Register      Login
Reproduction, Fertility and Development Reproduction, Fertility and Development Society
Vertebrate reproductive science and technology
RESEARCH ARTICLE

Interaction between differential gene expression profile and phenotype in bovine blastocysts originating from oocytes exposed to elevated non-esterified fatty acid concentrations

V. Van Hoeck A , D. Rizos B , A. Gutierrez-Adan B , I. Pintelon A , E. Jorssen A , I. Dufort C , M. A. Sirard C , A. Verlaet D , N. Hermans D , P. E. J. Bols A and J. L. M. R. Leroy A E
+ Author Affiliations
- Author Affiliations

A Department of Veterinary Sciences, Faculty of Biomedical, Pharmaceutical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

B Departamento de Reproducción Animal y Conservación de Recursos Zoogenéticos, INIA, Ctra. de la Coruna Km 5.9, 28040 Madrid, Spain.

C Département des Sciences Animales Pavillon des services, INAF, Université Laval, G1V 0A6 Québec, Canada.

D Departement Pharmaceutical Sciences, Faculty of Biomedical, Pharmaceutical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Wilrijk, Belgium.

E Corresponding author. Email: jo.leroy@uantwerpen.be

Reproduction, Fertility and Development 27(2) 372-384 https://doi.org/10.1071/RD13263
Submitted: 13 August 2013  Accepted: 28 October 2013   Published: 23 December 2013

Abstract

Maternal metabolic disorders linked to lipolysis are major risk factors for reproductive failure. A notable feature of such disorders is increased non-esterified fatty acid (NEFA) concentrations in the blood, which are reflected in the ovarian follicular fluid. Elevated NEFA concentrations impact on the maturing oocyte and even alter subsequent embryo physiology. The aetiological mechanisms have not been fully elucidated. Therefore, in the present study, bovine in vitro maturing cumulus–oocyte complexes were exposed (24 h) to three different maturation treatments containing: (1) physiological (72 µM) NEFA concentrations (= control); (2) elevated (75 µM) stearic acid (SA) concentrations (= HIGH SA); and (3) elevated (425 µM) NEFA concentrations (= HIGH COMBI). Zygotes were fertilised and cultured following standard procedures. Transcriptomic analyses in resulting Day 7.5 blastocysts revealed that the major pathways affected are related to lipid and carbohydrate metabolism in HIGH COMBI embryos and to lipid metabolism and cell death in HIGH SA embryos. Furthermore, lower glutathione content and a reduced number of lipid droplets per cell were observed in HIGH SA-exposed oocytes and resulting morulae, respectively, compared with their HIGH COMBI-exposed counterparts. Vitrified embryos originating from HIGH SA-exposed oocytes tended to exhibit lower survival rates compared with controls. These data suggest possible mechanisms explaining why females across species suffering lipolytic disorders experience difficulties in conceiving.

Additional keywords: embryo quality, fertility, lipolysis, maternal metabolism.


References

Aardema, H., Vos, P. L. A. M., Lolicato, F., Roelen, B. A. J., and Knijn, H. M. (2011). Oleic acid prevents detrimental effects of saturated fatty acids on bovine oocyte developmental competence. Biol. Reprod. 85, 62–69.
Oleic acid prevents detrimental effects of saturated fatty acids on bovine oocyte developmental competence.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXotFOls74%3D&md5=4761dcc8a802f4e466ee0c48cd40266bCAS | 21311036PubMed |

Aerts, J. M. J., De Clercq, J. B. P., Andries, S., Leroy, J. L. M. R., Van Aelst, S., and Bols, P. E. J. (2008). Follicle survival and growth to antral stages in short-term murine ovarian cortical transplants after Cryologic solid surface vitrification or slow-rate freezing. Cryobiology 57, 163–169.
Follicle survival and growth to antral stages in short-term murine ovarian cortical transplants after Cryologic solid surface vitrification or slow-rate freezing.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhtFyltrrE&md5=de158a88856ecaf94ccb4c433d494811CAS |

Bermejo-Alvarez, P., Rizos, D., Rath, D., Lonergan, P., and Gutierrez-Adan, A. (2010). Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts. Proc. Natl Acad. Sci. USA 107, 3394–3399.
Sex determines the expression level of one third of the actively expressed genes in bovine blastocysts.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXjtFymtbo%3D&md5=bfc5620ee964c2a4ee1e5b2c5e36742eCAS | 20133684PubMed |

