Molecular Biology of Reproduction and Development. PI: Rafael Oliva Virgili


The group of Molecular Biology of Reproduction and Development aims to characterize the molecular composition and biology of the human sperm and seminal plasma, from proteomic, transcriptomic and epigenmic perspectives as a step to further understand the function and basic mechanisms operating in the sperm cell, and to set up the basis to enable translational research in male infertility. A particular focus has been placed in differential distribution of the genes, RNAs and proteins potentially involved in regulatory roles after fertilization, and detection of signatures in infertile patients potentially involved in early embryo development.

Josep Lluis Ballescà Lagarda 

Ferran Barrachina Villalonga
Doctoral estudent

Judit Castillo Corullón

Salvadora Civico Vallejo

Alberto de la Iglesia Rodriguez
Doctorate student

Marta Guimerà Leal 

Meritxell Jodar Bifet

B. Jose Manuel Mayorga Torres
Doctorate student

Rafael Oliva Virgili

Ada Soler i Ventura
Doctorate student

  • Proteomic characterization and function of the sperm cell.
  • Chromatin transitions and mechanisms during spermatogenesis.
  • Small RNA, epigenetics and function of the sperm cell in transgenerational inheritance.
  • Exosome composition and function in semen.
  • Identification of genetic, epigenetic, RNA and proteomic abnormalities in infertile patients.

  • Title of the project/contract: Análisis proteómico y transcriptómico del semen e identificación de biomarcadores capaces de evaluar la contribución paterna a la fertilización y la embriogénesis.

Type of contract/Program: Ajuts a la Recerca
Company/Financing Administration: Ministerio de economia y Competitividad -ISCIII
Project/contract number: ISCIII PI16/00346 
Amount: 71.995€
Duration: from 01/01/2017 to 01/01/2019
Principal Investigator: Rafael Oliva Virgili
University or Research Institution: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)

  • Title of the project:Sperm cell proteome and identification of diagnostic and prognostic biomarkers in infertile patients

Principal Investigator: Rafael Oliva Virgili
Company/Financing Administration: Generalitat de Catalunya (PERIS 2016-2020)
Other participating entities: IDIBAPS
Project/contract number: SLT002/16/00337
Amount:104.821,10 €
Duration: from 01/02/2017 to 31/12/2019

  • Title of the project: Incorporació al Grup de Biologia Molecular de la Reproducció i el Desenvolupament

Financing Administration: Euvitro, S.L. (Clinica Eugin)
Participating entities: Universitat de Barcelona (Fundació Bosh Gimpera)
Reference of the concession: FBG 307854
Amount of subsidy: 70.380€
Duration: Data Inici: 30-04-2014    Data Fi: 30-09-2018

  • Title of the project/contract: Determinación de la composición proteómica y epigenética del espermatozoide y de sus alteraciones en pacientes infértiles

Type of contract/Program: Recursos Humans
Company/Financing Administration: Ministerio de educación, cultura y deporte
Project/contract number: FPU15/02306
Amount: 86.985,76€, (administrat per IDIBAPS RH041448)
Duration: from 01/10/2016 to 01/10/2020
Principal Investigator: Rafael Oliva Virgili (becari Ferran Barrachina Vilallonga)
University or Research Institution: Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS)

For more information for PI publications click in the link:
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Requena J, Alvarez-Palomo AB, Codina-Pascual M, Delgado-Morales R, Moran S, Esteller M, Sal M, Juan M, Boronat Barado A, Consiglio A, Bogle OA, Wolvetang E, Ovchinnikov D, Alvarez I, Jaraquemada D, Mezquita-Pla J, Oliva R, Edel MJ. Global Proteomic and Methylome Analysis in Human Induced Pluripotent Stem Cells Reveals Overexpression of a Human TLR3 Affecting Proper Innate Immune Response Signaling. Stem Cells. 2019 Apr;37(4): 476-488. doi: 10.1002/ stem.2966. Epub 2019 Feb 14. PMID: 30664289

