Mol. Hum. Reprod. Advance Access originally published online on August 31, 2007
Molecular Human Reproduction 2007 13(11):791-796; doi:10.1093/molehr/gam060
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Concentrations of monosaccharides and their amino and alcohol derivatives in human preovulatory follicular fluid
1Department of Gynecology, Medical University of Bialystok, Sklodowskiej 24 A, 15-276 Bialystok, Poland 2Department of Reproduction and Gynecological Endocrinology, Medical University of Bialystok, Sklodowskiej 24 A, 15-276 Bialystok, Poland 3Division of Perinatal Medicine, University of Colorado at Denver and Health Sciences Center, 13243 East 23rd Avenue, Aurora, CO 80045, USA
4 Correspondence address. Tel: +48-85-7468347; Fax: +48-85-7468682; E-mail: jozwikmc{at}interia.pl
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
The study purpose was to compare sugar and polyol concentrations in preovulatory ovarian follicular fluid (FF) with those in the circulation. Samples of FF and peripheral venous blood were obtained after an overnight fast from 14 women attending an IVF program. High performance liquid chromatography measurements of seven polyols, two aminohexoses and four hexoses were the main outcome measures. Glucose concentrations in FF and plasma were 2781.26 ± 205.64 and 4431.25 ± 65.17 µM, respectively (P < 0.001). Mannose concentration in FF was 38.99 ± 3.33 µM, significantly lower than plasma concentration (55.38 ± 2.29 µM; P < 0.001). A concentration gradient from plasma to FF was also significant for glycerol (99.41 ± 8.47 versus 74.32 ± 6.54 µM; P < 0.002), galactose (31.69 ± 1.58 versus 26.73 ± 1.93 µM; P < 0.01) and galactosamine (11.49 ± 0.69 versus 6.38 ± 0.59 µM; P < 0.001). The plasma-to-FF concentration difference was greatest for glucose (1649.99 ± 204.09 µM). There was a significant correlation between plasma and FF concentrations for galactose and glycerol. This study supports a substantial utilization of glucose by the oocyte/granulosa cells complex, and documents a significant concentration gradient from plasma to FF for glycerol, mannose, galactose and galactosamine. These plasma–FF differences may reflect both utilization of these carbohydrates by the cells of the preovulatory ovarian follicle and/or transport characteristics of these cells.
Key words: monosaccharides/plasma follicular fluid gradient/glucose/human preovulatory follicular fluid/polyol concentrations
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
The chemical composition of extracellular fluid in Graafian follicles is a matter of importance because this medium bathes developing oocytes and is an indicator of the secretory activity and metabolism of granulosa cells (Edwards, 1974; McNatty, 1981). The plasma–follicular fluid (FF) gradient may also reflect the utilization of carbohydrates by these cells.
Glucose is the most important energy substrate in most mammalian cells, and consequently, metabolism of this monosaccharide in somatic cells has been explored in great detail. In contrast, evidence regarding glucose metabolism in the human granulosa cells/oocyte complex is still a matter of investigation. Mature human oocytes express only one of the facilitative glucose transporter isoforms (GLUT-1), whereas the neighboring cumulus cells express four isoforms (Dan-Goor et al., 1997). In vitro, granulosa cells accumulate lactate derived from glycolysis, and this process remains under gonadotrophic control (Harlow et al., 1987). Insulin-stimulated uptake of glucose in these cells has been shown to depend in part on a transport system involving phosphatidyl-inositol-3 kinase (Poretsky et al., 2001). Also cumulus cells readily consume glucose in vitro, with resultant lactate production (Gardner et al., 1996). A comparison of FF glucose and lactate concentrations in hyperstimulated follicles strongly suggested that their metabolism of glucose in vivo is entirely, or almost entirely, by anaerobic glycolysis (Gull et al., 1999). In line with this observation, activities of respective enzymes glucose-6-phosphate dehydrogenase and lactate dehydrogenase-1 have been reported in ovarian FF (Caucig et al., 1971; Breitenecker et al., 1978; Sutton et al., 2003).