Bijttebier, J., Van Soom, A., Meyer, E., Mateusen, B., and Maes, D. (2008). Preovulatory follicular fluid during in vitro maturation decreases polyspermic fertilization of cumulus-intact porcine oocytes: in vitro maturation of porcine oocytes. Theriogenology 70, 715–724.
Preovulatory follicular fluid during in vitro maturation decreases polyspermic fertilization of cumulus-intact porcine oocytes: in vitro maturation of porcine oocytes.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1cvovVGhsw%3D%3D&md5=656e1488a940b0d1ac7bdcb0358d83b9CAS | 18572236PubMed |

Bonnard, C., Durand, A., Peyrol, S., Chanseaume, E., Chauvin, M. A., Morio, B., Vidal, H., and Rieusset, J. (2008). Mitochondrial dysfunction results from oxidative stress in the skeletal muscle of diet-induced insulin-resistant mice. J. Clin. Invest. 118, 789–800.
| 1:CAS:528:DC%2BD1cXhsFOmsL0%3D&md5=3b31864975c9aa8460684625bbb466cbCAS | 18188455PubMed |

Brasaemle, D. L., Rubin, B., Harten, I. A., Gruia-Gray, J., Kimmel, A. R., and Londos, C. (2000). Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis. J. Biol. Chem. 275, 38 486–38 493.
Perilipin A increases triacylglycerol storage by decreasing the rate of triacylglycerol hydrolysis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXoslymtrk%3D&md5=38d7a0f5bb9e865f253aeb9a270fb33eCAS |

Burton, G. J., Hempstock, J., and Jauniaux, E. (2003). Oxygen, early embryonic metabolism and free radical-mediated embryopathies. Reprod. Biomed. Online 6, 84–96.
Oxygen, early embryonic metabolism and free radical-mediated embryopathies.Crossref | GoogleScholarGoogle Scholar | 12626148PubMed |

Cagnone, G. L. M., Dufort, I., Vigneault, C., and Sirard, M. A. (2012). Differential gene expression profile in bovine blastocysts resulting from hyperglycemia exposure during early cleavage stages. Biol. Reprod. 86, 50.
Differential gene expression profile in bovine blastocysts resulting from hyperglycemia exposure during early cleavage stages.Crossref | GoogleScholarGoogle Scholar |

Carlsson, C., Hakan, B., and Welsh, N. (1999). Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro. Endocrinology 140, 3422–3428.
Sodium palmitate induces partial mitochondrial uncoupling and reactive oxygen species in rat pancreatic islets in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXkslKrtbw%3D&md5=573fcdc372ff469af05622bb15a95295CAS | 10433196PubMed |

Chavatte-Palmer, P., Al Gubory, K., Picone, O., and Heyman, Y. (2008). Maternal nutrition: effects on offspring fertility and importance of the periconceptional period on long-term development. Gynecol. Obstet. Fertil. 36, 920–929.
Maternal nutrition: effects on offspring fertility and importance of the periconceptional period on long-term development.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1cnjsVyjtg%3D%3D&md5=fa12e7252910866e2808ea4c542fd64aCAS | 18693060PubMed |

Cnop, M., Hannaert, J. C., Hoorens, A., Eizirik, D. L., and Pipeleers, D. G. (2001). Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation. Diabetes 50, 1771–1777.
Inverse relationship between cytotoxicity of free fatty acids in pancreatic islet cells and cellular triglyceride accumulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlslKnu74%3D&md5=4df9f825514a0aa7ccd51e566968f760CAS | 11473037PubMed |

de Matos, D. G., Furnus, C. C., Moses, D. F., and Baldassarre, H. (1995). Effect of cysteamine on glutathione level and developmental capacity of bovine oocyte matured in vitro. Mol. Reprod. Dev. 42, 432–436.
Effect of cysteamine on glutathione level and developmental capacity of bovine oocyte matured in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXpvVGisLc%3D&md5=26a80a85cca48de7e542dc149849104eCAS | 8607972PubMed |

de Matos, D. G., Furnus, C. C., Moses, D. F., Martinez, A. G., and Matkovic, M. (1996). Stimulation of glutathione synthesis of in vitro matured bovine oocytes and its effect on embryo development and freezability. Mol. Reprod. Dev. 45, 451–457.
Stimulation of glutathione synthesis of in vitro matured bovine oocytes and its effect on embryo development and freezability.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK28XnsVWgsr0%3D&md5=e362cb655dae97da332d7a202fff2bc6CAS | 8956283PubMed |

