Brain dopamine imbalance causes follicle death and underlies negative effect of high sugar diet during Drosophila oogenesis

Abstract

Unhealthy diets, obesity, and low fertility are associated in Drosophila and humans. We previously showed that a high sugar diet, but not obesity, reduces Drosophila female fertility owing to increased death of newly formed germline cysts and vitellogenic follicles. Drosophila strains carrying mutations in the yellow (y) and white (w) pigmentation genes are routinely used for investigating the effects of high sugar diets, but it has remained unclear how this genetic background interacts with high sugar. Here, we show that wildtype females retain normal fertility on high sugar compared to control diets, and that mutation of y is responsible for the previously observed vitellogenic follicle death on high sugar. The known requirement of y for melanin biosynthesis from dopamine, as well as the association between high sugar consumption and reduced dopamine in mammals and decreased dopamine responses in male Drosophila, prompted us to investigate potential connections between y, high sugar, dopamine and oogenesis. We found that global impairment of dopamine metabolism leads to vitellogenic follicle degeneration while alleviating dopamine imbalance in y mutant females prevents follicle death on a high sugar diet. Finally, lack of dopamine production in the central nervous system is sufficient for vitellogenic follicle death on a high sugar diet, and severe dopamine imbalance causes follicle death regardless of diet or genetic background. Our findings are broadly relevant to our understanding of how the effects of unhealthy diets might differ depending on genetic factors and highlight a key connection between brain dopamine metabolism and ovarian follicle survival. ARTICLE SUMMARYUnhealthy diets, obesity, and reduced fertility are associated in Drosophila and humans. Recently, we showed that a high sugar diet induces ovarian follicle death and reduces Drosophila fertility independently of obesity. Here, we report that follicle degeneration induced by a high sugar diet depends on genetic background in connection with brain dopamine imbalance. We also show that severe dopamine imbalance increases follicle death regardless of diet or genetic background. These findings are broadly relevant to our understanding of how the effects of unhealthy diets might differ depending on genetic factors and highlight an important connection between dopamine metabolism and oogenesis.