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首页> 外文期刊>Reproductive toxicology >Induction of dominant lethal mutations by Ascaris trypsin inhibitor in male mice.
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Induction of dominant lethal mutations by Ascaris trypsin inhibitor in male mice.

机译：A虫胰蛋白酶抑制剂在雄性小鼠中诱导显性致死突变。

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Trypsin inhibitor (ATI) isolated from Ascaris suum, a gastrointestinal nematode parasite, was tested for the induction of dominant lethal mutations in male mice. Dominant lethal effects of ATI for the main stages of germ cell development were analyzed by mating at specific time points after dosing. Three groups of adult BALB/c males received 50, 100 or 250mg/kg body weight (bw) single intraperitoneal (ip) injection of ATI in sterile phosphate-buffered saline (PBS). The control group received concurrent injection of PBS. After the administration of ATI or PBS, each male was mated with two untreated females. For fractionated examination with regard to successive germ cell stages (spermatozoa, spermatids, spermatocytes, and spermatogonia), every second week two other untreated virgin females were placed with each male for mating. The uteri of the females were inspected on the 15th day of gestation, and preimplantation loss and postimplantation loss determined from dominant lethal parameters. Exposure of mice germ cells to ATI did not impair mating activity of males. Pregnancy rates were reduced ( approximately 5-10%) by treatment of males with higher doses of ATI, but differences between treatment and control groups were not statistically significant (P>0.05). In the females bred to ATI-treated males, significant increase in preimplantation loss was observed at post-injection week 1 (reflecting exposure to spermatozoa) and 3 (reflecting exposure to mid and early spermatids) for higher doses of the inhibitor (P<0.05 or P<0.01). During mating days 15-21 a statistically significant increase in postimplantation loss and dominant lethal effects were observed for all doses of ATI. At higher doses, dominant lethal effects were restricted to spermatozoa (P<0.01). These data suggest that ATI induces dominant lethal mutations at postmeiotic stages of spermatogenesis, but spermatids are the most sensitive cell stage to the effect of ATI. These preliminary findings show that ATI may be one of the factors causing disturbances in spermatogenesis leading to a reduction of host reproductive success.
机译：测试了从猪，虫（一种胃肠道线虫寄生虫）分离的胰蛋白酶抑制剂（ATI）在雄性小鼠中诱导的主要致死突变的诱导。在给药后的特定时间点交配，分析了ATI对生殖细胞发育主要阶段的主要致死作用。三组成年BALB / c雄性动物在无菌磷酸盐缓冲盐水（PBS）中分别接受50、100或250mg / kg体重（bw）腹膜内（ip）注射ATI。对照组同时注射PBS。给予ATI或PBS后，每只雄性与两名未经治疗的雌性交配。为了对连续的生殖细胞阶段（精子，精子，精细胞和精原细胞）进行分级检查，每隔两周将另外两名未经治疗的处女雌性与每只雄性进行交配。在妊娠的第15天检查女性的子宫，并根据主要致死参数确定植入前损失和植入后损失。小鼠生殖细胞暴露于ATI不会损害雄性的交配活性。通过使用更高剂量的ATI治疗男性，妊娠率降低（约5-10％），但治疗组与对照组之间的差异无统计学意义（P> 0.05）。在以ATI治疗的雄性中繁殖的雌性中，较高剂量的抑制剂在注射后第1周（反映对精子的暴露）和第3周（反映对中，早期精子的暴露）在植入前损失显着增加（P <0.05或P <0.01）。在交配的第15-21天，对于所有剂量的ATI，观察到植入后损失和显着的致死作用的统计学显着增加。高剂量时，主要致死作用限于精子（P <0.01）。这些数据表明，ATI在精子发生的减数分裂后阶段诱导显性致死突变，但精子是对ATI作用最敏感的细胞阶段。这些初步发现表明，ATI可能是导致精子发生障碍，导致宿主繁殖成功率降低的因素之一。

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