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首页> 外文期刊>Biology of Reproduction: Offical Journal of the Society for the Study of Reproduction >Alkylated imino sugars, reversible male infertility-inducing agents, do not affect the genetic integrity of male mouse germ cells during short-term treatment despite induction of sperm deformities
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Alkylated imino sugars, reversible male infertility-inducing agents, do not affect the genetic integrity of male mouse germ cells during short-term treatment despite induction of sperm deformities

机译:烷基化的亚氨基糖,可逆的雄性不育诱导剂,尽管诱发了精子畸形,但在短期治疗期间不影响雄性小鼠生殖细胞的遗传完整性

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摘要

Reversible infertility can be induced in male mice by oral administration of the alkylated imino sugars N-butyideoxynojirimycin (NB-DNJ) and N-butyldeoxygalactonojirimycin (NB-DGJ). Spermatozoa of these mice have grossly misshapen heads and reduced motility. Because NB-DNJ and related compounds may hold promise as nonhormonal male contraceptives, a comprehensive examination of their effects on male reproduction is necessary. To this end, we further examined reproductive properties of the dysmorphic spermatozoa that are produced after short-term imino sugar administration at the minimal dose that completely abolishes the ability of male C57BL/6 mice to produce offspring by natural mating. Here, we report that, in vitro, the abnormal spermatozoa from the NB-DN/6 and NB-DG-treated mice were unable to fertilize oocytes. In addition, we investigated whether the imino sugars damage the genetic integrity of spermatozoa. To test this, we microsurgically injected deformed spermatozoa from imino sugar-treated males into oocytes. The deformed spermatozoa from the testis were able to activate oocytes very efficiently, but those from the cauda epididymis often failed to do so. This problem was overcome when the sperm-injected oocytes were treated with a parthenogenetic agent, Sr2+. Oocytes injected with the misshapen spermatozoa from NB-DNJ- and NB-DGJ-treated mice developed (with or without Sr2+ treatment) into live offspring that grew normally and were normally fertile. This indicates that during short-term administration, alkylated imino sugars alter sperm morphology and physiology but do not diminish the genetic potential of spermatozoa.
机译:可通过口服烷基化的亚氨基糖N-丁氧基脱氧野rim霉素(NB-DNJ)和N-丁基脱氧半乳糖脱氧野rim霉素(NB-DGJ)诱导雄性小鼠可逆性不育。这些小鼠的精子头严重畸形,运动能力降低。由于NB-DNJ和相关化合物有望作为非激素男性避孕药,因此有必要对它们对男性生殖的影响进行全面检查。为此,我们进一步检查了以最小剂量完全消灭雄性C57BL / 6小鼠通过自然交配产生后代能力的最小剂量的亚氨基糖短期服用后产生的畸形精子的生殖特性。在这里,我们报告,在体外,来自NB-DN / 6和NB-DG处理的小鼠的异常精子无法使卵母细胞受精。此外,我们调查了亚氨基糖是否损害了精子的遗传完整性。为了测试这一点,我们通过显微手术将亚氨基糖处理过的雄性变形的精子注射到卵母细胞中。来自睾丸的畸形精子能够非常有效地激活卵母细胞,但来自附睾马尾的卵母细胞却常常无法激活。当用单性生殖剂Sr2 +处理注入精子的卵母细胞时,可以克服此问题。从NB-DNJ和NB-DGJ处理的小鼠中注入畸形精子的卵母细胞发育成(经过或未经过Sr2 +处理的)成年后正常生长并正常繁殖的活后代。这表明在短期给药期间,烷基化的亚氨基糖会改变精子的形态和生理,但不会降低精子的遗传潜能。

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