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孕期大鼠围产期暴露于氯氰菊酯会延迟睾丸下降,损害F1代雄性后代的生育能力,导致F2代出现发育缺陷。

Perinatal exposure of pregnant rats to cypermethrin delays testicular descent, impairs fertility in F1 male progeny leading to developmental defects in F2 generation.

作者信息

Singh Dipty, Bhagat Sharad, Raijiwala Paula, Dighe Vikas, Vanage Geeta

机构信息

National Center for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health (ICMR), J M Street, Parel, Mumbai, Maharashtra 400 012, India.

National Center for Preclinical Reproductive and Genetic Toxicology, National Institute for Research in Reproductive Health (ICMR), J M Street, Parel, Mumbai, Maharashtra 400 012, India.

出版信息

Chemosphere. 2017 Oct;185:376-385. doi: 10.1016/j.chemosphere.2017.06.138. Epub 2017 Jul 4.

DOI:10.1016/j.chemosphere.2017.06.138
PMID:28709042
Abstract

Cypermethrin (CYP) is a widely used synthetic pyrethroid insecticide and regarded as a potential endocrine disruptor. CYP exposure may pose a great risk to human health including adverse effect on their reproductive functions. This study aimed to delineate the effects of perinatal exposure of rats to CYP on the sexual maturation and fertility of F1 male progeny. Pregnant rats (F0) were gavaged daily with CYP (0, 1, 10, 25 mg/kg BW/day) and Diethylestilbestrol (DES, 10 μg/kg BW/day), as positive control from gestation day 6 to postnatal day 21. The effects of CYP on body weight gain and reproductive functions were evaluated at the Juvenile (PND 22), peri-pubertal (PND 45) and adult (PND 75) stages of development. A significant delay in the age of testicular descent and prepuce separation was observed at 1 and 25 mg/kg doses of CYP. At the same dose level, reproductive organ development and their functions were also affected. A significant alteration in testicular histology, expression of steroid hormone receptors, and circulatory steroid hormones was observed throughout development. Reduced sperm count and motility were observed at PND 75 leading to subfertility and reduced litter size. These adult male rats when cohabitated with unexposed normal cycling females, the F2 fetuses exhibited developmental defects. Taken together, CYP perinatal exposure caused significant long lasting effects of the reproductive functions of F1 generation male rats, which were vertically transmitted to F2 generation leading to developmental defects. The mechanism of transgenerational effects needs to be explored in details.

摘要

氯氰菊酯(CYP)是一种广泛使用的合成拟除虫菊酯类杀虫剂,被认为是一种潜在的内分泌干扰物。接触氯氰菊酯可能对人类健康构成重大风险,包括对其生殖功能产生不利影响。本研究旨在阐明围产期大鼠接触氯氰菊酯对F1雄性后代性成熟和生育能力的影响。从妊娠第6天到出生后第21天,每天给怀孕大鼠(F0)灌胃氯氰菊酯(0、1、10、25毫克/千克体重/天)和己烯雌酚(DES,10微克/千克体重/天)作为阳性对照。在幼年(出生后第22天)、青春期前(出生后第45天)和成年(出生后第75天)发育阶段评估氯氰菊酯对体重增加和生殖功能的影响。在1和25毫克/千克剂量的氯氰菊酯组中观察到睾丸下降和包皮分离年龄显著延迟。在相同剂量水平下,生殖器官发育及其功能也受到影响。在整个发育过程中观察到睾丸组织学、类固醇激素受体表达和循环类固醇激素的显著改变。在出生后第75天观察到精子数量和活力降低,导致生育力下降和窝仔数减少。这些成年雄性大鼠与未接触的正常发情雌性大鼠同居时,F2胎儿出现发育缺陷。综上所述,围产期接触氯氰菊酯对F1代雄性大鼠的生殖功能产生了显著的长期影响,并垂直传递给F2代,导致发育缺陷。跨代效应的机制需要详细探讨。

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