Maternal Micronutrient Supplementation Modulates Fetal Brain Development and Neuronal Architecture in Male Wistar Rats

Abstract

Maternal nutrition, particularly micronutrient intake, is a major non-genetic determinant of fetal brain development. Maternal malnutrition remains a widespread cause of neurodevelopmental impairment, contributing to the global burden of undernutrition that affects approximately 840 million people and results in over six million childhood deaths annually. This study investigated the effects of selected micronutrients, iron, copper, and selenium, on the structural and biochemical development of the fetal brain in male Wistar rats (Rattus norvegicus). Eighteen female and six male rats were randomly assigned to six groups (three females and one male per group). Following confirmation of mating (gestation day 0), experimental diets were administered from gestation days 5 to 19. Group 1 received standard grower’s mash (control), while Group 2 was fed a chaff-and-water diet (malnourished control). Groups 3, 4, and 5 received diets supplemented with copper (8 mg/kg), iron (40 mg/kg), and selenium (0.2 mg/kg), respectively, and Group 6 received a combination of all three micronutrients at the same concentrations. On gestation day 20, the pregnant rats were euthanised; fetal morphometry and brain samples were collected for metal content analysis and histological assessment. Selenium supplementation significantly increased fetal crown-rump length and brain selenium concentration compared to all other groups (p < 0.0001). Iron supplementation produced the highest fetal and brain weights as well as increased brain iron levels (p < 0.0001). Histological analysis revealed that fetuses from the copper, iron, selenium, and combined-supplement groups exhibited well-defined pyramidal neurons. In contrast, fetuses from the control and chaff-fed groups showed disorganised or irregular neuronal architecture. Adequate maternal micronutrient intake, particularly of selenium and iron, is crucial for normal fetal brain development. Conversely, maternal undernutrition adversely affects neuronal cytoarchitecture, underscoring the need for improved maternal nutrition to prevent neurodevelopmental deficits.