Fedorcsák, P., Storneg, R., Dale, P. O., Tanbo, T., and Abyholm, T. (2000). Obesity is a risk factor for early pregnancy loss after IVF or ICSI. Acta Obstet. Gynecol. Scand. 79, 43–48.
Obesity is a risk factor for early pregnancy loss after IVF or ICSI.Crossref | GoogleScholarGoogle Scholar | 10646815PubMed |

Ferguson, E. M., and Leese, H. J. (1999). Triglyceride content of bovine oocytes and early embryos. J. Reprod. Fertil. 116, 373–378.
Triglyceride content of bovine oocytes and early embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXkslOltbc%3D&md5=1a1797e271c04cc7e69c0e31412f7fb5CAS | 10615263PubMed |

Furukawa, S., Fujita, T., Shimabukuro, M., Iwaki, M., Yamada, Y., Nakajima, Y., Makishima, O., Matsuda, M., and Shimomura, M. (2004). Increased oxidative stress in obesity and its impact on metabolic syndrome. J. Clin. Invest. 114, 1752–1761.
| 1:CAS:528:DC%2BD2cXhtFaiur7F&md5=88d134cccdd7caf23399a49484abeacaCAS | 15599400PubMed |

Geshi, M., Takenouchi, N., Yamauchi, N., and Nagai, T. (2000). Effects of sodium pyruvate in nonserum maturation medium on maturation, fertilization and subsequent development of bovine oocytes with or without cumulus cells. Biol. Reprod. 63, 1730–1734.
Effects of sodium pyruvate in nonserum maturation medium on maturation, fertilization and subsequent development of bovine oocytes with or without cumulus cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXosVKht70%3D&md5=accbf772d1bee99312ea508baed72fc3CAS | 11090443PubMed |

Grupen, C. G., Nagashima, H., and Nottle, M. B. (1995). Cysteamine enhances in vitro development of porcine oocytes matured and fertilized in vitro. Biol. Reprod. 53, 173–178.
Cysteamine enhances in vitro development of porcine oocytes matured and fertilized in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXmt12itb4%3D&md5=0480264b665fbd1af248cb6e46279e5cCAS | 7669846PubMed |

Iossa, S., Mollica, M. P., Lionetti, L., Crescenzo, R., Botta, M., and Liverini, G. (2002). Skeletal muscle oxidative capacity in rats fed high-fat diet. Int. J. Obes. Relat. Metab. Disord. 26, 65–72.
Skeletal muscle oxidative capacity in rats fed high-fat diet.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xhtleiu7Y%3D&md5=69fa108149ba717a09444f813a38aa75CAS | 11791148PubMed |

Jorritsma, R., Cesar, M. L., Hermans, J. T., Kruitwagen, C. L., and Vos, P. L. (2004). Effects of non-esterified fatty acids on bovine granulosa cells and developmental potential of oocytes in vitro. Anim. Reprod. Sci. 81, 225–235.
Effects of non-esterified fatty acids on bovine granulosa cells and developmental potential of oocytes in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhsleltr0%3D&md5=5d38a9335f2d13443b386e431443b473CAS | 14998649PubMed |

Jungheim, E. S., Louden, E. D., Chi, M. M., Frolova, A. I., Riley, J. K., and Moley, K. H. (2011a). Preimplantation exposure of mouse embryos to palmitic acid results in fetal growth restriction followed by catch-up growth in the offspring. Biol. Reprod. 85, 678–683.
Preimplantation exposure of mouse embryos to palmitic acid results in fetal growth restriction followed by catch-up growth in the offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXht12ht7zE&md5=c391fa5f64521f54ab6bebbdfacc6d38CAS | 21653893PubMed |

