The association between obesity and infertility is a long-standing one. Some date the first written reference to this connection as early as 400 B.C., and much scientific and medical research supports it.

But scientists are still trying to determine the precise nature of the obesity-infertility correlation, and the limitations of current research can confound the process. For example, existing studies do not distinguish between the effects of a high-sugar diet and obesity, which makes it difficult to investigate the underlying cause behind decreased fertility.

However, a recent study focused on high-sugar diet, spearheaded by Rodrigo Dutra Nunes and Daniela Drummond-Barbosa in the Department of Genetics, opens the door for breakthrough advancements in fertility research. Published in the journal Development, their research includes a unique analysis of the effects of a high-sugar diet, obesity, and water intake on metabolism, oogenesis (production of egg cells) and fertility. They used the common fruit fly, or Drosophila melanogaster, as their model organism for the study.

“One of the novelties of this paper is that we didn’t only show that a high-sugar diet reduces the fertility of flies, but we also showed which steps of oogenesis are affected, and which process in each step is being affected,” says Dutra Nunes, a scientist in Drummond-Barbosa’s lab.

“We were able to dissociate the effects of obesity and high sugar and show that obesity is not what causes the reduction in fertility,” adds Drummond-Barbosa, a genetics professor and investigator at the Morgridge Institute for Research on the UW campus. “This highlights the importance of carefully separating the contributions of diet versus obesity in future studies not only in fruit flies but also in mammals.”

Drosophila are commonly used in biomedical research, and they are the main tool for Dutra Nunes’s fertility research. He notes that the high degree of similarity between the genes in Drosophila and the genes in humans can provide an excellent model for experiments that are too challenging or simply not feasible to conduct on people, such as genetic manipulation or diet alteration.

“Fruit flies offer major advantages as we progress towards identifying the cellular and molecular mechanisms underlying the effects of a high-sugar diet,” Drummond-Barbosa says. “The powerful genetic tools available, fast generation time, and large sample sizes make it possible to combine cutting-edge research with high scientific rigor.”

Dutra Nunes and Drummond-Barbosa compared reproductive changes in Drosophila on a high-sucrose diet to that of a control group without manipulation of the diet. In the experimental flies, fat storage quickly increased in one week, reaching much higher levels than in the control group.

An additional group of Drosophila were genetically altered to increase fat accumulation and model obesity on a normal diet. Fertility remained unchanged in these manipulated flies.

The decrease in egg production and hatching rates of female flies maintained on a high-sugar diet (in contrast to the normal fertility of genetically obese flies) led Dutra Nunes and Drummond-Barbosa to conclude that a high-sugar diet — and not obesity — is the primary cause of female infertility.

They also observed an increase in death among developing germ cells at two distinct stages of oogenesis in the flies fed a high-sugar diet. “If you have some of the steps of oogenesis surviving less, that means you’ll have fewer eggs generated,” Dutra Nunes says. “That is what’s causing a decrease in fertility in flies.”

Apart from diet, Dutra Nunes also found that elevated water intake had a powerful metabolic effect counteracting high sugar consumption. “The dietary supplementation of water to obese flies on a high-sugar diet was able to reverse the negative effects on fertility without changing the level of obesity,” he says.

Water supplementation also reversed the high glucose levels in the flies on a high-sugar diet. The apparent healing effects of hydration provide a foundation for future studies to explore the relationship between water consumption, high glucose levels, and fertility.

Next, Dutra Nunes intends to explore under-researched elements and their roles in reproductive processes. “We are now taking unbiased approaches, such as proteomics and metabolomics, to discover new points of connection between high glucose, water, and other effectors of a high-sugar diet and test their effects on fertility,” he says. (Proteomics is the large-scale study of the structures and functions of proteins; metabolomics is the large-scale study of metabolites, which are small molecules found inside the cells, tissues, and fluids of living organisms.)

Dutra Nunes hopes his work with Drummond-Barbosa will inspire further research into possible therapeutic interventions in humans to reverse some of the effects of the Western diet that cause decreased fertility and other diseases.