Animal Reproduction (AR)
https://www.animal-reproduction.org/article/doi/10.21451/1984-3143-AR988
Animal Reproduction (AR)
Conference Paper

The role of L-carnitine during oocyte in vitro maturation: essential co-factor?

Kylie R. Dunning, Rebecca L. Robker

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Abstract

In vitro maturation (IVM) of oocytes is a promising technology for both the treatment of human infertility and in animal production as a means of improving genetic gain. However, IVM derived oocytes remain inferior to those matured in vivo with reduced developmental potential. The environment in which an oocyte matures in vitro is vastly different to in vivo where maturation takes place within the ovarian follicle. The in vitro environment differs in oxygen concentration, exposure to light, and metabolite composition of culture media vs. follicle fluid, to name a few. Human follicle fluid contains the metabolite Lcarnitine and has shown to be associated with human fertility. L-carnitine has known biological functions as an essential co-factor for beta-oxidation, regulating ATP production from lipids, and as a potent antioxidant. Importantly, it appears that cumulus cells and the oocyte lack the machinery to synthesize L-carnitine de novo. The inability for local production of L-carnitine during IVM and its importance in human fertility warrants investigation of its affects during IVM. The potential to improve oocyte quality by inclusion of L-carnitine in the culture media thus increasing the capacity for betaoxidation and/or antioxidant activity of the culture media is receiving increased attention. This review summarizes studies to date investigating the developmental importance of L-carnitine during IVM and the mechanisms by which improved developmental potential is elicited. Overall, the inclusion of L-carnitine during IVM of several species results in improved oocyte quality with increased development to blastocyst. This is likely due to the antioxidant capacity of L-carnitine and its ability to increase ATP production from intracellular lipid stores.

Keywords

antioxidant, beta-oxidation, in vitro maturation, L-carnitine, oocyte,

References

Aono N, Naganuma T, Abe Y, Hara K, Sasada H, Sato E, Yoshida H. 2003. Successful production of blastocysts following ultrarapid vitrification with stepwise equilibriation of germinal vesicle-stage mouse oocytes. J Reprod Dev, 49:501-506.

Aono N, Abe Y, Hara K, Sasada H, Sato E, Yoshida H. 2005. Production of live offspring from mouse germinal vesicle-stage oocytes vitrified by a modified stepwise method, SWEID. Fertil Steril, 84(suppl. 2):1078-1082.

Banwell KM, Lane M, Russell DL, Kind KL, Thompson JG. 2007. Oxygen concentration during mouse oocyte in vitro maturation affects embryo and fetal development. Hum Reprod, 22:2768-2775.

Bremer J. 1983. Carnitine--metabolism and functions. Physiol Rev, 63:1420-1480.

Brown HM, Dunning KR, Sutton-McDowall M, Gilchrist RB, Thompson JG, Russell DL. 2017. Failure to launch: aberrant cumulus gene expression during oocyte in vitro maturation. Reproduction, 153:R109-R120.

Buckett WM, Chian RC, Dean NL, Sylvestre C, Holzer HE, Tan SL. 2008. Pregnancy loss in pregnancies conceived after in vitro oocyte maturation, conventional in vitro fertilization, and intracytoplasmic sperm injection. Fertil Steril, 90:546-550.

Chankitisakul V, Somfai T, Inaba Y, Techakumphu M, Nagai T. 2013. Supplementation of maturation medium with L-carnitine improves cryo-tolerance of bovine in vitro matured oocytes. Theriogenology, 79:590-598.

Combelles CM, Gupta S, Agarwal A. 2009. Could oxidative stress influence the in-vitro maturation of oocytes? Reprod Biomed Online, 18:864-880.

Downs SM, Mosey JL, Klinger J. 2009. Fatty acid oxidation and meiotic resumption in mouse oocytes. Mol Reprod Dev, 76:844-853.

Dunning KR, Cashman K, Russell DL, Thompson JG, Norman RJ, Robker RL. 2010. Beta-oxidation is essential for mouse oocyte developmental competence and early embryo development. Biol Reprod, 83:909- 918.

Dunning KR, Akison LK, Russell DL, Norman RJ, Robker RL. 2011. Increased beta-oxidation and improved oocyte developmental competence in response to L-carnitine during ovarian in vitro follicle development in mice. Biol Reprod, 85:548-555.

