Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats.
Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats.
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慢性胎儿缺氧会破坏下一代成年雌性大鼠的围孕期环境。
DOI：
10.1113/jp277431
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发表时间：
2019
期刊：
影响因子：
--
通讯作者：
Aiken CE
中科院分区：
文献类型：
--
作者：
Aiken CE
要点妊娠期暴露于慢性低氧会影响长期的健康和发育，包括生殖能力。如果发育中的输卵管周围环境受到妊娠低氧的影响，那么这可能会对以后的生育和子代的健康产生影响。在本研究中，我们发现长期暴露于慢性低氧下的雌性大鼠输卵管端粒长度缩短，线粒体DNA生物合成减少和氧化应激增加本研究的结果表明，暴露在慢性妊娠低氧环境中会导致成年早期输卵管加速老化，这有助于我们了解发育期间暴露于低氧环境如何影响后代的生殖健康。摘要在胎儿发育过程中暴露于慢性低氧环境对后代的即刻和长期结局具有重要影响。对成年后代的不利影响包括心血管功能受损、代谢紊乱和卵巢加速老化。然而，目前还不清楚女性生殖系统的其他方面是否会受到类似的影响。在本研究中，我们研究了慢性妊娠低氧对发育中的输卵管的影响。Wistar大鼠从交配后第6天到分娩，随机分为常氧(21%)和低氧(13%)两组。产后雌性后代处于常氧状态，直到4个月大。在RNA(定量RT-PCR)和蛋白质(Western Blotting)水平检测输卵管基因的表达。Southern印迹法检测输卵管端粒长度。与常氧对照组相比，妊娠低氧暴露的动物输卵管端粒长度缩短(P<；P<；0.01)。这与妊娠低氧暴露组DNA-PK的KU70亚单位转录后特异性降低有关(P<；P<；0.05)。妊娠低氧暴露的输卵管还显示线粒体DNA生物合成减少，线粒体DNA拷贝数减少(P<；α)，Tfam和Pgc1基因表达降低(P<；Pgc1)。在低氧暴露的输卵管中，线粒体特异的抗氧化防御酶(MnSOD；P<；(0.01))上调。长期妊娠低氧会导致成年后输卵管加速老化。输卵管作为配子运输、联配和早期发育的场所，在早期发育中起着核心作用；因此，输卵管环境的加速老化可能对后代的生育和健康产生重要影响。
Key pointsExposure to chronic hypoxia during gestation influences long‐term health and development, including reproductive capacity, across generations.If the peri‐conceptual environment in the developing oviduct is affected by gestational hypoxia, then this could have implications for later fertility and the health of future generations.In the present study, we show that the oviducts of female rats exposed to chronic hypoxiain uterohave reduced telomere length, decreased mitochondrial DNA biogenesis and increased oxidative stressThe results of the present study show that exposure to chronic gestational hypoxia leads to accelerated ageing of the oviduct in early adulthood and they help us understand how exposure to hypoxia during development could influence reproductive health across generations.AbstractExposure to chronic hypoxia during fetal development has important effects on immediate and long‐term outcomes in offspring. Adverse impacts in adult offspring include impairment of cardiovascular function, metabolic derangement and accelerated ovarian ageing. However, it is not known whether other aspects of the female reproductive system may be similarly affected. In the present study, we examined the impact of chronic gestational hypoxia on the developing oviduct. Wistar rat dams were randomized to either normoxia (21%) or hypoxia (13%) from day 6 post‐mating until delivery. Post‐delivery female offspring were maintained in normoxia until 4 months of age. Oviductal gene expression was assayed at the RNA (quantitative RT‐PCR) and protein (western blotting) levels. Oviductal telomere length was assayed using Southern blotting. Oviductal telomere length was reduced in the gestational hypoxia‐exposed animals compared to normoxic controls (P< 0.01). This was associated with a specific post‐transcriptional reduction in the KU70 subunit of DNA‐pk in the gestational hypoxia‐exposed group (P< 0.05). Gestational hypoxia‐exposed oviducts also showed evidence of decreased mitochondrial DNA biogenesis, reduced mtDNA copy number (P< 0.05) and reduced gene expression ofTfam(P< 0.05) andPgc1α(P< 0.05). In the hypoxia‐exposed oviducts, there was upregulation of mitochondrial‐specific anti‐oxidant defence enzymes (MnSOD;P< 0.01). Exposure to chronic gestational hypoxia leads to accelerated ageing of the oviduct in adulthood. The oviduct plays a central role in early development as the site of gamete transport, syngamy, and early development; hence, accelerated ageing of the oviductal environment could have important implications for fertility and the health of future generations.