Jungheim, E. S., Macones, G. A., Odem, R. R., Patterson, B. W., Lanzendorf, S. E., Ratts, V. S., and Moley, K. H. (2011b). Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization. Fertil. Steril. 95, 1970–1974.
Associations between free fatty acids, cumulus oocyte complex morphology and ovarian function during in vitro fertilization.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXltFymt7s%3D&md5=07ebb2b6627f8accad433ed3579065feCAS | 21353671PubMed |

Koshkin, V., Wang, X., Scherers, P. E., Chan, C. B., and Wheeler, M. B. (2003). Mitochondrial functional state in clonal pancreatic β cells exposed to free fatty acids. J. Biol. Chem. 278, 19 709–19 715.
Mitochondrial functional state in clonal pancreatic β cells exposed to free fatty acids.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXktVaqtr8%3D&md5=f28671fd21bef027ea70d81348b67f1fCAS |

Latham, K. E., and Sapienza, C. (1998). Localization of genes encoding egg modifiers of paternal genome function to mouse chromosomes one and two. Development 125, 929–935.
| 1:CAS:528:DyaK1cXitlGqtrk%3D&md5=187c16537e106464e1334d4f77270684CAS | 9449675PubMed |

Leibo, S. P., and Loskutoff, N. M. (1993). Cryobiology of in vitro-derived bovine embryos. Theriogenology 39, 81–94.
Cryobiology of in vitro-derived bovine embryos.Crossref | GoogleScholarGoogle Scholar |

Leroy, J. L., Vanholder, T., Mateusen, B., Christophe, A., and Opsomer, G. (2005). Non-esterified fatty acids in follicular fluid of dairy cows and their effect on developmental capacity of bovine oocytes in vitro. Reproduction 130, 485–495.
Non-esterified fatty acids in follicular fluid of dairy cows and their effect on developmental capacity of bovine oocytes in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtFent7rJ&md5=cd82fd88938bb4bfbef1f4cb6ee5e020CAS | 16183866PubMed |

Leroy, J. L. M. R., Van Soom, A., Opsomer, G., Goovaerts, I. G., and Bols, P. E. (2008). Reduced fertility in high-yielding dairy cows: are the oocyte and embryo in danger? Part II. Mechanisms linking nutrition and reduced oocyte and embryo quality in high-yielding dairy cows. Reprod. Domest. Anim. 43, 623–632.
Reduced fertility in high-yielding dairy cows: are the oocyte and embryo in danger? Part II. Mechanisms linking nutrition and reduced oocyte and embryo quality in high-yielding dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD1cnksVeruw%3D%3D&md5=7319e9fdf58a72a76c883db8b8388712CAS |

Li, L. O., Klett, E. L., and Coleman, R. A. (2010). Acyl-CoA synthesis, lipid metabolism and lipotoxity. Biochim. Biophys. Acta 1801, 246–251.
Acyl-CoA synthesis, lipid metabolism and lipotoxity.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXitVejtL0%3D&md5=327b59c710ec3f328ae3e00ea3bdea3dCAS | 19818872PubMed |

Lu, Z. H., Mu, Y. M., Wang, B. A., Li, X. L., Lu, J. M., Li, J. Y., Pan, C. Y., Yanase, T., and Nawata, H. (2003). Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell. Biochem. Biophys. Res. Commun. 303, 1002–1007.
Saturated free fatty acids, palmitic acid and stearic acid, induce apoptosis by stimulation of ceramide generation in rat testicular Leydig cell.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXis12gsb8%3D&md5=00db173c29ef6ff48a9dc8499f7f7ee2CAS | 12684033PubMed |

Maedler, K., Spinas, G. A., Dyntar, D., Moritz, W., Kaiser, N., and Donath, M. Y. (2001). Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function. Diabetes 50, 69–76.
Distinct effects of saturated and monounsaturated fatty acids on beta-cell turnover and function.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXis1Ontg%3D%3D&md5=a63068afd19b51577df1e8b4b9c15f64CAS | 11147797PubMed |

Magielse, J., Verlaet, A., Breynaert, A., Keenoy, B. M. Y., Apers, S., Pieters, L., and Hermans, N. (2013). Investigation of the in vivo antioxidative activity of Cynara scolymus (artichoke) leaf extract. PhD Thesis University of Antwerp.

