Abstract
BackgroundMaternal obesity alters oocytes and subsequent fetal metabolism. An increasing number of studies have shown that the endoplasmic reticulums (ER) or mitochondria have important effects on oocyte quality, but there has been no study of the effect of mitochondria-associated ER membranes (MAMs) on oocyte quality. The present study was designed to assess whether the level of MAM and MAM-related proteins were different in oocytes from obese and control mice.ResultsFirst, oocytes from mice with high-fat-diet (HFD)-induced obesity had higher levels (either greater numbers or a higher proportion for the same numbers) of MAM than oocytes from control mice. The abundance of MAM-related proteins in oocytes from obese mice was significantly greater at both the messenger RNA and protein levels, including inositol 1,4,5-trisphosphate receptor, type 1 (IP3R1), inositol 1,4,5-trisphosphate receptor, type 2 (IP3R2) and phosphofurin acidic cluster sorting protein 2 (PACS-2). Further, there was an increase in mitochondrial Ca2+ ([Ca2+]m) which was associated with increased apoptosis and compromised cytoplasmic maturation in oocytes from obese mice. Down-regulation of MAM-related protein IP3R1 in oocytes from obese mice decreased [Ca2+]m and apoptosis and improved cytoplasmic maturation but did not reduce the overall MAM level. However, down-regulating MAM-related protein PACS-2 in oocytes from obese mice did reduce the level of MAM and [Ca2+]m, which decreased the rate of apoptosis and improved cytoplasmic maturation of oocytes from obese mice.ConclusionsIt is possible that enriched MAM could increase [Ca2+]m, and this increase has been found to be associated with increased apoptosis and compromised cytoplasmic maturation in oocytes from obese mice. This finding suggests a novel therapeutic target for obesity-induced oocyte defects.
Highlights
Maternal obesity alters oocytes and subsequent fetal metabolism
The current study investigated whether the content of mitochondria-associated ER membranes (MAM) and MAM-related proteins were different in oocytes from obese and control mice
HFD-induced obesity increases the amount of MAM in mouse oocytes The endoplasmic reticulums (ER) and mitochondria were in closer proximity to each other in oocytes from obese mice than in those from control mice (Fig. 1a)
Summary
Maternal obesity alters oocytes and subsequent fetal metabolism. Obesity in females of reproductive age increases their risks of developing insulin resistance, diabetes, and other diseases, but is linked to poor reproductive outcome [1,2,3]. Oocyte quality plays a key role in connecting maternal nutrition with reproductive outcome, and is dramatically impacted by maternal obesity [4, 5]. Obesity changes the ER membrane lipid composition and damages its ability to retain Ca2+, which alters the cytoplasmic homeostasis [11]. Prolonged Ca2+ release from the ER leads to altered mitochondrial membrane potential and the induction of intrinsic apoptotic pathways [13, 14]. Mitochondrial defects are thought to be the direct reason for the oocyte developmental deficits in obese females [15]
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