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围产期暴露于与人相关的持久性有机污染物混合暴露:对 CD-1 小鼠乳腺发育、卵巢卵泡发生和肝脏的影响。

Perinatal exposure to a human relevant mixture of persistent organic pollutants: Effects on mammary gland development, ovarian folliculogenesis and liver in CD-1 mice.

机构信息

Department of Production Animal Clinical Sciences, Norwegian University of Life Sciences, Ås, Norway.

Department of Preclinical Sciences and Pathology, Norwegian University of Life Sciences, Ås, Norway.

出版信息

PLoS One. 2021 Jun 10;16(6):e0252954. doi: 10.1371/journal.pone.0252954. eCollection 2021.

Abstract

The ability of persistent organic pollutants (POPs) with endocrine disrupting properties to interfere with the developing reproductive system is of increasing concern. POPs are transferred from dams to offspring and the high sensitivity of neonates to endocrine disturbances may be caused by underdeveloped systems of metabolism and excretion. The present study aimed to characterize the effect of in utero and lactational exposure to a human relevant mixture of POPs on the female mammary gland, ovarian folliculogenesis and liver function in CD-1 offspring mice. Dams were exposed to the mixture through the diet at Control, Low or High doses (representing 0x, 5000x and 100 000x human estimated daily intake levels, respectively) from weaning and throughout mating, gestation, and lactation. Perinatally exposed female offspring exhibited altered mammary gland development and a suppressed ovarian follicle maturation. Increased hepatic cytochrome P450 enzymatic activities indirectly indicated activation of nuclear receptors and potential generation of reactive products. Hepatocellular hypertrophy was observed from weaning until 30 weeks of age and could potentially lead to hepatotoxicity. Further studies should investigate the effects of human relevant mixtures of POPs on several hormones combined with female reproductive ability and liver function.

摘要

具有内分泌干扰特性的持久性有机污染物 (POPs) 能够干扰发育中的生殖系统,这引起了人们越来越多的关注。POPs 会从母体转移到后代身上,而新生儿对内分泌干扰的高度敏感性可能是由于代谢和排泄系统发育不完善所致。本研究旨在探讨宫内和哺乳期暴露于人类相关 POPs 混合物对 CD-1 后代小鼠乳腺、卵巢卵泡发生和肝功能的影响。从断奶到交配、妊娠和哺乳期,母体通过饮食暴露于混合物中,暴露水平分别为对照、低剂量和高剂量(分别代表人类估计每日摄入量的 0x、5000x 和 100000x)。围产期暴露的雌性后代表现出乳腺发育异常和卵巢卵泡成熟度降低。肝细胞色素 P450 酶活性的增加间接表明了核受体的激活和潜在的反应产物的产生。从断奶到 30 周龄,观察到肝细胞肥大,可能导致肝毒性。进一步的研究应该调查人类相关 POPs 混合物对几种激素的影响,结合女性生殖能力和肝功能进行研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/87a3/8191980/dad68744bbfb/pone.0252954.g001.jpg

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