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School of Paediatrics and Reproductive Health, The Robinson Institute, Research Centre for Reproductive Health, The University of Adelaide, Adelaide, South Australia 5005, Australia
Correspondence should be addressed to M L Sutton-McDowall; Email: melanie.mcdowall{at}adelaide.edu.au
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Abstract |
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 Top Abstract IntroductionAn overview of glucose...Metabolic pathways important to...Maternal environment and oocyte...ConclusionsDeclaration of interestAcknowledgementsReferences |
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Introduction |
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TopAbstractIntroductionAn overview of glucose...Metabolic pathways important to...Maternal environment and oocyte...ConclusionsDeclaration of interestAcknowledgementsReferences |
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The rapid and dynamic nature of the final stages of oocyte maturation means that COCs require different compounds, such as fatty acids, amino acids, electrolytes, purines and pyrimidines and metabolites. With regard to metabolites, mature bovine COCs consume twofold more glucose, oxygen and pyruvate than immature COCs (Sutton et al. 2003a). A long-established tenet of COC energy metabolism is that the oocyte itself has a poor capacity to utilise glucose (Biggers et al. 1967), and that the cumulus cells metabolise the bulk of the glucose consumed by the COC to supply metabolic intermediates to the oocyte. The maturing COC uses glucose for energy production and numerous other cellular processes such as nucleic acid and purine synthesis, mucification and cellular homoeostasis (Sutton et al. 2003b).
The environment to which the COC is exposed during maturation (both in vivo maturation and IVM) affects oocyte developmental competence and subsequent embryonic development. Suboptimal culture conditions during IVM result in reduced blastocyst development post-fertilisation (van de Sandt et al. 1990, Rose & Bavister 1992, Rose-Hellekant et al. 1998). Moreover, it is becoming increasingly evident that the consequences of poor maternal health, such as diabetes, obesity and poor diet, all result in hyperglycaemic increases in intra-follicular glucose levels, and that this is associated with poor oocyte viability in mice (Moley et al. 1998). Hence, the aim of this review is to examine the impact of glucose concentration and altering levels of glucose metabolism on oocyte and COC function. Considering the importance of the bi-directional communication between the oocyte and the cumulus vestment, the focus of this review will largely be on the metabolic activity of the COC as a whole unit. A general overview of glucose utilisation by the COC will be discussed, followed by the roles of glucose metabolic pathways during maturation, including glycolysis, the pentose phosphate pathway (PPP), the hexosamine biosynthesis pathway (HBP) and the polyol pathway, and the consequences of maternal hyperglycaemia on oocyte development competence will be examined.
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An overview of glucose metabolism |
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TopAbstractIntroductionAn overview of glucose...Metabolic pathways important to...Maternal environment and oocyte...ConclusionsDeclaration of interestAcknowledgementsReferences |
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The oocyte itself has low capacity for glucose uptake, despite facilitative glucose transporters 1, 3 and 8 (SLC2A1, SLC2A3 and SLC2A8) expression in bovine, human, sheep and rhesus monkey oocytes (Dan-Goor et al. 1997, Augustin et al. 2001, Zheng et al. 2007, Pisani et al. 2008). In comparison, cumulus cells express an additional glucose transporter, SLC2A4 (Williams et al. 2001, Roberts et al. 2004, Nishimoto et al. 2006), which has a high affinity for glucose (Km
2–5 mM) and is an insulin-sensitive transporter, so the rate of glucose transportation into cells by SLC2A4 tends to be more reliant on insulin and insulin-like growth factors levels than on glucose concentration (Charron et al. 1989).
In addition to having a poor capacity to take up glucose, the bovine oocyte has low phosphofructokinase activity (PFK, one of the rate-limiting enzymes of glycolysis (Cetica et al. 2002)), with the consequence that the oocyte has a low glycolytic rate (Saito et al. 1994, Harris et al. 2007), and instead, relies on the cumulus cells to convert glucose to substrates it can readily utilize such as pyruvate/lactate. In fact, we have calculated that when intake of glucose and oxygen is expressed per millilitre volume of tissue per hour, cumulus cells from immature COCs consume 23-fold more glucose (oocyte=2.2 µmol/ml tissue per h versus cumulus cells=50.3 µmol/ml tissue per h) and 3.2-fold less oxygen than oocytes (oocyte=334 µl/ml tissue per h versus cumulus cells=108 µl/ml tissue per h; Thompson et al. 2007). While this suggests that in the absence of glucose, denuded oocytes could undergo successful complete maturation if supplied with pyruvate and oxygen for energy, this is not the case as glucose is also metabolised via the PPP, HBP and polyol pathway (Fig. 3), and all these contribute to maturation and will be discussed in more detail below.
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-minimum essential medium, TCM199 and Waymouth medium, with glucose concentrations ranging from 0.2 mM glucose (KSOM) to 23 mM (Waymouth medium). The supply of adequate concentrations of glucose in IVM medium leads to improved nuclear maturation and developmental capacity of oocytes (Krisher & Bavister 1998, Rose-Hellekant et al. 1998, Zheng et al. 2001). However, concentrations too low (<2.3 mM glucose) or high (>10 mM glucose) are detrimental to oocyte development (Table 1). Culturing bovine COCs in medium containing physiological or lower concentrations of glucose (1.5–2.3 mM glucose) can lead to perturbations in the completion of nuclear maturation (Sutton-McDowall et al. 2005) and poor embryo development post-fertilisation (Rose-Hellekant et al. 1998, Eppig et al. 2000, Ali & Sirard 2002, Ali et al. 2003). van de Sandt et al. (1990) compared the developmental outcomes of mouse COC after IVM in different base medium, with oocytes cultured in Waymouth medium having improved blastocyst development and increased cell numbers than oocytes cultured in media containing significantly lower glucose levels, seemingly contradicting the notion that high glucose levels are detrimental to oocyte developmental competence. Waymouth medium contains hypoxanthine, an inhibitor of nuclear maturation, and this may negate the negative effects of high glucose. Also, Schelbach et al. (2010) have shown that the COC:medium volume ratio used is critical in determining the impact of hexose concentration. A description of COC:medium volume was not published in the study of van de Sandt et al. (1990), but if high, this could account for the disparity. Hence, glucose availability is important in IVM but can be managed by the presence of glucose levels that allow for appropriate nuclear and cytoplasmic maturation and appropriate management of COC:medium volume ratios.
