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Using a Murine Model of Psychosocial Stress in Pregnancy as a Translationally Relevant Paradigm for Psychiatric Disorders in Mothers and Infants
Published on: June 13, 2021
Prenatal stress programming of offspring feeding behavior and energy balance begins early in pregnancy
Diana E Pankevich1, Bridget R Mueller, Becky Brockel
1Department of Animal Biology, University of Pennsylvania, Philadelphia, PA 19104, United States.
Insights
Prenatal stress in mice programs offspring feeding behaviors and energy balance, with effects seen early in development. These changes were diet-dependent and sex-specific, impacting body weight and composition.
Area of Science:
- Reproductive biology
- Developmental biology
- Endocrinology
Background:
- Prenatal stress (PNS) can impact offspring health and behavior.
- Early gestation is a critical window for fetal programming.
- The long-term effects of early pregnancy stress on energy homeostasis are not fully understood.
Purpose of the Study:
- To investigate the long-term effects of stress during early gestation on offspring feeding behaviors and energy balance.
- To determine the sex-specific programming effects of prenatal stress.
- To explore the role of placental gene expression in mediating these effects.
Main Methods:
- Pregnant mice were exposed to stress during early pregnancy (days 1-7).
- Offspring were examined on chow and high-fat diets for feeding behavior and energy balance.
- Placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) and insulin-like growth factor 2 (IGF-2) expression was measured.
Main Results:
- PNS mice exhibited basal hyperphagia on a chow diet, which was ameliorated on a high-fat diet.
- PNS male mice had reduced body weights and altered body composition (less fat, more lean mass) on both diets.
- Early PNS was associated with increased placental IGF-2 expression and sex-dependent effects on 11 beta-HSD2.
Conclusions:
- Long-term programming of feeding behavior and energy homeostasis by prenatal stress begins earlier than previously thought.
- Prenatal stress can induce sex-specific, long-lasting changes in offspring metabolism.
- Placental gene expression changes may underlie the programming effects of early prenatal stress.
Abstract:
To examine the long-term effects of stress experienced early in gestation on the programming of offspring feeding behaviors and energy balance, pregnant mice were exposed to stress during early pregnancy (days 1-7) and adult offspring examined on chow and high fat diets for long-term outcomes. Placental 11 beta-hydroxysteroid dehydrogenase type 2 (11 beta-HSD2) and insulin-like growth factor 2 (IGF-2) expression was measured to determine the possible sex-specific contribution of prenatal stress (PNS) on fetal programming of embryo growth and development during early pregnancy. PNS mice showed a basal hyperphagia when on chow diet. Prenatal treatment differences were ameliorated when adult mice were on a high fat diet. Interestingly, PNS male mice also had significantly reduced body weights compared to control males on both chow and high fat diets. Body composition analyses revealed reduced body fat and increased lean mass in PNS mice on the high fat diet, but no differences were detected in plasma leptin or insulin-like growth factor 1 (IGF-1) levels. Mechanistic examination of gene expression in embryonic day 12 placentas found that early PNS was associated with increased IGF-2 expression and sex-dependent effects of stress on 11 beta-HSD2, supporting specific aspects of early pregnancy. These studies suggest that the long-term effects of stress during pregnancy on programming of feeding behavior and energy homeostasis begin much earlier in development than previously thought.
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