Insulin exposure during in vitro bovine oocyte maturation changes blastocyst gene expression and developmental potential

Denise Laskowski; Ylva Sjunnesson; Patrice Humblot; Marc-André Sirard; Göran Andersson; Hans Gustafsson; Renée Båge

doi:10.1071/RD15315

RESEARCH ARTICLE (Open Access)

Insulin exposure during in vitro bovine oocyte maturation changes blastocyst gene expression and developmental potential

Denise Laskowski ^A ^D , Ylva Sjunnesson ^A , Patrice Humblot ^A , Marc-André Sirard ^B , Göran Andersson ^C , Hans Gustafsson ^A and Renée Båge ^A

+ Author Affiliations

- Author Affiliations

^A Department of Clinical Sciences, Swedish University of Agricultural Sciences, P.O. Box 7054, SE-750 07 Uppsala, Sweden.

^B Departement des Sciences Animales, Centre de Recherche en Biologie de la Reproduction, Pavillon Des Services, local 2732, Université Laval, Québec G1V 0A6, Canada.

^C Department of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, P.O. Box 7054, SE-750 07 Uppsala, Sweden.

^D Corresponding author. Email: denise.laskowski@slu.se

Reproduction, Fertility and Development 29(5) 876-889 https://doi.org/10.1071/RD15315
Submitted: 1 August 2015 Accepted: 16 December 2015 Published: 29 February 2016

Journal Compilation © CSIRO Publishing 2017 Open Access CC BY-NC-ND

Abstract

Metabolic imbalance impairs fertility, because changes in concentrations of metabolites and hormones in the blood and follicular fluid create an unfavourable environment for early embryonic development. Insulin is a key metabolic hormone known for its effects on fertility: insulin concentrations are increased during energy balance disturbances in diabetes or metabolic syndrome. Still, insulin is frequently used at supraphysiological concentrations for embryo in vitro culture with unknown consequences for the developmental potential of the offspring. In the present study we investigated the effects of insulin exposure during in vitro bovine oocyte maturation on developmental rates, embryo quality and gene expression. Supplementation of the maturation media with insulin at 10 or 0.1 µg mL^–1 decreased blastocyst rates compared with an insulin-free control (19.8 ± 1.3% and 20.4 ± 1.3% vs 23.8 ± 1.3%, respectively; P < 0.05) and led to increased cell numbers (nearly 10% more cells on Day 8 compared with control; P < 0.05). Transcriptome analysis revealed significant upregulation of genes involved in lipid metabolism, nuclear factor (erythroid-derived 2)-like 2 (NRF2) stress response and cell differentiation, validated by quantitative polymerase chain reaction. To conclude, the results of the present study demonstrate that insulin exposure during in vitro oocyte maturation has a lasting effect on the embryo until the blastocyst stage, with a potential negative effect in the form of specific gene expression perturbations.

Additional keywords: dairy cow, embryo, metabolism, metabolic programming, metabolic syndrome, morphology, subfertility, transcriptome.

References

Abraham, M. C., Gustafsson, H., Ruete, A., and Brandt, Y. C. B. (2012). Breed influences on in vitro development of abattoir-derived bovine oocytes. Acta Vet. Scand. 54, 36.
| Breed influences on in vitro development of abattoir-derived bovine oocytes.Crossref | GoogleScholarGoogle Scholar | 22682104PubMed |

Acevedo, N., Ding, J., and Smith, G. D. (2007). Insulin signaling in mouse oocytes. Biol. Reprod. 77, 872–879.
| Insulin signaling in mouse oocytes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXht1Cnu77I&md5=1d2967e5ac7aa17a84b9b758d34d70e9CAS | 17625112PubMed |

Adamiak, S. J., Mackie, K., Watt, R. G., Webb, R., and Sinclair, K. D. (2005). Impact of nutrition on oocyte quality: cumulative effects of body composition and diet leading to hyperinsulinemia in cattle. Biol. Reprod. 73, 918–926.
| Impact of nutrition on oocyte quality: cumulative effects of body composition and diet leading to hyperinsulinemia in cattle.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXhtFGktb7L&md5=a352c18978ef408e1f8797cdcefcc538CAS | 15972884PubMed |

