« Previous AbstractMotivation and expectancy influences in placebo responding: the mediating role of attention    Next AbstractForages and pastures symposium: managing the tall fescue-fungal endophyte symbiosis for optimum forage-animal production »

J Physiol

Title:		Chronic fetal hypoxia disrupts the peri-conceptual environment in next-generation adult female rats
Author(s):		Aiken CE; Tarry-Adkins JL; Spiroski AM; Nuzzo AM; Ashmore TJ; Rolfo A; Sutherland MJ; Camm EJ; Giussani DA; Ozanne SE;
Address:		"University of Cambridge Metabolic Research Laboratories and MRC Metabolic Diseases Unit, Wellcome Trust-MRC Institute of Metabolic Science, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Cambridge, UK. University Department of Obstetrics and Gynaecology, University of Cambridge, Cambridge, UK. Department of Physiology, Development and Neuroscience, University of Cambridge, Cambridge, UK. Dipartimento di Scienze Chirurgiche, Universita degli Studi di Torino, Turin, Italy"
Journal Title:		J Physiol
Year:		2019
Volume:		20190324
Issue:		9
Page Number:		2391 - 2401
DOI:		10.1113/JP277431
ISSN/ISBN:		1469-7793 (Electronic) 0022-3751 (Print) 0022-3751 (Linking)
Abstract:		"KEY POINTS: Exposure 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 hypoxia in utero have reduced telomere length, decreased mitochondrial DNA biogenesis and increased oxidative stress The 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. ABSTRACT: Exposure 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 of Tfam (P < 0.05) and Pgc1alpha (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"
Keywords:		"Animals DNA, Mitochondrial/genetics Epigenesis, Genetic Female Fertility Fetal Hypoxia/complications/genetics/metabolism/*physiopathology Infertility/*etiology Oviducts/*metabolism/pathology Oxidative Stress Rats Rats, Wistar Telomere Homeostasis Transcri;"
Notes:		"MedlineAiken, Catherine E Tarry-Adkins, Jane L Spiroski, Ana-Mishel Nuzzo, Anna M Ashmore, Thomas J Rolfo, Alessandro Sutherland, Megan J Camm, Emily J Giussani, Dino A Ozanne, Susan E eng MC_UU_12012/4/MRC_/Medical Research Council/United Kingdom WT_/Wellcome Trust/United Kingdom PG/14/5/30546/BHF_/British Heart Foundation/United Kingdom RG/17/8/32924/BHF_/British Heart Foundation/United Kingdom FS/12/74/29778/BHF_/British Heart Foundation/United Kingdom PG/14/5/30547/BHF_/British Heart Foundation/United Kingdom BB/E002668/1/BB_/Biotechnology and Biological Sciences Research Council/United Kingdom RG/06/006/22028/BHF_/British Heart Foundation/United Kingdom MC_UU_00014/4/MRC_/Medical Research Council/United Kingdom Research Support, Non-U.S. Gov't England 2019/02/23 J Physiol. 2019 May; 597(9):2391-2401. doi: 10.1113/JP277431. Epub 2019 Mar 24"