Barrachina F, Jodar M, Delgado-Dueñas D, Soler-Ventura A, Estanyol JM, Mallofré C, Ballescà JL, Oliva R. Stable-protein Pair Analysis as A Novel Strategy to Identify Proteomic Signatures: Application To Seminal Plasma From Infertile Patients. Mol Cell Proteomics. 2019 Mar 15;18(Suppl 1): S77-S90. doi: 10.1074/ mcp.RA118.001248. Epub 2018 Dec 5. PMID: 30518674

Barrachina F, Anastasiadi D, Jodar M, Castillo J, Estanyol JM, Piferrer F, Oliva R. Identification of a complex population of chromatin-associated proteins in the European sea bass (Dicentrarchus labrax) sperm. Syst Biol Reprod Med. 2018 Dec;64(6): 502-517. doi: 10.1080/ 19396368.2018. 1482383. Epub 2018 Jun 25. PMID: 29939100

Castillo J, Jodar M, Oliva R. The contribution of human sperm proteins to the development and epigenome of the preimplantation embryo. Hum Reprod Update. 2018 Sep 1;24(5): 535555. doi: 10.1093/humupd/ dmy017. Review. PMID: 29800303

Alonso-Cerezo MC, Calero Ruiz M, Chantada-Abal V, de la Fuente-Hernández LA, García-Cobaleda I, García-Ochoa C, García-Sagredo JM, Nuñez R, Oliva R, Orera-Clemente M, Pintado-Vera D, Sanchez-Ramon S.Recommendations regarding the genetic and immunological study of reproductive dysfunction. Med Clin (Barc). 2018 Aug 22;151 (4):161.e1-161. e12. doi: 10.1016 /j.medcli.2018.02.008. Epub 2018 Apr 19. PMID: 29680457

Soler-Ventura A, Castillo J, de la Iglesia A, Jodar M, Barrachina F, Ballesca JL, Oliva R. Mammalian Sperm Protamine Extraction and Analysis: A Step-By-Step Detailed Protocol and Brief Review of Protamine Alterations. Protein Pept Lett. 2018;25 (5): 424-433. doi: 10.2174/ 0929866525666180412155205. Review. PMID: 29651936

Torra-Massana M, Barragán M, Bellu E, Oliva R, Rodríguez A, Vassena R. Sperm telomere length in donor samples is not related to ICSI outcome. J Assist Reprod Genet. 2018 Apr;35(4): 649-657. doi: 10.1007/ s10815-017-1104-2. Epub 2018 Jan 16. PMID: 29335812

Torabi F, Bogle OA, Estanyol JM, Oliva R, Miller D. Zona pellucida-binding protein 2 (ZPBP2) and several proteins containing BX7B motifs in human sperm may have hyaluronic acid binding or recognition properties  Mol Hum Reprod. 2017 Dec 1;23(12): 803-816. doi: 10.1093/ molehr/ gax053. PMID: 29126140

Bogle OA, Kumar K., Attardo-Parrinello C., Lewis SEM., Estanyol JM, Ballescà JL, Oliva R, Identification of Protein Changes in Human Sperm throughout the Cryopreservation Process, Andrology. 2017 Jan;5(1):10-22. doi: 10.1111/ andr.12279. Epub 2016 Nov 17. PMID: 27860400

Jodar M, Soler-Ventura A, Oliva R; Molecular Biology of Reproduction and Development Research Group. Semen proteomics and male infertility. J Proteomics. 2017 Jun 6;162:125-134. doi: 10.1016/j.jprot.2016.08.018. Epub 2016 Aug 26. Review. PMID: 27576136

Martínez-Zamora MA, Tàssies D, Reverter JC, Creus M, Casals G, Cívico S, Carmona F, Balasch J. Increased circulating cell-derived microparticlecount is associated with recurrent implantation failure after IVF and embryo transfer. Reprod Biomed Online. 2016 Aug;33(2): 168-73. doi: 10.1016 /j.rbmo.2016.05.005. Epub 2016 May 20. PMID: 27236712