Augustin, R., Pocar, P., Wrenzycki, C., Niemann, H., and Fischer, B. (2003). Mitogenic and anti-apoptotic activity of insulin on bovine embryo produced in vitro. Reproduction 126, 91–99.
| Mitogenic and anti-apoptotic activity of insulin on bovine embryo produced in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXlvFCnurs%3D&md5=66f3d80d48b2902947f0b05bafbac2c3CAS | 12814351PubMed |

Baumann, C. G., Morris, D. G., Sreenan, J. M., and Leese, H. J. (2007). The quiet embryo hypothesis: molecular characteristics favoring viability. Mol. Reprod. Dev. 74, 1345–1353.
| The quiet embryo hypothesis: molecular characteristics favoring viability.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2sXhtVCmtr7O&md5=783a2db3ee0ceb70f660a10bef6cd0bdCAS | 17342740PubMed |

Blazejczyk, M., Miron, M., and Nadon, R. (2007). FlexArray: a statistical data analysis software for gene expression microarrays. Available at http://genomequebec.mcgill.ca/FlexArray [verified 4 February 2016].

Bowles, C. M., and Lishman, A. W. (1998). Attempts to improve the yield of bovine blastocysts by incorporating insulin, selenium and transferrin in the in vitro system. S. Afr. J. Anim. Sci. 28, 30–37.
| 1:CAS:528:DyaK1cXmvVSls74%3D&md5=8afc49e3dfff852aeed7de1bbb2b22b9CAS |

Brewer, C. J., and Balen, A. H. (2010). The adverse effects of obesity on conception and implantation. Reproduction 140, 347–364.
| The adverse effects of obesity on conception and implantation.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1Cnu7fI&md5=4cf15ff689ed3cd957f9207de6c731c8CAS | 20395425PubMed |

Britt, J. H. (1992). Impacts of early postpartum metabolism on follicular development and fertility. In ‘Proceedings of the Annual Convention of the American Association of Bovine Practitioners 1992’, Volume 24. (Ed. E. I. Williams.) pp. 39–43. (Frontier Printers: Stillwater, OK.)

Butler, W. R., and Smith, R. D. (1989). Interrelationships between energy balance and postpartum reproductive function in dairy cattle. J. Dairy Sci. 72, 767–783.
| Interrelationships between energy balance and postpartum reproductive function in dairy cattle.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL1M3jsVyhtQ%3D%3D&md5=ac9f7926b81b6f5a4ee1d6427b0b2323CAS | 2654227PubMed |

Byrne, A. T., Southgate, J., Brison, D. R., and Leese, H. J. (2002). Regulation of apoptosis in the bovine blastocyst by insulin and the insulin-like growth factor IGF superfamily. Mol. Reprod. Dev. 62, 489–495.
| Regulation of apoptosis in the bovine blastocyst by insulin and the insulin-like growth factor IGF superfamily.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xlt1Klsrg%3D&md5=b0d2b6c76f1b0ac7aca3657c5db4e4caCAS | 12112582PubMed |

Cagnone, G., and Sirard, M. A. (2014). The impact of exposure to serum lipids during in vitro culture on the transcriptome of bovine blastocysts. Theriogenology 81, 712–722.e3.
| The impact of exposure to serum lipids during in vitro culture on the transcriptome of bovine blastocysts.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2cXhtlSlsLw%3D&md5=0ac721c0bbee096dd22b24cbfef1d1ccCAS | 24439163PubMed |

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 |

Colton, S. A., Pieper, G. M., and Downs, S. M. (2002). Altered meiotic regulation in oocytes from diabetic mice. Biol. Reprod. 67, 220–231.
| Altered meiotic regulation in oocytes from diabetic mice.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38XkvV2itb8%3D&md5=2b224f43932eb3d5e6b3601a9acf6b4eCAS | 12080021PubMed |

Eckel, R. H., Grundy, S. M., and Zimmet, P. Z. (2005). The metabolic syndrome. Lancet 365, 1415–1428.
| The metabolic syndrome.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjsVegtbg%3D&md5=1404c089aba4bf43e1330c321e3d5128CAS | 15836891PubMed |

