The pivotal role of glucose metabolism in determining oocyte developmental competence

Abstract

The environment that the cumulus oocyte complex (COC) is exposed to during either in vivo or in vitro maturation (IVM) can have profound effects on the success of fertilisation and subsequent embryo development. Glucose is a pivotal metabolite for the COC and is metabolised by glycolysis, the pentose phosphate pathway (PPP), the hexosamine biosynthesis pathway (HBP) and the polyol pathway. Over the course of oocyte maturation, a large proportion of total glucose is metabolised via the glycolytic pathway to provide substrates such as pyruvate for energy production. Glucose is also the substrate for many cellular functions during oocyte maturation, including regulation of nuclear maturation and redox state via the PPP and for the synthesis of substrates of extracellular matrices (cumulus expansion) and O-linked glycosylation (cell signalling) via the HBP. However, the oocyte is susceptible to glucose concentration-dependent perturbations in nuclear and cytoplasmic maturation, leading to poor embryonic development post-fertilisation. For example, glucose concentrations either too high or too low result in precocious resumption of nuclear maturation. This review will discuss the relevant pathways of glucose metabolism by COCs during in vivo maturation and IVM, including the relative contribution of the somatic and gamete compartments of the COC to glucose metabolism. The consequences of exposing COCs to abnormal glucose concentrations will also be examined, either during IVM or by altered maternal environments, such as during hyperglycaemia induced by diabetes and obesity.Reproduction (2010) 139 685-695

The impact of obesity on egg quality

“…It is unknown if GLUT8 or GLUT12 function in the oocyte or cumulus cells. The oocyte contains GLUTs 1, 3, and 8, but GLUT4 has not been reported in oocytes [31]. There are reports of GLUT4 in granulosa cells of the mouse by immunohistochemistry [86] in human granulosa cells by mRNA [33]; and in granulosa cells of sheep and cattle by mRNA [87,88].…”

“…The bidirectional communication that exists between the somatic cumulus cells and the oocyte [27,28] and the metabolic support from the cumulus cells [29,30] are both essential for oocyte viability and developmental competence. Suboptimal conditions during the oocyte maturation stage can negatively impact further embryo development [31].…”

“…As described above, the oocyte and cumulus cells exist together until after fertilization as the cumulus-oocyte-complex (COC). The cumulus cells metabolize the majority of the glucose in the COC and provide metabolic intermediates such as pyruvate to the oocyte and also accumulate these intermediates in the follicular fluid and oviduct [31,73,76]. In contrast to the low PFK activity in oocytes [75], the cumulus cells also have high PFK activity [77].…”

“…In women with high BMI there is elevated glucose and lactate in follicular fluid; however, the inverse correlation between glucose and lactate remained regardless of BMI indicating anaerobic glycolysis still occurred normally [33]. Even if the glycolytic pathway was not affected, other metabolic pathways in the COC such as the pentose phosphate pathway, hexosamine biosyntheis pathway, or polyol pathway could be altered [31]. Besides energy production, the COC uses glucose for nucleic acid and purine synthesis during maturation [79].…”

The effect of nutrition and metabolic status on the development of follicles, oocytes and embryos in ruminants

“…The role of glucose is essential in determining the quality of the oocyte (Sutton-McDowall et al, 2010) because it is its main energy source. In sheep, glucogenic treatments improve oocyte quality, evaluated by the kinetics of their in vitro development and by the production of blastocysts (Berlinguer et al, 2012).…”