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Published on: November 20, 2015
Maternal undernutrition during the preimplantation period of rat development causes blastocyst abnormalities and
W Y Kwong1, A E Wild, P Roberts
1Division of Cell Sciences, School of Biological Sciences, University of Southampton, Bassett Crescent East, Southampton SO16 7PX, UK.
Insights
Maternal protein undernutrition during early embryonic development can irreversibly program offspring for adult diseases like hypertension. This occurs even with later nutritional recovery, impacting fetal growth and postnatal physiology.
Area of Science:
- Developmental Biology
- Reproductive Medicine
- Nutritional Science
Background:
- Epidemiological studies link intrauterine growth restriction and low birth weight to adult hypertension and cardiovascular disease.
- The 'fetal origins of adult disease' hypothesis is relevant to preventative healthcare, but mechanisms of fetal programming remain unclear.
Purpose of the Study:
- To investigate the origin, embryonic phenotype, and maternal mechanisms of programming induced by maternal undernutrition during the preimplantation period.
- To determine if programming of postnatal growth and physiology can be initiated during this critical early developmental window.
Main Methods:
- A rat model was used, with maternal low protein diet (LPD) administered only during the preimplantation period (days 0-4.25 post-mating).
- Offspring were assessed for birth weight, postnatal growth, hypertension, and organ/body-weight ratios up to 12 weeks of age.
- Preimplantation embryos were analyzed for cell number, proliferation rates, and apoptosis. Maternal serum was analyzed for glucose, insulin, and amino acid levels.
Main Results:
- Maternal LPD during the preimplantation period induced programming of altered birth weight, postnatal growth, and hypertension in offspring.
- Preimplantation embryos showed reduced cell numbers, primarily due to slower proliferation, affecting both inner cell mass and trophectoderm lineages.
- Maternal serum exhibited reduced insulin and essential amino acid levels, with increased glucose levels by day 4 of development.
Conclusions:
- Long-term programming of postnatal growth and physiology can be irreversibly induced during the preimplantation period by maternal protein undernutrition.
- A maternal hyperglycemic and amino acid-depleted environment during early development may act as a programming mechanism, restricting embryonic proliferation and stem cell lineage development.
Abstract:
Epidemiological studies have indicated that susceptibility of human adults to hypertension and cardiovascular disease may result from intrauterine growth restriction and low birth weight induced by maternal undernutrition. Although the 'foetal origins of adult disease' hypothesis has significant relevance to preventative healthcare, the origin and biological mechanisms of foetal programming are largely unknown. Here, we investigate the origin, embryonic phenotype and potential maternal mechanisms of programming within an established rat model. Maternal low protein diet (LPD) fed during only the preimplantation period of development (0-4.25 days after mating), before return to control diet for the remainder of gestation, induced programming of altered birthweight, postnatal growth rate, hypertension and organ/body-weight ratios in either male or female offspring at up to 12 weeks of age. Preimplantation embryos collected from dams after 0-4.25 days of maternal LPD displayed significantly reduced cell numbers, first within the inner cell mass (ICM; early blastocyst), and later within both ICM and trophectoderm lineages (mid/late blastocyst), apparently induced by a slower rate of cellular proliferation rather than by increased apoptosis. The LPD regimen significantly reduced insulin and essential amino acid levels, and increased glucose levels within maternal serum by day 4 of development. Our data indicate that long-term programming of postnatal growth and physiology can be induced irreversibly during the preimplantation period of development by maternal protein undernutrition. Further, we propose that the mildly hyperglycaemic and amino acid-depleted maternal environment generated by undernutrition may act as an early mechanism of programming and initiate conditions of 'metabolic stress', restricting early embryonic proliferation and the generation of appropriately sized stem-cell lineages.