McGarry, J. D. (2002). Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes. Diabetes 51, 7–18.
Dysregulation of fatty acid metabolism in the etiology of type 2 diabetes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xlt1ejsQ%3D%3D&md5=7517afeab33345accfc68d058ce02f88CAS | 11756317PubMed |

McKeegan, P. J., and Sturmey, R. G. (2012). The role of fatty acids in oocyte and early embryo development. Reprod. Fertil. Dev. 24, 59–67.
The role of fatty acids in oocyte and early embryo development.Crossref | GoogleScholarGoogle Scholar |

Mohr, L. R., and Trounson, A. O. (1981). Structural changes associated with freezing of bovine embryos. Biol. Reprod. 25, 1009–1025.
Structural changes associated with freezing of bovine embryos.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL387htlymtA%3D%3D&md5=a936efce7b4789d4558a48538e5f2710CAS | 7326294PubMed |

Paczkowski, M., Silva, E., Schoolcraft, W. B., and Krisher, R. L. (2013). Comparative importance of fatty acid beta-oxidation to nuclear maturation, gene expression, and glucose metabolism in mouse, bovine, and porcine cumulus oocyte complexes. Biol. Reprod. 88, 111.
Comparative importance of fatty acid beta-oxidation to nuclear maturation, gene expression, and glucose metabolism in mouse, bovine, and porcine cumulus oocyte complexes.Crossref | GoogleScholarGoogle Scholar | 23536372PubMed |

Pasquali, R., Pelusi, C., Genghini, S., Cacciari, M., and Gembineri, A. (2003). Obesity and reproductive disorders in women. Hum. Reprod. Update 9, 359–372.
Obesity and reproductive disorders in women.Crossref | GoogleScholarGoogle Scholar | 12926529PubMed |

Perdomo, G., Commerford, S. R., Richard, A. M., Adams, S. H., Corkey, B. E., O’Doherty, R. M., and Brown, N. F. (2004). Increased beta-oxidation in muscle cells enhances insulin-stimulated glucose metabolism and protects against fatty acid-induced insulin resistance despite intramyocellular lipid accumulation. J. Biol. Chem. 279, 27 177–27 186.
Increased beta-oxidation in muscle cells enhances insulin-stimulated glucose metabolism and protects against fatty acid-induced insulin resistance despite intramyocellular lipid accumulation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXkvFGnsLk%3D&md5=7ad2b6358bdb2ca0a9a342e5a2eea5b5CAS |

Quinn, P., and Wales, R. G. (1973). The relationships between the ATP content of preimplantation mouse embryos and their development in vitro during culture. J. Reprod. Fertil. 35, 301–309.
The relationships between the ATP content of preimplantation mouse embryos and their development in vitro during culture.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE2cXjsFGisw%3D%3D&md5=134c710cef67928c02807079afefee39CAS | 4752146PubMed |

Reaven, G. M., Hollenbeck, C., Jeng, C. Y., Wu, M. S., and Chen, Y. D. (1988). Measurement of plasma glucose, free fatty acid, and insulin for 24 h in patients with NIDDM. Diabetes 37, 1020–1024.
Measurement of plasma glucose, free fatty acid, and insulin for 24 h in patients with NIDDM.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1c3ntFyisA%3D%3D&md5=b8ba81b4392a96c6a8e03ed505303b93CAS | 3292322PubMed |

Robker, R. L., Akison, L. K., Bennett, B. D., Thrupp, P. N., Chura, L. R., Russell, D. L., Lane, M., and Norman, R. J. (2009). Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women. J. Clin. Endocrinol. Metab. 94, 1533–1540.
Obese women exhibit differences in ovarian metabolites, hormones, and gene expression compared with moderate-weight women.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXlvVCqtrw%3D&md5=64e74dabbab655fb7b2c30636a9a8bb1CAS | 19223519PubMed |

Schmittgen, T. D., and Livak, K. J. (2008). Analysing real-time PCR data by the comparative C(T) method. Nat. Protoc. 3, 1101–1108.
Analysing real-time PCR data by the comparative C(T) method.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXmvVemt7c%3D&md5=1fdd4372bdd7c34b1431cc0c20708cacCAS | 18546601PubMed |

