title: Suboptimal nutrition in utero causes DNA damage and accelerated aging of the female reproductive tract.
abstract: Early life exposure to adverse environments can lead to a variety of metabolic and cardiovascular diseases in offspring. We hypothesize that female reproductive function may also be affected, with subsequent implications for fertility. We used an established maternal low-protein model where animals are born small but undergo rapid postnatal catch-up growth by suckling a control-fed dam (recuperated offspring). Markers of oxidative stress and cellular aging in reproductive tract tissues were assessed at 3 and 6 mo of age. Recuperated offspring had lower birth weight than controls (P<0.01) but caught up during lactation. 4-Hydroxynonenal (4HNE; an indicator of oxidative stress) was increased in recuperated animals compared with controls in both ovaries and oviducts at 6 mo. At 3 and 6 mo, ovaries and oviducts of recuperated offspring had increased mitochondrial (mt)DNA copy number (P<0.01). By contrast, germ-line cells showed no difference in mtDNA copy number, suggesting they were protected from suboptimal maternal nutrition. Oviduct and somatic ovarian telomere length declined more rapidly with age in recuperated animals. This accelerated cellular aging was associated with a declined ovarian reserve in developmentally programmed animals. These findings have significant clinical implications in light of worldwide trends to delayed childbearing.
authors.affiliation: 1University of Cambridge Metabolic Research Laboratories, Institute of Metabolic Science, Level 4, Box 289, Addenbrooke's Treatment Centre, Addenbrooke's Hospital, Hills Rd., Cambridge, CB2 OQQ, UK. cema2@cam.ac.uk.
authors.forename: Catherine E
authors.initials: CE
authors.lastname: Aiken
authors.forename: Jane L
authors.initials: JL
authors.lastname: Tarry-Adkins
authors.forename: Susan E
authors.initials: SE
authors.lastname: Ozanne
mesh_terms: D000818:Animals; D054304:Anti-Mullerian Hormone / Q000097:blood; D001786:Blood Glucose; D001835:Body Weight; D004249:DNA Damage; D004272:DNA, Mitochondrial; D004044:Dietary Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D039382:Maternal Nutritional Physiological Phenomena; D009929:Organ Size; D006080:Ovarian Follicle; D010057:Oviducts / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017208:Rats, Wistar
chemical_list: D001786:Blood Glucose; D004272:DNA, Mitochondrial; D004044:Dietary Proteins; D054304:Anti-Mullerian Hormone
keywords: developmental programming; mitochondrial DNA; reproduction; senescence