However, there should be monosaccharides other than glucose present in FF, reflecting, in part, the composition of plasma. Initial research has detected a five-carbon sugar ribulose-containing compound of peptide nature in human FF (Hayashi et al., 1973; Amano et al., 1974). Another study reported glucose and fructose concentrations in preovulatory FFs obtained from patients undergoing ovarian stimulation as part of an IVF program (Suchá et al., 2002). For both sugars, concentration gradients from peripheral venous blood to FF have been found, suggestive of downhill transport and/or utilization of these hexoses by the granulosa cells/oocyte complex. A significant correlation for both carbohydrates between their blood and FF concentrations has also been established. Further research indicated the presence of a six-carbon sugar alcohol myo-inositol in human FF (Chiu et al., 2002). To date, no previous study has addressed the in vivo composition and concentration of other hexoses and their amino and polyol derivatives in FF from humans or other species.
In the current study, our null hypothesis was that: (i) there are other carbohydrates besides glucose and fructose present in FF, (ii) amino sugars and polyols are present in FF and (iii) there is a correlation between their plasma and FF concentrations. For this purpose, we measured concentrations of four hexoses, two aminohexoses and seven polyols in FF in the final stage of the oocyte's growth, namely, shortly before ovulation. Glucose concentration was measured as a reference concentration.
|
Materials and Methods |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Patients' stimulation protocols
We studied 14 randomly selected women, aged 32.2 ± 1.2 years (range 26–41 years), attending an IVF program for either tubal, male factor or unexplained infertility. These women were white Caucasians in good general health, non-smokers and had no history of liver disease or chronic illness, including diabetes. None of them was taking glucosamine as a dietary supplement. All patients gave informed consent to the study that was approved by the Ethics Committee of the Medical University of Bialystok.
The protocol of ovarian stimulation and the details of medical management have been described elsewhere (Józwik et al., 1999; Józwik et al., 2006). Briefly, a short protocol of stimulation was applied. Subcutaneous injections of the gonadotrophin-releasing hormone agonist triptorelin acetate (Decapeptyl; Ferring GmbH, Kiel, Germany) 0.1 mg starting on Day 1 were followed by gonadotrophins, follicle-stimulating hormone and/or human menopausal gonadotrophin administered in individual doses for every patient starting on Day 3 of her cycle. The stimulation was monitored using: (i) serum estradiol concentrations and (ii) ultrasound measurements of follicle numbers and diameters. The ovulation induction with human chorionic gonadotrophin was performed when the leading follicle reached 18–20 mm in diameter and the serum estradiol concentration per follicle was 150–200 ng/l.
Sample collection
Preovulatory ovarian FF (volume of 4–6 ml) from the leading follicle was collected from the women between 9 a.m. and 10 a.m. after an overnight fast during transvaginal ultrasound-guided oocyte retrieval when the follicle's diameter ranged from 24 to 26 mm. Only FFs from follicles containing a mature oocyte and macroscopically free from blood were retained (Józwik and Wolczynski, 1998). Oocyte maturity was confirmed with the Veeck (1988) and Testart et al. (1983) criteria. Each FF sample represented fluid from a single follicle in each patient, i.e. no FFs were pooled.
The FFs were collected and placed into capped disposable polypropylene tubes. Each patient's blood was sampled (1.5 ml) from an antecubital vein prior to an anesthetic administration for the oocyte retrieval procedure. The blood samples were collected and placed into capped disposable preheparinized plastic tubes. A high-purity, high-molecular-weight heparin (5000 IU/ml) in the form of a sodium salt (Polfa, Warsaw, Poland) was used. All the tubes were from Life Sciences (Denver, CO, USA). Both fluids were centrifuged at 2500g in 4°C for 5 min, and the aliquots of plasma and FF were snap frozen in liquid nitrogen and stored at –44°C until analysis. Previously, samples from these patients were used for analysis of amino acid concentration (Józwik et al., 2006).
Analytical methods
Hexose, aminohexose and polyol concentrations were determined by high performance liquid chromatography (HPLC) using a Dionex HPLC analyzer (Dionex Corp., Sunnyvale, CA, USA), as previously described (Brusati et al., 2005; Jauniaux et al., 2005). Briefly, the sample of plasma or FF was quickly thawed and deproteinized with a following solution: 0.1 ml of 0.3 N zinc sulfate containing 30 mg% xylitol as internal standard was added to 0.1 ml of plasma. After mixing, another 0.1 ml of 0.3 N barium hydroxide was added. The mixture was centrifuged at 14 000g in 4°C for 10 min, and the supernatant was filtered through a microsphere membrane (pore size 0.45 µm; Millipore, Bedford, MA, USA) before loading on a refrigerated autosampler for HPLC analysis.
