title: Maternal High-Fat Diet-Induced Loss of Fetal Oocytes Is Associated with Compromised Follicle Growth in Adult Rat Offspring.
abstract: Maternal obesity predisposes offspring to metabolic and reproductive dysfunction. We have shown previously that female rat offspring born to mothers fed a high-fat (HF) diet throughout pregnancy and lactation enter puberty early and display aberrant reproductive cyclicity. The mechanisms driving this reproductive phenotype are currently unknown thus we investigated whether changes in ovarian function were involved. Wistar rats were mated and randomized to: dams fed a control diet (CON) or dams fed a HF diet from conception until the end of lactation (HF). Ovaries were collected from fetuses at Embryonic Day (E) 20, and neonatal ovaries at Day 4 (P4), prepubertal ovaries at P27 and adult ovaries at P120. In a subset of offspring, the effects of a HF diet fed postweaning were evaluated. The present study shows that fetuses of mothers fed a HF diet had significantly fewer oocytes at E20, and in neonates, have reduced AMH signaling that may facilitate an increased number of assembled primordial follicles. Both prepubertally and in adulthood, ovaries show increased follicular atresia. As adults, offspring have reduced FSH responsiveness, low expression levels of estrogen receptor alpha (Eralpha), the oocyte-secreted factor, Gdf9, oocyte-specific RNA binding protein, Dazl, and high expression levels of the granulosa-cell derived factor, AMH, in antral follicles. Together, these data suggest that ovarian compromise in offspring born to HF-fed mothers may arise from changes already observable in the fetus and neonate and in the long term, associated with increased follicular atresia through adulthood.
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Tsoulis
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Pauline E
authors.initials: PE
authors.lastname: Chang
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Caroline J
authors.initials: CJ
authors.lastname: Moore
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Kaitlyn A
authors.initials: KA
authors.lastname: Chan
authors.affiliation: Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
authors.forename: Wajiha
authors.initials: W
authors.lastname: Gohir
authors.affiliation: Department of Obstetrics and Gynecology, McMaster University, Hamilton, Ontario, Canada Department of Biomedical Sciences, University of Guelph, Guelph, Ontario, Canada.
authors.forename: James J
authors.initials: JJ
authors.lastname: Petrik
authors.affiliation: Liggins Institute and Gravida, National Centre for Growth and Development, University of Auckland, Aukland, New Zealand.
authors.forename: Mark H
authors.initials: MH
authors.lastname: Vickers
authors.affiliation: Department of Health Sciences, Carleton University, Ottawa, Ontario, Canada.
authors.forename: Kristin L
authors.initials: KL
authors.lastname: Connor
authors.affiliation: 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.forename: Deborah M
authors.initials: DM
authors.lastname: Sloboda
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D005315:Fetal Diseases / Q000209:etiology* / Q000473:pathology; D009865:Oocytes; D006080:Ovarian Follicle / Q000254:growth & development* / Q000473:pathology; D010641:Phenotype; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
keywords: atresia; maternal nutrition; ovary; primordial follicle; reproduction