Jain CV, Jessmon P, Kilburn BA, Jodar M, Sendler E, Krawetz SA, Armant DR. Regulation of HBEGF by Micro-RNA for Survival of Developing Human Trophoblast Cells. PLoS One. 2016; 11(10): e0163913. Published online 2016 Oct 4. doi: 10.1371/ journal.pone. 0163913. PMIC: 5049799

Johnson GD, Jodar M, Pique-Regi R, Krawetz SA. Nuclease Footprints in Sperm Project Past and Future Chromatin Regulatory Events. Sci Rep. 2016 May 17;6:25864. Published online 2016 May 17. doi: 10.1038/ srep25864. PMIC: 4869110

Jodar M, Sendler E, Moskovtsev SI, Librach CL, Goodrich R, Swanson S, Hauser R, Diamond MP, Krawetz SA. Response to Comment on "Absence of sperm RNA elements correlates with idiopathic male infertility". SciTranslMed. 2016 Aug 24;8(353): 353tr1. doi: 10.1126/scitranslmed.aaf4550. PMID: 27559098

Carrell DT, Aston KI, Oliva R, Emery BR, De Jonge CJ. The "omics" of human male infertility: integrating big data in a systems biology approach. Cell Tissue Res. 2016;363: 295-312. doi: 10.1007/ s00441-015-2320-7. Epub 2015 Dec 10. PMID: 26661835

Codina C, Estanyol JM, Fidalgo MJ, Ballescà JL, Oliva R. Advances in sperm proteomics: best-practise methodology and clinical potential. Expert Review of Proteomics. 2015;12:255-77. doi: 10.1586/ 14789450.2015. 1040769. Epub 2015 Apr 28. Review. PMID: 25921224

Paiva C, Amaral A, Rodriguez M, Canyellas N, Correig X, Ballesca JL, Ramalho-Santos J, Oliva R. Identification of endogenous metabolites in human sperm cells using 1H-NMR and GC-MS. Andrology. 2015; 3:496-505. doi: 10.1111/ andr. 12027. Epub 2015 Apr 8. PMID: 25854681

Castillo J, Estanyol JM, Ballescà JL, Oliva R, Human sperm chromatin epigenetic potential: genomics, proteomics, and male infertility. Asian Journal of Andrology 2015; 17:601-9. doi: 10.4103/ 1008-682X. 153302. PMID: 25926607

Pantano L, Jodar M, Bak M, Ballescà JL, Tommerup N, Oliva R, Vavouri T. The small RNA content of human sperm reveals pseudogene-derived piRNAs complementary to protein coding genes. RNA, 2015;21: 1085-95. doi: 10.1261/ rna.046482.114. Epub 2015 Apr 22. PMID: 25904136

Vilagran I, Yeste M, Sancho S, Castillo J, Oliva R, Bonet S. Comparative analysis of boar seminal plasma proteome from different freezability ejaculates and identification of Fibronectin 1 as sperm freezability marker. Andrology, 2015; 3: 345-56. doi: 10.1111/ andr.12009. Epub 2015 Feb 9. PMID: 25678437

Castillo J, Amaral A, Azpiazu R, Vavouri T, Estanyol JM, Ballescà JL, Oliva R. Genomic and proteomic dissection and characterization of the human sperm chromatin. Mol Hum Reprod. 2014;20: 1041-53. doi: 10.1093/ molehr/ gau079. Epub 2014 Sep 5. PMID: 25193639

Amaral A, Paiva C, Attardo Parrinello C, Estanyol JM, Ballescà JL, Ramalho-Santos J, Oliva R. Identification of Proteins Involved in Human Sperm Motility Using High-Throughput Differential Proteomics. J Proteome Res. 2014;13:5670-84. doi: 10.1021/ pr500652y. Epub 2014 Oct 7. PMID: 25250979