A Dionex HPLC analyzer equipped with a CarboPac MA1 anion-exchange column (Dionex Corp.; Cat. No. 044066; 4 mm x 250 mm) was used for the separation of the hexoses and polyols from a 25 µl sample of supernatant. The analysis was run isocratically with 500 mM sodium hydroxide for 13 min, followed by a step change to 300 mM sodium hydroxide for 32 min at ambient temperature. The flow rate was 0.4 ml/h. The sodium hydroxide solution was prepared with degassed, deionized water.
Samples were run separately for analysis of galactose and aminohexoses. A 25 µl sample of supernatant was loaded on a CarboPac PA10 column (Dionex Corp.; Cat. No. 046110; 4 mm x 250 mm). The system was run isocratically with 18 mM sodium hydroxide for 30 min, followed by a step change to 20 mM sodium hydroxide for 20 min at ambient temperature. The flow rate was 0.6 ml/h.
All the peaks were quantified using a pulse amperometric detector (Dionex ED40 Electrochemical Detector) with a gold working electrode. The Dionex PeakNet software was used for instrument operation and data analysis. The concentrations of each sugar were calculated using the integrated area under the peak. The internal standard was used to correct for instrument variances. The variance within the run was ±2%.
In previous studies (Teng et al., 2002), the identity of the compounds was verified with gas chromatography-mass spectroscopy. Also, we verified the presence in both compartments of glucosamine and galactosamine alone. Single standards of D-glucosamine-6-phosphate (Sigma Chemical Co., St Louis, MO, USA; Cat. No. G-5509), N-acetyl-D-glucosamine (Sigma; Cat. No. A-8625) and N-acetyl-D-galactosamine (Sigma; Cat. No. A-2795) were run and, based on the retention times of these standards, the concentrations of these compounds were too low to be detected by our HPLC system.
Statistical analysis
Data are expressed as means ± standard error of mean (SEM). For each compound under study, plasma-to-FF concentration differences and ratios were calculated. The distribution of data was confirmed for its agreement with normal distribution using the Kolmogorov–Smirnov goodness of fit test. Further, statistical analysis was performed with two-tailed Student's t-test for paired samples, confirmed by multiple regression analysis. Correlations between plasma and FF concentrations and between concentration difference and plasma or FF concentrations were assessed using Pearson's correlation (two-tailed significance). The statistical package was SPSS® 8.0 for Windows PL (SPSS, Chicago, IL, USA). A P-value of <0.05 was considered statistically significant.
|
Results |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Figure 1 presents the hexose, galactosamine, glucosamine and polyol peaks detected in FF and blood plasma. The highest concentration in both compartments was found for glucose. In FF, concentrations of glycerol, mannose, myo-inositol, galactose and arabitol were above 20 µM. There were detectable (below 10 µM) concentrations of erythritol, sorbitol, galactosamine and glucosamine (Table 1). Ribitol and mannitol were detectable in some plasma or FF samples. Similarly, in a few samples, there were trace amounts of fructose.
|
|
The highest concentration difference between plasma and FF was found for glucose: 1650 µM. The concentration differences for other carbohydrates were much less: for glycerol, 25 µM; for mannose, 16 µM; for galactosamine, 5.2 µM; for galactose, 5.0 µM (Table 1). All the gradients for the hexoses were statistically significant (Fig. 2), as were the gradients for galactosamine and glycerol (Fig. 3). Differences for other compounds were not significant.
|
|
The highest plasma-to-FF concentration ratios were found for galactosamine and glucose: 3.34 and 1.73, respectively (Table 1). The lowest value of the ratio (0.46) was found for mannitol.
There was a significant correlation between plasma and FF concentrations for galactose and glycerol (Table 2).
|
In order to examine the activity of the polyol pathway in FF, a number of correlations of interest were verified. Plasma glucose concentration was not significantly correlated with FF sorbitol (P = 0.540; r = 0.1791) or FF myo-inositol (P = 0.872; r =–0.0475) concentrations, nor with sorbitol (P = 0.222; r = 0.3486) or myo-inositol (P = 0.949; r =–0.0190) concentration differences.
Also, glucose concentration difference inversely correlated with FF mannose concentration (P = 0.003; r = –0.7394), and directly correlated with mannose concentration difference (P = 0.002; r = 0.7509). Glucose and mannose concentrations in FF were correlated (P = 0.006; r = 0.6928).
