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RESEARCH ARTICLE

Proteomic analysis of follicular fluid in carriers and non-carriers of the Trio allele for high ovulation rate in cattle

Mamat H. Kamalludin A B , Alvaro Garcia-Guerra C D , Milo C. Wiltbank C and Brian W. Kirkpatrick A C E
+ Author Affiliations
- Author Affiliations

A Department of Animal Sciences, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, 53706, USA.

B Department of Animal Science, Universiti Putra Malaysia, 43400 UPM Serdang, Selangor Darul Ehsan, Malaysia.

C Department of Dairy Science, University of Wisconsin-Madison, 1675 Observatory Drive, Madison, WI, 53706, USA.

D Present address: Department of Animal Sciences, The Ohio State University, 2029 Fyffe Road, Columbus, OH, 43210, USA.

E Corresponding author. Email: bwkirkpa@wisc.edu

Reproduction, Fertility and Development 30(12) 1643-1650 https://doi.org/10.1071/RD17252
Submitted: 3 July 2017  Accepted: 5 May 2018   Published: 1 June 2018

Abstract

This study was conducted to characterise differences in follicular fluid proteins between carriers and non-carriers of a bovine allele for high ovulation rate. A total of four non-carrier and five carrier females were used in an initial study with four and six additional non-carriers and carriers respectively used in a validation study. Emergence of the follicular wave was synchronised and the ovaries containing the dominant follicle(s) were extracted by ovariectomy for follicular fluid collection. A hexapeptide ligand library was used to overcome the masking effect of high-abundance proteins and to increase detection of low-abundance proteins in tandem mass spectrometry. After correcting for multiple comparisons, only two proteins, glia-derived nexin precursor (SERPINE2) and inhibin β B chain precursor (INHBB), were significantly differentially expressed (false-discovery rate <0.05). In a replicate study of analogous design differential expression was confirmed (P < 0.05). Joint analysis of results from the two studies indicated that three additional proteins were consistently differentially expressed between genotypes. For three of these five, previous studies have indicated that expression is increased by transforming growth factor-β–bone morphogenetic protein signalling; their reduction in follicular fluid from carrier animals is consistent with the ~9-fold overexpression of SMAD family member 6 (SMAD6) in carriers that is inhibitory to this pathway.

Additional keywords: bovine, SMAD6, follicle, SERPINE2, inhibin.


References

Ambekar, A. S., Nirujogi, R. S., Srikanth, S. M., Chavan, S., Kelkar, D. S., Hinduja, I., Zaveri, K., Prasad, T. S. K., Harsha, H. C., Pandey, A., and Mukherjee, S. (2013). Proteomic analysis of human follicular fluid: a new perspective towards understanding folliculogenesis. J. Proteomics 87, 68–77.
Proteomic analysis of human follicular fluid: a new perspective towards understanding folliculogenesis.Crossref | GoogleScholarGoogle Scholar |

Angelucci, S., Ciavardelli, D., Di Giuseppe, F., Eleuterio, E., Sulpizio, M., Tiboni, G. M., Giampietro, F., Palumbo, P., and Di Ilio, C. (2006). Proteome analysis of human follicular fluid. Biochimica et Biophysica Acta (BBA) - Proteins and Proteomics 1764, 1775–1785.
Proteome analysis of human follicular fluid.Crossref | GoogleScholarGoogle Scholar |

Beg, M. A., and Ginther, O. J. (2006). Follicle selection in cattle and horses: role of intrafollicular factors. Reproduction 132, 365–377.
Follicle selection in cattle and horses: role of intrafollicular factors.Crossref | GoogleScholarGoogle Scholar |

Beg, M. A., Bergfelt, D. R., Kot, K., and Ginther, O. J. (2002). Follicle selection in cattle: dynamics of follicular fluid factors during development of follicle dominance. Biol. Reprod. 66, 120–126.
Follicle selection in cattle: dynamics of follicular fluid factors during development of follicle dominance.Crossref | GoogleScholarGoogle Scholar |

Boschetti, E., and Righetti, P. G. (2008). The ProteoMiner in the proteomic arena: a non-depleting tool for discovering low-abundance species. J. Proteomics 71, 255–264.
The ProteoMiner in the proteomic arena: a non-depleting tool for discovering low-abundance species.Crossref | GoogleScholarGoogle Scholar |

