Abstract
Maternal obesity can cause reduced oocyte quality and subfertility. Mitochondrial dysfunction plays a central role here, and most often inbred mouse models are used to study these pathways. We hypothesized that the mouse genetic background can influence the impact of high fat diet (HFD)-induced obesity on oocyte quality. We compared the inbred C57BL/6 (B6) and the outbred Swiss strains after feeding a HFD for 13w. HFD-mice had increased body weight gain, hypercholesterolemia, and increased oocyte lipid droplet (LD) accumulation in both strains. LD distribution was strain-dependent. In Swiss mouse oocytes, HFD significantly increased mitochondrial inner membrane potential (MMP), reactive oxygen species concentrations, mitochondrial ultrastructural abnormalities (by 46.4%), and endoplasmic reticulum (ER) swelling, and decreased mtDNA copy numbers compared with Swiss controls (P < 0.05). Surprisingly, B6-control oocytes exhibited signs of cellular stress compared to the Swiss controls (P < 0.05); upregulated gene expression of ER- and oxidative stress markers, high mitochondrial ultrastructural abnormalities (48.6%) and ER swelling. Consequently, the HFD impact on B6 oocyte quality was less obvious, with 9% higher mitochondrial abnormalities, and no additive effect on MMP and stress marks compared to B6 control (P > 0.1). Interestingly, mtDNA in B6-HFD oocytes was increased suggesting defective mitophagy. In conclusion, we show evidence that the genetic background or inbreeding can affect mitochondrial functions in oocytes and may influence the impact of HFD on oocyte quality. These results should create awareness when choosing and interpreting data obtained from different mouse models before extrapolating to human applications.
Highlights
Maternal obesity can cause reduced oocyte quality and subfertility
High fat diet (HFD) is commonly used to induce obesity in mouse models. This results in hyperlipidemia, systemic lipotoxicity and oxidative stress, which is reflected in the ovarian follicle microenvironment[10]
This study aimed to investigate mitochondrial dysfunction in oocytes at the structural, functional and molecular level in response to high fat diet (HFD)-induced obesity
Summary
Maternal obesity can cause reduced oocyte quality and subfertility. Mitochondrial dysfunction plays a central role here, and most often inbred mouse models are used to study these pathways. We hypothesized that the mouse genetic background can influence the impact of high fat diet (HFD)induced obesity on oocyte quality. We show evidence that the genetic background or inbreeding can affect mitochondrial functions in oocytes and may influence the impact of HFD on oocyte quality These results should create awareness when choosing and interpreting data obtained from different mouse models before extrapolating to human applications. Outbred strains such as Swiss mice are more fertile and display better nurturing behavior They are metabolically sensitive to HFD, and develop hypercholesterolemia, obesity, and insulin resistance[16,17]. The effect of the genetic background on reproductive parameters has been examined only in a few studies comparing inbred and outbred mice and focusing on sensitivity to hormonal stimulation and oocyte developmental competence[18,19,20,21]. The potential interplay of genetic background and the response to HFD-induced obesity at the oocyte level has not been described yet
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