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Oocyte growth and development are entirely dependent on the nurturing capacity of the follicle. The provision and utilization of nutrients from the circulation, and of energy substrates in particular, is reflected by their gradient from blood to FF. Most research concentrated on the role of glucose as a principal substrate for the oocyte (Sutton et al., 2003). Granulosa cells utilize glucose via glycolysis (Harlow et al., 1987). A recent review elegantly integrating previous work underlines the possibility that pyruvate derived from glycolysis in cumulus cells could also be an important substrate for the oocyte (Sutton et al., 2003). Animal studies with denuded and cumulus cell-enclosed mouse oocytes support this concept (Downs et al., 2006).
The present investigation demonstrated the presence of a gradient from plasma to FF for glucose, mannose and galactose, as well as for glycerol and galactosamine. This is the first in vivo study of concentrations of polyols and aminohexoses in human preovulatory FF after controlled ovarian hyperstimulation. Previously, another group (Chiu et al., 2002) determined serum and FF myo-inositol concentrations using an enzymatic assay, and presented values that are slightly higher than ours. Suchá et al. (2002) measured fructose with the Foreman colorimetric method and reported preovulatory FF concentration of approximately 11 µg/ml, or 60 µM, but this method is relatively non-specific. The normal systemic blood concentration in humans is much less (8 ± 1 µM). Diabetic patients demonstrate values of 12 ± 4 µM (Kawasaki et al., 2002). Adequate processing and selection of appropriate anticoagulant are of importance to assure the lack of fructose formation in the specimen after sampling (Guppy et al., 1990). With HPLC methodology, we were unable to detect this ketohexose.
Glucose concentration in human FF has been reported to be approximately 3.44 mM (Leese and Lenton, 1990), 3.39 mM (Gull et al., 1999), and 3.75 mM (Suchá et al., 2002), values slightly higher than our data of 2.78 mM. Differences may have arisen from the methods used or the fact that our patients were sampled late in the morning after an overnight fast. This would be in accordance with plasma glucose concentrations from the present study (
4430 µM), close to those typical for short-term fasting in humans (Kyner et al., 1976).
The concentration difference between plasma and FF was greatest for glucose among all sugars and their derivatives (Table 1). This supports the hypothesis that glucose is one of the principal metabolic fuels for the preovulatory ovarian follicle, and the supply of glucose may be an important determinant of follicular growth. A small (5.0 µM) but significant concentration difference for galactose may result from the use of this sugar for glycolysis within the follicle. Alternatively and more likely, this difference may originate from the conversion of galactose into uridine diphosphate galactose, or UDP-galactose. The latter provides galactosyl residues for the synthesis of complex proteoglycans and polysaccharides (Stryer, 1988). Also the concentration difference for mannose, together with related correlations, may reflect mannose incorporation into intrafollicular proteoglycans. Mannose is required for N-glycosylation and glycophospholipid anchor synthesis. It may be derived primarily from plasma and only to a lesser extent from intracellular conversion of glucose (Alton et al., 1998). Glycerol and myo-inositol are the essential alcohol moieties necessary for the synthesis of membrane phospholipids (Stryer, 1988).
As for the galactosamine concentration difference, aminohexoses found in biological fluids have been considered to be the hydrolytic products of proteoglycans and polysaccharides (Pigman, 1957). However, glycosaminoglycans, such as hyaluronan and proteoglycans chondroitin sulfate and heparan sulfate, are present in human FF in appreciable concentrations of 1–2 mg/ml (Salustri et al., 1999). Their structure has been characterized in considerable detail (Eriksen et al., 1999). They have a significant role in preovulatory expansion of follicular volume and remodeling of the cumulus–oocyte complex due to extracellular matrix synthesis (Salustri et al., 1999). The presence in bovine FF of enzymatic activity capable of splitting these compounds has been confirmed in early studies (Jensen and Zachariae, 1958). It is generally acknowledged that chondroitin sulfate contains N-acetylgalactosamine residues in its structure, whereas heparan sulfate contains N-acetylglucosamine residues (Salustri et al., 1999). Interestingly, in human FF, these proteoglycans have been reported to contain both aminohexose residues (Eriksen et al., 1999). In gonadotrophin-stimulated mice, injection with [3H]glucosamine resulted in its rapid uptake into the preovulatory FF, incorporation into granulosa and cumulus cells, and presence in glycoconjugates localized close to the oocyte (Fowler, 1988). Some studies suggest that glucosamine is favored over glucose for the synthesis of extracellular matrix surrounding bovine oocyte (Sutton-McDowall et al., 2004).