Boschetti, E., Lomas, L., Citterio, A., and Righetti, P. G. (2007). Romancing the “hidden proteome”, Anno Domini two zero zero seven. J. Chromatogr. A 1153, 277–290.
Romancing the “hidden proteome”, Anno Domini two zero zero seven.Crossref | GoogleScholarGoogle Scholar |

Bouton, M.-C., Boulaftali, Y., Richard, B., Arocas, V. r., Michel, J.-B., and Jandrot-Perrus, M. (2012). Emerging role of serpinE2/protease nexin-1 in hemostasis and vascular biology. Blood 119, 2452–2457.
Emerging role of serpinE2/protease nexin-1 in hemostasis and vascular biology.Crossref | GoogleScholarGoogle Scholar |

Bustos-Valenzuela, J. C., Fujita, A., Halcsik, E., Granjeiro, J. M., and Sogayar, M. C. (2011). Unveiling novel genes upregulated by both rhBMP2 and rhBMP7 during early osteoblastic transdifferentiation of C2C12 cells. BMC Res. Notes 4, 370.
Unveiling novel genes upregulated by both rhBMP2 and rhBMP7 during early osteoblastic transdifferentiation of C2C12 cells.Crossref | GoogleScholarGoogle Scholar |

Cao, M., Sahmi, M., Lussier, J. G., and Price, C. A. (2004). Plasminogen activator and serine protease inhibitor-E2 (protease nexin-1) expression by bovine granulosa cells in vitro. Biol. Reprod. 71, 887–893.
Plasminogen activator and serine protease inhibitor-E2 (protease nexin-1) expression by bovine granulosa cells in vitro.Crossref | GoogleScholarGoogle Scholar |

Cao, M., Buratini, J., Lussier, J. G., Carrière, P. D., and Price, C. A. (2006a). Expression of protease nexin-1 and plasminogen activators during follicular growth and the periovulatory period in cattle. Reproduction 131, 125–137.
Expression of protease nexin-1 and plasminogen activators during follicular growth and the periovulatory period in cattle.Crossref | GoogleScholarGoogle Scholar |

Cao, M., Nicola, E., Portela, V. M., and Price, C. A. (2006b). Regulation of serine protease inhibitor-E2 and plasminogen activator expression and secretion by follicle stimulating hormone and growth factors in non-luteinizing bovine granulosa cells in vitro. Matrix Biol. 25, 342–354.
Regulation of serine protease inhibitor-E2 and plasminogen activator expression and secretion by follicle stimulating hormone and growth factors in non-luteinizing bovine granulosa cells in vitro.Crossref | GoogleScholarGoogle Scholar |

Ducolomb, Y., González-Márquez, H., Fierro, R., Jiménez, I., Casas, E., Flores, D., Bonilla, E., Salazar, Z., and Betancourt, M. (2013). Effect of porcine follicular fluid proteins and peptides on oocyte maturation and their subsequent effect on in vitro fertilization. Theriogenology 79, 896–904.
Effect of porcine follicular fluid proteins and peptides on oocyte maturation and their subsequent effect on in vitro fertilization.Crossref | GoogleScholarGoogle Scholar |

Edwards, R. G. (1974). Follicular fluid. J. Reprod. Fertil. 37, 189–219.
Follicular fluid.Crossref | GoogleScholarGoogle Scholar |

Fahiminiya, S., Reynaud, K., Labas, V., Batard, S., Chastant-Maillard, S., and Gerard, N. (2010). Steroid hormones content and proteomic analysis of canine follicular fluid during the preovulatory period. Reprod. Biol. Endocrinol. 8, 132.
Steroid hormones content and proteomic analysis of canine follicular fluid during the preovulatory period.Crossref | GoogleScholarGoogle Scholar |

Fahiminiya, S., Labas, V., Dacheux, J. L., and Gérard, N. (2011a). Improvement of 2D-PAGE resolution of human, porcine and equine follicular fluid by means of hexapeptide ligand library. Reprod. Domest. Anim. 46, 561–563.
Improvement of 2D-PAGE resolution of human, porcine and equine follicular fluid by means of hexapeptide ligand library.Crossref | GoogleScholarGoogle Scholar |

Fahiminiya, S., Labas, V., Roche, S., Dacheux, J.-L., and Gerard, N. (2011b). Proteomic analysis of mare follicular fluid during late follicle development. Proteome Sci. 9, 54.
Proteomic analysis of mare follicular fluid during late follicle development.Crossref | GoogleScholarGoogle Scholar |