Edgar, R., Domrachev, M., and Lash, A. E. (2002). Gene Expression Omnibus: NCBI gene expression and hybridization array data repository. Nucleic Acids Res. 30, 207–210.
| Gene Expression Omnibus: NCBI gene expression and hybridization array data repository.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xht12kurs%3D&md5=c744ec5dcf54fb7714e661befbba232dCAS | 11752295PubMed |

Fleige, S., and Pfaffl, M. W. (2006). RNA integrity and the effect on the real-time qRT-PCR performance. Mol. Aspects Med. 27, 126–139.
| RNA integrity and the effect on the real-time qRT-PCR performance.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XisF2gsrg%3D&md5=252e294f19bab6bf3578e20dd0823d07CAS | 16469371PubMed |

Fleming, T. P., Lucas, E. S., Watkins, A. J., and Eckert, J. (2012). Adaptive responses of the embryo to maternal diet and consequences for post implantation development. Reprod. Fertil. Dev. 24, 35–44.
| Adaptive responses of the embryo to maternal diet and consequences for post implantation development.Crossref | GoogleScholarGoogle Scholar |

Fouladi-Nashta, A. A., and Campbell, K. H. S. (2006). Dissociation of oocyte nuclear and cytoplasmic maturation by the addition of insulin in cultured bovine antral follicles. Reproduction 131, 449–460.
| Dissociation of oocyte nuclear and cytoplasmic maturation by the addition of insulin in cultured bovine antral follicles.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28Xjs12js7k%3D&md5=b82c2c9dd07f346534454f608b720fe7CAS | 16514188PubMed |

Freret, S., Grimard, B., Ponter, A., Joly, C., Ponsart, V., and Humblot, P. (2006). Reduction of body-weight gain enhances in vitro embryo production in overfed superovulated dairy heifers. Reproduction 131, 783–794.
| Reduction of body-weight gain enhances in vitro embryo production in overfed superovulated dairy heifers.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD28XltV2jt7o%3D&md5=5fc7a3c996786b56dd4df8d504a34804CAS | 16595729PubMed |

Garnsworthy, P. C., Fouladi-Nashta, A. A., Mann, G. E., Sinclair, K. D., and Webb, R. (2009). Effect of dietary-induced changes in plasma insulin concentrations during the early post partum period on pregnancy rate in dairy cows. Reproduction 137, 759–768.
| Effect of dietary-induced changes in plasma insulin concentrations during the early post partum period on pregnancy rate in dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXosl2nur4%3D&md5=e67243242035bca0a1a8d2a4fcb4c2dcCAS | 19129370PubMed |

Gilbert, I., Scantland, S., Sylvestre, E.-L., Dufort, I., Sirard, M.-A., and Robert, C. (2010). Providing a stable methodological basis for comparing transcript abundance of developing embryos using microarrays. Mol. Hum. Reprod. 16, 601–616.
| Providing a stable methodological basis for comparing transcript abundance of developing embryos using microarrays.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXptlegt7Y%3D&md5=e48013a41c09cf4e262b1ebfc1dd38e6CAS | 20479066PubMed |

Gong, J. G., Lee, W. J., Garnsworthy, P. C., and Webb, R. (2002). Effect of dietary-induced increases in circulating insulin concentrations during the early postpartum period on reproductive function in dairy cows. Reproduction 123, 419–427.
| Effect of dietary-induced increases in circulating insulin concentrations during the early postpartum period on reproductive function in dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xit1Cls74%3D&md5=7bc921258a2b1842162da30bcc7a014cCAS | 11882019PubMed |

Gordon, I. R. (2003). ‘Laboratory Production of Cattle Embryos.’ 2nd edn. (CAB International, Cambridge University Press: Wallingford.)