The hexosamine pathway involving glucosamine is also directed to O-linked glycosylation. Recently, the presence of extensive O-linked glycosylation within bovine cumulus cells has been documented (Sutton-McDowall et al., 2006). In various cells, the process can lead to the disruption of signal transduction by the inactivation of such molecules as phosphatidyl-inositol-3 kinase (Sutton-McDowall et al., 2006). Importantly, glucose metabolism depends on the activity of this protein in human granulosa cells and murine blastocysts (Poretsky et al., 2001; Riley et al., 2006). Thus, the low FF concentrations of glucosamine could be beneficial for oocyte metabolism.
Our null hypothesis was that there is a good correlation between plasma and FF carbohydrates, as reported for glucose, fructose, and myo-inositol in humans (Chiu et al., 2002; Suchá et al., 2002), and for glucose and ß-hydroxybutyrate in cows (Leroy et al., 2004). This hypothesis turned out to be only partly true. Unlike amino acids (Józwik et al., 2006), a close relationship between plasma and FF concentrations was found only for galactose and glycerol (Table 2). The plasma-to-FF ratio indicates that there is an appreciable downhill gradient from plasma to FF, which fits with the general hypothesis that the transport of most carbohydrates utilizes non-energy-dependent transporters, such as the GLUT family of transporters for glucose. It is a bit surprising that only galactose and glycerol had a significant relationship between plasma and FF concentrations. One would have expected such a correlation to extend to glucose, and perhaps to mannose as well.
The design of the current study provides an insight into whether the polyol and pentose phosphate pathways are present in the preovulatory graafian follicle. The polyol pathway is an important, phylogenetically old pathway aiming at maintaining the regeneration of the oxidized form of nicotinamide adenine dinucleotide, or NAD+, from its reduced form, or NADH. For glycolysis to continue and provide essential adenosine triphosphate, or ATP, there is a need to constantly regenerate NAD+ from NADH. The intrafollicular metabolism of glucose is thought to be by anaerobic glycolysis (Gull et al., 1999). Of interest, aldose reductase, the enzyme that converts glucose to sorbitol, has been shown to be present and active in both rat oocytes and granulosa cells (Iwata et al., 1990, 1996). However, the lack of correlation between plasma glucose concentration and either FF sorbitol concentration or sorbitol concentration difference suggests that the polyol pathway is not a dominant glucose pathway within the follicle. The oxygen content in human FF is high and comparable with that in woman's arterial circulation (Fischer et al., 1992; Huey et al., 1999). Under such aerobic conditions, the regeneration of NAD+ takes place via electron transport to the enzymes of the mitochondrial respiratory chain, reducing the necessity of an active polyol pathway. The intracellular glucose concentration is another important factor: at high glucose concentrations, hexokinase becomes saturated and the excess glucose is then metabolized by aldose reductase. Noteworthy, in hyperglycemic conditions in culture, preimplantation mouse embryos have been shown to demonstrate increased intracellular concentrations of sorbitol and fructose, associated with delayed development (Moley et al., 1996). Mouse oocytes, when subjected to high concentrations of sorbitol, exhibit a significant reduction in gonadotrophin-stimulated maturation (Colton and Downs, 2004). It would be of interest to examine sorbitol and fructose concentrations in FF obtained from women with well and poorly controlled diabetes. The detection of these compounds in FF might be an early indicator of IVF failure. The present study was restricted to non-diabetic subjects.
The pentose phosphate pathway catalyzes the interconversion of three-, four-, five-, and six-carbon sugars, provides pentose phosphates for the build-up of nucleic acids, and generates the reduced form of nicotinamide adenine dinucleotide phosphate (NADPH) involved in the regulation of the cellular redox state (Stryer, 1988). Interestingly, the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase have been reported in FFs obtained during both spontaneous and stimulated cycles in women (Menezo et al., 1982). These are the initial enzymes of this metabolic pathway which may be operating within the human preovulatory follicle, even if FF ribitol concentrations found in the present study were very low. A number of excellent in vitro studies indicate that the pentose phosphate pathway is an important regulatory route controlling meiotic maturation of murine cumulus cell-enclosed oocytes (Downs et al., 1998), whereas, in fertilized bovine and murine oocytes, this pathway is a vital source of NADPH during gamete fusion (Comizzoli et al., 2003; Urner and Sakkas, 2005).
