University of Cambridge Metabolic Research Laboratories and Medical Research Council (MRC) Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, United Kingdom.
Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, United Kingdom.
FASEB J. 2019 Jun;33(6):7758-7766. doi: 10.1096/fj.201802772R. Epub 2019 Mar 19.
Chronic fetal hypoxia is a common complication observed in human pregnancy, impacting pregnancies across global contexts. Exposure to chronic intrauterine hypoxia has major short- and long-term consequences for offspring health. However, the impact of chronic gestational hypoxia on female reproductive system development is unknown. We aimed to understand the impact of exposure to chronic fetal hypoxia on the developing female reproductive system. Wistar rat dams underwent normoxia (21%) or hypoxia (13%) during pregnancy. Postnatally, all female offspring were maintained in normoxic conditions into early adulthood. Female rats exposed to chronic gestational hypoxia (13%) during their intrauterine development had decreased ovarian primordial follicular reserve compared to controls ( < 0.05). Adult females who had been exposed to chronic fetal hypoxia had significantly reduced somatic ovarian telomere length ( < 0.05) and reduced ovarian protein expression of KU70, a critical component of the DNA-activated protein kinase repair complex ( < 0.01). Gene expression of NADPH oxidase 2-mediated oxidative stress markers was increased ( < 0.05). Exposure to chronic hypoxia during fetal development leads to accelerated aging of the somatic ovary and decreased ovarian reserve in adulthood. Ovarian aging is highly sensitive to gestational hypoxia, with implications for future fertility in next-generation offspring of high-risk pregnancies.-Aiken, C. E., Tarry-Adkins, J. L., Spiroski, A.-M., Nuzzo, A. M., Ashmore, T. J., Rolfo, A., Sutherland, M. J., Camm, E. J., Giussani, D. A., Ozanne, S. E. Chronic gestational hypoxia accelerates ovarian aging and lowers ovarian reserve in next-generation adult rats.
慢性胎儿缺氧是人类妊娠中常见的并发症，影响着全球范围内的妊娠。暴露于慢性宫内缺氧会对后代的健康产生重大的短期和长期后果。然而，慢性妊娠期缺氧对女性生殖系统发育的影响尚不清楚。我们旨在了解暴露于慢性胎儿缺氧对发育中女性生殖系统的影响。Wistar 大鼠孕鼠在孕期接受常氧（21%）或缺氧（13%）。产后，所有雌性后代均在常氧条件下维持至成年早期。与对照组相比，在宫内发育过程中暴露于慢性妊娠期缺氧（13%）的雌性大鼠卵巢原始卵泡储备减少（<0.05）。在成年期暴露于慢性胎儿缺氧的雌性大鼠的体卵巢端粒长度显著缩短（<0.05），卵巢中 DNA 激活蛋白激酶修复复合物的关键组成部分 KU70 的蛋白表达减少（<0.01）。NADPH 氧化酶 2 介导的氧化应激标志物的基因表达增加（<0.05）。在胎儿发育过程中暴露于慢性缺氧会导致体卵巢加速衰老和成年后卵巢储备减少。卵巢衰老对妊娠期缺氧高度敏感，对高危妊娠下一代的未来生育能力有影响。-Aiken, C. E., Tarry-Adkins, J. L., Spiroski, A.-M., Nuzzo, A. M., Ashmore, T. J., Rolfo, A., Sutherland, M. J., Camm, E. J., Giussani, D. A., Ozanne, S. E. 慢性妊娠期缺氧加速卵巢衰老并降低下一代成年大鼠的卵巢储备。
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