Zatecka E, Castillo J, Elzeinova F, Kubatova A, Ded L, Peknicova J, Oliva R. The effect of tetrabromobisphenol A on protamine content and DNA integrity in mouse sperm. Andrology 2014;2: 910-7. doi: 10.1111/ j.2047-2927. 2014.00257.x. Epub 2014 Aug 22. PMID: 25146423

Azpiazu R, Amaral A, Castillo J, Estanyol JM, Guimerà M, Ballescà JL,  Balasch J, Oliva R. High-throughput sperm differential proteomics suggests that epigenetic alterations contribute to failed assisted reproduction. Hum Reprod. 2014;29: 1225-37. doi: 10.1093/ humrep/ deu073. Epub 2014 Apr 29. PMID: 24781426

Giacco DL, Chianese C, Sánchez-Curbelo J, Bassas L, Ruiz P, Rajmil O, Sarquella J, Vives A, Ruiz-Castañé E, Oliva R, Ars E, Krausz C. Clinical relevance of Y-linked CNV screening in male infertility: new insights based on the 8-year experience of a diagnostic genetic laboratory. Eur J Hum Genet. 2014 Jun;22(6): 754-61. doi: 10.1038/ ejhg.2013.253. Epub 2013 Nov 6. PMID: 24193344

Jodar M, Oliva R. Protamine alterations in human spermatozoa. Adv Exp Med Biol. 2014;791: 83-102. doi: 10.1007/ 978-1-4614- 7783-9_6. PMID: 23955674

Amaral A, Castillo J, Ramalho-Santos J, Oliva R. 2014. The combined human sperm proteome: cellular pathways and implications for basic and clinical science. Human Reproduction Update 2014 Jan-Feb;20(1): 40-62. doi: 10.1093/ humupd/ dmt046. Epub 2013 Sep 29. PMID: 24082039

Castillo J, Amaral A, Oliva R. Sperm nuclear proteome and its epigenetic potential. Andrology. 2014 May;2(3): 326-38. doi: 10.1111/ j.2047-2927. 2013.00170.x. Epub 2013 Dec 10. PMID: 24327354

Silva F, Rodriguez-Revenga L, Madrigal I, Alvarez-Mora MI, Oliva R, Milà M. High apolipoprotein E4 allele frequency in FXTAS patients. Genet Med. 2013 Aug;15(8): 639-42. doi: 10.1038/ gim.2013.12. Epub 2013 Mar 14. PMID: 23492875

Vilagran I, Castillo J, Bonet S, Sancho S, Yeste M, Estanyol JM, Oliva R. Acrosin-binding protein (ACRBP) and triosephosphate isomerase (TPI) are good markers to predict boar sperm freezing capacity. Theriogenology. 2013 Sep 15;80(5): 443-50. doi: 10.1016/ j.theriogenology. 2013.05.006. Epub 2013 Jun 14. PMID: 23768753

Amaral A, Castillo J, Estanyol JM, Ballesca JL, Ramalho-Santos J, Oliva R. Human sperm tail proteome suggests new endogenous metabolic pathways. Mol Cell Proteomics. 2013 Feb;12(2): 330-42 doi: 10.1074/ mcp.M112 .020552. Epub 2012 Nov 15. PMID: 23161514

de Mateo S, Estanyol JM, Oliva R. Methods for the analysis of the sperm proteome. Methods Mol Biol. 2013; 927: 411-22. PMID: 22992932

Oliva R. SBiRM: Focus on proteomics and reproduction. Preface. Syst Biol Reprod Med. 2012 Aug; 58(4): 177-8. doi: 10.3109/ 19396368. 2012. 699587. PMID: 22788529

Jodar M, Kalko S, Castillo J, Ballescà JL, Oliva R. Differential RNAs in the sperm cells of asthenozoospermic patients. Hum Reprod. 2012 May;27(5): 1431-8. doi: 10.1093/ humrep/des021. Epub 2012 Feb 21. PMID: 22353264

Oliva R, Luís Ballescà J. Altered histone retention and epigenetic modifications in the sperm of infertile men. Asian J Androl. 2012 Mar;14(2): 239-240. Published online 2011 Nov 7. doi: 10.1038/aja.2011.159. PMID: 22057381.