Hayashi, I., Larner, J., and Sato, G. (1978). Hormonal growth control of cells in culture. In Vitro 14, 23–30.
| Hormonal growth control of cells in culture.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaE1cXhtFGlsr0%3D&md5=40ede3b1f8f395d9dc40e6798c037bd3CAS | 624557PubMed |

Heerwagen, M. J. R., Miller, M. R., Barbour, L. A., and Friedman, J. E. (2010). Maternal obesity and fetal metabolic programming: a fertile epigenetic soil. Am. J. Physiol. Regul. Integr. Comp. Physiol. 299, R711–R722.
| Maternal obesity and fetal metabolic programming: a fertile epigenetic soil.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXht1WgurvI&md5=529734f878f65fbf23976edb5dadb369CAS |

Herrler, A., Krusche, C. A., and Beier, H. M. (1998). Insulin and insulin-like growth factor-I promote rabbit blastocyst development and prevent apoptosis. Biol. Reprod. 59, 1302–1310.
| Insulin and insulin-like growth factor-I promote rabbit blastocyst development and prevent apoptosis.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXnvVKku70%3D&md5=31504d499753c0a5f6d13bb3f17c08b1CAS | 9828171PubMed |

Hyttel, P., Fair, T., Callesen, H., and Greve, T. (1997). Oocyte growth, capacitation and final maturation in cattle. Theriogenology 47, 23–32.
| Oocyte growth, capacitation and final maturation in cattle.Crossref | GoogleScholarGoogle Scholar |

International Embryo Transfer Society (IETS) (2010). ‘Manual of the International Embryo Transfer Society.’ 4th edn. (IETS: Champaign, IL.)

Lam, J. K., Matsubara, S., Mihara, K., Zheng, X., Mooradian, A. D., and Wong, N. C. W. (2003). Insulin induction of apolipoprotein AI, role of Sp1. Biochemistry 42, 2680–2690.
| Insulin induction of apolipoprotein AI, role of Sp1.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3sXhtVaktb4%3D&md5=459f1db65b53e9059fdf97f5d59a47efCAS | 12614163PubMed |

Landau, S., Braw-Tal, R., Kaimb, M., Borb, A., and Bruckental, I. (2000). Preovulatory follicular status and diet affect the insulin and glucose content of follicles in high-yielding dairy cows. Anim. Reprod. Sci. 64, 181–197.
| Preovulatory follicular status and diet affect the insulin and glucose content of follicles in high-yielding dairy cows.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3cXovFWis7c%3D&md5=417b49d05967502ec764c8934070bb82CAS | 11121895PubMed |

Leese, H. J., Sturmey, R. G., Baumann, C. G., and McEvoy, T. G. (2007). Embryo viability and metabolism: obeying the quiet rules. Hum. Reprod. 22, 3047–3050.
| Embryo viability and metabolism: obeying the quiet rules.Crossref | GoogleScholarGoogle Scholar | 17956925PubMed |

Leibfried-Rutledge, M. L., Critser, E. S., Eyestone, W. H., Northey, D. L., and First, N. L. (1987). Development potential of bovine oocytes matured in vitro or in vivo. Biol. Reprod. 36, 376–383.
| Development potential of bovine oocytes matured in vitro or in vivo.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaL2s3hsVemsQ%3D%3D&md5=5a241cdb6afa8213cb9eb21d82351e3fCAS | 3580458PubMed |

Leroy, J. L. M. R., Rizos, D., Sturmey, R., Bossaert, P., Gutierrez-Adan, A., Van Hoeck, V., Valckx, S., and Bols, P. E. (2012). Intrafollicular conditions as a major link between maternal metabolism and oocyte quality: a focus on dairy cow fertility. Reprod. Fertil. Dev. 24, 1–12.
| Intrafollicular conditions as a major link between maternal metabolism and oocyte quality: a focus on dairy cow fertility.Crossref | GoogleScholarGoogle Scholar |

Lewis, A. M., Kaye, P. L., Lising, R., and Cameron, R. D. (1992). Stimulation of protein synthesis and expansion of pig blastocysts by insulin in vitro. Reprod. Fertil. Dev. 4, 119–123.
| Stimulation of protein synthesis and expansion of pig blastocysts by insulin in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK38XlsVeqsL4%3D&md5=b4c9b329e2cf5a39885e670c9413adc6CAS | 1585007PubMed |

Lindner, G. M., and Wright, R. W. (1983). Bovine embryo morphology and evaluation. Theriogenology 20, 407–416.
| Bovine embryo morphology and evaluation.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BD283pvVKgsg%3D%3D&md5=91876147b11b0a3613a4f81549d84ad6CAS | 16725857PubMed |