Fang, X., and Zhang, W.-W. (2008). Affinity separation and enrichment methods in proteomic analysis. J. Proteomics 71, 284–303.
Affinity separation and enrichment methods in proteomic analysis.Crossref | GoogleScholarGoogle Scholar |

García-Guerra, A., Kirkpatrick, B. W., and Wiltbank, M. C. (2017). Follicular waves and hormonal profiles during the estrous cycle of carriers and non-carriers of the Trio allele, a major bovine gene for high ovulation and fecundity. Theriogenology 100, 100–113.
Follicular waves and hormonal profiles during the estrous cycle of carriers and non-carriers of the Trio allele, a major bovine gene for high ovulation and fecundity.Crossref | GoogleScholarGoogle Scholar |

Garcia-Guerra, A., Kamalludin, M. H., Kirkpatrick, B. W., and Wiltbank, M. C. (2018a). Trio, a bovine high fecundity allele: II. Hormonal profile and follicular dynamics underlying the high ovulation rate. Biol. Reprod. 98, 335–349.
Trio, a bovine high fecundity allele: II. Hormonal profile and follicular dynamics underlying the high ovulation rate.Crossref | GoogleScholarGoogle Scholar |

García-Guerra, A., Canavessi, A.M.O., Monteiro, P.L.J., Mezera, M. A., Sartori, R., Kirkpatrick, B. W., and Wiltbank, M. C. (2018b). Trio, a novel bovine high fecundity allele: III. Acquisition of dominance and ovulatory capacity at a smaller follicle size. Biol. Reprod. 98, 350–365.

Ginther, O. J., Bergfelt, D. R., Kulick, L. J., and Kot, K. (2000). Selection of the dominant follicle in cattle: role of estradiol. Biol. Reprod. 63, 383–389.
Selection of the dominant follicle in cattle: role of estradiol.Crossref | GoogleScholarGoogle Scholar |

Harrison, C. A., Wiater, E., Gray, P. C., Greenwald, J., Choe, S., and Vale, W. (2004). Modulation of activin and BMP signaling. Mol. Cell. Endocrinol. 225, 19–24.
Modulation of activin and BMP signaling.Crossref | GoogleScholarGoogle Scholar |

Hayashi, K.-G., Ushizawa, K., Hosoe, M., and Takahashi, T. (2011). Differential gene expression of serine protease inhibitors in bovine ovarian follicle: possible involvement in follicular growth and atresia. Reprod. Biol. Endocrinol. 9, 72.
Differential gene expression of serine protease inhibitors in bovine ovarian follicle: possible involvement in follicular growth and atresia.Crossref | GoogleScholarGoogle Scholar |

Hillier, S. G. (2009). Paracrine support of ovarian stimulation. Mol. Hum. Reprod. 15, 843–850.
Paracrine support of ovarian stimulation.Crossref | GoogleScholarGoogle Scholar |

Jaatinen, R., Bondestam, J., Raivio, T., Hilden, K., Dunkel, L., Groome, N., and Ritvos, O. (2002). Activation of the bone morphogenetic protein signaling pathway induces inhibin beta(B)-subunit mRNA and secreted inhibin B levels in cultured human granulosa-luteal cells. J. Clin. Endocrinol. Metab. 87, 1254–1261.

Kamalludin, M. H., Guerra, A. G., Wiltbank, M., and Kirkpatrick, B. W. (2018). Trio, a novel high fecundity allele: I. Transcriptome analysis of granulosa cells from carriers and non-carriers of a major gene for bovine ovulation rate. Biol. Reprod. 98, 323–334.
Trio, a novel high fecundity allele: I. Transcriptome analysis of granulosa cells from carriers and non-carriers of a major gene for bovine ovulation rate.Crossref | GoogleScholarGoogle Scholar |

Kirkpatrick, B. W., and Morris, C. A. (2015). A major gene for bovine ovulation rate. PLoS One 10, e0129025.
A major gene for bovine ovulation rate.Crossref | GoogleScholarGoogle Scholar |

Knight, P. G., and Glister, C. (2006). TGF-β superfamily members and ovarian follicle development. Reproduction 132, 191–206.
TGF-β superfamily members and ovarian follicle development.Crossref | GoogleScholarGoogle Scholar |

Knight, P. G., Satchell, L., and Glister, C. (2012). Intra-ovarian roles of activins and inhibins. Mol. Cell. Endocrinol. 359, 53–65.
Intra-ovarian roles of activins and inhibins.Crossref | GoogleScholarGoogle Scholar |

