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High-Fat Diet Causes Subfertility and Compromised Ovarian Function Independent of Obesity in Mice.

ABSTRACT: Excess calorie consumption, particularly of a diet high in fat, is a risk factor for both obesity and reproductive disorders. Animal model studies indicate that elevated dietary fat can influence some reproductive functions independent of obesity. In the current study we sought to determine whether a high-fat diet (HFD) impacts ovarian function, long-term fertility, and local and systemic markers of inflammation independent of obesity. Five-week-old mice were fed either low-fat diet (control group-LF-Ln) or HFD for 10 wk and were divided based on body weight into high-fat obese (HF-Ob: >25 g) and high-fat lean (HF-Ln: <22 g). Ovaries were collected to assess ovarian follicles and to determine the degree of local inflammation. Serum proinflammatory cytokines were also measured. A group of animals was followed for breeding trials for 5 mo while being exposed to LFD or HFD. We found that both 10-wk and 32-wk exposure to HFD resulted in depleted primordial follicles regardless of obesity phenotype. Macrophage counts revealed increased tissue inflammation in the ovary independent of obesity. In addition, serum proinflammatory cytokines were increased in HF-Ln and HF-Ob in comparison to LF-Ln mice. Moreover, HFD had a sustained effect on litter production rate and number of pups per litter regardless of obese phenotype. This study describes for the first time that exposure to HFD causes significant reduction in primordial follicles, compromised fertility, produced higher proinflammatory cytokine levels, and increased ovarian macrophage infiltration, independent of obesity. The negative effects of HFD on primordial follicles may be mediated by increased tissue inflammation.

SUBMITTER: Skaznik-Wikiel ME

PROVIDER: S-EPMC4939738 | biostudies-literature | 2016 May

REPOSITORIES: biostudies-literature

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High-Fat Diet Causes Subfertility and Compromised Ovarian Function Independent of Obesity in Mice.

Skaznik-Wikiel Malgorzata E ME Swindle Delaney C DC Allshouse Amanda A AA Polotsky Alex J AJ McManaman James L JL

Biology of reproduction 20160330 5

Excess calorie consumption, particularly of a diet high in fat, is a risk factor for both obesity and reproductive disorders. Animal model studies indicate that elevated dietary fat can influence some reproductive functions independent of obesity. In the current study we sought to determine whether a high-fat diet (HFD) impacts ovarian function, long-term fertility, and local and systemic markers of inflammation independent of obesity. Five-week-old mice were fed either low-fat diet (control gro ...[more]

PMID: 27030045

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Project description:A maternal high-fat diet (HFD) has been shown to exert deleterious effects on fetal programming by impairing embryo growth, and exerts a long-term effect on the health of offspring. The present study aimed to evaluate the effect of a maternal HFD on the ovaries of offspring from the perspective of oxidative stress. Female C57BL/6J mice were randomly assigned to four groups fed various HFDs during the preconception (4 weeks) and gestation-lactation periods. Offspring were fed a normal diet after weaning, and serum and ovaries were collected at 10 weeks of age. The developmental status of follicles was observed using hematoxylin and eosin staining. The serum oxidative stress levels and insulin resistance were detected using ELISA test kits. The expression of phosphorylated form of H2AX histone variant (γH2AX), forkhead box protein O3a (FOXO3a), Bcl-2-like protein 11 (Bim)and insulin-like growth factor (IGF)-1 in ovarian tissue was analyzed using reverse transcription-quantitative PCR and western blot analyses to further explore the pathogenic mechanism. Prenatal exposure to a maternal HFD resulted in a reduced number of primordial and preantral follicles in the ovaries of offspring. Exposure to an HFD in the preconception period exerted a greater effect on the offspring compared with exposure to an HFD in the gestation-lactation period. A reduction in fat intake during the preconception, gestation and lactation periods significantly reduced the associated adverse outcomes. The expression of genes (FOXO3a, IGF-1, γH2AX and Bim) involved in oxidative stress showed a decreasing trend (high-fat/high-fat>high-fat/control>control/high-fat >control/control) in the ovaries of offspring. Overall, HFD exposure during the preconception period exerted a greater effect on offspring compared with HFD exposure during the gestation-lactation period. The long-term effect on follicular growth and development may be associated with increased oxidative stress and the activation of the insulin/PI3K/Akt pathway.

Dataset Information

High-Fat Diet Causes Subfertility and Compromised Ovarian Function Independent of Obesity in Mice.

Publications

High-Fat Diet Causes Subfertility and Compromised Ovarian Function Independent of Obesity in Mice.

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