All in all, the present study demonstrates that many simple carbohydrates other than glucose are present in the human preovulatory FF. Our data support the hypothesis of utilization across the follicle's wall of many carbohydrate compounds necessary for the synthesis of basic structural cellular elements. Their roles and significance in numerous metabolic pathways in different cells of the preovulatory ovarian follicle merit further investigation.
|
Funding |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Research Program #5-29 597 of the Medical University of Bialystok; National Institutes of Health (5 RO1 HD034837-09); General Clinical Research Centers (MO1 RR00 069); General Clinical Research Centers Program; National Centers for Research Resources.
|
Acknowledgements |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Statistical assistance of Jerzy Sienkiewicz, PhD, Department of Medical Statistics, Medical University of Bialystok, is kindly acknowledged. During this study, Dr. Marcin Jozwik was recipient of a post-doctoral research fellowship from the Fulbright Commission to the Animal Reproduction and Biotechnology Laboratory, Department of Biomedical Sciences, Colorado State University, Fort Collins, CO, USA.
|
References |
|---|
|
TopAbstractIntroductionMaterials and MethodsResultsDiscussionFundingAcknowledgementsReferences |
|---|
Alton G, Hasilik M, Niehues R, Panneerselvam K, Etchison JR, Fana F, Freeze HH. Direct utilization of mannose for mammalian glycoprotein biosynthesis. Glycobiology (1998) 8:285–295.
Amano H, Yanagisawa I, Hayashi H, Nagoaka S, Ito M. Ribulose-peptide isolated from human follicular fluid and seminal fluid. Eur J Obstet Gynecol Reprod Biol (1974) 4(Suppl_1):S89–S90.[ISI][Medline]
Breitenecker G, Friedrich F, Kemeter P. Further investigations on the maturation and degeneration of human ovarian follicles and their oocytes. Fertil Steril (1978) 29:336–341.[ISI][Medline]
Brusati V, Józwik M, Józwik M, Teng C, Paolini C, Marconi AM, Battaglia FC. Fetal and maternal non-glucose carbohydrates and polyols concentrations in normal human pregnancies at term. Pediatr Res (2005) 58:700–704.[CrossRef][ISI][Medline]
Caucig H, Friedrich F, Hager R, Golob E. Enzymuntersuchungen in Follikel- und Zystenflüssigkeit des menschlichen Ovars (Abstract). Acta Endocrinol (Copenh) (1971) (Suppl 152):52.
Chiu TTY, Rogers MS, Law ELK, Briton-Jones CM, Cheung LP, Haines CJ. Follicular fluid and serum concentrations of myo-inositol in patients undergoing IVF: relationship with oocyte quality. Hum Reprod (2002) 17:1591–1596.
Colton SA, Downs SM. Potential role for the sorbitol pathway in the meiotic dysfunction exhibited by oocytes from diabetic mice. J Exp Zool (2004) 301A:439–448.[CrossRef]
Comizzoli P, Urner F, Sakkas D, Renard JP. Up-regulation of glucose metabolism during male pronucleus formation determines the early onset of the S phase in bovine zygotes. Biol Reprod (2003) 68:1934–1940.
Dan-Goor M, Sasson S, Davarashvili A, Almagor M. Expression of glucose transporter and glucose uptake in human oocytes and preimplantation embryos. Hum Reprod (1997) 12:2508–2510.
Downs SM, Humpherson PG, Leese HJ. Meiotic induction in cumulus cell-enclosed mouse oocytes: involvement of the pentose phosphate pathway. Biol Reprod (1998) 58:1084–1094.
