Altered maternal nutrition affects the stress axis of the mother and offspring

Offspring health can be affected by maternal nutrition during pregnancy. For instance, a low-protein diet may pose a greater risk to their physical and neurological development. Therefore, dietary supplements such as soybeans, which are rich in phytoestrogens, particularly Genistein (GEN), are recommended to address deficiencies in maternal diets during pregnancy. Phytoestrogens, particularly Genistein (GEN), are classified as endocrine disruptors due to their ability to bind to estrogen receptors, affecting various estrogen-sensitive neural systems, including the stress axis. In this study, we examined the effects on the HPA axis both directly of the mothers and in the offspring in Sprague Dawley rats of a chronic maternal diet low in protein (8%) with and without GEN. Molecular analysis by RT-PCR of the brains of mothers sacrificed at the end of lactation demonstrate a strong alteration of the stress axis, mainly with reduced expression of glucocorticoid receptors at both hypothalamic and hippocampal levels in all treated groups. The brain is particularly sensitive to changes in energy production that occur during sustained stress signaling, analysis by WB revealed alterations in ATP production within the treated groups in the hypothalamus and hippocampus. Moreover, analysis of breast milk revealed lower protein and fat content in two experimental groups, pups born to these mothers from birth are smaller and have never resumed normal development, remaining consistently underweight. The HPA axis analysis at PND1 of these pups demonstrated a sexually dimorphic effect with altered stress axis, especially in females, as well as reduced energy production. In adulthood, these animals were subjected to behavioral tests (Open Field and Elevated Plus Maze), and the females showed anxiety-like behaviors, particularly in females born to mothers on a low-protein diet supplemented with GEN. In conclusion, these results show that maternal diet is essential to preserve in a delicate phase such as pregnancy the stress axis. In fact, the diet if inadequate could turn into a chronic maternal stressor that if enriched with endocrine interferents can lead to sexually dimorphic alterations in the neurodevelopment of the offspring.