Advertisement

Cell and Tissue Research

, Volume 363, Issue 1, pp 85–96 | Cite as

The protein and transcript profiles of human semen

  • Meritxell Jodar
  • Edward Sendler
  • Stephen A. KrawetzEmail author
Review

Abstract

The increasing use of “-omics” (genomic, transcriptomic, proteomic, epigenomic, and metabolomic) high-throughput measurement technologies over the past decade is beginning to reveal the complexity of human biology and physiology through the interactions of DNA, RNA, related proteins and small molecules. In reproductive medicine, the majority of this work, has thus far focused on the female factors, e.g., the oocyte, since they provide both the environment and the majority of elements required for embryogenesis. State-of-the-art sequencing and computational analyses have enabled a deeper understanding of the underlying components. Contrary to being simply a silent delivery vehicle to the oocyte of the packaged male DNA, sperm provide both a specific epigenetically marked genome together with a complex population of RNAs and proteins that are crucial for early embryogenesis. In addition to the sperm, seminal fluid appears to serve multiple roles providing a supplementary series of components that allow the sperm to successfully reach and fertilize the oocyte and prepare the female immune system to tolerate the semiallosteric embryo. A global analysis and review of what is presently known regarding the unique role of each component of the male factor and their associated interactions begins to shed light on this emergent field.

Keywords

Spermatozoa Seminal fluid Proteomics RNA-sequencing 

Abbreviations

FPKM

Fragments per kilobase of exon per million fragments mapped

GO

Gene Ontology

Notes

Acknowledgments

This work was supported by the Charlotte B. Failing Professorship to SAK. The authors would like to thank Dr. Sergey I. Moskovtsev, Dr. Clifford L. Librach and Ms. Paula Mackie from CReATe Fertility Centre, Toronto, Ontario, Canada and Department of Obstetrics and Gynaecology, University of Toronto, Ontario, Canada for providing sperm samples for their RNA-seq analysis and Mr. G. Johnson for his review of the manuscript. We apologize to the many other contributors to the field whose contributions we were not able to include.

Supplementary material

441_2015_2237_MOESM1_ESM.xlsx (92 kb)
Supplemental Table 1 List of sperm and seminal fluid specific proteins and those detected in both proteomes. (XLSX 91 kb)
441_2015_2237_MOESM2_ESM.xlsx (203 kb)
Supplemental Table 2 Interaction of sperm proteins and sperm, testes and seminal fluid RNAs (XLSX 203 kb)

