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Transgenerational Developmental Programming of Ovarian Reserve.

Published version
Peer-reviewed

Type

Article

Change log

Authors

Aiken, CE 
Tarry-Adkins, JL 
Ozanne, SE 

Abstract

Exposure to an adverse early-life environment leads to long-term health problems, many of which are recapitulated in subsequent generations. The female reproductive tract is particularly sensitive to early-life influences, and plays a pivotal role in programming the conceptus. We examine the influence of suboptimal grandmaternal diet on reproductive potential of granddaughters in the absence of any further dietary manipulations in the daughters in a rat low-protein diet model. Exposure to low-protein grand-maternal diet leads to decreased ovarian reserve and increased intra-abdominal fat mass in granddaughters, accompanied by accelerated accumulation of oxidative stress and mtDNA copy number instability in the ovaries. Ovarian telomere length declines more rapidly in the exposed granddaughters, indicating accelerated ageing in the reproductive tract. Thus, we demonstrate that suboptimal grandmaternal diet during pregnancy accelerates reproductive ageing across subsequent generations. These findings have important implications for understanding both individual rates of decline in fertility with age, and the clinical impact of current global trends towards delayed childbearing.

Description

Keywords

Aging, Aldehydes, Animals, Anti-Mullerian Hormone, Antioxidants, Blood Glucose, Body Weight, DNA, Mitochondrial, Diet, Protein-Restricted, Enzyme-Linked Immunosorbent Assay, Female, Gene Dosage, Intra-Abdominal Fat, Ovarian Reserve, Ovary, Oxidative Stress, Pregnancy, Rats, Telomere

Journal Title

Sci Rep

Conference Name

Journal ISSN

2045-2322
2045-2322

Volume Title

5

Publisher

Springer Science and Business Media LLC
Sponsorship
British Heart Foundation (None)
Medical Research Council (MC_UU_12012/4)
Medical Research Council (MC_UU_12012/5)
Medical Research Council (MC_PC_12012)
This study was funded jointly by grants from the Academy of Medical Sciences, the Addenbrooke’s Charitable Trust, an Isaac Newton Trust/Wellcome Trust ISSF/ University of Cambridge Joint Research Grant and the MRC (MRC_MC_UU_12012/4).