Acylcarnitine esters profiling of serum and follicular fluid in patients undergoing in vitro fertilization

Reproductive Biology and Endocrinology

Béla Melegh⁴  József Bódis²  Gábor L Kovács¹  Endre Sulyok³  Judit Bene⁴  Ákos Várnagy² 

[1] Institute of Laboratory Medicine, Faculty of Medicine, University of Pécs, Ifjúság u.15, H-7624, Pécs, Hungary;Department of Obstetrics and Gynecology, Faculty of Medicine, University of Pécs, Édesanyák u. 17, H-7624, Pécs, Hungary;Institute of Public Health and Health Promotion, Faculty of Health Sciences, University of Pécs, Vörösmarty u.4, H-7621, Pécs, Hungary;Department of Medical Genetics, Faculty of Medicine, University of Pécs, Szigeti u.12, H-7624, Pécs, Hungary

关键词: Oocyte number;    Acylcarnitines;    Follicular fluid;    In vitro fertilization;   

Others  :  811057
DOI  :  10.1186/1477-7827-11-67

 received in 2013-03-29, accepted in 2013-07-15,  发布年份 2013

【 摘 要 】

Background

L-carnitine-mediated beta-oxidation of fatty acids has a well established role in energy supply of oocytes and embryos. Disturbed carnitine metabolism may impair the reproductive potential in IVF and can serve as a biomarker of pregnancy outcome.

Methods

Our study was performed between March 24, 2011 and May 9, 2011. We performed 44 unselected IVF cycles, (aged 23–40 years (mean: 32.3+/−5.1 years) and had BMI of 17.3-34.7 (mean: 23.80+/−4.9). Samples were also obtained from 18 healthy women of similar age admitted for minor elective surgery to serve as control for plasma carnitine profile. Serum and follicular fluid (FF) free carnitine (FC) and 20 major acylcarnitines (ACs) were measured by ESI/MS/MS method.

Results

Serum FC and AC levels in IVF patients were comparable to those in healthy control women. In FF FC and short-chain AC concentrations were similar to those in maternal serum, however, the levels of medium-chain, and long-chain AC esters were markedly reduced (p<0.05). The serum to FF ratio of individual carnitine compounds increased progressively with increasing carbon chain length of AC esters (p<0.05). There was a marked reduction in total carnitine, FC and AC levels of serum and FF in patients with oocyte number of >9 and/or with embryo number of >6 as compared to the respective values of <9 and/or <6 (p<0.05).

Conclusions

In IVF patients with better reproductive potential the carnitine/AC pathway appears to be upregulated that may result in excess carintine consumption and relative depletion of carnitine pool. Consequently, IVF patients may benefit from carnitine supplementation.