Lonergan, P., Khatir, H., Piumi, F., Rieger, D., Humblot, P., and Boland, M. P. (1999). Effect of time interval from insemination to first cleavage on the developmental characteristics, sex and pregnancy rates following transfer of bovine preimplantation embryos. J. Reprod. Fertil. 117, 159–167.
| Effect of time interval from insemination to first cleavage on the developmental characteristics, sex and pregnancy rates following transfer of bovine preimplantation embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXmtlaltLo%3D&md5=a386395cd34ae93f9a5d3c8653f8a7e9CAS | 10645257PubMed |

Lucy, M. (2006). Mechanisms linking growth hormone, insulin and reproduction: lessons from the postpartum dairy cow. Cattle Pract. 14, 23–27.

Matsui, M., Takahashi, Y., Hishinuma, M., and Kanagawa, H. (1995). Stimulatory effects of insulin on the development of bovine embryos fertilized in vitro. J. Vet. Med. Sci. 57, 331–336.
| Stimulatory effects of insulin on the development of bovine embryos fertilized in vitro.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXmt1Gnurc%3D&md5=bc950c3fac97f9b2955e655405771d34CAS | 7492656PubMed |

Matsui, M., Takahashi, Y., Hishinuma, M., and Kanagawa, H. (1997). Stimulation of the development of bovine embryos by insulin and insulin-like growth factor-I IGF-I is mediated through the IGF-I receptor. Theriogenology 48, 605–616.
| Stimulation of the development of bovine embryos by insulin and insulin-like growth factor-I IGF-I is mediated through the IGF-I receptor.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2sXmt1WhsL8%3D&md5=10981eeb672ee88c2a65358dafb12ec2CAS | 16728156PubMed |

Meijer, H. A., Van De Paver, S. A., Stroband, H. W. J., and Boerjan, M. L. (2000). Expression of the organizer specific homeobox gene Goosecoid gsc in porcine embryos. Mol. Reprod. Dev. 55, 1–7.
| Expression of the organizer specific homeobox gene Goosecoid gsc in porcine embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1MXnvFynsbY%3D&md5=50eee08d7f21ee01f7759a847f80ff3cCAS | 10602267PubMed |

Mihalik, J., Rehak, P., and Koppel, J. (2000). The influence of insulin on the in vitro development of mouse and bovine embryos. Physiol. Res. 49, 347–354.
| 1:CAS:528:DC%2BD3cXmsV2ksbY%3D&md5=1aaf66d2f5ccd87ce3588b9c9180ebdaCAS | 11043922PubMed |

Mooradian, A. D., Haas, M. J., and Wong, N. C. W. (2004). Transcriptional control of apolipoprotein A-I gene expression in diabetes. Diabetes 53, 513–520.
| Transcriptional control of apolipoprotein A-I gene expression in diabetes.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2cXhvFeltbk%3D&md5=83590d4f7ae3e548763af30f1c18a4feCAS | 14988232PubMed |

Murao, K., Wada, Y., Nakamura, T., Taylor, A. H., Mooradian, A. D., and Wong, N. C. W. (1998). Effects of glucose and insulin on rat apolipoprotein A-I gene expression. J. Biol. Chem. 273, 18 959–18 965.
| Effects of glucose and insulin on rat apolipoprotein A-I gene expression.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK1cXltFGrtrY%3D&md5=16fbcff3a3d440ca91dc8ee61ff8ad20CAS |

Nishioka, N., Yamamoto, S., Kiyonari, H., Sato, H., Sawada, A., Ota, M., Nakao, K., and Sasaki, H. (2008). Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos. Mech. Dev. 125, 270–283.
| Tead4 is required for specification of trophectoderm in pre-implantation mouse embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXhslGjt78%3D&md5=9987157b4c3be1bcbff2731201e950a6CAS | 18083014PubMed |

O’Callaghan, D., and Boland, M. P. (1999). Nutritional effects on ovulation, embryo development and the establishment of pregnancy in ruminants. Anim. Sci. 68, 299–314.

