Liggett, Marjorie R. et al. (2013) International Worm Meeting "Sugar Stress Reduces Fertility in C. elegans via Multiple Mechanisms."

Engstrom, Amanda K., Mastroianni, Michael, Mondoux, Michelle A., Liggett, Marjorie R., Ho, Uyen

[International Worm Meeting, 2013]

High glucose diets have been linked to obesity, diabetes, and cardiovascular disease, and high galactose diets are implicated in liver failure and neurotoxicity. Previous studies using C. elegans as a model for high sugar diets have shown that exposing hermaphrodites to high glucose decreases fertility and delays reproductive timing. We have further characterized the glucose stress response and tested whether this response is sex-specific and/or glucose-specific. We find that glucose stress perturbs reproduction in both sexes at multiple points in the lifecycle. In hermaphrodites, the reduction in fertility and reproductive delay are separable phenotypes dependent on glucose stress during adulthood and development, respectively. We hypothesize that glucose decreases gamete survival via an increase in germline apoptosis, as ced-3 caspase mutants show no loss of fertility in the presence of glucose stress. Male fertilization success was also decreased on high glucose in an adult-specific manner. We found an increased sensitivity of males to glucose stress, as male fertilization success was compromised at glucose concentrations that had no effect on hermaphrodite fertility. The reduction in male fertility was not due to defects in courtship, as mating behaviors and the number of successful mating events were unchanged on high glucose. In addition to decreased brood size, we found a significant reduction in male progeny in the male-hermaphrodite cross, suggesting that glucose decreases the competitiveness of male sperm and thus gamete quality. We tested whether this response was glucose specific by assaying fertility in response to a high galactose diet. We found that C. elegans is sensitive to galactose, as fertility was decreased and reproductive timing delayed; however, worms were less sensitive to galactose than to glucose. Together, our data suggest that multiple types of sugar stress reduce fertility by reducing both gamete quality and survival in C. elegans, but that the mechanisms are different in the different sexes and sensitivities to different sugars vary.

Mondoux, Michelle et al. (2021) International Worm Meeting "A High-Glucose Diet Reduces Male Fertility and Sperm Quality in C. elegans"

Larkin, Kerry, Mondoux, Michelle, Garcia-Chope, Jose, Mastroianni, Michael, Davis, Caroline, Erichsen, Jason, Liggett, Marjorie

[International Worm Meeting, 2021]

Infertility affects ~15% of Americans of reproductive age. High-sugar diets, obesity, and type 2 diabetes have all been associated with infertility, and have been correlated with decreases in sperm and oocyte quality and viability. Despite the burden of infertility and the prevalence of high-sugar diets, the cellular and molecular mechanisms that link diet to fertility are unknown. As in humans, a high-glucose diet leads to reduced fertility in C. elegans hermaphrodites. We found that high-glucose diet also reduces male fertility in a dose-dependent manner. Concentrations of glucose that have no effect on hermaphrodite self-fertility disrupted mated fertility, which allows us to separate the effects of glucose on males from the effects on hermaphrodites or fog-2 females. We tested several aspects of male fertilization success and find multiple defects on a high-glucose diet. First, a high-glucose diet reduces male sperm competitiveness. On a control diet, male sperm is used almost exclusively when males are mated to hermaphrodites. However, on a high-glucose diet, we find that although male sperm are still used preferentially, there was a dose-dependent reduction in the percentage of offspring dervied from male sperm, suggesting a reduction in sperm quality. We then measured sperm size, which is known to correlate with sperm competitiveness, and found that male sperm size is significantly decreased on a high-glucose diet. We also find a decrease in male spermatid production on a high-glucose diet. However, a high-glucose diet had no effect on spermatid transfer during mating or in mating behavior. We are currently testing other known indicators of sperm quality to determine whether glucose affects other facets of male fertility, and whether the fertility defects we observe are separabale phenotypes. Understanding how a high-glucose diet affects male gametes contributes to our understanding of how diet affects fertility in C. elegans and can provide insight into the range of cell biological responses to excess glucose.