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The presence of acylated ghrelin during in vitro maturation of bovine oocytes induces cumulus cell DNA damage and apoptosis, and impairs early embryo development

Published online by Cambridge University Press:  20 September 2017

Matias A. Sirini ,
Juan Mateo Anchordoquy ,
Juan Patricio Anchordoquy ,
Ana M. Pascua ,
Noelia Nikoloff ,
Ana Carranza ,
Alejandro E. Relling  and
Cecilia C. Furnus
Matias A. Sirini
Affiliation:
IGEVET – Instituto de Genética Veterinaria ‘Ing. Fernando N Dulout’ (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, Calles 60 y 118, B1904AMA La Plata, Buenos Aires, Argentina.
Juan Mateo Anchordoquy
Affiliation:
IGEVET – Instituto de Genética Veterinaria ‘Ing. Fernando N Dulout’ (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, Calles 60 y 118, B1904AMA La Plata, Buenos Aires, Argentina.
Juan Patricio Anchordoquy
Affiliation:
IGEVET – Instituto de Genética Veterinaria ‘Ing. Fernando N Dulout’ (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, Calles 60 y 118, B1904AMA La Plata, Buenos Aires, Argentina.
Ana M. Pascua
Affiliation:
IGEVET – Instituto de Genética Veterinaria ‘Ing. Fernando N Dulout’ (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, Calles 60 y 118, B1904AMA La Plata, Buenos Aires, Argentina.
Noelia Nikoloff
Affiliation:
IGEVET – Instituto de Genética Veterinaria ‘Ing. Fernando N Dulout’ (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, Calles 60 y 118, B1904AMA La Plata, Buenos Aires, Argentina.
Ana Carranza
Affiliation:
IGEVET – Instituto de Genética Veterinaria ‘Ing. Fernando N Dulout’ (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, Calles 60 y 118, B1904AMA La Plata, Buenos Aires, Argentina.
Alejandro E. Relling
Affiliation:
IGEVET – Instituto de Genética Veterinaria ‘Ing. Fernando N Dulout’ (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, Calles 60 y 118, B1904AMA La Plata, Buenos Aires, Argentina. Department of Animal Sciences, The Ohio State University, 1680 Madison Ave., Wooster, Ohio 44691, USA.
Cecilia C. Furnus*
Affiliation:
IGEVET – Instituto de Genética Veterinaria ‘Ing. Fernando N Dulout’ (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, Calles 60 y 118, B1904AMA La Plata, Buenos Aires, Argentina.
*
All correspondence to: Cecilia C. Furnus. IGEVET – Instituto de Genética Veterinaria ‘Ing. Fernando N Dulout’ (UNLP-CONICET LA PLATA), Facultad de Ciencias Veterinarias UNLP, Calles 60 y 118, B1904AMA La Plata, Buenos Aires, Argentina. Tel.: +54 221 4211799. E-mail: [email protected]
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Summary

The aim of this study was to investigate the effects of acylated ghrelin supplementation during in vitro maturation (IVM) of bovine oocytes. IVM medium was supplemented with 20, 40 or 60 pM acylated ghrelin concentrations. Cumulus expansion area and oocyte nuclear maturation were studied as maturation parameters. Cumulus–oocyte complexes (COC) were assessed with the comet, apoptosis and viability assays. The in vitro effects of acylated ghrelin on embryo developmental capacity and embryo quality were also evaluated. Results demonstrated that acylated ghrelin did not affect oocyte nuclear maturation and cumulus expansion area. However, it induced cumulus cell (CC) death, apoptosis and DNA damage. The damage increased as a function of the concentration employed. Additionally, the percentages of blastocyst yield, hatching and embryo quality decreased with all acylated ghrelin concentrations tested. Our study highlights the importance of acylated ghrelin in bovine reproduction, suggesting that this metabolic hormone could function as a signal that prevents the progress to reproductive processes.