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Oocyte-secreted factors and metabolism
Considering the importance of the cumulus vestment to oocyte developmental competence, the influence of oocyte-secreted factors on cumulus cell metabolic activity was examined. Glucose consumption by intact cattle COCs and oocytectomised complexes (OOX, surgical removal of the ooplasm, while retaining the cumulus vestment intact) was measured over a 24-h IVM period. Oocyte-secreted factors did not appear to affect the rate of glucose consumption, as cattle COCs, OOX and OOX co-cultured with denuded oocytes all showed similar rates of glucose consumption over a 24-h culture period (Sutton et al. 2003a). In contrast, mouse OOX display decreased expression of genes encoding glycolytic enzymes (including PFK, PFKP and lactate dehydrogenase, LDHA) and a tenfold decrease in glycolytic activity compared to intact COCs and OOX co-cultured with denuded oocytes (Sugiura et al. 2005).
There are several possible explanations for the differences in the two patterns of glucose metabolism reported between cattle and mouse cumulus cells. First, differences in glucose metabolism may be attributed to the addition of FSH to the cattle COCs and OOX cultures, whereas no hormones were added to mouse IVM system. Sugiura et al. (2005) suggest hormone stimulation during IVM negates the oocyte-mediated promotion of glycolysis that was seen within mouse cumulus cells. Furthermore, in the mouse study, COCs and OOX were cultured in the presence of milrinone, a modulator of nuclear maturation, hence arresting or delaying nuclear maturation. In comparison, the bovine study used a spontaneous maturation model. Alternatively, oocyte-mediated regulation of cumulus cell glycolysis may be a species-specific phenomenon, as is the case for FSH-stimulated cumulus expansion, which requires oocyte-secreted factors in the mouse (Buccione et al. 1990), but not in bovine and porcine COCs (Ralph et al. 1995, Nagyova et al. 1999).
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Metabolic pathways important to cumulus oocyte development |
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TopAbstractIntroductionAn overview of glucose...Metabolic pathways important to...Maternal environment and oocyte...ConclusionsDeclaration of interestAcknowledgementsReferences |
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Glycolysis
The glycolytic pathway accounts for a large proportion of glucose metabolism by the COC and allows for energy production in the form of ATP and metabolites that can be readily utilised by the oocyte, such as pyruvate and lactate (Downs & Utecht 1999, Harris et al. 2007, 2009) and, therefore, has a fundamental role in the capacity for normal oocyte metabolism. The high capacity of cumulus cells to metabolise glucose is characterised by the presence of SLC2A1 and SLC2A4, as well as high activity of glycolytic enzymes such as 6-phosphogluconate and PFK (Downs et al. 1996). Once within the oocyte, pyruvate and lactate are metabolised via the tricarboxylic acid cycle, followed by oxidative phosphorylation, the predominant ATP-producing pathways within the oocyte (Steeves & Gardner 1999), while there is comparatively little glycolytic activity (Fig. 1D).
However, numerous groups have demonstrated that despite the low glycolytic activity in the oocyte, there appears to be an important positive relationship between this relatively low glycolytic activity and developmental competence of oocytes (Krisher & Bavister 1999, Spindler et al. 2000, Durkin et al. 2001, Herrick et al. 2006). For example, oocytes derived from pre-pubertal cattle and sheep (which have lower developmental competence) have delayed increases in glycolytic activity during maturation compared to oocytes derived from adult animals (higher developmental competence), with the rate of glucose metabolism in adult oocytes constantly increasing over a 24-h period, compared to increases in activity at the end of maturation in pre-pubertal derived oocytes (O'Brien et al. 1996, Steeves & Gardner 1999). Furthermore, glucose metabolism of IVM oocytes (denuded of cumulus cells prior to measurement) is lower in pig oocytes (Durkin et al. 2001) compared to in vivo matured oocytes (collected from pre-ovulatory follicles or oviductal flushing).
While the importance of the glycolytic pathway is well known, changes in the flux of glucose through this pathway during IVM have not been widely investigated. We measured the consumption and production of metabolites by cattle COCs, and while there was a significant increase in glucose consumption over a 24-h IVM period, lactate production remained constant (Sutton et al. 2003a). Using the assumption that two lactate molecules are produced for one molecule of glucose consumed through the glycolytic pathway, we calculated that the flux of glucose through glycolysis remains constant during maturation (Table 2; Sutton et al. 2003a). The increased glucose consumed as COCs undergo maturation is accounted for by other metabolic pathways. It remains to be determined whether an altered flux of glucose through glycolysis within the COC has an effect on developmental competence.
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The pathway can be divided into oxidative and non-oxidative stages, and glucose can enter the PPP at either stage. The oxidation of glucose-6-phosphate to 6-phosphogluconolactone by G6PDH results in the production of NADPH, and fructose-6-phosphate can also be utilised via the non-oxidative arm of the PPP by transketolase (Fig. 3). Products of the PPP include NADPH, which is utilised for cytoplasmic integrity and redox state through the reduction of glutathione (GSSG to GSH). Another product of PPP is phosphoribosylpyrophosphate, a substrate for de novo and salvage purine synthesis and subsequent control of nuclear maturation (Fig. 1D).
