Monocyte chemotactic protein-1 plays a role in ovarian dysfunction related to high-fat diet-induced obesity

ABSTRACT

Obesity, known to cause a systemic elevation in monocyte chemotactic protein-1 (MCP-1), adversely affects normal ovarian function. The aim of this study was to determine whether MCP-1 plays a role in ovarian dysfunction that is related to obesity induced by high-fat (HF) diet intake. Wild type (WT) C57BL/6J mice were fed either normal chow (NC) (Group 1, control group) or HF diet (Group 2). To assess whether MCP-1 is involved in HF-diet-induced ovarian dysfunction, MCP-1 knock-out mice were fed HF diet (Group 3). Body weight, body fat composition, number of oocytes collected following ovarian superovulation with gonadotropins, ovarian macrophage markers and expression of genes important in folliculogenesis and steroidogenesis were quantified in the 3 groups of animals. Animals in Group 2 gained significant body weight and body mass, produced the fewest number of oocytes following superovulation, and had significant alterations in ovarian genes involved in folliculogenesis and steroidogenesis as well as genes involved in inflammation. Although animals in Group 3 had the highest body weight and body fat composition, they produced similar number of oocytes compared to animals in Group 1 but had different ovarian gene expression compared to Group 2. These findings suggest that MCP-1 gene knockout could reverse some of the adverse effects of obesity induced by HF diet intake. Future studies assessing ovarian histology in MCP-1 knock out mouse model will confirm our findings. MCP-1 inhibition could represent a future therapeutic target to protect ovarian health from the adverse effects of HF diet ingestion.

KEYWORDS:

• Monocyte chemotactic protein-1 (MCP-1)
• ovarian dysfunction
• high-fat diet
• steroidogenesis
• folliculogenesis

Disclosure statement

The authors declare that they have no conflict of interest.

Ethics approval

All protocols were conducted in accordance with the National Institutes of Health guide for the care and use of laboratory animals and were approved by the Institutional Animal Care and Use Committee of Albert Einstein College of Medicine.

Authors contribution

Designed the study, performed experiments, and wrote major parts of the manuscript, Figures and Tables: O.A, K.T, Z.M, E.B, L.W Helped with study design, performed some of the experiments, and wrote parts of the manuscript: Y.S, X.Q.D, D.S.B, S.J Helped with study design, supervised all the experiments, provided feedback on the progress of the study, and wrote parts of the manuscript: M.J.C.

Supplementary material

Supplemental data for this article can be accessed here.

Additional information

Funding

Support for this work was obtained by grants from Albert Einstein College of Medicine Institutional Grant to EB and the American Diabetes Association [1-13-CE-06 to MJC]. Additional support was provided by the Einstein-Mount Sinai Diabetes Research Center [P30 DK020541]. LW was the recipient of a National Institutes of Health, Ruth Kirschstein predoctoral fellowship [F31 DK093332]. Grant from the American Society for Reproductive Medicine and grant from the Society for Reproductive Investigation-Bayer to Z.M.