Dunning KR, Robker RL. 2012. Promoting lipid utilization with l-carnitine to improve oocyte quality. Anim Reprod Sci, 134:69-75.

Dunning KR, Anastasi MR, Zhang VJ, Russell DL, Robker RL. 2014a. Regulation of fatty acid oxidation in mouse cumulus-oocyte complexes during maturation and modulation by PPAR agonists. PloS One, 9:e87327.

Dunning KR, Russell DL, Robker RL. 2014b. Lipids and oocyte developmental competence: the role of fatty acids and beta-oxidation. Reproduction, 148:R15-27.

Ferguson EM, Leese HJ. 2006. A potential role for triglyceride as an energy source during bovine oocyte maturation and early embryo development. Mol Reprod Dev, 73:1195-1201.

Gilchrist RB, Thompson JG. 2007. Oocyte maturation: emerging concepts and technologies to improve developmental potential in vitro. Theriogenology, 67:6-15.

Giorgi VS, Da Broi MG, Paz CC, Ferriani RA, Navarro PA. 2016. N-acetyl-cysteine and L-carnitine prevent meiotic oocyte damage induced by follicular fluid from infertile women with mild endometriosis. Reprod Sci, 23:342-351.

Gomes CM, Silva CA, Acevedo N, Baracat E, Serafini P, Smith GD. 2008. Influence of vitrification on mouse metaphase II oocyte spindle dynamics and chromatin alignment. Fertil Steril, 90:1396-1404.

Gulcin I. 2006. Antioxidant and antiradical activities of L-carnitine. Life Sci, 78:803-811.

Hashimoto S. 2009. Application of in vitro maturation to assisted reproductive technology. J Reprod Dev, 55:1-10.

Huang JY, Chen HY, Park JY, Tan SL, Chian RC. 2008. Comparison of spindle and chromosome configuration in in vitro- and in vivo-matured mouse oocytes after vitrification. Fertil Steril, 90:1424-1432.

Huynh FK, Green MF, Koves TR, Hirschey MD. 2014. Measurement of fatty acid oxidation rates in animal tissues and cell lines. Methods Enzymol, 542:391-405.

Kolodziejczyk J, Saluk-Juszczak J, Wachowicz B. 2011. L-Carnitine protects plasma components against oxidative alterations. Nutrition, 27:693-699.

Lane M, Robker RL, Robertson SA. 2014. Parenting from before conception. Science, 345:756-760.

Lee YS, VandeVoort CA, Gaughan JP, Midic U, Obradovic Z, Latham KE. 2011. Extensive effects of in vitro oocyte maturation on rhesus monkey cumulus cell transcriptome. Am J Physiol Endocrinol Metab, 301:E196-209.

McGarry JD, Brown NF. 1997. The mitochondrial carnitine palmitoyltransferase system. From concept to molecular analysis. Eur J Biochem, 244:1-14.

McKeegan PJ, Sturmey RG. 2011. The role of fatty acids in oocyte and early embryo development. Reprod Fertil Dev, 24:59-67.

Mishra A, Reddy IJ, Gupta P, Mondal S. 2016a. Developmental regulation and modulation of apoptotic genes expression in sheep oocytes and embryos cultured in vitro with L-carnitine. Reprod Domest Anim, 51:1020-1029.

Mishra A, Reddy IJ, Gupta PS, Mondal S. 2016b. Lcarnitine mediated reduction in oxidative stress and alteration in transcript level of antioxidant enzymes in sheep embryos produced in vitro. Reprod Domest Anim, 51:311-321.

Moawad AR, Tan SL, Xu B, Chen HY, Taketo T. 2013. L-carnitine supplementation during vitrification of mouse oocytes at the germinal vesicle stage improves preimplantation development following maturation and fertilization in vitro. Biol Reprod, 88:104. doi: 10.1095/biolreprod.112.107433.

Moawad AR, Xu B, Tan SL, Taketo T. 2014. Lcarnitine supplementation during vitrification of mouse germinal vesicle stage-oocytes and their subsequent in vitro maturation improves meiotic spindle configuration and mitochondrial distribution in metaphase II oocytes. Hum Reprod, 29:2256-2268.