It is well established that the addition of glucose to IVM medium results in increased rates or acceleration of nuclear maturation (Sutton-McDowall et al. 2005, Sato et al. 2007, Funahashi et al. 2008). However, Downs et al. (1996, 1998) were the first to demonstrate that the flux of glucose through PPP, rather than through glycolysis, influences the resumption of nuclear maturation in mouse COCs. Inhibition of glycolysis does not affect mouse oocyte nuclear maturation (Downs et al. 1996) and media containing pyruvate as the sole metabolite, result in less mouse COCs completing nuclear maturation (MII) compared to media containing glucose (Downs & Hudson 2000). Furthermore, stimulation of PPP using electron acceptors such as phenazine ethosulphate and pyrroline-5-carboxylate results in a dose-dependent increase in the rate of meiotic resumption (GV breakdown) and increased glucose metabolism (Downs et al. 1998).
While Downs et al. explored the influence of glucose and PPP activity on the resumption of meiosis, PPP is also involved in progression of all stages of meiosis in the oocyte, including the resumption of meiosis, MI–MII transition and the resumption of meiosis post-fertilisation (Sutton-McDowall et al. 2005, Herrick et al. 2006). Supplementing IVM medium with diphenyleneiodonium (inhibits NADPH oxidase) decreased PPP activity in porcine oocytes, resulting in reduced meiotic resumption and completion and decreased cleavage and blastocyst development post-fertilisation (Herrick et al. 2006).
Therefore, PPP activity within the oocytes is important for both nuclear and cytoplasmic maturation through the provision of substrates for purine synthesis (nuclear maturation) and intra-oocyte redox state.
Hexosamine biosynthesis pathway
Glucose can also enter the HBP, which is a major fuel-sensing pathway and is responsible for generating substrates used in matrix production (Fig. 1D). The HBP metabolises glucose-6-phosphate to fructose-6-phosphate, which is converted to glucosamine-6-phosphate by glucosamine:fructose-6-phosphate transaminase (GFPT, rate-limiting enzyme), and the end product of the pathway is UDP-N-acetyl glucosamine (Fig. 3). In cumulus cells, most UDP-N-acetyl glucosamine would be converted to hyaluronic acid by hyaluronic acid synthase 2 (HAS2). However, an alternative fate is the utilisation of UDP-N-acetyl glucosamine for O-linked glycosylation of proteins (Wells et al. 2003).
Cumulus expansion during oocyte maturation involves the synthesis of extracellular matrices (ECM) by cumulus cells in response to the LH surge in vivo and epidermal growth factor/FSH stimulation in vitro (Buccione et al. 1990). The major structural backbone of cumulus cell-derived ECM is hyaluronic acid, and both glucose and glucosamine are major substrates for hyaluronic acid synthesis (Salustri et al. 1989, Chen et al. 1990). Importantly, glucosamine is converted to hyaluronic acid via the hexosamine pathway, but enters downstream of GFPT (Fig. 3).
As previously mentioned (section Glycolysis), 25% of glucose consumed by bovine COCs in the later period of IVM is not metabolised via glycolysis (Sutton et al. 2003b). Supplementing IVM with glucosamine resulted in a significant decrease in glucose consumption and less incorporation of radio-labelled glucose in the ECM of COCs after FSH stimulation (Sutton-McDowall et al. 2004), indicating a flux of glucose through the HBP. Furthermore, inhibition of HBP using the GFPT inhibitor 6-diazo-5-oxo-L-norleucine results in decreased cumulus expansion and glucose uptake by COCs (Gutnisky et al. 2007). Hence, the increased rate of glucose consumption by COCs towards the end of IVM is to generate matrix via the HBP.
While cumulus expansion is commonly associated with improved developmental competence, for example, HAS2 expression in cumulus cells is associated with increased oocyte developmental competence (Assidi et al. 2008), increased activity of the HBP can have deleterious effects on oocyte health. In somatic cells, HBP is involved in fuel sensing and under euglycaemic conditions accounts for 1–3% of total glucose metabolism (Marshall et al. 1991). The fuel-sensing role of HBP appears to be mediated by O-linked glycosylation of proteins. There is a close relationship between phosphorylation and O-linked glycosylation. Serines and threonines can be targets of O-linked glycosylation and some can be either glycosylated or phosphorylated, resulting in upregulation or downregulation of protein signalling pathways (Wells et al. 2003). Increased flux of glucose through the HBP leads to increased O-linked glycosylation, leading to changes in the target protein conformation and subsequent in/activation of downstream targets. Indeed, increased activity of the HBP is recognised as one of the contributing factors of the diabetic pathology in human somatic cells (Brownlee 2001).
The influence of hyperglycaemic conditions on the activity of the HBP within the COC has not been determined. However, glucosamine is commonly used in somatic cell cultures to upregulate HBP activity as glucosamine enters downstream from GFPT, hence mimicking hyperglycaemic environments (Andreozzi et al. 2004). Glucosamine supplementation during IVM does not affect nuclear maturation or cleavage rates post-fertilisation in cattle, pig and mouse oocytes (Sutton-McDowall et al. 2006, Schelbach et al. 2010). However, glucosamine supplementation during IVM severely perturbed post-compaction embryo development, most likely by increasing O-linked glycosylation in cumulus cells (Sutton-McDowall et al. 2006, Schelbach et al. 2010). The pathways targeted by O-linked glycosylation within cumulus cells are yet to be determined.