Keywords

Active ghrelinApoptosisCumulus cellsDNA damageIn vitro embryo development
Type
Research Article
Information
Zygote , Volume 25 , Issue 5 , October 2017 , pp. 601 - 611
Copyright
Copyright © Cambridge University Press 2017 

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References

Arash, K., Omid, D. & Masoud, A. (2014). Ghrelin is a regulator of cellular apoptosis and proliferation in the rat ovary. Int. J. Pept. Res. Ther. 20, 289–98.Google Scholar
Barreiro, M.L., Gaytan, F., Caminos, J.E., Pinilla, L., Casanueva, F.F., Aguilar, E., Dieguez, C. & Tena-Sempere, M. (2002). Cellular location and hormonal regulation of ghrelin expression in rat testis. Biol. Reprod. 67, 1768–76.CrossRefGoogle ScholarPubMed
Barreiro, M.L. & Tena-Sempere, M. (2004). Ghrelin and reproduction: a novel signal linking energy status and fertility? Mol. Cell. Endocrinol. 226, 1–9.Google Scholar
Bell, A.W. (1995). Regulation of organic nutrient metabolism during transition from late pregnancy to early lactation. J. Anim. Sci. 73, 2804–19.CrossRefGoogle ScholarPubMed
Bradford, B.J. & Allen, M.S. (2008). Negative energy balance increases periprandial ghrelin and growth hormone concentrations in lactating dairy cows. Domest. Anim. Endocrinol. 34, 196–203.Google Scholar
Britt, J.H. (1992). Impacts of early postpartum metabolism on follicular development and fertility. Bov. Proc. 24, 39–43.Google Scholar
Butler, W.R. (2003). Energy balance relationships with follicular development., ovulation and fertility in postpartum dairy cows. Livestock Prod. Sci. 83, 211–8.Google Scholar
Caminos, J.E., Tena-Sempere, M., Gaytan, F., Sanchez-Criado, J.E., Barreiro, M.L., Nogueiras, R., Casanueva, F.F., Aguilar, E. & Dieguez, C. (2003). Expression of ghrelin in the cyclic and pregnant rat ovary. Endocrinology 144, 1594–602.Google Scholar
Collins, A.R. (2004). The comet assay for DNA damage and repair: principles., applications., and limitations. Mol. Biotechnol. 26, 249–61.Google Scholar
Corn, C.M., Hauser-Kronberger, C., Moser, M., Tews, G. & Ebner, T. (2005). Predictive value of cumulus cell apoptosis with regard to blastocyst development of corresponding gametes. Fertil. Steril. 84, 627–33.CrossRefGoogle ScholarPubMed
Cowley, M.A., Smith, R.G., Diano, S., Tschöp, M., Pronchuk, N., Grove, K.L., Strasburger, C.J., Bidlingmaier, M., Esterman, M., Heiman, M.L., García-Segura, L.M., Nillni, E.A., Mendez, P., Low, M.J., Sotonyi, P., Friedman, J.M., Liu, H., Pinto, S., Colmers, W.F., Cone, R.D. & Horvath, T.L. (2003). The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Neuron 37649–61.Google Scholar
Deaver, S.E., Hoyer, P.B., Dial, S.M., Field, M.E., Collier, R.J. & Rhoads, M.L. (2013). Localization of ghrelin and its receptor in the reproductive tract of Holstein heifers. J. Dairy Sci. 96, 150–7.Google Scholar
Dovolou, E., Messinis, I.E., Periquesta, E., Dafopoulos, K., Gutierrez-Adan, A. & Amiridis, G.S. (2014). Ghrelin accelerates in vitro maturation of bovine oocytes. Reprod. Domest. Anim. 49, 665–72.Google Scholar
Du, C., Xilingaowa, C.G., Wang, C., Li, H., Zhao, Y. & Siqingaowa, C.J. (2009). Expression of the orexigenic peptide ghrelin in the sheep ovary. Domest. Anim. Endocrinol. 36, 89–98.Google Scholar
Dupont, J., Maillard, V., Coyral-Castel, S., Rame, C. & Froment, P. (2010). Ghrelin in female and male reproduction. Int. J. Pep. Article ID 158102, 8 pp.Google Scholar
