In vitro maturation impacts cumulus–oocyte complex metabolism and stress in cattle

Abstract

The influence of maturation (IVM) in oocytes is still not totally understood. The aim of this study was to determine the influence of IVM on the metabolism and homeostasis of bovine cumulus-oocyte complexes. In the present study, we demonstrated that IVM leads to accumulation of neutral lipids associated with differential levels of the mono-, di- and triacylglycerols in both cumulus cells and oocytes. We observed that-matured oocytes exhibited decreased glutathione and reactive oxygen species levels and a lower ATP/ADP ratio when compared to -matured oocytes, with no significant differences in metabolism and stress-related mRNA or miRNA levels. Moreover, in addition to an increase in lipids in-matured cumulus cells, fatty acid synthesis and accumulation as well as glycolysis pathway genes were upregulated, whereas those affiliated with the β-oxidation pathway were decreased. Our gene expression data in cumulus cells suggest the disruption of endoplasmic reticulum stress, apoptosis and cellular stress response pathways during IVM. Furthermore, a total of 19 miRNAs were significantly altered by the maturation process in cumulus cells. These results indicate some new negative influences of the system in cumulus-oocyte complexes, demonstrating the occurrence of functional disruption in lipid metabolism and stress pathways and showing evidences suggesting the occurrence of altered mitochondrial activity and energy metabolism during IVM, with a massive dysregulation of the corresponding transcripts in the surrounding cumulus cells.

The bovine cumulus proteome is influenced by maturation condition and maturational competence of the oocyte

“…Further functions like oxidative stress defence were also attributed to proteins involved in cholesterol biosynthesis 72 . Especially the altered cumulus cell lipid metabolism after IVM is already known 22 . The underrepresentation of these pathways involved in cholesterol biosynthesis and homeostasis under in vitro maturation conditions indicates that the COC matured under non-physiological Figure 6.…”

“…The influence of in vitro maturation on gene expression in cumulus cells and oocytes was evaluated in several previous studies 9,[19][20][21][22][23] . Data on the altered cumulus-oocyte complex (COC) proteome after maturation in vitro are only scarce.…”

Maternal transmission of mitochondrial diseases

“…Given this is a critical period of oocyte development, which encompasses meiotic resumption from prophase I (dictyate) to metaphase II, any perturbation in oocyte homeostasis may lead to missegregation of chromosomes and aneuploidy (Greaney et al, 2017;Danadova et al, 2017). In addition, in vitro maturation on its own leads to metabolic alterations that mimic those of oocytes from obese donors (i.e., mitochondrial dysfunction and increased lipid content), potentially impacting the next generation (Farin et al, 2006;Li et al, 2014;del Collado et al, 2017a;del Collado et al, 2017b;Wang et al, 2018). Thus, these alternatives are not currently available in humans.…”

Analysis of the equine “cumulome” reveals major metabolic aberrations after maturation in vitro

“…Most of the available “Omics” studies on cumulus cells are transcriptomic analyses of pooled cumulus or cumulus oocyte complexes (COCs) that relate the gene expression profile to the developmental competence of the oocyte [23–30]. Other studies examined changes in the cumulus transcriptome between in vitro and in vivo matured COCs [31–34]. All these studies were performed in species other than the horse.…”

“…Data on the cumulus cell metabolome are even scarcer across species. Comparison of in vitro matured with in vivo matured COCs revealed altered cellular metabolism-related genes along with increased triglycerides in bovine cumulus cells matured in vitro [34]. Glycosidic residues showed significant quantitative and qualitative differences in equine and porcine COCs after in vitro and in vivo maturation [52].…”