in response to ATR (≥50 mg/kg). In contrast, bolus doses of ATR (≥50 mg/kg) inhibited the peak and area under the curve for the preovulatory LH surge in SD but not LE animals. Likewise, only bolus-treated SD, not LE, rats displayed reduced mean number of corpora lutea and ova. There were no effects of ATR administered by gavage on mating, gravid number, or fetus number. Dietary administration had no effect on any reproductive parameter measured. These findings indicate that short duration, high-bolus doses of ATR can inhibit the LH surge and reduce the number of follicles ovulated; however, dietary administration has no effect on any endocrine or reproductive outcomes.
在去卵巢大鼠中,通过灌胃给予阿特拉津(ATR,50 - 100毫克/千克/天,持续4天)会减弱激素诱导的促黄体生成素(LH)激增。在本研究中,我们确定了通过灌胃(大剂量)或添加到饮食中给予的可比剂量是否会降低LH激增,并随后影响完整雌性大鼠的生育能力。在一个完整的4天发情周期内,从发情当天开始,通过灌胃(0、0.75、1.5、3、6、10、12、50或100毫克/千克/天)或饮食(0、30、100、160、500、660或1460 ppm)每天给完整的雌性斯普拉格 - 道利(SD)大鼠或长埃文斯(LE)大鼠施用ATR。评估发情状态、黄体、卵子和LH血浆浓度。在第四个治疗日,将第二组动物进行交配。在妊娠第20天评估生育指标。与SD大鼠相比,在预处理期间以及对ATR(≥50毫克/千克)的反应中,LE大鼠中有更高比例出现发情周期不同步。相比之下,大剂量的ATR(≥50毫克/千克)抑制了SD但未抑制LE动物排卵前LH激增的峰值和曲线下面积。同样,只有经大剂量处理的SD大鼠,而不是LE大鼠,黄体和卵子的平均数量减少。灌胃给予ATR对交配、妊娠数或胎儿数没有影响。饮食给药对所测量的任何生殖参数均无影响。这些发现表明,短时间、高剂量的ATR可抑制LH激增并减少排卵卵泡的数量;然而,饮食给药对任何内分泌或生殖结果均无影响。