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FASEB J. 2019 Mar 19:fj201802772R. doi: 10.1096/fj.201802772R. [Epub ahead of print]

Chronic gestational hypoxia accelerates ovarian aging and lowers ovarian reserve in next-generation adult rats.

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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.
Department of Physiology, Development, and Neuroscience, University of Cambridge, Cambridge, United Kingdom.
Dipartimento di Scienze Chirurgiche, Universita degli Studi di Torino, Turin, Italy.


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 ( P < 0.05). Adult females who had been exposed to chronic fetal hypoxia had significantly reduced somatic ovarian telomere length ( P < 0.05) and reduced ovarian protein expression of KU70, a critical component of the DNA-activated protein kinase repair complex ( P < 0.01). Gene expression of NADPH oxidase 2-mediated oxidative stress markers was increased ( P < 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.


developmental programming; fetal hypoxia; follicles; ovary; reproductive aging


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