Maternal high-protein diet impairs fetal growth via placental oxidative stress and reduced amino acid transport in mice

Background and Aim: Maternal dietary protein intake plays a vital role in fetal development, placental function, and pregnancy outcomes. This study aimed to evaluate the effects of different levels of maternal dietary protein on reproductive performance in mice, with an emphasis on placental function.
Materials and Methods: A total of 45 female C57BL/6 mice were fed isocaloric purified diets containing 10% (low protein, LP), 20% (moderate protein, MP), or 40% (high protein, HP) protein from conception until gestational day (GD) 18.5. On GD18.5, tissue and blood were collected. The number of total and live fetuses, as well as individual fetal and placental weights, were recorded.
Results: Maternal protein intake did not significantly affect total litter size, live litter size, total litter weight, or average placental weight. However, the HP group exhibited reduced average fetal weight and placental efficiency, suggesting impaired placental function. This impairment was accompanied by elevated oxidative stress in the placenta. Additionally, the expression of genes involved in antioxidant defense and animal acid transport was downregulated in the HP group. In contrast, the LP group showed mild oxidative stress but enhanced antioxidant activity.
Conclusion: In conclusion, although both protein deficiency and excess can disrupt physiological balance, our findings highlight that excessive protein intake was associated with the downregulation of placental amino acid transporters and heightened oxidative stress. These findings highlight a nonlinear response to maternal protein intake and emphasize the importance of maintaining optimal protein levels during pregnancy to support healthy placental function and favorable pregnancy outcomes.