“A Western Diet Side Story”: The Effects of Transitioning to a Western-Type Diet on Fertility

The Western dietary pattern (WDP) is likely the most popular diet in developed countries, and it is gaining increasing popularity in developing countries. In fact, it is considered as one of the symbols of an adoption of the Western culture when Coca Cola signs and McDonald stands start to appear in a country’s landscape. The WDP is characterized by a high intake of red and processed meats, high-fat foods, refined grains, and high-sugar drinks and desserts, whereas it is relatively low in fruits, vegetables, whole-grain foods, poultry, and fish (1). A lot has been said about the WDP and its negative effect on health, specifically on the risk for obesity, type 2 diabetes, metabolic syndrome, and cardiovascular disease as well as cancer (2–5). However, despite its unhealthy profile, the WDP enjoys increasing popularity as many cultures abandon their traditional prudent diet in favor of a sweeter and greasier menu. The introduction of a high caloric intake made more available by the adoption of the fast food culture in parts of the world where nutritious foods were scarce had changed the nature of nutrition-related morbidity and mortality. Lozano at al (6), in their 2013 report on the global burden of disease, have shown for the first time that worldwide obesity-related deaths had surpassed hunger-related mortality. The study by Chaffin et al (12), in this issue of the Journal, tells a side story of the consequence of transitioning to the Western diet and the effect on fertility. In this study, the authors fed healthy adult female rhesus macaques with half of the equivalent amount of refined sugars typically included in the WDP (100 g/d) for 6 months. Then they injected this group of monkeys, as well as group of monkeys that was kept on the standard diet (2.6 g sucrose per kilogram of body weight), with gonadotropins to stimulate follicular maturation. Next they retrieved the oocytes, examined the morphology, and fertilized them. The embryos were cultured to the blastocyst stage and then biopsied. The authors conducted a microarray analysis of gene expression from blastocysts of the two groups as well as granulosa cells, cumulus cells, and MII stage oocytes. The authors detected 1100 differentially expressed genes comparing the mRNA extracted from blastocysts from the treatment and control group. However, an even more striking finding was the extremely poor rate of mature oocytes in the high-sugar fed monkeys in comparison with the standard diet group, 18.5% vs 86%, respectively. This difference is even more intriguing in light of the lack of a significant weight gain in the sugar-treated monkeys. As mentioned earlier, populations transitioning to WDP show an increase in the prevalence of obesity and type 2 diabetes. These populations also show an increased prevalence of the polycystic ovarian syndrome (PCOS) (7). PCOS is an enigmatic endocrinopathy of unknown origins that is mostly associated with anovulatory infertility. It is, however, strongly associated with obesity and insulin resistance. In fact, Andrea Dunaif, one of the leading PCOS researchers, coined the term syndrome XX to emphasize the major metabolic implications of PCOS (8). It is well known that diabetic patients and PCOS patients with impaired glucose tolerance frequently show an abnormally large percentage of immature oocytes in in vitro fertilization. Hyperglycemia was also shown to be embryotoxic, at least in part due to oxidative stress and leading to an increased risk for fetal malformation (9). Sabatini et al (10) created a transgenic mutant mouse that is leptin deficient. As a result, these mice exhibit obesity, hyperphagia, glucose intolerance, elevated plasma insulin, and subfertility. These leptin-deficient mice showed an abnormally large percentage of immature oocytes that was normalized after 7 weeks of treatment with metformin to improve their insulin resistance. I was puzzled by the fact that the normal-weight, healthy monkeys showed such a poor yield of mature oocytes, whereas clinically, our healthy in vitro fertilization patients, most of whom have been raised on a WDP, show an oocyte yield that is similar to the control group in this study. Is the discrepancy in the outcome the result of some sort of tolerance to high-sugar consumption inferred by prolonged exposure? A study by Colton et al (11) may provide the answer to this question. In this study the authors used a streptozotocin-induced diabetic mouse to show that hyperglycemia inhibits the resumption of the maturation of oocytes. This inhibition was corrected by treatment with insulin to normalize serum glucose. However, when they incubated the oocytes from the control and diabetic mice with a high concentration of glucose, the percentage of mature oocytes was significantly higher in the diabetic mice. The control of resumption of meiosis and oocyte maturation depends on the net effect of inhibitory and stimulatory signals crossing from the cumulus cells to the oocyte and vice versa through gap junctions. Cumulus-oocyte complexes from persons with diabetes show both inhibited and accelerated maturation as well as spontaneous maturation. This suggests a dysfunction of the fine regulatory mechanism that controls the resumption of maturation due to the loss of cell-to-cell communication. Hyperglycemic conditions are embryotoxic. The cumulus oocyte complex possesses a fine regulatory mechanism that halts the resumption of meiosis under these conditions, thereby preventing the formation of a malformed embryo. However, with long-standing hyperglycemia, this regulatory mechanism may be damaged showing a less strict control of maturation in the face of hyperglycemia. Therefore, subjects who have recently transitioned to the high-glucose WDP with a yet-undamaged cell-to-cell communication system are likely more sensitive to hyperglycemic conditions, with a more dramatic reduction in the number of mature oocytes. Disclosure Summary: The author has nothing to disclose. polycystic ovarian syndrome Western dietary pattern.

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