References

  1. Amaral A, Castillo J, Estanyol JM, Ballesca JL, Ramalho-Santos J, Oliva R (2012) Human sperm tail proteome suggests new endogenous metabolic pathways. Mol Cell ProteomicsGoogle Scholar
  2. Amaral A, Castillo J, Ramalho-Santos J, Oliva R (2014) The combined human sperm proteome: cellular pathways and implications for basic and clinical science. Hum Reprod Update 20:40–62PubMedCrossRefGoogle Scholar
  3. Anton E, Krawetz SA (2012) Spermatozoa as biomarkers for the assessment of human male infertility and genotoxicity. Syst Biol Reprod Med 58:41–50PubMedCrossRefGoogle Scholar
  4. Asquith KL, Harman AJ, McLaughlin EA, Nixon B, Aitken RJ (2005) Localization and significance of molecular chaperones, heat shock protein 1, and tumor rejection antigen gp96 in the male reproductive tract and during capacitation and acrosome reaction. Biol Reprod 72:328–337PubMedCrossRefGoogle Scholar
  5. Baker MA, Hetherington L, Reeves GM, Aitken RJ (2008) The mouse sperm proteome characterized via IPG strip prefractionation and LC-MS/MS identification. Proteomics 8:1720–1730PubMedCrossRefGoogle Scholar
  6. Baker MA, Naumovski N, Hetherington L, Weinberg A, Velkov T, Aitken RJ (2013) Head and flagella subcompartmental proteomic analysis of human spermatozoa. Proteomics 13:61–74PubMedCrossRefGoogle Scholar
  7. Behrens A, Genoud N, Naumann H, Rulicke T, Janett F, Heppner FL, Ledermann B, Aguzzi A (2002) Absence of the prion protein homologue Doppel causes male sterility. EMBO J 21:3652–3658PubMedPubMedCentralCrossRefGoogle Scholar
  8. Bibb JA, Snyder GL, Nishi A, Yan Z, Meijer L, Fienberg AA, Tsai LH, Kwon YT, Girault JA, Czernik AJ, Huganir RL, Hemmings HC Jr, Nairn AC, Greengard P (1999) Phosphorylation of DARPP-32 by Cdk5 modulates dopamine signalling in neurons. Nature 402:669–671PubMedCrossRefGoogle Scholar
  9. Bjorkgren I, Gylling H, Turunen H, Huhtaniemi I, Strauss L, Poutanen M, Sipila P (2015) Imbalanced lipid homeostasis in the conditional Dicer1 knockout mouse epididymis causes instability of the sperm membrane. FASEB J 29:433–442PubMedCrossRefGoogle Scholar
  10. Bjorndahl L, Kvist U (2011) A model for the importance of zinc in the dynamics of human sperm chromatin stabilization after ejaculation in relation to sperm DNA vulnerability. Syst Biol Reprod Med 57:86–92PubMedCrossRefGoogle Scholar
  11. Bourc’his D, Voinnet O (2010) A small-RNA perspective on gametogenesis, fertilization, and early zygotic development. Science 330:617–622PubMedCrossRefGoogle Scholar
  12. Breitbart H, Cohen G, Rubinstein S (2005) Role of actin cytoskeleton in mammalian sperm capacitation and the acrosome reaction. Reproduction 129:263–268PubMedCrossRefGoogle Scholar
  13. Carone BR, Fauquier L, Habib N, Shea JM, Hart CE, Li R, Bock C, Li C, Gu H, Zamore PD, Meissner A, Weng Z, Hofmann HA, Friedman N, Rando OJ (2010) Paternally induced transgenerational environmental reprogramming of metabolic gene expression in mammals. Cell 143:1084–1096PubMedPubMedCentralCrossRefGoogle Scholar
  14. Carr DW, Acott TS (1984) Inhibition of bovine spermatozoa by caudal epididymal fluid: I. Studies of a sperm motility quiescence factor. Biol Reprod 30:913–925PubMedCrossRefGoogle Scholar
  15. Chalbi M, Barraud-Lange V, Ravaux B, Howan K, Rodriguez N, Soule P, Ndzoudi A, Boucheix C, Rubinstein E, Wolf JP, Ziyyat A, Perez E, Pincet F, Gourier C (2014) Binding of sperm protein Izumo1 and its egg receptor Juno drives Cd9 accumulation in the intercellular contact area prior to fusion during mammalian fertilization. Development 141:3732–3739PubMedCrossRefGoogle Scholar
  16. Chalmel F, Com E, Lavigne R, Hernio N, Teixeira-Gomes AP, Dacheux JL, Pineau C (2014) An integrative omics strategy to assess the germ cell secretome and to decipher sertoli-germ cell crosstalk in the Mammalian testis. PLoS ONE 9:e104418PubMedPubMedCentralCrossRefGoogle Scholar
  17. Cohen DJ, Maldera JA, Weigel Munoz M, Ernesto JI, Vasen G, Cuasnicu PS (2011) Cysteine-rich secretory proteins (CRISP) and their role in mammalian fertilization. Biol Res 44:135–138PubMedCrossRefGoogle Scholar
  18. Cooper TG (2005) Cytoplasmic droplets: the good, the bad or just confusing? Hum Reprod 20:9–11PubMedCrossRefGoogle Scholar
  19. Cooper TG, Yeung C-H, Fetic S, Sobhani A, Nieschlag E (2004) Cytoplasmic droplets are normal structures of human sperm but are not well preserved by routine procedures for assessing sperm morphology. Hum Reprod 19:2283–2288PubMedCrossRefGoogle Scholar
