High-fat high-sugar diet induces polycystic ovary syndrome in a rodent model†

Abstract

Obesity has been linked with a host of metabolic and reproductive disorders including polycystic ovary syndrome (PCOS). While a clear association exists between obesity and PCOS, the exact nature of this relationship remains unexplained. The primary symptoms of PCOS include hyperandrogenism, anovulation, and polycystic ovaries. Most animal models utilize androgen treatments to induce PCOS. However, these models often fail to address the underlying causes of the disease and do not effectively reproduce key metabolic features such as hyperinsulinemia. Here, we present a novel rodent model of diet-induced obesity that recapitulates both the metabolic and reproductive phenotypes of human PCOS. Rats on a high-fat high-sugar (HFHS) diet not only demonstrated signs of metabolic impairment, but they also developed polycystic ovaries and experienced irregular estrous cycling. Though hyperandrogenism was not characteristic of HFHS animals as a group, elevated testosterone levels were predictive of high numbers of ovarian cysts. Alterations in steroidogenesis and folliculogenesis gene expression were also found via RNA sequencing of ovarian tissue. Importantly, the PCOS-like symptoms induced in these rats may share a similar etiology to PCOS in humans. Therefore, this model offers a unique opportunity to study PCOS at its genesis rather than following the development of disease symptoms.

High-Fat, High-Sugar Diet Disrupts the Preovulatory Hormone Surge and Induces Cystic Ovaries in Cycling Female Rats

“…In our previous study, we found an increase in follicular cysts and decrease in CL as a result of a HFHS diet [ 21 ]. However, in the present study, the rats were maintained on the diet for a longer period (4 additional weeks).…”

“…However, although a clear connection exists between obesity and reproductive impairment, the underlying mechanisms are unclear. In our previous study, we used a high-fat, high-sugar (HFHS) diet to induce obesity in rats and demonstrated the appearance of multicystic ovaries and disrupted estrous cyclicity, both indicators of reproductive impairment [ 21 ]. The diet, administered after weaning, provides a method to examine the natural progression of these adverse reproductive impairments as they develop.…”

Early Exposure to High-Sucrose Diet Leads to Deteriorated Ovarian Health

“…Likewise, Nino et al (37) found that a high-carbohydrate diet was able to increase the number of atretic follicles in rats. Furthermore, Roberts et al (38) have shown that animals fed a high-fat, high-sugar diet had higher frequency of cystic follicles when compared to control animals. It is yet unclear how the ingestion of HSD or other types of hypercaloric diets lead to ovarian dysfunction, however feasible underlying mechanisms include: hyperinsulinemia culminating in higher production of ovarian androgens in synergy with the luteinizing hormone (10), increased expression of anti-mullerian hormone in granulosa cells (19) and increased production of reactive oxygen species (39).…”

Animal Models for Human Polycystic Ovary Syndrome (PCOS) Focused on the Use of Indirect Hormonal Perturbations: A Review of the Literature

“…Therefore, the impaired LH surge may result in the development of cystic ovaries in this model. In a similar study from the same group, rats that received the HDHS diet for 11 weeks manifested hyperinsulinemia but not hyperandrogenemia [74]. In addition, the authors analysed changes in gene expressions caused by the HDHS diet in the ovary; the expressions of ovarian genes related to the primary follicle stage (e.g., epiregulin, Ereg ), estrogen metabolism (e.g., Cbr1 or Ste2 ), and insulin receptors ( Insrr ) were mostly shifted.…”