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HPA axis programming by maternal undernutrition in the male rat offspring
Didier Vieau1, Naima Sebaai, Marion Léonhardt
1Laboratory of Adaptative Neurosciences and Physiology, Perinatal Stress Unit, University of Lille1, 59655 Villeneuve d'Ascq Cedex, France. didier.vieau@univ-lille1.fr
Insights
Maternal undernutrition during pregnancy programs the hypothalamic-pituitary-adrenal (HPA) axis, leading to altered stress responses and potential chronic adult diseases with neurodevelopmental origins.
Area of Science:
- Endocrinology
- Developmental Biology
- Neuroscience
Background:
- Perinatal undernutrition is linked to adult chronic diseases.
- Early life nutrition impacts the hypothalamic-pituitary-adrenal (HPA) axis throughout life.
- Existing research on fetal programming yields variable results due to diverse experimental designs.
Purpose of the Study:
- To investigate the long-term effects of severe maternal undernutrition on male rat offspring's HPA axis activity from fetal stage to adulthood.
- To establish a consistent experimental protocol for studying fetal programming of the HPA axis.
Main Methods:
- Maternal rats received 50% of normal intake (FR50) during the last week of gestation and lactation.
- HPA axis activity was assessed in fetuses, at weaning, and in young (4-month) and older (8-month) adult male offspring.
- Placental 11beta-HSD2 activity and transplacental glucocorticoid transfer were measured.
Main Results:
- FR50 fetuses showed reduced HPA axis function, decreased placental 11beta-HSD2 activity, and increased glucocorticoid transfer.
- At weaning, offspring exhibited reduced HPA axis activity following stress.
- Young adults displayed subtle HPA axis alterations, while older adults showed chronic hyperactivity.
Conclusions:
- Severe maternal undernutrition during gestation and lactation programs the HPA axis, causing lasting changes in stress response.
- These HPA axis alterations may contribute to adult pathologies like metabolic, cognitive, immune, and inflammatory diseases.
- Fetal undernutrition represents a significant neurodevelopmental origin for adult-onset chronic diseases.
Abstract:
Epidemiological and experimental studies have demonstrated that perinatal alterations such as maternal undernutrition are frequently associated with the onset of several chronic adult diseases. Although the physiological mechanisms involved in this "fetal programming" remain largely unknown, it has been shown that early exposure to undernutrition programs hypothalamic-pituitary-adrenal (HPA) axis throughout lifespan. However, the wide spectrum of experimental paradigms used (species, sex, age of the animals, and duration and severity of undernutrition exposure) has given rise to variable results that are difficult to interpret. To circumvent this problem, we used the same experimental protocol of maternal food restriction to study the effects of a severe maternal undernutrition on the HPA axis activity in the male rat offspring throughout the life, namely from fetal stage to adulthood. Mothers exposed to food restriction received 50% (FR50) of the daily intake of pregnant dams during the last week of gestation and lactation. In FR50 fetuses, HPA axis function was reduced and associated with a decreased placental 11beta-HSD2 activity and a greater transplacental transfer of glucocorticoids. At weaning, maternal food restriction reduced HPA axis activity in response to an ether inhalation stress. In young adults (4-month-old), only fine HPA axis alterations were observed, whereas in older ones (8-month-old), maternal undernutrition was associated with chronic hyperactivity of this neuroendocrine axis. Interestingly, excessive glucocorticoids production is observed in a growing number of pathologies such as metabolic, cognitive, immune and inflammatory diseases, suggesting that they could, at least in part, result from fetal undernutrition and thus have a neurodevelopmental origin.