Knippenberg, M., Helder, M. N., Doulabi, B. Z., Bank, R. A., Wuisman, P. I., and Klein-Nulend, J. (2009). Differential effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on gene expression of collagen-modifying enzymes in human adipose tissue-derived mesenchymal stem cells. Tissue Eng. Part A 15, 2213–2225.
Differential effects of bone morphogenetic protein-2 and transforming growth factor-beta1 on gene expression of collagen-modifying enzymes in human adipose tissue-derived mesenchymal stem cells.Crossref | GoogleScholarGoogle Scholar |

Law, R. H. P., Zhang, Q., McGowan, S., Buckle, A. M., Silverman, G. A., Wong, W., Rosado, C. J., Langendorf, C. G., Pike, R. N., Bird, P. I., and Whisstock, J. C. (2006). An overview of the serpin superfamily. Genome Biol. 7, 216.
An overview of the serpin superfamily.Crossref | GoogleScholarGoogle Scholar |

Li, S.-H., Lin, M.-H., Hwu, Y.-M., Lu, C.-H., Yeh, L.-Y., Chen, Y.-J., and Lee, R. (2015). Correlation of cumulus gene expression of GJA1, PRSS35, PTX3, and SERPINE2 with oocyte maturation, fertilization, and embryo development. Reprod. Biol. Endocrinol. 13, 93.
Correlation of cumulus gene expression of GJA1, PRSS35, PTX3, and SERPINE2 with oocyte maturation, fertilization, and embryo development.Crossref | GoogleScholarGoogle Scholar |

Luo, W., Gumen, A., Haughian, J. M., and Wiltbank, M. C. (2011). The role of luteinizing hormone in regulating gene expression during selection of a dominant follicle in cattle. Biol. Reprod. 84, 369–378.
The role of luteinizing hormone in regulating gene expression during selection of a dominant follicle in cattle.Crossref | GoogleScholarGoogle Scholar |

Makanji, Y., Zhu, J., Mishra, R., Holmquist, C., Wong, W. P., Schwartz, N. B., Mayo, K. E., and Woodruff, T. K. (2014). Inhibin at 90: from discovery to clinical application, a historical review. Endocr. Rev. 35, 747–794.
Inhibin at 90: from discovery to clinical application, a historical review.Crossref | GoogleScholarGoogle Scholar |

Mortarino, M., Vigo, D., Maffeo, G., and Ronchi, S. (1999). Two-dimensional polyacrylamide gel electrophoresis map of bovine ovarian fluid proteins. Electrophoresis 20, 866–869.
Two-dimensional polyacrylamide gel electrophoresis map of bovine ovarian fluid proteins.Crossref | GoogleScholarGoogle Scholar |

Nesvizhskii, A. I. (2014). Proteogenomics: concepts, applications and computational strategies. Nat. Methods 11, 1114–1125.
Proteogenomics: concepts, applications and computational strategies.Crossref | GoogleScholarGoogle Scholar |

Nesvizhskii, A. I., Keller, A., Kolker, E., and Aebersold, R. (2003). A statistical model for identifying proteins by tandem mass spectrometry. Anal. Chem. 75, 4646–4658.
A statistical model for identifying proteins by tandem mass spectrometry.Crossref | GoogleScholarGoogle Scholar |

Nio-Kobayashi, J., Trendell, J., Giakoumelou, S., Boswell, L., Nicol, L., Kudo, M., Sakuragi, N., Iwanaga, T., and Duncan, W. C. (2015). Bone morphogenetic proteins are mediators of luteolysis in the human corpus luteum. Endocrinology 156, 1494–1503.
Bone morphogenetic proteins are mediators of luteolysis in the human corpus luteum.Crossref | GoogleScholarGoogle Scholar |

Patel, B. B., Barrero, C. A., Braverman, A., Kim, P. D., Jones, K. A., Chen, D. E., Bowler, R. P., Merali, S., Kelsen, S. G., and Yeung, A. T. (2012). Assessment of two immunodepletion methods: off-target effects and variations in immunodepletion efficiency may confound plasma proteomics. J. Proteome Res. 11, 5947–5958.
Assessment of two immunodepletion methods: off-target effects and variations in immunodepletion efficiency may confound plasma proteomics.Crossref | GoogleScholarGoogle Scholar |

Renuse, S., Chaerkady, R., and Pandey, A. (2011). Proteogenomics. Proteomics 11, 620–630.
Proteogenomics.Crossref | GoogleScholarGoogle Scholar |

Righetti, P. G., and Boschetti, E. (2013) Low-abundance protein access by combinatorial peptide libraries. In ‘Low-abundance proteome discovery’. pp. 79–157. (Elsevier: Boston, MA, USA.)