Shimabukuro, M., Ohneda, M., Lee, Y., and Unger, R. H. (1997). Role of nitric oxide in obesity-induced beta cell disease. J. Clin. Invest. 100, 290–295.
Role of nitric oxide in obesity-induced beta cell disease.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXkslKnsr8%3D&md5=e4b2cd34d7f2ff913e3d39558f647069CAS | 9218505PubMed |

Shimabukuro, M., Zhou, Y. T., Levi, M., and Unger, R. H. (1998). Fatty acid-induced β-cell apoptosis: a link between obesity and diabetes. Proc. Natl Acad. Sci. USA 95, 2498–2502.
Fatty acid-induced β-cell apoptosis: a link between obesity and diabetes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXhslehs7Y%3D&md5=3480a999a5bc5d7f8e05fa554861ce59CAS | 9482914PubMed |

Štolba, P., Kvapil, M., Wichterle, D., and Dvořák, P. (1993). Kinetics of free fatty acids in hypertriglyceridemia. Evidence for different types of insulin resistance. Ann. N. Y. Acad. Sci. 683, 373–375.
Kinetics of free fatty acids in hypertriglyceridemia. Evidence for different types of insulin resistance.Crossref | GoogleScholarGoogle Scholar | 8352469PubMed |

Souza, S. C., Muliro, K. V., Liscum, L., Lien, P., Yamamoto, M. T., Schaffer, J. E., Dallal, G. E., Wang, X., Kraemer, F. B., Obin, M., and Greenberg, A. S. (2002). Modulation of hormone-sensitive lipase and protein kinase A-mediated lipolysis by perilipin A in an adenoviral reconstituted system. J. Biol. Chem. 277, 8267–8272.
Modulation of hormone-sensitive lipase and protein kinase A-mediated lipolysis by perilipin A in an adenoviral reconstituted system.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XitFymtrc%3D&md5=9bbbe30cbed1456d1ece8b0bf50de09eCAS | 11751901PubMed |

Sutton-McDowall, M. L., Gilchrist, R. B., and Thompson, J. G. (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.
Cumulus expansion and glucose utilisation by bovine cumulus–oocyte complexes during in vitro maturation: the influence of glucosamine and follicle-stimulating hormone.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXot1KitLk%3D&md5=f8e07ce67421d20b258a3fb3e2856904CAS | 15333782PubMed |

Tanghe, S., Van Soom, A., Nauwynck, H., Coryn, M., and de Kruif, A. (2002). Minireview: functions of the cumulus oophorus during oocyte maturation, ovulation, and fertilization. Mol. Reprod. Dev. 61, 414–424.
Minireview: functions of the cumulus oophorus during oocyte maturation, ovulation, and fertilization.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XhsFCgtbk%3D&md5=c6af8da67df1e073438d40be8d97cb88CAS | 11835587PubMed |

Tarín, J. J. (1996). Potential effects of age-associated oxidative stress on mammalian oocytes/embryos. Mol. Hum. Reprod. 2, 717–724.
Potential effects of age-associated oxidative stress on mammalian oocytes/embryos.Crossref | GoogleScholarGoogle Scholar | 9239688PubMed |

Ulloth, J. E., Casiano, C. A., and De Leon, M. (2003). Palmitic and stearic fatty acids induce caspase-dependent and -independent cell death in nerve growth factor differentiated PC12 cells. J. Neurochem. 84, 655–668.
Palmitic and stearic fatty acids induce caspase-dependent and -independent cell death in nerve growth factor differentiated PC12 cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXht1amsb4%3D&md5=cc7a722137659efb78fcc32b47a33466CAS | 12562510PubMed |

Vajta, G., Holm, P., Kuwayama, M., Booth, P. J., Jacobsen, H., Greve, T., and Callesen, H. (1998). Open pulled straw (OPS) vitrification: a new way to reduce cryoinjuries of bovine ova and embryos. Mol. Reprod. Dev. 51, 53–58.
Open pulled straw (OPS) vitrification: a new way to reduce cryoinjuries of bovine ova and embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXltVGrs7g%3D&md5=49d4e9194babffb16608d70dd43f2acdCAS | 9712317PubMed |

