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暴露于生精细胞形成和增殖过程中的锰会扰乱大鼠早期睾丸发育。

Exposure to manganese during sertoli cell formation and proliferation disturbs early testicular development in rats.

机构信息

Laboratory of Experimental Toxicology - LATOEX, Universidade Federal de São Paulo, Instituto do Mar, Carvalho de Mendonça, 144, 11070-100 Santos, SP, Brazil.

Laboratory of Experimental Toxicology - LATOEX, Universidade Federal de São Paulo, Instituto do Mar, Carvalho de Mendonça, 144, 11070-100 Santos, SP, Brazil.

出版信息

Reprod Toxicol. 2023 Sep;120:108447. doi: 10.1016/j.reprotox.2023.108447. Epub 2023 Jul 25.

Abstract

Manganese (Mn) is a metal and important micronutrient. However, exposure to supraphysiological levels of Mn, which occur through fungicides, atmospheric emissions, drainages, and spills, has been related to health risks, including morphometric changes in the male reproductive organs and impairment on gametogenesis and sperm quality, impacting the fertile ability of adult animals. Despite the relevance of the fetal/perinatal period for toxicological studies on Mn, previous data only deal with the physical and neurological development of the offspring, without mentioning their reproductive development. The present study investigated whether exposure to Mn during fetal/perinatal phase, specifically during the period of formation and proliferation of Sertoli cells, impairs the reproductive development of male offspring in early postnatal life. Therefore, pregnant Wistar rats were randomly distributed into 3 experimental groups: Ctl (received saline solution), Mn-9 (received 9 mg/kg of MnCl), and Mn-90 (received 90 mg/kg of MnCl). The female rats received the experimental treatment by gavage from gestational day 13 to lactational day 15, i.e., postnatal day (PND) 15 of the pups. Oxidative damage to the genetic material of germ and Sertoli cells, together with a decrease in connexin 43 immunolabeling were observed in the testis of male pups evaluated at PND 15. In addition, an increase in the seminiferous tubules presenting slight epithelium vacuolization and cells with eosinophilic cytoplasm were observed, without apparent epididymal changes. In conclusion, it was demonstrated that Mn perturbed the initial testicular development by altering Sertoli cell integrity through oxidative insult, which may compromise the spermatogenesis in the long-term.

摘要

锰(Mn)是一种金属和重要的微量元素。然而,通过杀菌剂、大气排放、排水和溢出等途径接触超生理水平的锰与健康风险有关,包括男性生殖器官的形态变化和配子发生和精子质量受损,从而影响成年动物的生育能力。尽管胎儿/围产期对于锰的毒理学研究很重要,但以前的数据仅涉及后代的身体和神经发育,而没有提到他们的生殖发育。本研究调查了胎儿/围产期(特别是在支持细胞形成和增殖期间)暴露于锰是否会损害雄性后代在出生后早期的生殖发育。因此,将怀孕的 Wistar 大鼠随机分为 3 个实验组:Ctl(接受生理盐水)、Mn-9(接受 9mg/kg 的 MnCl)和 Mn-90(接受 90mg/kg 的 MnCl)。从妊娠第 13 天到哺乳期第 15 天,即幼崽的出生后第 15 天,雌性大鼠通过灌胃接受实验处理。在出生后第 15 天评估雄性幼崽的睾丸时,观察到生殖细胞和支持细胞的遗传物质氧化损伤以及连接蛋白 43 免疫标记减少。此外,观察到一些曲细精管出现轻微上皮空泡化和嗜酸性细胞质的细胞增加,但附睾没有明显变化。总之,研究表明,锰通过氧化损伤改变支持细胞的完整性来干扰初始睾丸发育,这可能会在长期内损害精子发生。

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