Montjean D, Entezami F, Lichtblau I, Belloc S, Gurgan T, Menezo Y. 2012. Carnitine content in the follicular fluid and expression of the enzymes involved in beta oxidation in oocytes and cumulus cells. J Assist Reprod Genet, 29:1221-1225.

Nada MA, Rhead WJ, Sprecher H, Schulz H, Roe CR. 1995. Evidence for intermediate channeling in mitochondrial beta-oxidation. J Biol Chem, 270:530- 535.

Paczkowski M, Schoolcraft WB, Krisher RL. 2014. Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence. Reproduction, 148:429-439.

Phongnimitr T, Liang Y, Srirattana K, Panyawai K, Sripunya N, Treetampinich C, Parnpai R. 2013. Effect of L-carnitine on maturation, cryo-tolerance and embryo developmental competence of bovine oocytes. Anim Sci J, 84:719-725.

Reader KL, Cox NR, Stanton JA, Juengel JL. 2015. Effects of acetyl-L-carnitine on lamb oocyte blastocyst rate, ultrastructure, and mitochondrial DNA copy number. Theriogenology, 83:1484-1492.

Rebouche CJ. 1992. Carnitine function and requirements during the life cycle. FASEB J, 6:3379- 3386.

Ribas GS, Manfredini V, de Marco MG, Vieira RB, Wayhs CY, Vanzin CS, Biancini GB, Wajner M, Vargas CR. 2010. Prevention by L-carnitine of DNA damage induced by propionic and L-methylmalonic acids in human peripheral leukocytes in vitro. Mutat Res, 702:123-128.

Rizos D, Ward F, Duffy P, Boland MP, Lonergan P. 2002. Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality. Mol Reprod Dev, 61:234-248.

Sanchez-Lazo L, Brisard D, Elis S, Maillard V, Uzbekov R, Labas V, Desmarchais A, Papillier P, Monget P, Uzbekova S. 2014. Fatty acid synthesis and oxidation in cumulus cells support oocyte maturation in bovine. Mol Endocrinol, 28:1502-1521.

Sener G, Paskaloglu K, Satiroglu H, Alican I, Kacmaz A, Sakarcan A. 2004. L-carnitine ameliorates oxidative damage due to chronic renal failure in rats. J Cardiovasc Pharmacol, 43:698-705.

Silva-Adaya D, Perez-De La Cruz V, HerreraMundo MN, Mendoza-Macedo K, VilledaHernandez J, Binienda Z, Ali SF, Santamaria A. 2008. Excitotoxic damage, disrupted energy metabolism, and oxidative stress in the rat brain: antioxidant and neuroprotective effects of L-carnitine. J Neurochem, 105:677-689.

Somfai T, Kaneda M, Akagi S, Watanabe S, Haraguchi S, Mizutani E, Dang-Nguyen TQ, Geshi M, Kikuchi K, Nagai T. 2011. Enhancement of lipid metabolism with L-carnitine during in vitro maturation improves nuclear maturation and cleavage ability of follicular porcine oocytes. Reprod Fertil Dev, 23:912- 920.

Sovernigo TC, Adona PR, Monzani PS, Guemra S, Barros F, Lopes FG, Leal C. 2017. Effects of supplementation of medium with different antioxidants during in vitro maturation of bovine oocytes on subsequent embryo production. Reprod Domest Anim. doi: 10.1111/rda.12946.

Spindler RE, Pukazhenthi BS, Wildt DE. 2000. Oocyte metabolism predicts the development of cat embryos to blastocyst in vitro. Mol Reprod Dev, 56:163- 171.

Spricigo JF, Morato R, Arcarons N, Yeste M, Dode MA, Lopez-Bejar M, Mogas T. 2017. Assessment of the effect of adding L-carnitine and/or resveratrol to maturation medium before vitrification on in vitromatured calf oocytes. Theriogenology, 89:47-57.

Sturmey RG, O'Toole PJ, Leese HJ. 2006. Fluorescence resonance energy transfer analysis of mitochondrial:lipid association in the porcine oocyte. Reproduction, 132:829-837.

