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Updated: Feb 4, 2026
Author Spotlight: Studying the Impact of Maternal Dietary Deficiencies on Long-Term Offspring Health Outcomes
Published on: June 28, 2024
Maternal low-protein diet programmes low ovarian reserve in offspring
Amy L Winship1, Sarah E Gazzard2, Luise A Cullen-McEwen2
1Department of Anatomy and Developmental Biology, Ovarian Biology Laboratory, Biomedicine Discovery Institute, Monash University, Melbourne, Australia.
Insights
Maternal protein restriction from preconception through weaning significantly depletes offspring primordial follicles and increases follicle atresia, impacting future fertility. This highlights the critical role of maternal nutrition in reproductive health.
Area of Science:
- Reproductive Biology
- Developmental Programming
- Nutritional Science
Background:
- Ovarian reserve, established during fetal development, dictates female fertility.
- Maternal undernutrition during gestation and lactation is known to negatively affect offspring reproductive capacity.
- The impact of extended maternal nutritional deficits, encompassing preconception through weaning, on offspring ovarian reserve remains less understood.
Purpose of the Study:
- To investigate the long-term effects of maternal protein restriction, initiated before conception and continued through weaning, on the programming of offspring ovarian reserve.
- To assess the impact of maternal dietary protein levels on primordial follicle numbers and follicle health markers in offspring at different developmental stages.
Main Methods:
- C57BL6/J female mice were fed either a normal (20%) or low (8%) protein diet throughout preconception, pregnancy, and lactation.
- Ovarian tissue was collected from mothers at weaning and from offspring at postnatal day 21 and 24 weeks of age.
- Follicle counts (total and primordial) and assessments of follicle atresia (TUNEL, cleaved caspase-3) and proliferation (pH3) were performed using histological analysis.
Main Results:
- Maternal protein restriction did not affect maternal follicle numbers.
- Offspring exhibited a significant depletion of primordial follicles: 37% at postnatal day 21 and 51% at 24 weeks of age.
- Increased follicle atresia was observed in protein-restricted offspring at both time points, with no changes in other follicle classes or proliferation rates.
Conclusions:
- Maternal dietary protein levels during the critical periods of preconception, in utero development, and early postnatal life significantly influence the ovarian reserve and follicle health of offspring.
- The findings underscore the importance of optimizing maternal nutrition prior to and during pregnancy for long-term offspring reproductive health.
- Further research is warranted to elucidate the mechanisms underlying diet-induced programming of the ovarian reserve.
Abstract:
The ovarian reserve of primordial follicle oocytes is formed during in utero development and represents the entire supply of oocytes available to sustain female fertility. Maternal undernutrition during pregnancy and lactation diminishes offspring ovarian reserve in rats. In mice, maternal oocyte maturation is also susceptible to undernutrition, causing impaired offspring cardiovascular function. We aimed to determine whether programming of the ovarian reserve is impacted in offspring when maternal undernutrition extends from preconception oocyte development through to weaning. C57BL6/J female mice were fed normal protein (20%) or low-protein (8%) diet during preconception, pregnancy and lactation periods. Maternal ovaries were harvested at weaning and offspring ovaries were collected at postnatal day (PN)21 and 24 weeks of age. Total follicle estimates were obtained by histologically sampling one ovary per animal (n = 5/group). There was no impact of diet on maternal follicle numbers. However, in offspring, maternal protein restriction significantly depleted primordial follicles by 37% at PN21 and 51% at 24 weeks (P < 0.05). There were no effects of diet on other follicle classes. Histological analysis showed no differences in the proportion of proliferative follicles (pH3 positive), but increased atresia (cleaved caspase-3-positive, or TUNEL-positive) was detected in ovaries of protein-restricted offspring at both ages (P < 0.05). Our data show that maternal diet during the preconception period, in utero development and early life has significant impacts on follicle endowment and markers of follicle health later in life. This highlights the need for further investigation into the importance of maternal preconception diet for offspring reproductive development and health.
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