Maternal undernutrition induces premature reproductive senescence in adult female rat offspring.

Maternal undernutrition induces premature reproductive senescence in adult female rat offspring.
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DOI:
10.1016/j.fertnstert.2014.09.026
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发表时间:
2015-01
影响因子:
6.7
通讯作者:
Desai, Mina
Desai, Mina
中科院分区:
医学2区
文献类型:
--
作者:
Khorram, Omid;Keen-Rinehart, Erin;Chuang, Tsai-Der;Ross, Michael G.;Desai, Mina

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探讨母亲营养不良(MUN)对衰老子代生殖轴的影响。动物(大鼠)研究。研究实验室。雌性SD大鼠。妊娠后半期限制大鼠进食。1日龄(P1)和老年成年子代的血液促性腺激素、抗苗勒氏激素(AMH)、卵巢形态、动情周期和下丘脑和卵巢基因表达的研究。模拟水坝的后代出生体重低,成年后出现肥胖。8月龄时,80%的成年LBW子代动情周期中断,大多数动物处于持续发情状态。卵巢形态与无周期一致,卵巢呈大的囊状结构,黄体减少。与对照组相比,LBW成年子代血液睾酮(T)水平升高,雄激素合成相关酶的卵巢表达增加,血浆亮氨酸化(L H)/卵泡刺激素(FSH)水平升高,雌二醇(E_2)水平降低,AMH水平无明显变化。下丘脑瘦素受体(OBRb)、雌激素受体-α(ER-α)和促性腺激素释放激素(GnRH)蛋白的表达呈年龄依赖性改变,下丘脑P1、LBW的ObRb、ER-α的表达增加,而成年LBW的表达模式相反。我们的数据表明,母体营养环境通过改变下丘脑-垂体-性腺轴来规划后代的生殖潜力。LBW后代的过早生殖衰老可能是这些动物成年后肥胖和高瘦素血症发展的继发性疾病。
To determine the effects of maternal undernutrition (MUN) on the reproductive axis of aging offspring. Animal (rat) study. Research Laboratory. Female Sprague-Dawley rats. Food restriction during the second half of pregnancy in rats. Circulating gonadotropins, Anti-Mullerian Hormone (AMH), ovarian morphology, estrous cyclicity and gene expression studies in the hypothalamus and ovary in 1 day old (P1) and aging adult offspring. Offspring of MUN dams had low birth weight (LBW) and by adult age developed obesity. 80% of adult LBW offspring had disruption of estrous cycle by 8 months of age with the majority of animals in persistent estrous. Ovarian morphology was consistent with acyclicity with ovaries exhibiting large cystic structures and reduced corpora lutea. There was an elevation in circulating testosterone (T), increased ovarian expression of enzymes involved in androgen synthesis, an increase in plasma Leuteinizing (LH/)/Follicle Stimulating hormone (FSH) levels, reduced estradiol (E2) levels and no changes in AMH in adult LBW offspring compared to control offspring. Hypothalamic expression of leptin receptor (OBRb), estrogen receptor-α (ER-α) and Gonadotropin Releasing hormone (GnRH) protein were altered in an age-dependent manner with increased ObRb, ER-α expression in P1 LBW hypothalami and a reversal of this expression pattern in adult LBW hypothalami. Our data indicates that the maternal nutritional environment programs reproductive potential of the offspring through alteration of the hypothalamic-pituitary-gonadal axis. The premature reproductive senescence in LBW offspring could be secondary to development of obesity and hyperleptinemia in these animals in adult life.
DOI: 10.1126/science.275.5296.88
发表时间: 1997-01-03
期刊: SCIENCE
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