【 授权许可】

   
2013 Várnagy et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

【 参考文献 】

• [1]Biggers JD, Whittingham DG, Donahue RP: The pattern of energy metabolism in the mouse oocyte and zygote. Proc Natl Acad Sci USA 1967, 58:560-567.
• [2]Van Blerkom JU, Davis PW, Lee J: ATP content of human oocytes and developmental potential and outcome after in vitro fertilization and embryo transfer. Hum Reprod 1995, 10:415-424.
• [3]Nagano M, Katagiri S, Takahashi Y: ATP content and maturational/developmental ability of bovine oocytes with various cytoplasmic morphologies. Zygote 2006, 14:299-304.
• [4]Thompson JG, Lane M, Gilchrist RB: Metabolism of the bovine cumulus-oocyte complex and influence on subsequent developmental competence. Soc Reprod Fertil Suppl 2007, 64:179-190.
• [5]Hillman N, Flynn TJ: The metabolism of endogenous fatty acids by preimplantation mouse embryos developing in vitro. J Embryol Exp Morphol 1980, 56:157-168.
• [6]Downs SM, Mosey JL, Klinger J: Fatty acid oxidation and meiotic resumption in mouse oocytes. Mol Reprod Dev 2009, 76:844-853.
• [7]Sturmey RG, Reis A, Leese HJ, McEvoy TG: Role of fatty acids in energy provision during oocyte maturation and early embryo development. Reprod Domest Anim 2009, 44:50-58.
• [8]McKeegan PJ, Sturmey RG: The role of fatty acids in oocyte and early embryo development. Reprod Fert Develop 2011, 24:59-67.
• [9]Matorras R, Ruiz JI, Mendoza R, Ruiz N, Sanjurjo P, Rodriguez-Escudero FJ: Fatty acid composition of fertilization-failed human oocytes. Human Reprod 1998, 13:2227–2230. Br J Nutr 2007, 98:345-350.
• [10]Leroy JLMR, Vanholder T, Mateusen B, Christophe A, Opsomer G, de Kruif A, Genicot G, Van Soom A: Non-esterified fatty acids in AC of dairy cows and their effect on developmental capacity of bovine oocytes in vitro. Reproduction 2005, 130:485-495.
• [11]Van Hoeck V, Sturmey RG, Bermejo-Alvarez P, Rizos D, Gutierrez-Adan A, Leese HJ, Bois PEJ, Leroy JLMR: Elevated non-esterified fatty acid concentrations during bovine oocyte maturation compromise early embryo physiology. PLoS ONE 2011, 6:e23183.
• [12]Melegh B, Sumegi B, Sherry AD: Preferential elimination of pivalate with supplemental carnitine via formation of pivaloylcarnitine in man. Xenobiotica 1993, 23:1255-1261.
• [13]Melegh B, Pap M, Morava E, Molnar D, Dani M, Kurucz J: Carnitine-dependent changes of metabolic fuel consumption during long-term treatment with valproic acid. J Pediatr 1994, 125:317-321.
• [14]Melegh B, Kerner J, Acsadi G, Lakatos J, Sandor A: L-carnitine replacement therapy in chronic valproate treatment. Neuropediatrics 1990, 21:40-43.
• [15]Vaz FM, Melegh B, Bene J, Cuebas D, Gage DA, Bootsma A, Vreken P, van Gennip AH, Bieber LL, Wanders RJ: Analysis of carnitine biosynthesis metabolites in urine by HPLC-electrospray tandem mass spectrometry. Clin Chem 2002, 48:826-834.
• [16]Melegh B, Kerner J, Sandor A, Vinceller M, Kispal G: Effects of oral L-carnitine supplementation in low-birth-weight premature infants maintained on human milk. Biol Neonate 1987, 51:185-193.
• [17]Kispal G, Melegh B, Alkonyi I, Sandor A: Enhanced uptake of carnitine by perfused rat liver following starvation. Biochim Biophys Acta 1987, 896:96-102.
• [18]Hoppel C: The role of carnitine in normal and altered fatty acid metabolism. Am J Kidney Dis 2003, 41(Suppl 4):S4-S12.
• [19]Bremer J: Carnitine metabolism and function. Physiol Rev 1983, 63:1420-1480.
• [20]Mansour G, Abdelrazik H, Sharma RK, Radwan E, Falcone T, Argarwal A: L-carnitine supplementation reduces oocyte cytoskeleton damage and embryo apoptosis induced by incubation in peritoneal fluid from patients with endometriosis. Fertil Steril 2009, 91:2079-2086.
• [21]Dunning KR, Cashman K, Russell DL, Thompson JG, Norman RJ, Robker RL: Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development. Biol Reprod 2010, 83:909-918.
• [22]Dunning KR, Akison LK, Russel DL, Norman RJ, Robker RL: Increased beta-oxidation and improved oocyte developmental competence in response to l-carnitine during ovarian in vitro follicle development in mice. Biol Reprod 2011, 85:548-555.
• [23]Wu G-Q, Jia B-Y, Li JJ, Fu X-W, Zhou G-B, Hou Y-P, Zhu S-E: L-carnitine enhances oocyte maturation and development of parthenogenetic embryos in pigs. Theriogenol 2011, 76:785-793.