Rodgers, R. J., and Irving-Rodgers, H. F. (2010). Formation of the ovarian follicular antrum and follicular fluid. Biol. Reprod. 82, 1021–1029.
Formation of the ovarian follicular antrum and follicular fluid.Crossref | GoogleScholarGoogle Scholar |

Silverman, G. A., Bird, P. I., Carrell, R. W., Church, F. C., Coughlin, P. B., Gettins, P. G., Irving, J. A., Lomas, D. A., Luke, C. J., Moyer, R. W., Pemberton, P. A., Remold-O’Donnell, E., Salvesen, G. S., Travis, J., and Whisstock, J. C. (2001). The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature. J. Biol. Chem. 276, 33293–33296.
The serpins are an expanding superfamily of structurally similar but functionally diverse proteins. Evolution, mechanism of inhibition, novel functions, and a revised nomenclature.Crossref | GoogleScholarGoogle Scholar |

Smith, M. P. W., Wood, S. L., Zougman, A., Ho, J. T. C., Peng, J., Jackson, D., Cairns, D. A., Lewington, A. J. P., Selby, P. J., and Banks, R. E. (2011). A systematic analysis of the effects of increasing degrees of serum immunodepletion in terms of depth of coverage and other key aspects in top-down and bottom-up proteomic analyses. Proteomics 11, 2222–2235.
A systematic analysis of the effects of increasing degrees of serum immunodepletion in terms of depth of coverage and other key aspects in top-down and bottom-up proteomic analyses.Crossref | GoogleScholarGoogle Scholar |

Storey, J. D., and Tibshirani, R. (2003). Statistical significance for genomewide studies. Proc. Natl. Acad. Sci. USA 100, 9440–9445.
Statistical significance for genomewide studies.Crossref | GoogleScholarGoogle Scholar |

Stouffer, S. A., Suchman, E. A., DeVinney, L. C., Star, S. A., and Williams, R. M. (1949) Adjustment during army life. In ‘The American soldier’. pp. 117–120. (Princeton University Press: Princeton, NJ, USA.)

Thulasiraman, V., Lin, S., Gheorghiu, L., Lathrop, J., Lomas, L., Hammond, D., and Boschetti, E. (2005). Reduction of the concentration difference of proteins in biological liquids using a library of combinatorial ligands. Electrophoresis 26, 3561–3571.
Reduction of the concentration difference of proteins in biological liquids using a library of combinatorial ligands.Crossref | GoogleScholarGoogle Scholar |

Tu, C., Rudnick, P. A., Martinez, M. Y., Cheek, K. L., Stein, S. E., Slebos, R. J. C., and Liebler, D. C. (2010). Depletion of abundant plasma proteins and limitations of plasma proteomics. J. Proteome Res. 9, 4982–4991.
Depletion of abundant plasma proteins and limitations of plasma proteomics.Crossref | GoogleScholarGoogle Scholar |

Welt, C. K., Smith, Z. A., Pauler, D. K., and Hall, J. E. (2001). Differential regulation of inhibin A and inhibin B by luteinizing hormone, follicle-stimulating hormone, and stage of follicle development. J. Clin. Endocrinol. Metab. 86, 2531–2537.

Welt, C., Sidis, Y., Keutmann, H., and Schneyer, A. (2002). Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium. Exp. Biol. Med. 227, 724–752.
Activins, inhibins, and follistatins: from endocrinology to signaling. A paradigm for the new millennium.Crossref | GoogleScholarGoogle Scholar |

Whitlock, M. C. (2005). Combining probability from independent tests: the weighted Z-method is superior to Fisher’s approach. J. Evol. Biol. 18, 1368–1373.
Combining probability from independent tests: the weighted Z-method is superior to Fisher’s approach.Crossref | GoogleScholarGoogle Scholar |

Zamah, A. M., Hassis, M., Albertolle, M., and Williams, K. (2015). Proteomic analysis of human follicular fluid from fertile women. Clin. Proteomics 12, 5.
Proteomic analysis of human follicular fluid from fertile women.Crossref | GoogleScholarGoogle Scholar |