Polyol pathway
The polyol pathway involves the oxidation of glucose to sorbitol and fructose by aldose reductase (AR) and sorbitol dehydrogenase (SDH). Under normal glycaemic conditions, the polyol pathway accounts for very little of total glucose metabolism by somatic cells, largely due to AR having a low affinity for glucose compared to other enzymes, such as hexokinase. However, in a hyperglycaemic environment, the flux of glucose through the polyol pathway can increase to between 11 and 33% (human erythrocytes and eye lens respectively) as the hexokinase enzyme becomes saturated. Increased activity of the polyol pathway is thought to manifest diabetic pathology through numerous different mechanisms, including intracytoplasmic accumulation of sorbitol and fructose, both of which have poor membrane permeability; decreased levels of NADPH (a co-factor of AR); pseudo-hypoxia by increasing NADH/NAD+ (NAD+ is a co-factor of SDH) or altering lactate/pyruvate ratios mediated by SDH and activation of protein kinase C (Brownlee 2001).
Under normal glycaemic conditions, SDH and AR are expressed in reproductive tissues, and the highest levels of protein and enzymatic activity are found in the ovary (Kaneko et al. 2003). AR is expressed in rat granulosa cells and oocytes, and SDH is highly expressed in the oocyte (Iwata et al. 1990, Kaneko et al. 2003). While cumulus cells have high levels of glycolytic activity to provide the oocyte with metabolites for oxidative phosphorylation (Sutton et al. 2003b), localisation of both enzymes suggests that granulosa cells convert glucose to sorbitol, providing the oocyte with alternative substrates for energy production, namely fructose. To date, sorbitol and fructose levels within the oocyte or COC have not yet been measured. However, when fructose is the sole hexose source during IVM, significantly less oocytes complete nuclear maturation compared to COCs cultured in the presence of glucose (Wongsrikeao et al. 2006), supporting the requirement of glucose for nuclear maturation.
Limited data are available about the roles of SDH and AR during oocyte maturation. Within the ovary AR mRNA levels in granulosa cells increase in the absence of oestrogen and during follicle atresia (Svanberg et al. 2000), suggesting the polyol pathway is involved in ovarian tissue differentiation and remodelling during the oestrous cycle.
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Maternal environment and oocyte developmental competence |
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TopAbstractIntroductionAn overview of glucose...Metabolic pathways important to...Maternal environment and oocyte...ConclusionsDeclaration of interestAcknowledgementsReferences |
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The effect of maternal type I diabetes (and associated hyperglycaemia) on oocyte maturation has been largely studied in either transgenic or chemically-induced diabetic rodent models. In comparison, there is currently limited data on the influences of maternal type II diabetes on oocyte developmental competence, and this is surprising considering the increased incidence in western societies. Hence, the effects of maternal hyperglycaemia on oocyte developmental competence will be discussed using the type I diabetes model. Hyperglycaemia is defined as fasting blood glucose levels of 240–300 mg/dl or greater (13.3–16.7 mM glucose) and can be induced in mice by streptozotocin-mediated destruction of pancreatic β-cells (Like & Rossini 1976).
Oocytes derived from mice with type I diabetes and hyperglycaemia have poor developmental competence due to poor folliculogenesis, oogenesis and oocyte maturation. Induction of diabetes in mice results in perturbed folliculogenesis and increases the incidence of follicular apoptosis, hence reducing ovulation rates (Chang et al. 2005). In addition, mouse oocytes from pre-ovulatory follicles are 30% smaller in size compared to oocytes from control animals (Chang et al. 2005). Secondly, COCs from chemically induced diabetic mice exhibit aberrant nuclear maturation, with precocious resumption of meiosis during spontaneous maturation and decreased efficiency of induced maturation, leading to an MI–MII transition block in both models (Kim et al. 2007). Poor nuclear maturation was attributed to decreased de novo purine and cAMP synthesis as a result of decreased flux of glucose through PPP (Colton et al. 2003). Interestingly, the flux of glucose through glycolysis was not affected (Colton et al. 2003), with excess glucose shunted through the polyol pathway (Colton & Downs 2004).
Although Colton et al. (2003) reported no alterations in the flux of glucose through the glycolytic pathway, another study reported increased AMP:ATP ratios in denuded oocytes from diabetic mice (Ratchford et al. 2007). Increased AMP:ATP ratios indicate a rapid use of intra cellular ATP and is associated with a response to stress. It is likely that AMP-dependent kinases are involved, which have been associated with altered developmental competence cow, mouse and pig oocytes (Richard et al. 1997, Downs et al. 2002, Downs & Chen 2006, Mayes et al. 2007). Furthermore, it was suggested that glycolytic activity was blocked, indicated by the accumulation of fructose bisphosphate and low ATP levels (Ratchford et al. 2007).
Poor oocyte growth, meiotic competence and glucose metabolism within COCs derived from diabetic mice may also be attributed to decreased gene and protein expression of connexins, the structural units making up gap junction channels, resulting in 60% less gap-junction communication between the oocyte and cumulus vestment (Ratchford et al. 2008). This is significant considering the reliance of the oocyte on cumulus cell communication for developmental competence.
While there are very few studies relating obesity, hyperinsulinaemia and hyperglycaemia during the peri-conception period and human oocyte developmental competence, the follicular fluid composition of patients undergoing assisted reproduction with different body mass indexes (BMIs, kg/m2) was analysed and compared to oocyte collection, embryo development and pregnancy rates (Robker et al. 2009). Oocyte quality was significantly affected by increasing BMI with less oocytes collected and less embryos produced from obese patients (BMI
30). Increasing BMI also resulted in alterations in follicular fluid composition, in particular increases in follicular insulin, glucose and lactate concentrations (Robker et al. 2009). Considering one of the main glucose transporter expressed in cumulus cells is the insulin sensitive SLC2A4 (section COC versus the oocyte), oocytes derived from obese women (BMI30) are likely to be exposed to significantly higher glucose levels through a combination of higher follicular glucose levels and increased activity of glucose transporters within cumulus cells. Hence, exposure to high glucose levels may be a major contributor to poor oocyte quality in obese women. Glucose:lactate ratios were not altered between the different groups, indicating that glycolytic activity was not affected (Robker et al. 2009). Therefore, it is highly likely that excess follicular glucose may be directed through the hexosamine biosynthesis and polyol pathways, both fuel-sensing pathways that have negative consequences on oocyte competence.
