Transgenerational Inheritance of Reproductive and Metabolic Phenotypes in PCOS Rats

Transgenerational Inheritance of Reproductive and Metabolic Phenotypes in PCOS Rats
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PCOS 大鼠生殖和代谢表型的跨代遗传

DOI:
10.3389/fendo.2020.00144
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发表时间:
2020-03
影响因子:
5.2
通讯作者:
Qiao Jie
Qiao Jie
中科院分区:
医学2区
文献类型:
--
作者:
Zhang Haolin;Yi Ming;Li Dong;Li Rong;Zhao Yue;Qiao Jie

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女性胎儿的雄激素暴露可能是多囊卵巢综合征(PCOS)在后代发展的一个重要因素。本研究旨在探讨PCOS对大鼠第一代和第二代后代生长、生殖和代谢的跨代影响。雌性F0大鼠接受过量的脱氢表雄酮(DHEA)暴露,以建立PCOS或相同数量的车辆作为对照。将这些F0代雌性与正常雄性杂交,以获得对照(C)和DHEA(D)F1代后代,而F2代后代则通过4组F1代大鼠间杂交获得:(1)C组-C组;(2)D组-C组;(3)C组-D组和(4)D组-D组。与对照组相比,祖先DHEA暴露的F1和F2后代随着年龄的增加体重增加。此外,雌性F1和F2后代与祖先DHEA暴露表现出PCOS样的生殖和代谢表型,包括中断发情周期和多囊卵巢,以及血清睾酮水平升高,葡萄糖耐量受损和广泛的代谢异常。祖先DHEA暴露的雄性后代表现出较低的精子质量。这些发现证实了女性胎儿过量暴露于雄激素对后代的负面影响。
Androgen exposure of female fetuses could be an important factor in the development of polycystic ovary syndrome (PCOS) in subsequent generations. The present study aimed to investigate the transgenerational effects of PCOS on the growth, reproduction, and metabolism of the first- and second-generation offspring in rats. Female F0 rats received excessive dehydroepiandrosterone (DHEA) exposure to establish PCOS or the same amount of vehicle as controls. These F0 females were crossed with normal males to obtain control (C) and DHEA (D) F1 offspring, whereas F2 offspring were obtained by inter-crossing between F1 rats for 4 groups: (1) C♂-C♀; (2) D♂-C♀; (3) C♂-D♀ and (4) D♂-D♀. Compared with control groups, F1 and F2 offspring with ancestral DHEA exposure showed higher body weight with increasing age. In addition, female F1 and F2 offspring with ancestral DHEA exposure exhibited PCOS-like reproductive and metabolic phenotypes, including disrupted estrous cycles and polycystic ovaries, as well as increased serum levels of testosterone, impaired glucose tolerance and widespread metabolic abnormalities. Male offspring with ancestral DHEA exposure exhibited lower quality of sperms. These findings confirm the negative effects of excessive androgen exposure of female fetuses on subsequent generations.
DOI: 10.1017/s0033291719000424
发表时间: 2020-03-01
影响因子: 6.9
作者:
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通讯作者: Rosenqvist, Mina A.
DOI: 10.1210/jc.2007-1036
发表时间: 2007-12-01
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发表时间: 2010-02-01
期刊: ENDOCRINOLOGY
影响因子: 4.8
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DOI: 10.3390/medsci7080086
发表时间: 2019-08
期刊: Medical Sciences
影响因子: --
作者:
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高脂肪饮食夸大了 DHEA 诱导的 PCOS 大鼠模型的内分泌和代谢表型
DOI: 10.1530/rep-15-0542
发表时间: 2016-04-01
期刊: REPRODUCTION
影响因子: 3.8
作者:
Zhang, Haolin;Yi, Ming;Qiao, Jie
通讯作者: Qiao, Jie