Sutton ML, Gilchrist RB, Thompson JG. 2003. 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, 9:35-48.

Sutton-McDowall ML, Feil D, Robker RL, Thompson JG, Dunning KR. 2012. Utilization of endogenous fatty acid stores for energy production in bovine preimplantation embryos. Theriogenology, 77:1632-1641.

Truong TT, Soh YM, Gardner DK. 2016. Antioxidants improve mouse preimplantation embryo development and viability. Hum Reprod, 31:1445-1454. Uppangala S, Dhiman S, Salian SR, Singh VJ, Kalthur G, Adiga SK. 2015. In vitro matured oocytes are more susceptible than in vivo matured oocytes to mock ICSI induced functional and genetic changes. PloS One, 10:e0119735.

Valckx SD, De Pauw I, De Neubourg D, Inion I, Berth M, Fransen E, Bols PE, Leroy JL. 2012. BMIrelated metabolic composition of the follicular fluid of women undergoing assisted reproductive treatment and the consequences for oocyte and embryo quality. Hum Reprod, 27:3531-3539.

Valsangkar D, Downs SM. 2013. A requirement for fatty acid oxidation in the hormone-induced meiotic maturation of mouse oocytes. Biol Reprod, 89:43. doi: 10.1095/biolreprod.113.109058.

Van Blerkom J, Davis PW, Lee J. 1995. ATP content of human oocytes and developmental potential and outcome after in-vitro fertilization and embryo transfer. Hum Reprod, 10:415-424.

Varnagy A, Bene J, Sulyok E, Kovacs GL, Bodis J, Melegh B. 2013. Acylcarnitine esters profiling of serum and follicular fluid in patients undergoing in vitro fertilization. Reprod Biol Endocrinol, 11:67. doi: 10.1186/1477-7827-11-67.

Vaz FM, Wanders RJ. 2002. Carnitine biosynthesis in mammals. Biochem J, 361:417-429.

Wu GQ, Jia BY, Li JJ, Fu XW, Zhou GB, Hou YP, Zhu SE. 2011. L-carnitine enhances oocyte maturation and development of parthenogenetic embryos in pigs. Theriogenology, 76:785-793.

Wu LL, Russell DL, Norman RJ, Robker RL. 2012. Endoplasmic reticulum (ER) stress in cumulus-oocyte complexes impairs pentraxin-3 secretion, mitochondrial membrane potential (DeltaPsi m), and embryo development. Mol Endocrinol, 26:562-573.

Yazaki T, Hiradate Y, Hoshino Y, Tanemura K, Sato E. 2013. L-carnitine improves hydrogen peroxideinduced impairment of nuclear maturation in porcine oocytes. Anim Sci J, 84:395-402.

Ye J, Li J, Yu Y, Wei Q, Deng W, Yu L. 2010. Lcarnitine attenuates oxidant injury in HK-2 cells via ROS-mitochondria pathway. Regul Pept, 161:58-66.

You J, Lee J, Hyun SH, Lee E. 2012. L-carnitine treatment during oocyte maturation improves in vitro development of cloned pig embryos by influencing intracellular glutathione synthesis and embryonic gene expression. Theriogenology, 78:235-243.

Zare Z, Masteri Farahani R, Salehi M, Piryaei A, Ghaffari Novin M, Fadaei Fathabadi F, Mohammadi M, Dehghani-Mohammadabadi M. 2015. Effect of Lcarnitine supplementation on maturation and early embryo development of immature mouse oocytes selected by brilliant cresyle blue staining. J Assist Reprod Genet, 32:635-643.

Zeng HT, Richani D, Sutton-McDowall ML, Ren Z, Smitz JE, Stokes Y, Gilchrist RB, Thompson JG. 2014. Prematuration with cyclic adenosine monophosphate modulators alters cumulus cell and oocyte metabolism and enhances developmental competence of in vitro-matured mouse oocytes. Biol Reprod, 91:47.

Zhao H, Zhao Y, Li T, Li M, Li J, Li R, Liu P, Yu Y, Qiao J. 2015. Metabolism alteration in follicular niche: The nexus among intermediary metabolism, mitochondrial function, and classic polycystic ovary syndrome. Free Radic Biol Med, 86:295-307.

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