Patrycja A Jazwiec1, Xinglin Li1, Brad Matushewski2,3,4,5,6, Bryan S Richardson2,3,4,5,6, Deborah M Sloboda1,7,8. 1. Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Canada. 2. Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada. 3. Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada. 4. Department of Pediatrics, University of Western Ontario, London, Ontario, Canada. 5. Children's Health Research Institute, University of Western Ontario, London, Ontario, Canada. 6. Schulich School of Medicine and Dentistry, University of Western Ontario, London, Ontario, Canada. 7. Departments of Pediatrics and Obstetrics and Gynecology, McMaster University, Hamilton, Canada. 8. Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton, Canada.
Abstract
BACKGROUND: The mechanisms mediating the impacts of fetal growth restriction (FGR) on follicular development are commonly studied in mouse/rat models, where ovarian development occurs largely during the early postnatal period. These models have shown that FGR is associated with premature follicle loss, early pubertal onset, and accelerated ovarian aging. Whether the same occurs in precocious species is unknown. OBJECTIVE: Since guinea pig follicle development occurs in utero in a manner consistent with human ovarian development, we sought to determine whether FGR had similar impacts on guinea pig ovarian development. METHODS: Dunkin-Hartley guinea pig dams were randomized to receive a control (CON) or a nutrient-restricted diet (FGR) prior to conception until weaning. Offspring ovaries were collected at prepubertal (postnatal day [P] 25) and young adult (P110) time points. RESULTS: Prepubertal offspring exposed to FGR showed little differences in ovarian transcript levels and follicle counts. Young adult FGR offspring, however, showed reductions in the number of transitioning, primary, and antral follicles, as well as corpora lutea. This loss in follicles was associated with reduced insulin-like growth factor receptor and growth differentiation factor-9 messenger RNA levels in FGR P110 offspring compared to CON. CONCLUSION: We demonstrate that FGR in guinea pigs is accompanied by perturbations in signaling pathways essential for proper follicle growth and manifests as reductions in growing follicles in offspring, but these changes do not manifest until postpuberty. These data support the fact that accelerated reproductive maturation/aging is a conserved phenotype that is associated with in utero nutritional adversity.
BACKGROUND: The mechanisms mediating the impacts of fetal growth restriction (FGR) on follicular development are commonly studied in mouse/rat models, where ovarian development occurs largely during the early postnatal period. These models have shown that FGR is associated with premature follicle loss, early pubertal onset, and accelerated ovarian aging. Whether the same occurs in precocious species is unknown. OBJECTIVE: Since guinea pig follicle development occurs in utero in a manner consistent with human ovarian development, we sought to determine whether FGR had similar impacts on guinea pig ovarian development. METHODS: Dunkin-Hartley guinea pig dams were randomized to receive a control (CON) or a nutrient-restricted diet (FGR) prior to conception until weaning. Offspring ovaries were collected at prepubertal (postnatal day [P] 25) and young adult (P110) time points. RESULTS: Prepubertal offspring exposed to FGR showed little differences in ovarian transcript levels and follicle counts. Young adult FGR offspring, however, showed reductions in the number of transitioning, primary, and antral follicles, as well as corpora lutea. This loss in follicles was associated with reduced insulin-like growth factor receptor and growth differentiation factor-9 messenger RNA levels in FGR P110 offspring compared to CON. CONCLUSION: We demonstrate that FGR in guinea pigs is accompanied by perturbations in signaling pathways essential for proper follicle growth and manifests as reductions in growing follicles in offspring, but these changes do not manifest until postpuberty. These data support the fact that accelerated reproductive maturation/aging is a conserved phenotype that is associated with in utero nutritional adversity.
Authors: Angelika V Timofeeva; Ivan S Fedorov; Alexander G Brzhozovskiy; Anna E Bugrova; Vitaliy V Chagovets; Maria V Volochaeva; Natalia L Starodubtseva; Vladimir E Frankevich; Evgeny N Nikolaev; Roman G Shmakov; Gennady T Sukhikh Journal: Diagnostics (Basel) Date: 2021-04-20