Valckx, S., Bols, P. E. J., De Neubourg, D., Berth, M., De Pauw, I., and Leroy, J. L. M. R. (2010). Maternal metabolism and the influence on fertility: a study of the follicular environment. In ‘Proceedings of the 3rd Meeting of Gemini, Soustons, France, 1–3 October 2010.’ Available at http://www.cost-gemini.eu/ISBN%20Productions%20(electronic%20copy)/9780956369451_GEMINI_Programme_Booklet_1_3_Oct_2010.pdf

Van Blerkom, J., Davis, P. W., and 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.
| 1:STN:280:DyaK2M3os1OrtQ%3D%3D&md5=50a81f49241162b20287e6b23be53051CAS | 7769073PubMed |

Van Hoeck, V., Sturmey, R. G., Bermejo-Alvarez, P., Rizos, D., Gutierrez-Adan, A., Leese, H. J., Bols, P. E. J., and Leroy, J. L. M. R. (2011). Elevated non-esterified fatty acid concentrations during bovine oocyte maturation compromise early embryo physiology. PLoS One 6, e23183.
Elevated non-esterified fatty acid concentrations during bovine oocyte maturation compromise early embryo physiology.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFKmsLjM&md5=f70186f2c08e5bed5699f82fa441a304CAS | 21858021PubMed |

Van Hoeck, V., Leroy, J. L. M. R., Arias-Álvarez, M., Rizos, D., Gutierrez-Adan, A., Schnorbusch, K., Bols, P. E. J., Leese, H. J., and Sturmey, R. G. S. (2013). Oocyte developmental failure in response to elevated non-esterified fatty acid concentrations: mechanistic insights. Reproduction 145, 33–44.
Oocyte developmental failure in response to elevated non-esterified fatty acid concentrations: mechanistic insights.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3sXhslGisb8%3D&md5=cb04380e95149bf2c146be08d67949b3CAS | 23108110PubMed |

Vanholder, T., Leroy, J. L., Van Soom, A., Opsomer, G., Maes, D., Coryn, M., and de Kruif, A. (2005). Effect of non-esterified fatty acids on bovine granulosa cell steroidogenesis and proliferation in vitro. Anim. Reprod. Sci. 87, 33–44.
Effect of non-esterified fatty acids on bovine granulosa cell steroidogenesis and proliferation in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXktVOju74%3D&md5=df3d7202ce6adae70e3a89068a8765e3CAS | 15885439PubMed |

Watkins, A. J., Wilkins, A., Cunningham, C., Perry, V. H., Seet, M. J., Osmond, C., Eckert, J. J., Torrens, C., Cagampang, F. R. A., Cleal, J., Gray, W. P., Hanson, M. A., and Fleming, T. P. (2008). Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring. J. Physiol. 586, 2231–2244.
Low protein diet fed exclusively during mouse oocyte maturation leads to behavioural and cardiovascular abnormalities in offspring.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXlsFent7Y%3D&md5=a4bb156186d57fb7d85935577f9b1324CAS | 18308825PubMed |

Wu, D., and Cederbaum, A. (2000). Ethanol and arachidonic acid produce toxicity in hepatocytes from pyrazole-treated rats with high levels of CYP2E1. Mol. Cell. Biochem. 204, 157–167.
Ethanol and arachidonic acid produce toxicity in hepatocytes from pyrazole-treated rats with high levels of CYP2E1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXhvValuro%3D&md5=20dcd874daa6d55f5e6b8f0e1ae68996CAS | 10718635PubMed |

Zhang, X., and Zhang, K. (2012). Endoplasmic reticulum stress-associated lipid droplet formation and type II diabetes. Biochem. Res. Int. 2012, Article ID 247275.
Endoplasmic reticulum stress-associated lipid droplet formation and type II diabetes.Crossref | GoogleScholarGoogle Scholar |

Zhang, W. Y., Schwartz, E., Wang, Y., Atrep, J., Li, Z., and Reaven, P. (2006). Elevated concentrations of nonesterified fatty acids increase monocyte expression of CD11b and adhesion to endothelial cells. Arterioscler. Thromb. Vasc. Biol. 26, 514–519.
Elevated concentrations of nonesterified fatty acids increase monocyte expression of CD11b and adhesion to endothelial cells.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XisFars70%3D&md5=0d613f6add254ae31988af0bb5dac64dCAS | 16357311PubMed |