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Conclusions |
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TopAbstractIntroductionAn overview of glucose...Metabolic pathways important to...Maternal environment and oocyte...ConclusionsDeclaration of interestAcknowledgementsReferences |
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Within the COC, glucose is metabolised via four main pathways, and substrates of these pathways affect oocyte cytoplasmic and nuclear maturation (Fig. 1D). As the oocyte itself is exposed to lower glucose levels compared to the follicular fluid concentrations, most likely differential regulation of metabolic pathways and products of glucose metabolism affect developmental competence, rather than simply glucose alone. Further understanding of glucose metabolism during oocyte maturation may lead to the development of improved IVM culture conditions, as well as intervention plans and treatment for women with low fertility who are obese, insulin resistant or diabetic.
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Declaration of interest |
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TopAbstractIntroductionAn overview of glucose...Metabolic pathways important to...Maternal environment and oocyte...ConclusionsDeclaration of interestAcknowledgementsReferences |
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Funding |
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Acknowledgements |
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TopAbstractIntroductionAn overview of glucose...Metabolic pathways important to...Maternal environment and oocyte...ConclusionsDeclaration of interestAcknowledgementsReferences |
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Received August 11, 2009
First decision September 22, 2009
Revised manuscript received December 10, 2009
Accepted January 20, 2010
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References |
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TopAbstractIntroductionAn overview of glucose...Metabolic pathways important to...Maternal environment and oocyte...ConclusionsDeclaration of interestAcknowledgementsReferences |
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Albertini DF, Combelles CM, Benecchi E & Carabatsos MJ 2001 Cellular basis for paracrine regulation of ovarian follicle development. Reproduction 121 647–653.[Abstract]
Ali A & Sirard MA 2002 Effect of the absence or presence of various protein supplements on further development of bovine oocytes during in vitro maturation. Biology of Reproduction 66 901–905.
Ali AA, Bilodeau JF & Sirard MA 2003 Antioxidant requirements for bovine oocytes varies during in vitro maturation, fertilization and development. Theriogenology 59 939–949.[CrossRef][Web of Science][Medline]
Andreozzi F, D'Alessandris C, Federici M, Laratta E, Del Guerra S, Del Prato S, Marchetti P, Lauro R, Perticone F & Sesti G 2004 Activation of the hexosamine pathway leads to phosphorylation of IRS-1 on Ser307 and Ser612 and impairs the phosphatidylinositol 3-kinase/Akt/mTOR insulin biosynthetic pathway in RIN pancreatic β-cells. Endocrinology 145 2845–2857.
Assidi M, Dufort I, Ali A, Hamel M, Algriany O, Dielemann S & Sirard MA 2008 Identification of potential markers of oocyte competence expressed in bovine cumulus cells matured with follicle-stimulating hormone and/or phorbol myristate acetate in vitro. Biology of Reproduction 79 209–222.
Augustin R, Pocar P, Navarrete-Santos A, Wrenzycki C, Gandolfi F, Niemann H & Fischer B 2001 Glucose transporter expression is developmentally regulated in in vitro derived bovine preimplantation embryos. Molecular Reproduction and Development 60 370–376.[CrossRef][Web of Science][Medline]
Barker DJ 2004 Developmental origins of adult health and disease. Journal of Epidemiology and Community Health 58 114–115.
Berg DK, Beaumont SE, Berg MC, Hull CD & Tervit HR 2003 Oxygen and carbon dioxide tension in days 14–15 dominant bovine follicles measured in vivo or 4 hours post-mortem. Theriogenology 59 406.
Biggers JD, Whittingham DG & Donahue RP 1967 The pattern of energy metabolism in the mouse oocyte and zygote. Zoology 58 560–567.
Brownlee M 2001 Biochemistry and molecular cell biology of diabetic complications. Nature 414 813–820.[CrossRef][Medline]
Buccione R, Vanderhyden BC, Caron PJ & Eppig JJ 1990 FSH-induced expansion of the mouse cumulus oophorus in vitro is dependent upon a specific factor(s) secreted by the oocyte. Developmental Biology 138 16–25.[CrossRef][Web of Science][Medline]
Cetica P, Pintos L, Dalvit G & Beconi M 2002 Activity of key enzymes involved in glucose and triglyceride catabolism during bovine oocyte maturation in vitro. Reproduction 124 675–681.[Abstract]
Chang AS, Dale AN & Moley KH 2005 Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosis. Endocrinology 146 2445–2453.[CrossRef][Web of Science][Medline]
Charron MJ, Brosius FC III, Alper SL & Lodish HF 1989 A glucose transport protein expressed predominately in insulin-responsive tissues. PNAS 86 2535–2539.
Chen L, Wert SE, Hendrix EM, Russell PT, Cannon M & Larsen WJ 1990 Hyaluronic acid synthesis and gap junction endocytosis are necessary for normal expansion of the cumulus mass. Molecular Reproduction and Development 26 236–247.[CrossRef][Web of Science][Medline]
Clark AR, Stokes YM, Lane M & Thompson JG 2006 Mathematical modelling of oxygen concentration in bovine and murine cumulus–oocyte complexes. Reproduction 131 999–1006.
Colton SA & Downs SM 2004 Potential role for the sorbitol pathway in the meiotic dysfunction exhibited by oocytes from diabetic mice. Journal of Experimental Zoology. Part A, Comparative Experimental Biology 301 439–448.[Medline]
Colton SA, Humpherson PG, Leese HJ & Downs SM 2003 Physiological changes in oocyte–cumulus cell complexes from diabetic mice that potentially influence meiotoc regulation. Biology of Reproduction 69 761–770.
