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母亲暴露于尼古丁会影响成年后代的卵子质量和生殖能力吗?

Does maternal exposure to nicotine affect the oocyte quality and reproductive capacity in adult offspring?

机构信息

Developmental Biology Laboratory, Department of Morphology and Genetics, Federal University of Sao Paulo, Sao Paulo, Brazil.

Developmental Biology Laboratory, Department of Morphology and Genetics, Federal University of Sao Paulo, Sao Paulo, Brazil.

出版信息

Toxicol Appl Pharmacol. 2021 Sep 1;426:115638. doi: 10.1016/j.taap.2021.115638. Epub 2021 Jul 6.

Abstract

Gonadal development begins in the intrauterine phase and females from most species are born with an established oocyte reserve. Exposure to drugs during gestation can compromise the offspring health, also affecting the gametes quality. Nicotine, the main component of cigarettes, is an oxidant agent capable of altering the fertility in men and women. As female gametes are susceptible to oxidative stress, this drug can damage the oolemma and affect oocyte maturation, induce errors during chromosomal segregation and DNA fragmentation. Oocyte mitochondria are particularly susceptible to injuries, contributing to the oocyte quality loss and embryonic development disruption. Thus, considering the high number of women who smoke during pregnancy, while significant events are occurring in the embryo for future fertility of offspring, we seek to verify the quality of the oocytes from adult rats exposed to nicotine during intrauterine phase and breastfeeding. Pregnant Wistar rats received nicotine by osmotic mini-pumps and the female progenies were evaluated in adulthood for oocyte quality (viability, lipid peroxidation, generation of reactive oxygen species and mitochondrial integrity) and reproductive capacity. Embryos (3dpc) and fetuses (20dpc) generated by these rats were also evaluated. The results showed that the dose of 2 mg/kg/day of nicotine through placenta and breast milk does not affect the number of oocytes and the fertility capacity of adult rats. However, it causes some morphological alterations in oocytes, mitochondrial changes, embryonic fragmentation and disruption of fetal development. The malformations in fetuses generated from these gametes can also indicate the occurrence of epigenetic modifications.

摘要

性腺发育始于宫内阶段,大多数物种的雌性在出生时就具有已建立的卵母细胞储备。在妊娠期接触药物会损害后代的健康,也会影响配子的质量。香烟中的主要成分尼古丁是一种氧化剂,能够改变男性和女性的生育能力。由于女性配子容易受到氧化应激的影响,这种药物会损害卵母细胞膜并影响卵母细胞成熟,诱导染色体分离和 DNA 片段化过程中的错误。卵母细胞线粒体特别容易受到损伤,导致卵母细胞质量下降和胚胎发育中断。因此,考虑到怀孕期间吸烟的女性人数众多,而胚胎正在发生对后代未来生育能力有重大影响的事件,我们试图验证暴露于尼古丁的成年大鼠的卵母细胞质量。怀孕的 Wistar 大鼠通过渗透微型泵接受尼古丁,成年雌性后代的卵母细胞质量(活力、脂质过氧化、活性氧生成和线粒体完整性)和生殖能力进行评估。还评估了这些大鼠产生的胚胎(3dpc)和胎儿(20dpc)。结果表明,胎盘和母乳中 2mg/kg/天的尼古丁剂量不会影响成年大鼠的卵母细胞数量和生育能力。然而,它会导致卵母细胞出现一些形态改变、线粒体变化、胚胎碎片化和胎儿发育中断。这些配子产生的胎儿的畸形也可能表明发生了表观遗传修饰。

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