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Drummond-Barbosa, D.

Publications and source records attributed to Drummond-Barbosa, D..

3 recordsLinked to original sources

Distinct transcriptional responses to mild cold versus warm temperatures in adult Drosophila melanogaster ovaries

Temperature influences fertility across diverse organisms, yet the mechanisms underlying how suboptimal temperatures affect gamete production and quality remain largely unknown. We previously showed that chronic exposure of adult Drosophila melanogaster females to mild cold promotes the maintenance of germline stem cells (GSCs) and high oocyte quality over time despite reducing the rates of oogenesis, while exposure to warm temperature causes death of early germline cysts and vitellogenic follicles and a severe decrease in oocyte quality. To explore potential mechanisms underlying these highly distinct responses, we compared the ovarian transcriptomes of females maintained at these temperatures (18{degrees}C or 29{degrees}C) to that of 25{degrees}C controls. We found that 18{degrees}C upregulates or downregulates ~2.5 times as many genes as 29{degrees}C, indicating that the ovary mounts active physiological responses to mild cold and warm temperatures--as opposed to simply undergoing passive changes driven by thermodynamics. Gene set enrichment analysis revealed modulation of genes involved in neuronal signaling in opposite directions at 18{degrees}C versus 29{degrees}C. Most genes, however, exhibit temperature-specific regulation: 29{degrees}C upregulates synaptic transmission genes and downregulates lipid biosynthesis genes, whereas 18{degrees}C upregulates actin cytoskeleton genes and downregulates cell adhesion and lipid organization genes. Notably, mild cold or warm temperature specifically modulated (either up or down) the expression of distinct sets of transposable elements (TEs), suggesting the existence of temperature-dependent TE regulatory mechanisms and/or downstream effects. Finally, we show that GSCs at 18{degrees}C have increased retrotransposon R2 transcript levels, larger nucleolar size, and elevated levels of the known stemness factor phosphorylated Mad, leading to a working model whereby elevated ribosome biogenesis supports increased stemness signaling to promote GSC maintenance in mild cold. These findings suggest potential mechanisms and open new questions for investigation towards a deeper understanding of how temperature modulates gene expression and impacts germline development and quality--which are essential for the perpetuation of species.

developmental biology↗

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

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.

developmental biology↗

A high sugar diet, but not obesity, reduces female fertility in Drosophila melanogaster

Many studies from Drosophila to humans show a strong link between obesity and reduced fertility. However, obesity is often induced by changes in diet or eating behavior, such that it remains unclear whether reduced fertility is a consequence of obesity itself, diet, or both. Here, we report that a high sugar diet reduces Drosophila female fertility by increasing death of early germline cysts (prior to follicle formation) and degeneration of vitellogenic follicles; that obesity in and of itself does not impair fertility; and that high glucose levels closely correlate with reduced fertility on a high sugar diet. Females on a high sugar diet rapidly develop obesity (and display high glycogen, glucose, and trehalose levels, and insulin resistance) and decreased fertility. In stark contrast to high-sugar-obese females, females in which similar levels of obesity are induced by adipocyte-specific knockdown of anti-obesity genes brummer or adipose have normal fertility and sugar metabolic indicators. Remarkably, females on a high sugar diet supplemented with a separate source of water also have normal fertility and glucose levels, despite persistent obesity, high glycogen and trehalose levels, and insulin resistance markers. These results strengthen our conclusion that obesity itself does not impair fertility, show an inverse correlation between high glucose levels and fertility, and demonstrate that insulin signaling levels remain sufficiently high to maintain insulin-dependent processes during oogenesis irrespective of insulin resistance markers.

physiology↗