Pasquali, R., Patton, L., and Gambineri, A. (2007). Obesity and infertility. Curr. Opin. Endocrinol. Diabetes Obes. 14, 482–487.
| Obesity and infertility.Crossref | GoogleScholarGoogle Scholar | 17982356PubMed |

Pinborg, A., Gaarslev, C., and Hougaard, C. O. (2011). Influence of female bodyweight on IVF outcome: a longitudinal multicentre cohort study of 487 infertile couples. Reprod. Biomed. Online 23, 490–499.
| Influence of female bodyweight on IVF outcome: a longitudinal multicentre cohort study of 487 infertile couples.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DC%2BC3Mfpt1Sguw%3D%3D&md5=f37b33efa85f948e1f092b34750b20cdCAS | 21856228PubMed |

Plante, L., Plante, C., Shepard, D. L., and King, W. A. (1994). Cleavage and 3H-uridine incorporation in bovine embryos of high in vitro developmental potential. Mol. Reprod. Dev. 39, 375–383.
| Cleavage and ³H-uridine incorporation in bovine embryos of high in vitro developmental potential.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXisFWjtro%3D&md5=970607b6ce75706669263fca25de545dCAS | 7893486PubMed |

Purcell, S. H., Chi, M. M., and Moley, K. H. (2012). Insulin-stimulated glucose uptake occurs in specialized cells within the cumulus oocyte complex. Endocrinology 153, 2444–2454.
| Insulin-stimulated glucose uptake occurs in specialized cells within the cumulus oocyte complex.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XmsVKnu7g%3D&md5=251ceabd4a76652c852e7481a79c11baCAS | 22408172PubMed |

Rao, L. V., Wikarczuk, M. L., and Heyner, S. (1990). Functional roles of insulin and insulin-like growth factors in preimplantation mouse embryo development. In Vitro Cell. Dev. Biol. 26, 1043–1048.
| Functional roles of insulin and insulin-like growth factors in preimplantation mouse embryo development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3MXksVagt70%3D&md5=7f73f4b4d3f72e3ff5d35843a3450b39CAS | 1703523PubMed |

Reik, W., Dean, W., and Walter, J. (2001). Epigenetic reprogramming in mammalian development. Science 293, 1089–1093.
| 1:CAS:528:DC%2BD3MXmtVWltL8%3D&md5=6009e5d8f2eaa405f3e5574d9599590dCAS | 11498579PubMed |

Rekik, W., Dufort, I., and Sirard, M.-A. (2011). Analysis of the gene expression pattern of bovine blastocysts at three stages of development. Mol. Reprod. Dev. 78, 226–240.
| Analysis of the gene expression pattern of bovine blastocysts at three stages of development.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXkvFaju7o%3D&md5=e90f2dc940583c37a36fee0ddb0eccc2CAS | 21509852PubMed |

Richards, J. S. (2005). Ovulation: new factors that prepare the oocyte for fertilization. Mol. Cell. Endocrinol. 234, 75–79.
| Ovulation: new factors that prepare the oocyte for fertilization.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD2MXjt1SqtLk%3D&md5=637403b83f62f99b5932e16a6ffe0a41CAS | 15836955PubMed |

Rizos, D., Ward, F., Duffy, P., Boland, M. P., and 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.
| Consequences of bovine oocyte maturation, fertilization or early embryo development in vitro versus in vivo: implications for blastocyst yield and blastocyst quality.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD38Xlt1Giug%3D%3D&md5=fd530554a4e416cc604ed66ebc4922a4CAS | 11803560PubMed |

Robert, C., Nieminen, J., Dufort, I., Gagné, D., Grant, J. R., Cagnone, G., Plourde, D., Nivet, A.-L., Fournier, É., Paquet, É., Blazejczyk, M., Rigault, P., Juge, N., and Sirard, M.-A. (2011). Combining resources to obtain a comprehensive survey of the bovine embryo transcriptome through deep sequencing and microarrays. Mol. Reprod. Dev. 78, 651–664.
| Combining resources to obtain a comprehensive survey of the bovine embryo transcriptome through deep sequencing and microarrays.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3MXhtFGns7vK&md5=75c686b8c32e9ef12dc16ac2d4268e37CAS | 21812063PubMed |

