title: Early life exposure to undernutrition induces ER stress, apoptosis, and reduced vascularization in ovaries of adult rat offspring.
abstract: Maternal nutritional restriction has been shown to induce impairments in a number of organ systems including the ovary. We have previously shown that maternal undernutrition induces fetal growth restriction and low birth weight, and results in an offspring ovarian phenotype characteristic of premature ovarian aging with reduced ovarian reserve. In the present study, we set out to investigate the underlying mechanisms that lead offspring of undernourished mothers to premature ovarian aging. Pregnant dams were randomized to 1) a standard diet throughout pregnancy and lactation (control), 2) a calorie-restricted (50% of control) diet during pregnancy, 3) a calorie-restricted (50% of control) diet during pregnancy and lactation, or 4) a calorie-restricted (50% of control) diet during lactation alone. The present study shows that early life undernutrition-induced reduction of adult ovarian follicles may be mediated by increased ovarian endoplasmic reticulum stress in a manner that increased follicular apoptosis but not autophagy. These changes were associated with a loss of ovarian vessel density and are consistent with an accelerated ovarian aging phenotype. Whether these changes are mediated specifically by a reduction in the local antioxidant environment is unclear, although our data suggest the possibility that ovarian melatonin may play a part in early life nutritional undernutrition and impaired offspring folliculogenesis.
authors: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Kaitlyn A
authors: KA
authors: Chan
authors: Liggins Institute and Gravida: National Centre for Growth and Development, University of Auckland, New Zealand.
authors: Angelica B
authors: AB
authors: Bernal
authors: Liggins Institute and Gravida: National Centre for Growth and Development, University of Auckland, New Zealand.
authors: Mark H
authors: MH
authors: Vickers
authors: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors: Wajiha
authors: W
authors: Gohir
authors: Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
authors: Jim J
authors: JJ
authors: Petrik
authors: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada sloboda@mcmaster.ca.
authors: Deborah M
authors: DM
authors: Sloboda
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000502:physiology; D000071186:Beclin-1; D031204:Caloric Restriction; D059865:Endoplasmic Reticulum Stress; D005260:Female; D044342:Malnutrition / Q000503:physiopathology*; D039382:Maternal Nutritional Physiological Phenomena; D018919:Neovascularization, Physiologic; D006080:Ovarian Follicle / Q000378:metabolism / Q000502:physiology; D010053:Ovary / Q000098:blood supply* / Q000254:growth & development; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D000975:Antioxidants; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C512829:Becn1 protein, rat; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: ER stress; apoptosis; follicles; maternal nutrition; ovary; reproduction