Evans, J.J. & Anderson, G.M. (2012). Balancing ovulation and anovulation: integration of the reproductive and energy balance axes by neuropeptides. Hum. Reprod. Update 3, 313–32.Google Scholar
Fernandez-Fernandez, R., Martini, AC., Navarro, V.M., Castellano, J.M., Dieguez, C., Aguilar, E., Pinilla, L. & Tena-Sempere, M. (2006). Novel signals for the integration of energy balance and reproduction. Mol. Cell. Endocrinol. 25, 127–32.Google Scholar
Fukui, Y., McGowan, L.T., James, R.W., Pugh, P.A. & Tervit, H.R. (1991). Factors affecting the in. vitro development to blastocysts of bovine oocytes matured and fertilized in vitro . J. Reprod. Fertil. 92, 125–31.Google Scholar
Furnus, C., de Matos, D., Martínez, A. & Matkovic, M. (1997). Effect of glucose on embryo quality and post-thaw viability of in-vitro-produced bovine embryos. Theriogenology 47, 481–90.Google Scholar
Furnus, C.C., de Matos, D.G., Picco, S., GarcÍa, P.P., Inda, A.M., Mattioli, G. & Errecalde, A.L. (2008). Metabolic requirements associated with GSH synthesis during in vitro maturation of cattle oocytes. Anim. Reprod. Sci. 109, 88–99.Google Scholar
Gardner, D.K., Lane, M., Spitzer, A. & Batt, PA. (1994). Enhanced rates of cleavage and development for sheep zygotes cultured to the blastocyst stage in vitro in the absence of serum and somatic cells: amino acids, vitamins, and culturing embryos in groups stimulate development. Biol. Reprod. 50, 390–40.Google Scholar
Gaytan, F., Barreiro, M.L., Chopin, L.K., Herington, A.C., Morales, C., Pinilla, L., Casanueva, F.F., Aguilar, E., Dieguez, C. & Tena-Sempere, M. (2003). Immunolocalization of ghrelin and its functional receptor., type 1a growth hormone secretagogue receptor., in the cyclic human ovary. J. Clin. Endocrinol. Metab. 88, 879–87.Google Scholar
Gualillo, O., Caminos, J. & Blanco, M. (2001). Ghrelin, a novel placental- derived hormone. Endocrinology 142, 788–94.Google Scholar
Hattori, N., Saito, T., Yagyu, T., Jiang, B.H., Kitagawa, K. & Inagaki, C. (2001). GH, GH receptor, GH secretagogue receptor, and ghrelin expression in human T cells, B cells, and neutrophils. J. Clin. Endocrinol. Metab. 86, 4284–91.Google Scholar
Hayashida, T.K., Murakami, K., Mogi, M., Nishihara, M., Nakazato, M.S., Mondal, Y., Horii, M., Kojima, K., Kangawa, K. & Murakami, N. (2001). Ghrelin in domestic animals: distribution in the stomach and its possible role. Domest. Anim. Endocrinol. 21, 17–24.CrossRefGoogle ScholarPubMed
Hoppe, R. & Bavister, B. (1984). Evaluation of the fluorescein diacetate (FDA) vital dye viability test with hamster and bovine embryos. Anim. Reprod. Sci. 6, 323–5.Google Scholar
Kawamura, K., Sato, N., Fukuda, J., Kodama, H., Kumegai, J., Tanikawa, H., Nakamura, A., Honda, Y., Sato, T. & Tanaka, T. (2003). Ghrelin inhibits the development of mouse preimplantation embryos in vitro . Endocrinology 144, 2623–33.Google Scholar
Kojima, M. & Kangawa, K. (2005). Ghrelin: structure and function. Physiol. Rev. 85, 495–522.CrossRefGoogle ScholarPubMed
Kojima, M., Hosoda, H., Date, Y., Nakazato, M., Matsuo, H. & Kangawa, K. (1999). Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 402, 656–60.CrossRefGoogle ScholarPubMed
Korbonits, M., Bustin, S.A., Kojima, M., Jordan, S., Adams, E.F., Lowe, D.G., Kangawa, K. & Grossman, A.B. (2001). The expression of the growth hormone secretagogue receptor ligand ghrelin in normal and abnormal human pituitary and other neuroendocrine tumors. J. Clin. Endocrinol. Metab. 86, 881–7.Google Scholar