Oliva R, Badenas C, Clària J, Coll MA; del grupo de trabajo para la estandarización de los informes asistenciales en Genética Molecular. [Molecular genetic reports in clinical practice: content and nomenclature of mutations]. Med Clin (Barc). 2011 Mar 26;136(8): 356-61. doi: 10.1016/ j.medcli.2009. 06.017. Epub 2009 Oct 22. PMID: 19853263

Simon L, Castillo J, Oliva R, Lewis SE. Relationships between human sperm protamines, DNA damage and assisted reproduction outcomes. Reprod Biomed Online. 2011 Dec;23(6): 724-34. doi: 10.1016/ j.rbmo.2011.08.010. Epub 2011 Sep 10. PMID: 22036908

Jodar M, Oriola J, Mestre G, Castillo J, Giwercman A, Vidal-Taboada JM, Ballescà JL, Oliva R. Polymorphisms, haplotypes and mutations in the protamine 1 and 2 genes. Int J Androl. 2011 Oct; 34(5 Pt 1): 470-85. doi: 10.1111/ j.1365-2605.2010.01115.x. Epub 2010 Oct 1. PMID: 21029114

de Mateo S, Ramos L, de Boer P, Meistrich M, Oliva R. Protamine 2 precursors and processing. Protein Pept Lett. 2011 Aug; 18(8): 778-85. PMID: 21443491

de Mateo S, Ramos L, van der Vlag J, de Boer P, Oliva R. Improvement in chromatin maturity of human spermatozoa selected through density gradient centrifugation. Int J Androl. 2011 Jun;34(3): 256-67. doi: 10.1111 /j.1365-2605. 2010. 01080.x. PMID: 20569271

Castillo J, Simon L, de Mateo S, Lewis S, Oliva R. Protamine/DNA ratios and DNA damage in native and density gradient centrifuged sperm from infertile patients. J Androl. 2011 May-Jun; 32(3): 324-32. doi: 10.2164 /jandrol.110. 011015. Epub 2010 Oct 21. PMID: 20966423

de Mateo S, Castillo J, Estanyol JM, Ballescà JL, Oliva R. Proteomic characterization of the human sperm nucleus. Proteomics. 2011 Jul;11(13):2714-26. doi: 10.1002/pmic.201000799. Epub 2011 Jun 1. PMID: 21630459.

Antonell A, Balasa M, Oliva R, Lladó A, Bosch B, Fabregat N, Fortea J, Molinuevo JL, Sánchez-Valle R. A novel PSEN1 gene mutation (L235R) associated with familial early-onset Alzheimer's disease. Neurosci Lett. 2011 May 27; 496(1): 40-2. doi: 10.1016 /j.neulet. 2011.03.084. Epub 2011 Apr 9. PMID: 21501661

Fortea J, Lladó A, Bosch B, Antonell A, Oliva R, Molinuevo JL, Sánchez-Valle R. Cerebrospinal fluid biomarkers in Alzheimer's disease families with PSEN1 mutations. Neurodegener Dis. 2011; 8(4): 202-7. doi: 10.1159/ 000322229. Epub 2011 Jan 5. PMID: 21212633

  • Offers from the University of Barcelona:

Work UB

  • Offers from the Research Group:

The Molecular Biology of Reproduction and Development Group, led by Dr. Rafael Oliva, is looking for a candidate to develop a DOCTORAL THESIS within the research project “Molecular maturity of sperm chromatin and sperm selection in the treatments of assisted reproduction”, funded by the Ministry of Science and Innovation and the Carlos III Institute of Health (ref. PI20 / 00936).