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=760ea5af15a944a7834ccc057f620791CAS | 19223519PubMed |

Schultz, G. A., Hogan, A., Watson, A. J., Smith, R. M., and Heyner, S. (1992). Insulin, insulin-like growth factors and glucose transporters: temporal patterns of gene expression in early murine and bovine embryos. Reprod. Fertil. Dev. 4, 361–371.
| Insulin, insulin-like growth factors and glucose transporters: temporal patterns of gene expression in early murine and bovine embryos.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3sXlt1yhsA%3D%3D&md5=ab6d740b608083d6a413048686fea789CAS | 1461988PubMed |

Shimizu, T., Murayama, C., Sudo, N., Kawashima, C., Tetsuka, M., and Miyamoto, A. (2008). Involvement of insulin and growth hormone GH during follicular development in the bovine ovary. Anim. Reprod. Sci. 106, 143–152.
| Involvement of insulin and growth hormone GH during follicular development in the bovine ovary.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1cXktlCqsbk%3D&md5=169baf43c7be1cfdf56b3cd8c7579918CAS | 17507188PubMed |

Smyth, G. K. (2004). Linear models and empirical bayes methods for assessing differential expression in microarray experiments. Stat. Appl. Genet. Mol. Biol. 3, 1–25.
| Linear models and empirical bayes methods for assessing differential expression in microarray experiments.Crossref | GoogleScholarGoogle Scholar |

Spicer, L. J., and Echternkamp, S. E. (1995). The ovarian insulin and insulin-like growth factor system with an emphasis on domestic animals. Domest. Anim. Endocrinol. 12, 223–245.
| The ovarian insulin and insulin-like growth factor system with an emphasis on domestic animals.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK2MXnt1Ort78%3D&md5=bf0f9ac8cb17d219fcc06b2c127d443eCAS | 7587167PubMed |

Sutton-McDowall, M. L., Gilchrist, R. B., and Thompson, J. G. (2010). The pivotal role of glucose metabolism in determining oocyte developmental competence. Reproduction 139, 685–695.
| The pivotal role of glucose metabolism in determining oocyte developmental competence.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC3cXltFajtr0%3D&md5=c465b83355bc254d53da580f2c639bcbCAS | 20089664PubMed |

Valckx, S. D., De Pauw, I., De Neubourg, D., Inion, I., Berth, M., Fransen, E., Bols, P. E., and Leroy, J. L. M. R. (2012). BMI-related 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.
| BMI-related metabolic composition of the follicular fluid of women undergoing assisted reproductive treatment and the consequences for oocyte and embryo quality.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC38XhslKrsLrL&md5=00dad46ba8011e880d6cd44e25ec241fCAS | 23019302PubMed |

Vallée, M., Dufort, I., Desrosiers, S., Labbe, A., Gravel, C., Gilbert, I., Robert, C., and Sirard, M.-A. (2009). Revealing the bovine embryo transcript profiles during early in vivo embryonic development. Reproduction 138, 95–105.
| Revealing the bovine embryo transcript profiles during early in vivo embryonic development.Crossref | GoogleScholarGoogle Scholar | 19383715PubMed |

Van Gelder, R. N., Von Zastrow, M. E., Yool, A., Dement, W. C., Barchas, J. D., and Eberwine, J. H. (1990). Biochemistry amplified RNA synthesized from limited quantities of heterogeneous cDNA. Proc. Natl Acad. Sci. USA 87, 1663–1667.
| Biochemistry amplified RNA synthesized from limited quantities of heterogeneous cDNA.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXhsFejsLg%3D&md5=1f99026d1617cc93b6031ed89837d86bCAS | 1689846PubMed |

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=a0b552d20a6393da836bc87c594fdd9eCAS | 21858021PubMed |

