EFFECTS OF MATERNAL LOW-PROTEIN AND PHYTOESTROGEN-ENRICHED DIETS ON THE CORRELATION BETWEEN EATING BEHAVIORS AND ANXIETY IN OFFSPRING

Ricci E^1,2, Ontiveros N¹, Bellantoni MT³, Lafaenza S^1,4, Gotti S^1,2 and Marraudino M^1,2 | ¹Neuroscience Institute Cavalieri Ottolenghi (NICO), Orbassano (TO), Italy; ²Department of Neuroscience Rita Levi Montalcini, University of Torino, Torino, Italy; ³Department of Medicine and Surgery, Neuroscience Unit, University of Parma; ⁴Department of Science and Technological Innovation, DISIT, University of Eastern Piedmont

Maternal nutrition during pregnancy and lactation represents a crucial determinant of offspring health, with long-term effects on metabolic and neurobehavioral development. This study examined the effects of altered diets during pregnancy and lactation on adult rat pups that received a standard postnatal diet. Since in often altered low-protein diets proteins are supplemented with foods rich in phytoestrogens, such as soy, four groups were compared: low-protein maternal diet (LOW), genistein-enriched diet (GEN), a combination of both (LOWGIN), and a control group (CON). Maternal milk composition and various offspring parameters were analyzed, including metabolic measures, (body weight and intake), behavioral assessments (EPM and OF tests), and neurochemical markers of the hypothalamic POMC system and serotonergic systems (immunohistochemistry for 5-HT in the Raphe, and POMC, 5-HT, and 5-HT₂C in the arcuate nucleus of the hypothalamus). Maternal protein restriction significantly reduced milk protein and fat content, hindered neonatal growth, and decreased POMC expression, while also increasing 5-HT₂C receptors levels, making it more difficult for the neonate to adapt to changes and new stimuli. The phytoestrogen Genistein, increased milk lipid content and neonatal weight, suggesting a potential obesogenic effect in female pups. The long-term effects of genistein were sexspecific: males exhibited enhanced serotonergic sensitivity, characterized by increased expression of the 5-HT system, and an anxiolytic behavioral profile. In contrast, females showed serotonergic hyperactivity. The combination of the two diets displayed milk composition and metabolic parameters similar to those of the LOW group, suggesting a predominant effect of protein restriction that overrides the potential benefits of genistein. Behaviorally, profiles were sexually dimorphic: males showed anxiety, whereas females displayed an anxiolytic profile similar to GEN females, highlighting greater female sensitivity to genistein’s estrogenic effects. Overall, the results demonstrate that early nutritional programming has a stable influence on the development of metabolic and emotional circuits in a sex-specific manner, underscoring the importance of adequate protein intake during pregnancy and lactation, as well as the cautious evaluation of phytoestrogen consumption during critical periods, when maternal dietary choices can have lasting consequences for offspring health.