Dan-Goor M, Sasson S, Davarashvili A & Almagor M 1997 Expression of glucose transporter and glucose uptake in human oocytes and preimplantation embryos. Human Reproduction 12 2508–2510.
Doblado M & Moley KH 2007 Glucose metabolism in pregnancy and embryogenesis. Current Opinion in Endocrinology, Diabetes and Obesity 14 488–493.
Downs SM & Chen J 2006 Induction of meiotic maturation in mouse oocytes by adenosine analogs. Molecular Reproduction and Development 73 1159–1168.[CrossRef][Web of Science][Medline]
Downs SM & Hudson ED 2000 Energy substrates and the completion of spontaneous meiotic maturation. Zygote 8 339–351.[CrossRef][Web of Science][Medline]
Downs SM & Utecht AM 1999 Metabolism of radiolabeled glucose by mouse oocytes and oocyte–cumulus cell complexes. Biology of Reproduction 60 1446–1452.
Downs SM, Humpherson PG, Martin KL & Leese HJ 1996 Glucose utilization during gonadotropin-induced meiotic maturation in cumulus cell-enclosed mouse oocytes. Molecular Reproduction and Development 44 121–131.[CrossRef][Web of Science][Medline]
Downs SM, Humpherson PG & Leese HJ 1998 Meiotic induction in cumulus cell-enclosed mouse oocytes: involvement of the pentose phosphate pathway. Biology of Reproduction 58 1084–1094.
Downs SM, Hudson ER & Hardie DG 2002 A potential role for AMP-activated protein kinase in meiotic induction in mouse oocytes. Developmental Biology 245 200–212.[CrossRef][Web of Science][Medline]
Durkin RE, Swain JE, Bormann CL, Frederick AM & Krisher RL 2001 Metabolism of porcine oocytes matured in vivo and in vitro. Proceedings of the Society for the Study of Reproduction , 34th Annual Meeting, Ottawa, ON, Canada. Abstract 81.
Edwards RG 1965 Maturation in vitro of mouse, sheep, cow, pig, rhesus monkey and human ovarian oocytes. Nature 208 349–351.[CrossRef][Medline]
Eppig JJ 1991 Intercommunication between mammalian oocytes and companion somatic cells. BioEssays 13 569–574.[CrossRef][Web of Science][Medline]
Eppig JJ, Hosoe M, O'Brien MJ, Pendola FM, Requena A & Watanabe S 2000 Conditions that affect acquisition of developmental competence by mouse oocytes in vitro: FSH, insulin, glucose and ascorbic acid. Molecular and Cellular Endocrinology 163 109–116.[CrossRef][Web of Science][Medline]
Funahashi H, Koike T & Sakai R 2008 Effect of glucose and pyruvate on nuclear and cytoplasmic maturation of porcine oocytes in a chemically defined medium. Theriogenology 70 1041–1047.[CrossRef][Web of Science][Medline]
Gilchrist RB & Thompson JG 2007 Oocyte maturation: emerging concepts and technologies to improve developmental potential in vitro. Theriogenology 67 6–15.[CrossRef][Web of Science][Medline]
Gilchrist RB, Ritter LJ & Armstrong DT 2004 Oocyte–somatic cell interactions during follicle development in mammals. Animal Reproduction Science 82–83 431–446.
Gull I, Geva E, Lerner-Geva L, Lessing J, Wolman I & Amit A 1999 Anaerobic glycolysis. The metabolism of the preovulatory human oocyte. European Journal of Obstetrics, Gynecology, and Reproductive Biology 85 225–228.[CrossRef][Web of Science][Medline]
Gutnisky C, Dalvit GC, Pintos LN, Thompson JG, Beconi MT & Cetica PD 2007 Influence of hyaluronic acid synthesis and cumulus mucification on bovine oocyte in vitro maturation, fertilisation and embryo development. Reproduction, Fertility, and Development 19 488–497.[CrossRef][Medline]
Harris SE, Gopichandran N, Picton HM, Leese HJ & Orsi NM 2005 Nutrient concentrations in murine follicular fluid and the female reproductive tract. Theriogenology 64 992–1006.[CrossRef][Web of Science][Medline]
Harris SE, Adriaens I, Leese HJ, Gosden RG & Picton HM 2007 Carbohydrate metabolism by murine ovarian follicles and oocytes grown in vitro. Reproduction 134 415–424.
Harris SE, Leese HJ, Gosden RG & Picton HM 2009 Pyruvate and oxygen consumption throughout the growth and development of murine oocytes. Molecular Reproduction and Development 76 231–238.[CrossRef][Web of Science][Medline]
Hashimoto S 2009 Application of in vitro maturation to assisted reproductive technology. Journal of Reproduction and Development 55 1–10.[CrossRef][Web of Science]
Hashimoto S, Minami N, Yamada M & Imai H 2000 Excessive concentration of glucose during in vitro maturation impairs the developmental competence of bovine oocytes after in vitro fertilization: relevance to intracellular reactive oxygen species and glutathione contents. Molecular Reproduction and Development 56 520–526.[CrossRef][Web of Science][Medline]
Herrick JR, Brad AM & Krisher RL 2006 Chemical manipulation of glucose metabolism in porcine oocytes: effects on nuclear and cytoplasmic maturation in vitro. Reproduction 131 289–298.
Iwata N, Inazu N & Satoh T 1990 The purification and properties of aldose reductase from rat ovary. Archives of Biochemistry and Biophysics 282 70–77.[CrossRef][Web of Science][Medline]
Johnson AE, Lane M, Gardner DK, Diekman MA, Krisher RL 2001 Changes in follicular fluid environment between 5 mm and 10 mm follicles. Proceedings of the Society for the Study of Reproduction, 34th Annual Meeting, Ottawa, ON, Canada. Abstract 128.