Krisher, R.L. (2004). The effect of oocyte quality on development. J. Anim. Sci. 82, 14–23.Google ScholarPubMed
Lee, K.S., Joo, B.S., Na, Y.J., Yoon, M.S., Choi, O.H. & Kim, W.W. (2001). Cumulus cell apoptosis as an indicator to predict the quality of oocytes and the outcome of IVF-ET. J. Assist. Reprod. Genet. 18, 490–8.Google Scholar
Lorenzi, T., Meli, R., Marzioni, D., Morroni, M., Baragli, A., Castellucci, M., Gualillo, O. & Muccioli, G. (2009). Ghrelin: a metabolic signal affecting the reproductive system. Cytokine Growth Factor Rev. 20, 137–52.Google Scholar
Lucy, M. (2003). Mechanisms linking nutrition and reproduction in postpartum cows. Reprod. Suppl. 61, 415–7.Google Scholar
Moor, R.M., Dai, Y., Lee, C. & Fulka, J. Jr. (1998). Oocyte maturation and embryonic failure. Hum. Reprod. Update 4, 223–6.Google Scholar
Moor, R.M. & Trounson, A.O. (1977). Hormonal and follicular factors affecting maturation of sheep oocytes in vitro and their subsequent developmental capacity. J. Reprod. Fert. 49, 101–9.Google Scholar
Mori, K., Yoshimoto, A., Takaya, K., Hosoda, K., Ariyasu, H., Yahata, K., Mukoyama, M., Sugawara, A., Hosoda, H., Kojima, M., Kangawa, K. & Nakao, K. (2000). Kidney produces a novel acylated peptide, ghrelin. FEBS Lett. 486, 213–6.Google Scholar
O'Hara, L., Forde, N., Kelly, A.K. & Lonergan, P. (2014). Effect of bovine blastocyst size at embryo transfer on day 7 on conceptus length on day 14: can supplementary progesterone rescue small embryos? Theriogenology 81, 1123–8.Google Scholar
Olive, P.L. (1999). DNA damage and repair in individual cells: applications of the comet assay in radiobiology. Int. J. Radiat. Biol. 75, 395–405.Google Scholar
Parrish, J.J., Susko-Parrish, J., Leibfried-Rutledge, M.L., Critser, E.S., Eyestone, W.H. & First, N.F. (1986). Bovine in vitro fertilization with frozen–thawed semen. Theriogenology 25, 591–600.Google Scholar
Pitarque, M., Vaglenov, A., Nosko, M., Hirvonen, A., Norppa, H. & Creus, A. (1999). Evaluation of DNA damage by the Comet assay in shoe workers exposed to toluene and other organic solvents. Mutat. Res. 441, 115–27.Google Scholar
Pläsier, B., Lloyd, D.R., Paul, G.C., Thomas, C.R. & Al-Rubeai, M. (1999). Automatic image analysis for quantification of apoptosis in animal cell culture by annexin-V affinity assay. J. Immunol. Methods 229, 81–95.CrossRefGoogle ScholarPubMed
Rak, A., Szczepankiewicz, D. & Gregoraszczuk, E.L. (2009). Expression of ghrelin receptor., GHSR-1a, and its functional role in the porcine ovarian follicles. Growth Horm. IGF Res. 19, 68–76.Google Scholar
Rui-Xia, B., Peng, W.Z. & Gui-fang, C. (2013). Effect of ghrelin on the expression of bcl-20 BAX mRNA in in vitro maturation ovine oocytes. Indian J. Anim. Sci. 83, 37–9.Google Scholar
Seino, T., Saito, H., Kaneko, T., Takahashi, T., Kawachiya, S. & Kurachi, H. (2002). Eight-hydroxy-2′-deoxyguanosine in granulosa cells is correlated with the quality of oocytes and embryos in an in vitro fertilization-embryo transfer program. Fertil. Steril. 77, 1184–90.Google Scholar
Singh, N.P., McCoy, M.T., Tice, R.R. & Schneider, E.L. (1988). A simple technique for quantitation of low levels of DNA damage in individual cells. Exp. Cell. Res. 175, 184–91.Google Scholar
Sirotkin, A.V., Grossmann, R., María-Peon, M.T., Roa, J., Tena-Sempere, M. & Klein, S. (2006). Novel expression and functional role of ghrelin in chicken ovary. Mol. Cell. Endocrinol. 26, 257–8.Google Scholar