Downs SM, Gilles R, Vanderhoef C, Humpherson PG, Leese HJ. Differential response of cumulus cell-enclosed and denuded mouse oocytes in a meiotic induction model system. Mol Reprod Dev (2006) 73:379–389.[CrossRef][ISI][Medline]
Edwards RG. Follicular fluid. J Reprod Fertil (1974) 37:189–219.[Medline]
Eriksen GV, Carlstedt I, Mörgelin M, Uldbjerg N, Malmström A. Isolation and characterization of proteoglycans from human follicular fluid. Biochem J (1999) 340:613–620.[CrossRef][ISI][Medline]
Fischer B, Künzel W, Kleinstein J, Gips H. Oxygen tension in follicular fluid falls with follicle maturation. Eur J Obstet Gynecol Reprod Biol (1992) 43:39–43.[CrossRef][ISI][Medline]
Fowler RE. An autoradiographic study of gonadotrophin regulation of labelled glycoconjugates within preovulatory mouse follicles during the final stages of oocyte maturation, using [3H]glucosamine as the radioactive precursor. J Reprod Fertil (1988) 83:759–772.[Abstract]
Gardner DK, Lane M, Calderon I, Leeton J. Environment of the preimplantation human embryo in vivo: metabolite analysis of oviduct and uterine fluids and metabolism of cumulus cells. Fertil Steril (1996) 65:349–353.[ISI][Medline]
Gull I, Geva E, Lerner-Geva L, Lessing JB, Wolman I, Amit A. Anaerobic glycolysis. The metabolism of the preovulatory human oocyte. Eur J Obstet Gynecol Reprod Biol (1999) 85:225–228.[CrossRef][ISI][Medline]
Guppy M, Sabaratnam R, Devadason S, Whisson ME. Fructose formation in stored blood. Biochem Int (1990) 21:219–224.[ISI][Medline]
Harlow CR, Winston RM, Margara RA, Hillier SG. Gonadotrophic control of human granulosa cell glycolysis. Hum Reprod (1987) 2:649–653.
Hayashi H, Hayashi M, Amano H, Yanagisawa I. Separation of a substance containing ribulose in human follicular fluid. (1973) 7th World Congress of Fertility and Sterility: Tokyo. Excerpta Medica Foundation. 125.
Huey S, Abuhamad A, Barroso G, Hsu M-I, Kolm P, Mayer J, Oehninger S. Perifollicular blood flow Doppler indices, but not follicular pO2, pCO2, or pH, predict oocyte developmental competence in in vitro fertilization. Fertil Steril (1999) 72:707–712.[CrossRef][ISI][Medline]
Iwata N, Inazu N, Satoh T. The purification and properties of aldose reductase from rat ovary. Arch Biochem Biophys (1990) 282:70–77.[CrossRef][ISI][Medline]
Iwata N, Hara S, Nishimura C, Takahashi M, Mukai T, Takayama M, Endo T. Hormonal regulation of aldose reductase in rat ovary during the estrous cycle. Eur J Biochem (1996) 235:444–448.[ISI][Medline]
Jauniaux E, Hempstock J, Teng C, Battaglia FC, Burton GJ. Polyol concentrations in the fluid compartments of the human conceptus during the first trimester of pregnancy: maintenance of redox potential in a low oxygen environment. J Clin Endocrinol Metab (2005) 90:1171–1175.
Jensen CE, Zachariae F. Studies on the mechanism of ovulation. Isolation and analysis of acid mucopolysaccharides in bovine follicular fluid. Acta Endocrinol (1958) 27:356–368.[Medline]
Józwik M, Wolczynski S. Technical note: blood contamination of aspirated follicular fluid. J Assist Reprod Genet (1998) 15:409–410.[ISI][Medline]
Józwik M, Wolczynski S, Józwik M, Szamatowicz M. Oxidative stress markers in preovulatory follicular fluid in humans. Mol Hum Reprod (1999) 5:409–413.
Józwik M, Józwik M, Teng C, Battaglia FC. Amino acid, ammonia and urea concentrations in human preovulatory ovarian follicular fluid. Hum Reprod (2006) 21:2776–2782.
Kawasaki T, Akanuma H, Yamanouchi T. Increased fructose concentrations in blood and urine in patients with diabetes. Diabetes Care (2002) 25:353–357.
Kyner JL, Levy RI, Soeldner JS, Gleason RE, Fredrickson DS. Lipid, glucose, and insulin interrelationships in normal, prediabetic, and chemical diabetic subjects. J Lab Clin Med (1976) 88:345–358.[ISI][Medline]
Leese HJ, Lenton EA. Glucose and lactate in human follicular fluid: concentrations and interrelationships. Hum Reprod (1990) 5:915–919.