Kaneko T, Iuchi Y, Takahashi M & Fujii J 2003 Colocalization of polyol-metabolizing enzymes and immunological detection of fructated proteins in the female reproductive system of the rat. Histochemistry and Cell Biology 119 309–315.[Web of Science][Medline]
Kim K, Kim CH, Moley KH & Cheon YP 2007 Disordered meiotic regulation of oocytes by duration of diabetes mellitus in BBdp rat. Reproductive Sciences 14 467–474.
Krisher RL & Bavister BD 1998 Responses of oocytes and embryos to the culture environment. Theriogenology 49 103–114.[CrossRef][Web of Science][Medline]
Krisher RL & Bavister BD 1999 Enhanced glycolysis after maturation of bovine oocytes in vitro is associated with increased developmental competence. Molecular Reproduction and Development 53 19–26.[CrossRef][Web of Science][Medline]
Leese HJ & Lenton EA 1990 Glucose and lactate in human follicular fluid: concentrations and interrelationships. Human Reproduction 5 915–919.
Like AA & Rossini AA 1976 Streptozotocin-induced pancreatic insulitis: new model of diabetes mellitus. Science 193 415–417.
Marshall S, Bacote V & Traxinger RR 1991 Complete inhibition of glucose-induced desensitization of the glucose transport system by inhibitors of mRNA synthesis. Evidence for rapid turnover of glutamine:fructose-6-phosphate amidotransferase. Journal of Biological Chemistry 266 10155–10161.
Mayes MA, Laforest MF, Guillemette C, Gilchrist RB & Richard FJ 2007 Adenosine 5'-monophosphate kinase-activated protein kinase (PRKA) activators delay meiotic resumption in porcine oocytes. Biology of Reproduction 76 589–597.
Moley KH, Chi MM, Knudson CM, Korsmeyer SJ & Mueckler MM 1998 Hyperglycemia induces apoptosis in pre-implantation embryos through cell death effector pathways. Nature Medicine 4 1421–1424.[CrossRef][Web of Science][Medline]
Nagyova E, Prochazka R & Vanderhyden BC 1999 Oocytectomy does not influence synthesis of hyaluronic acid by pig cumulus cells: retention of hyaluronic acid after insulin-like growth factor-I treatment in serum-free medium. Biology of Reproduction 61 569–574.
Nandi S, Kumar VG, Manjunatha BM & Gupta PS 2007 Biochemical composition of ovine follicular fluid in relation to follicle size. Development, Growth & Differentiation 49 61–66.[Web of Science]
Nandi S, Girish Kumar V, Manjunatha BM, Ramesh HS & Gupta PS 2008 Follicular fluid concentrations of glucose, lactate and pyruvate in buffalo and sheep, and their effects on cultured oocytes, granulosa and cumulus cells. Theriogenology 69 186–196.[CrossRef][Web of Science][Medline]
Nishimoto H, Matsutani R, Yamamoto S, Takahashi T, Hayashi KG, Miyamoto A, Hamano S & Tetsuka M 2006 Gene expression of glucose transporter (GLUT) 1, 3 and 4 in bovine follicle and corpus luteum. Journal of Endocrinology 188 111–119.
O'Brien JK, Dwarte D, Ryan JP, Maxwell WM & Evans G 1996 Developmental capacity, energy metabolism and ultrastructure of mature oocytes from prepubertal and adult sheep. Reproduction, Fertility, and Development 8 1029–1037.[CrossRef][Medline]
Orsi NM, Gopichandran N, Leese HJ, Picton HM & Harris SE 2005 Fluctuations in bovine ovarian follicular fluid composition throughout the oestrous cycle. Reproduction 129 219–228.
Pisani LF, Antonini S, Pocar P, Ferrari S, Brevini TA, Rhind SM & Gandolfi F 2008 Effects of pre-mating nutrition on mRNA levels of developmentally relevant genes in sheep oocytes and granulosa cells. Reproduction 136 303–312.
Ralph JH, Telfer EE & Wilmut I 1995 Bovine cumulus cell expansion does not depend on the presence of an oocyte secreted factor. Molecular Reproduction and Development 42 248–253.[CrossRef][Web of Science][Medline]
Ratchford AM, Chang AS, Chi MM, Sheridan R & Moley KH 2007 Maternal diabetes adversely affects AMP-activated protein kinase activity and cellular metabolism in murine oocytes. American Journal of Physiology. Endocrinology and Metabolism 293 E1198–E1206.
Ratchford AM, Esguerra CR & Moley KH 2008 Decreased oocyte–granulosa cell gap junction communication and connexin expression in a type 1 diabetic mouse model. Molecular Endocrinology 22 2643–2654.
Richard FJ, Fortier MA & Sirard MA 1997 Role of the cyclic adenosine monophosphate-dependent protein kinase in the control of meiotic resumption in bovine oocytes cultured with thecal cell monolayers. Biology of Reproduction 56 1363–1369.[Abstract]
Roberts R, Stark J, Iatropoulou A, Becker DL, Franks S & Hardy K 2004 Energy substrate metabolism of mouse cumulus–oocyte-complexes: response to follicle-stimulating hormone is mediated by the phosphatidylinositol 3-kinase pathway and is associated with oocyte maturation. Biology of Reproduction 71 199–209.
Robker RL, Akison LK, Bennett BD, Thrupp PN, Chura LR, Russell DL, Lane M & Norman RJ 2009 Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women. Journal of Clinical Endocrinology and Metabolism 94 1533–1540.