• [24]Somfai T, Kaneda M, Akagi S, Watanabe S, Haraguchi S, Mizutanie E, Dang-Nguyen TQ, Geshi M, Kikuchi K, Nagai T: Enhancement of lipid metabolism with l-carnitine during in vitro maturation improves nuclear maturation and cleavage ability of follicular porcine oocytes. Reprod Fertil Develop 2011, 23:912-920.
• [25]Bene J, Komlósi K, Magyari L, Talian G, Horváth K, Gasztonyi B, Miheller P, Figler M, Mózsik G, Tulassay Z, Melegh B: Plasma carnitine ester profiles in Crohn’s disease patients characterized for SLC22A4 C1672T and SLC 22A5 G-207C genotypes. Br J Nutr 2007, 98(2):345-50.
• [26]Centers for disease control and prevention, Newborn screening Quality assurance program. https://wwwn.cdc.gov/nsqap/Public/default.aspx webcite
• [27]Baka S, Malamitsi-Puchner A: Novel follicular fluid factors influencing oocyte developmental potential in IVF: a review. Reprod BioMed online 2006, 12:500-506.
• [28]Revelli A, Piane LD, Casano S, Molinari E, Massobrio M, Rinaudo P: Follicular fluid content and oocyte quality¨from single biochemical markers to metabolomics. Reprod Biol Endocrinol 2009, 7:40. BioMed Central Full Text
• [29]Seli E, Botros L, Sakkas D, Burns DH: Noninvasive metabolomic profiling of embryo culture media using proton nuclear magnetic resonance correlates with reproductive potential of embryos in women undergoing in vitro fertilization. Fertil Steril 2008, 90:2183-2189.
• [30]Estes SJ, Ye B, Qiu W, Cramer D, Hornstein MD, Missmer SA: A proteomic analysis of IVF follicular fluid in women < 32 years old. Fertil Steril 2009, 92:1569-1578.
• [31]Pinero-Sagredo E, Nunes S, De Los Santos MJ, Celda D, Esteve V: NMR metabolic profile of human follicular fluid. NMR Biomed 2010, 23:485-495.
• [32]Wallace M, Cottell E, Gibney MJ, McAuliffe FM, Windfield M, Brennan L: An investigation into the relationship between the metabolic profile of follicular fluid, oocyte developmental potential, and implantation outcome. Fertil Steril 2012, 97:1078-1084.
• [33]Abdelrazik H, Sharma R, Mahfouz R, Agarwal A: L-carnitine decreases DNA damage and improves the in vitro blastocyst development rate in mouse embryos. Fertil Steril 2009, 91:589-596.
• [34]Mingrone G, Greco AV, Capristo E, Benedetti G, Giancaterini A, DeGaetano A, Gasbarrini G: L-carnitine improves glucose disposal in type 2 diabetic patients. J Am Coll Nutr 1999, 18:77-82.
• [35]Phongnimitr T, Liang Y, Srirattana K, Panyawai K, Sripunya N, Treetampinich C, Parnpai R: Effect of L-carnitine on maturation, cryo-tolerance and embryo developmental competence of bovine oocytes. Anim Sci J 2013. [Epub ahead of print]
• [36]Moawad AR, Tan SL, Xu B, Chen HY, Taketo T: L-carnitine supplementation during vitrification of mouse oocytes at the germinal vesicle stage improves preimplantation development following maturation and fertilization in vitro. Biol Reprod. 2013, 88:104.
• [37]Sutton-McDowall ML, Feil D, Robker RL, Thompson JG, Dunning KR: Utilization of endogenous fatty acid stores for energy production in bovine preimplantation embryos. Theriogenology 2012, 77:1632-1641.
• [38]Dunning KR, Robker RL: Promoting lipid utilization with l-carnitine to improve oocyte quality. Anim Reprod Sci 2012, 134:69-75.
• [39]Montjean D, Entezami F, Lichtblau I, Belloc S, Gurgan T, Menezo Y: Carnitine content in the follicular fluid and expression of the enzymes involved in beta oxidation in oocytes and cumulus cells. J Assist Reprod Genet 2012, 29:1221-1225.
• [40]Ramsay RR, Gandour R, van der Leij FR: Molecular enzymology of carnitine transfer and transport. Biochim Biophys Acta 2001, 1546:21-43.
• [41]Longo N, Amat di SanFilippo C, Pasquali M: Disorders of carnitine transport and the carnitine cycle. Am J Med Genet C Semin Med Genet 2006, 142C:77-85.
• [42]Dreval D, Bernstein D, Zakut H: Carnitine palmitoyltransferase deficiency in pregnancy – a case report. Am J Obstet Gynecol 1994, 170:1390-1392.
• [43]Lilker S, Kasodekar S, Goldszmith E: Anesthetic management of a parturient with carnitine palmitoyltransferase II deficiency. Can J Anaesth 2006, 53:482-486.
• [44]Ramsey PS, Biggio JR: Carnitine palmitoyltransferase deficiency in pregnancy. J Matern Fetal Neonat Med 2005, 18:357-359.
• [45]Hull ML, Nemeth D, Hague WM, Wilkinson C, Liebelt J, Lane M, Feil D, Hons BS: Mitochondrial fatty acid transport enzyme deficiency – implications for in vitro fertilization. Fertil Steril 2009, 91(2732):11-14.