Abstract
Diet significantly affects reproductive outcomes across species, yet the precise effects of macronutrient compositions beyond caloric intake on reproductive aging are understudied. Existing literature presents conflicting views on the fertility impacts of nutrient-rich versus nutrient-poor developmental diets, underscoring a notable research gap. This study addresses these gaps by examining effects of isocaloric diets with varied protein-to-carbohydrate ratios during both developmental and adult stages on reproductive aging of a large, outbred Drosophila melanogaster population (n = ∼2100). Our results clearly demonstrate an age-dependent dietary impact on reproductive output, initially dominated by the developmental diet, then by a combination of developmental and adult diets in early to mid-life, and ultimately by the adult diet in later life. Importantly, we found that the effects of developmental and adult diets on reproductive output are independent, with no significant interaction. Further investigations into the mechanisms revealed that the effect of developmental diet on fecundity is regulated via ovarioles formation and vitellogenesis; while, the effect of adult diet on fecundity is mostly regulated only via vitellogenesis. These insights resolve disputes in the literature about dietary impacts on fertility and offer valuable perspectives for optimizing fertility strategies in improving public health and conservation efforts in this changing world.