Rose TA & Bavister BD 1992 Effect of oocyte maturation medium on in vitro development of in vitro fertilized bovine embryos. Molecular Reproduction and Development 31 72–77.[CrossRef][Web of Science][Medline]
Rose-Hellekant TA, Libersky-Williamson EA & Bavister BD 1998 Energy substrates and amino acids provided during in vitro maturation of bovine oocytes alter acquisition of developmental competence. Zygote 6 285–294.[CrossRef][Web of Science][Medline]
Saito T, Hiroi M & Kato T 1994 Development of glucose utilization studied in single oocytes and preimplantation embryos from mice. Biology of Reproduction 50 266–270.[Abstract]
Salustri A, Yanagishita M & Hascall VC 1989 Synthesis and accumulation of hyaluronic acid and proteoglycans in the mouse cumulus cell–oocyte complex during follicle-stimulating hormone-induced mucification. Journal of Biological Chemistry 264 13840–13847.
van de Sandt JJ, Schroeder AC & Eppig JJ 1990 Culture media for mouse oocyte maturation affect subsequent embryonic development. Molecular Reproduction and Development 25 164–171.[CrossRef][Web of Science][Medline]
Sato H, Iwata H, Hayashi T, Kimura K, Kuwayama T & Monji Y 2007 The effect of glucose on the progression of the nuclear maturation of pig oocytes. Animal Reproduction Science 99 299–305.[CrossRef][Web of Science][Medline]
Schelbach CJ, Kind KL, Lane M & Thompson JG 2010 Mechanisms contributing to the reduced developmental competence of glucosamine exposed mouse oocytes. Reproduction, Fertility, and Development[in press].
Spindler RE, Pukazhenthi BS & Wildt DE 2000 Oocyte metabolism predicts the development of cat embryos to blastocyst in vitro. Molecular Reproduction and Development 56 163–171.[CrossRef][Web of Science][Medline]
Steeves TE & Gardner DK 1999 Metabolism of glucose, pyruvate, and glutamine during the maturation of oocytes derived from pre-pubertal and adult cows. Molecular Reproduction and Development 54 92–101.[CrossRef][Web of Science][Medline]
Stokes YM, Clark AR & Thompson JG 2008 Mathematical modeling of glucose supply toward successful in vitro maturation of mammalian oocytes. Tissue Engineering. Part A 14 1539–1547.[CrossRef][Web of Science][Medline]
Sugiura K, Pendola FL & Eppig JJ 2005 Oocyte control of metabolic cooperativity between oocytes and companion granulosa cells: energy metabolism. Developmental Biology 279 20–30.[CrossRef][Web of Science][Medline]
Sutton ML, Cetica PD, Beconi MT, Kind KL, Gilchrist RB & Thompson JG 2003a Influence of oocyte-secreted factors and culture duration on the metabolic activity of bovine cumulus cell complexes. Reproduction 126 27–34.[Abstract]
Sutton ML, Gilchrist RB & Thompson JG 2003b Effects of in-vivo and in-vitro environments on the metabolism of the cumulus–oocyte complex and its influence on oocyte developmental capacity. Human Reproduction Update 9 35–48.
Sutton-McDowall ML, Gilchrist RB & Thompson JG 2004 Cumulus expansion and glucose utilisation by bovine cumulus–oocyte complexes during in vitro maturation: the influence of glucosamine and follicle-stimulating hormone. Reproduction 128 313–319.
Sutton-McDowall ML, Gilchrist RB & Thompson JG 2005 Effect of hexoses and gonadotrophin supplementation on bovine oocyte nuclear maturation during in vitro maturation in a synthetic follicle fluid medium. Reproduction, Fertility, and Development 17 407–415.[CrossRef][Medline]
Sutton-McDowall ML, Mitchell M, Cetica P, Dalvit G, Pantaleon M, Lane M, Gilchrist RB & Thompson JG 2006 Glucosamine supplementation during in vitro maturation inhibits subsequent embryo development: possible role of the hexosamine pathway as a regulator of developmental competence. Biology of Reproduction 74 881–888.
Svanberg B, Ling C, Svensson PA, Johnson M, Carlsson B & Billig H 2000 Isolation of differentially expressed aldose reductase in ovaries after estrogen withdrawal from hypophysectomized diethylstilbestrol treated rats: increased expression during apoptosis. Molecular and Cellular Endocrinology 164 183–190.[CrossRef][Web of Science][Medline]
Thompson JG, Lane M & Gilchrist RB 2007 Metabolism of the bovine cumulus–oocyte complex and influence on subsequent developmental competence. Society of Reproduction and Fertility Supplement 64 179–190.
Trounson A, Anderiesz C & Jones G 2001 Maturation of human oocytes in vitro and their developmental competence. Reproduction 121 51–75.[Abstract]
Urner F & Sakkas D 1999 A possible role for the pentose phosphate pathway of spermatozoa in gamete fusion in the mouse. Biology of Reproduction 60 733–739.
Wells L, Whalen SA & Hart GW 2003 O-GlcNAc: a regulatory post-translational modification. Biochemical and Biophysical Research Communications 302 435–441.[CrossRef][Web of Science][Medline]
Williams SA, Blache D, Martin GB, Foot R, Blackberry MA & Scaramuzzi RJ 2001 Effect of nutritional supplementation on quantities of glucose transporters 1 and 4 in sheep granulosa and theca cells. Reproduction 122 947–956.[Abstract]
Wongsrikeao P, Otoi T, Taniguchi M, Karja NW, Agung B, Nii M & Nagai T 2006 Effects of hexoses on in vitro oocyte maturation and embryo development in pigs. Theriogenology 65 332–343.[CrossRef][Web of Science][Medline]
Zheng P, Bavister BD & Ji W 2001 Energy substrate requirement for in vitro maturation of oocytes from unstimulated adult rhesus monkeys. Molecular Reproduction and Development 58 348–355.[CrossRef][Web of Science][Medline]
Zheng P, Vassena R & Latham KE 2007 Effects of in vitro oocyte maturation and embryo culture on the expression of glucose transporters, glucose metabolism and insulin signaling genes in rhesus monkey oocytes and preimplantation embryos. Molecular Human Reproduction 13 361–371.
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