The impact of a high folic acid and low vitamin B12 diet on oxidative stress in dams at delivery and young offspring: Sex matters.

Maternal micronutrient imbalances during pregnancy can interfere with fetal development by affecting oxidative stress pathways. Folic acid (FA) and vitamin B12, essential components of one-carbon metabolism, are especially crucial. This study examined the effects of a high-folic-acid and low-vitamin-B12 (HFALB12) diet on oxidative stress markers in pregnant mice and their offspring, with a focus on sex-specific responses. Female C57BL/6 mice were fed either a HFALB12 or a control (normal FA and B12) diet before and during pregnancy until weaning. Offspring were exposed to the same maternal diet post-weaning until 60-65 days of age. Total homocysteine (tHcy) was measured in plasma, while markers of oxidative stress-thiobarbituric acid reactive substances (TBARS), protein carbonyls, and glutathione (tGSH, rGSH, GSSG)-were assessed in placentas and liver tissues of dams and adult offspring. Dams of the HFALB12 diet had significantly elevated tHcy, and their livers and placentas showed higher TBARS (p < 0.05). Offspring from the HFALB12 group were heavier at weaning than those from the control group. In adult offspring, HFALB12 exposure increased hepatic tGSH and GSSG; notably, only females showed elevated rGSH and reduced carbonyl content, indicating a sex-specific redox response. Results demonstrated that a maternal HFALB12 diet alters oxidative stress profiles in maternal livers and placentas, and in offspring tissues, as a consequence of a combined maternal and post-weaning diet, with enhanced redox adaptation in females. These findings support the concept of early sex-specific developmental programming in response to micronutrient imbalance before and after weaning.