Suzuki, H., Sasaki, Y., Shimizu, M., Matsuzaki, M., Hashizume, T. & Kuwayama, H. (2010). Ghrelin and leptin did not improve meiotic maturation of porcine oocytes cultured in. vitro . Reprod. Domest. Anim. 45, 927–30.Google Scholar
Tanghe, S., Van Soom, A., Nauwynck, H., Coryn, M. & de Kruif, A. (2002). Minireview: Functions of the cumulus oophorus during oocyte maturation, ovulation, and fertilization. Mol. Reprod. Dev. 61, 414–24.Google Scholar
Tena-Sempere, M., Barreiro, M.L., Gonzalez, L.C., Gaytan, F., Zhang, F.P., Caminos, J.E., Pinilla, L., Casanueva, F.F., Dieguez, C. & Aguilar, E. (2002). Novel expression and functional role of ghrelin in rat testis. Endocrinology 143, 717–25.Google Scholar
Tena-Sempere, M. (2008). Ghrelin and reproduction: ghrelin as novel regulator of the gonadotropic axis. Vitam. Horm. 77, 285–90.Google Scholar
Tervit, H.R., Whittingham, D.G. & Rowson, L.E.A. (1972). Successful culture in vitro of sheep and cattle ova. J. Reprod. Fertil. 30, 93–7.Google Scholar
Thouas, G.A., Korfiatis, N.A., French, A.J., Jones, G.M. & Trounson, A.O. (2001). Simplified technique for differential staining of inner cell mass and trophectoderm cells of mouse and bovine blastocysts. Reprod. Biomed. Online 3, 25–9.Google Scholar
Tice, R.R. & Strauss, G.H. (1995). The single cell gel electrophoresis/comet assay: a potential tool for detecting radiation-induced DNA damage in humans. Stem Cells 1, 207–14.Google Scholar
van der Lely, A.J., Tschöp, M., Heiman, M.L. & Ghigo, E. (2004). Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr. Rev. 25, 426–57.Google Scholar
van Engeland, M., Nieland, L.J., Ramaekers, F.C., Schutte, B. & Reutelingsperger, C.P. (1998). Annexin-V-affinity assay: a review on an apoptosis detection system based on phosphatidylserine exposure. Cytometry 31, 1–9.Google Scholar
van Knegsel, A.T., van den Brand, H., Dijkstra, J., Tamminga, S. & Kemp, B. (2005). Effect of dietary energy source on energy balance, production, metabolic disorders and reproduction in lactating dairy cattle. Reprod. Nutr. Dev. 45, 665–88.Google Scholar
Van Soom, A., Ysebaert, M.T. & de Kruif, A. (1997). Relationship between timing of development., morula morphology and cell allocation to inner cell mass and trophectoderm in in-vitro produced bovine embryos. Mol. Reprod. Dev. 47, 47–56.Google Scholar
Volante, M., Fulcheri, E., Allia, E., Cerrato, M., Pucci, A. & Papotti, M. (2002). Ghrelin expression in fetal, infant, and adult human lung. J. Histochem. Cytochem. 50, 1013–21.Google Scholar
Wang, J.Y.J. (2001). DNA damage and apoptosis. Cell Death Differ. 8, 1047–8.Google Scholar
Wang, Z., Lin, P. & Yu, S. (2013). Effects of ghrelin on developmental competence and gene expression of in vitro fertilized ovine embryos. Theriogenology 79, 695–701.CrossRefGoogle ScholarPubMed
Wertz-Lutz, A.E., Knight, T.J., Pritchard, R.H., Daniel, J.A., Clapper, J.A. & Smart, A.J. (2006). Circulating ghrelin concentrations fluctuate relative to nutritional status and influence feeding behavior in cattle. Anim. Sci. 84, 3285–300.Google Scholar
Yuan, Y.Q., Van Soom, A., Leroy, J.L., Dewulf, J., Van Zeveren, A., de Kruif, A. & Peelman, L.J. (2005). Apoptosis in cumulus cells., but not in oocytes., may influence bovine embryonic developmental competence. Theriogenology 63, 2147–63.Google Scholar
Zhang, W., Lei, Z., Su, J. & Chen, S. (2008). Expression of ghrelin in the porcine hypothalamo-pituitary–ovary axis during the estrous cycle. Anim. Reprod. Sci. 109, 356–67.Google Scholar