Leroy JLMR, Vanholder T, Delanghe JR, Opsomer G, Van Soom A, Bols PEJ, de Kruif A. Metabolite and ionic composition of follicular fluid from different-sized follicles and their relationship to serum concentrations in dairy cows. Anim Reprod Sci (2004) 80:201–211.[CrossRef][ISI][Medline]
McNatty KP. Hormonal correlates of follicular development in the human ovary. Aust J Biol Sci (1981) 34:249–268.[Medline]
Menezo Y, Testart J, Thebault A, Frydman R, Khatchadourian C. The preovulatory follicular fluid in the human: influence of hormonal pretreatment (Clomiphene-hCG) on some biochemical and biophysical variables. Int J Fertil (1982) 27:47–51.[ISI][Medline]
Moley KH, Chi MM-Y, Manchester JK, McDougal DB Jr, Lowry OH. Alterations of intraembryonic metabolites in preimplantation mouse embryos exposed to elevated concentrations of glucose: a metabolic explanation for the developmental retardation seen in preimplantation embryos from diabetic animals. Biol Reprod (1996) 54:1209–1216.[Abstract]
Pigman W (ed). The Carbohydrates. Chemistry, Biochemistry, Physiology (1957) Academic Press. 465.
Poretsky L, Seto-Young D, Shrestha A, Dhillon S, Mirjany M, Liu HC, Yih MC, Rosenwaks Z. Phosphatidyl-inositol-3 kinase-independent insulin action pathway(s) in the human ovary. J Clin Endocrinol Metab (2001) 86:3115–3119.
Riley JK, Carayannopoulos MO, Wyman AH, Chi M, Moley KH. Phosphatidylinositol 3-kinase activity is critical for glucose metabolism and embryo survival in murine blastocysts. J Biol Chem (2006) 281:6010–6019.
Salustri A, Camaioni A, Di Giacomo M, Fulop C, Hascall VC. Hyaluronan and proteoglycans in ovarian follicles. Hum Reprod Update (1999) 5:293–301.
Stryer L. Biochemistry (1988) 3rd edn. WH Freeman and Company. 284–287.
Suchá R, Ul
ová-Gallová Z, Pavelková-Seifertová P, K
i
anovská K, Bou
e V, 
vábek L, Rokyta P, Balvín M, Pecen L, Rokyta Z. Fructose and glucose in follicular fluid and serum of women undergoing stimulation in an in vitro fertilization program. (in Czech). Ceska Gynekol (2002) 67:144–148.[Medline]
Sutton ML, Gilchrist RB, Thompson JG. Effects of in-vivo and in-vitro environments on the metabolism of the cumulus–oocyte complex and its influence on oocyte developmental capacity. Hum Reprod Update (2003) 9:35–48.
Sutton-McDowall ML, Gilchrist RB, Thompson JG. Cumulus expansion and glucose utilisation by bovine cumulus–oocyte complexes during in vitro maturation: the influence of glucosamine and follicle-stimulating hormone. Reproduction (2004) 128:313–319.
Sutton-McDowall ML, Mitchell M, Cetica P, Dalvit G, Pantaleon M, Lane M, Gilchrist RB, Thompson JG. Glucosamine supplementation during in vitro maturation inhibits subsequent embryo development: possible role of the hexosamine pathway as a regulator of developmental competence. Biol Reprod (2006) 74:881–888.
Teng CC, Tjoa S, Fennessey PV, Wilkening RB, Battaglia FC. Transplacental carbohydrate and sugar alcohol concentrations and their uptakes in ovine pregnancy. Exp Biol Med (Maywood) (2002) 227:189–195.
Testart J, Frydman R, De Mouzon J, Lassalle B, Belaisch JC. A study of factors affecting the success of human fertilization in vitro. I. Influence of ovarian stimulation upon the number and condition of oocytes collected. Biol Reprod (1983) 28:415–424.[CrossRef][ISI][Medline]
Urner F, Sakkas D. Involvement of the pentose phosphate pathway and redox regulation in fertilization in the mouse. Mol Reprod Dev (2005) 70:494–503.[CrossRef][ISI][Medline]
Veeck LL. Oocyte assessment and biological performance. Ann N Y Acad Sci (1988) 541:259–274.[ISI][Medline]
Submitted on July 7, 2007; resubmitted on August 15, 2007; accepted on August 20, 2007.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||