Van Hoeck, V., Rizos, D., Gutierrez-Adan, A., Pintelon, I., Jorssen, E., Dufort, I., Sirard, M.-A., Verlaet, A., Hermans, N., Bols, P. E. J., and Leroy, J. L. M. R. (2015). Interaction between differential gene expression profile and phenotype in bovine blastocysts originating from oocytes exposed to elevated non-esterified fatty acid concentrations. Reprod. Fertil. Dev. 27, 372–384.
| Interaction between differential gene expression profile and phenotype in bovine blastocysts originating from oocytes exposed to elevated non-esterified fatty acid concentrations.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BC2MXhslegtrc%3D&md5=c2983d160738a33eb399550736a125d2CAS | 24360349PubMed |

van Montfoort, A. P. A., Plösch, T., Hoek, A., and Tietge, U. J. F. (2014). Impact of maternal cholesterol metabolism on ovarian follicle development and fertility. J. Reprod. Immunol. 104–105, 32–36.
| Impact of maternal cholesterol metabolism on ovarian follicle development and fertility.Crossref | GoogleScholarGoogle Scholar |

Vigneault, C., Gravel, C., Vallée, M., McGraw, S., and Sirard, M. A. (2009). Unveiling the bovine embryo transcriptome during the maternal-to-embryonic transition. Reproduction 137, 245–257.
| Unveiling the bovine embryo transcriptome during the maternal-to-embryonic transition.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD1MXovV2ksL8%3D&md5=a3093644ae8b6a7abc5dce51b47ba0fbCAS | 18987256PubMed |

Ward, F., Rizos, D., Corridan, D., Quinn, K., Boland, M., and Lonergan, P. (2001). Paternal influence on the time of the first embryonic cleavage post insemination and the implications for subsequent bovine embryos development in vitro and fertility in vivo. Mol. Reprod. Dev. 60, 47–55.
| Paternal influence on the time of the first embryonic cleavage post insemination and the implications for subsequent bovine embryos development in vitro and fertility in vivo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DC%2BD3MXlvFWisrY%3D&md5=a664c32c5e6627ab0c055324be82a358CAS | 11550267PubMed |

Ward, F., Enright, B., Rizos, D., Boland, M., and Lonergan, P. (2002). Optimization of in vitro bovine embryo production: effect of duration of maturation, length of gamete co-incubation, sperm concentration and sire. Theriogenology 57, 2105–2117.
| Optimization of in vitro bovine embryo production: effect of duration of maturation, length of gamete co-incubation, sperm concentration and sire.Crossref | GoogleScholarGoogle Scholar | 12066869PubMed |

Wu, L. L. Y., Norman, R. J., and Robker, R. L. (2012). The impact of obesity on oocytes: evidence for lipotoxicity mechanisms. Reprod. Fertil. Dev. 24, 29–34.
| The impact of obesity on oocytes: evidence for lipotoxicity mechanisms.Crossref | GoogleScholarGoogle Scholar |

Yadav, B. R., King, W. A., and Betteridge, K. J. (1993). Relationships between the completion of first cleavage and the chromosomal complement, sex, and developmental rates of bovine embryos generated in vitro. Mol. Reprod. Dev. 36, 434–439.
| Relationships between the completion of first cleavage and the chromosomal complement, sex, and developmental rates of bovine embryos generated in vitro.Crossref | GoogleScholarGoogle Scholar | 1:STN:280:DyaK2c7jslCmtA%3D%3D&md5=6153a7b328d7a647a3d5404ea506fe68CAS | 8305205PubMed |

Zhang, X., and Armstrong, D. T. (1990). Presence of amino acids and insulin in a chemically defined medium improves development of 8-cell rat embryos in vitro and subsequent implantation in vivo. Biol. Reprod. 42, 662–668.
| Presence of amino acids and insulin in a chemically defined medium improves development of 8-cell rat embryos in vitro and subsequent implantation in vivo.Crossref | GoogleScholarGoogle Scholar | 1:CAS:528:DyaK3cXktFyis7Y%3D&md5=558db0a5d014b9470d1b687c9b386e90CAS | 2189503PubMed |

Zhang, L., Blakewood, E. G., Denniston, R. S., and Godke, R. A. (1991). The effect of insulin on maturation and development of in vitro-fertilized bovine oocytes. Theriogenology 35, 301.
| The effect of insulin on maturation and development of in vitro-fertilized bovine oocytes.Crossref | GoogleScholarGoogle Scholar |