  20. de Mateo S, Martinez-Heredia J, Estanyol JM, Dominguez-Fandos D, Vidal-Taboada JM, Ballesca JL, Oliva R (2007) Marked correlations in protein expression identified by proteomic analysis of human spermatozoa. Proteomics 7:4264–4277PubMedCrossRefGoogle Scholar
  21. de Mateo S, Castillo J, Estanyol JM, Ballesca JL, Oliva R (2011) Proteomic characterization of the human sperm nucleus. Proteomics 11:2714–2726PubMedCrossRefGoogle Scholar
  22. Dias BG, Ressler KJ (2014) Parental olfactory experience influences behavior and neural structure in subsequent generations. Nat Neurosci 17:89–96PubMedPubMedCentralCrossRefGoogle Scholar
  23. Fu J, Keurentjes JJ, Bouwmeester H, America T, Verstappen FW, Ward JL, Beale MH, de Vos RC, Dijkstra M, Scheltema RA, Johannes F, Koornneef M, Vreugdenhil D, Breitling R, Jansen RC (2009) System-wide molecular evidence for phenotypic buffering in Arabidopsis. Nat Genet 41:166–167PubMedCrossRefGoogle Scholar
  24. Gapp K, Jawaid A, Sarkies P, Bohacek J, Pelczar P, Prados J, Farinelli L, Miska E, Mansuy IM (2014) Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice. Nat Neurosci 17:667–669PubMedPubMedCentralCrossRefGoogle Scholar
  25. Ghazalpour A, Bennett B, Petyuk VA, Orozco L, Hagopian R, Mungrue IN, Farber CR, Sinsheimer J, Kang HM, Furlotte N, Park CC, Wen PZ, Brewer H, Weitz K, Camp DG 2nd, Pan C, Yordanova R, Neuhaus I, Tilford C, Siemers N, Gargalovic P, Eskin E, Kirchgessner T, Smith DJ, Smith RD, Lusis AJ (2011) Comparative analysis of proteome and transcriptome variation in mouse. PLoS Genet 7:e1001393PubMedPubMedCentralCrossRefGoogle Scholar
  26. Goodrich RJ, Anton E, Krawetz SA (2013) Isolating mRNA and small noncoding RNAs from human sperm. Methods Mol Biol 927:385–396PubMedCrossRefGoogle Scholar
  27. Goto M, O’Brien DA, Eddy EM (2010) Speriolin is a novel human and mouse sperm centrosome protein. Hum Reprod 25:1884–1894PubMedPubMedCentralCrossRefGoogle Scholar
  28. Haider S, Pal R (2013) Integrated analysis of transcriptomic and proteomic data. Curr Genomics 14:91–110PubMedPubMedCentralCrossRefGoogle Scholar
  29. Hargrove JL, Schmidt FH (1989) The role of mRNA and protein stability in gene expression. FASEB J 3:2360–2370PubMedGoogle Scholar
  30. Ickowicz D, Finkelstein M, Breitbart H (2012) Mechanism of sperm capacitation and the acrosome reaction: role of protein kinases. Asian J Androl 14:816–821PubMedPubMedCentralCrossRefGoogle Scholar
  31. Jodar M, Oliva R (2014) Protamine alterations in human spermatozoa. Adv Exp Med Biol 791:83–102PubMedCrossRefGoogle Scholar
  32. Jodar M, Kalko S, Castillo J, Ballesca JL, Oliva R (2012) Differential RNAs in the sperm cells of asthenozoospermic patients. Hum Reprod 27:1431–1438PubMedCrossRefGoogle Scholar
  33. Jodar M, Selvaraju S, Sendler E, Diamond MP, Krawetz SA, Reproductive Medicine N (2013) The presence, role and clinical use of spermatozoal RNAs. Hum Reprod Update 19:604–624PubMedPubMedCentralCrossRefGoogle Scholar
  34. Johnson GD, Lalancette C, Linnemann AK, Leduc F, Boissonneault G, Krawetz SA (2011a) The sperm nucleus: chromatin, RNA, and the nuclear matrix. Reproduction 141:21–36PubMedCrossRefGoogle Scholar
  35. Johnson GD, Sendler E, Lalancette C, Hauser R, Diamond MP, Krawetz SA (2011b) Cleavage of rRNA ensures translational cessation in sperm at fertilization. Mol Hum Reprod 17:721–726PubMedPubMedCentralCrossRefGoogle Scholar
  36. Johnson G, Mackie P, Jodar M, Moskovtsev SI, Krawetz SA (2015) Chromatin and extracellular vesicle associated sperm RNAs. Nucl Acids Res. doi: 10.1093/nar/gkv591
  37. Kiani J, Grandjean V, Liebers R, Tuorto F, Ghanbarian H, Lyko F, Cuzin F, Rassoulzadegan M (2013) RNA-mediated epigenetic heredity requires the cytosine methyltransferase Dnmt2. PLoS Genet 9:e1003498PubMedPubMedCentralCrossRefGoogle Scholar
  38. Klug A (2010) The discovery of zinc fingers and their applications in gene regulation and genome manipulation. Annu Rev Biochem 79:213–231PubMedCrossRefGoogle Scholar
  39. Krawetz SA, Kruger A, Lalancette C, Tagett R, Anton E, Draghici S, Diamond MP (2011) A survey of small RNAs in human sperm. Hum Reprod 26:3401–3412PubMedPubMedCentralCrossRefGoogle Scholar
  40. Kumari D, Nair N, Bedwal RS (2011) Testicular apoptosis after dietary zinc deficiency: ultrastructural and TUNEL studies. Syst Biol Reprod Med 57:233–243PubMedCrossRefGoogle Scholar
  41. Laity JH, Lee BM, Wright PE (2001) Zinc finger proteins: new insights into structural and functional diversity. Curr Opin Struct Biol 11:39–46PubMedCrossRefGoogle Scholar
  42. Lalancette C, Platts AE, Lu Y, Lu S, Krawetz SA (2008) Computational identification of transcription frameworks of early committed spermatogenic cells. Mol Genet Genomics 280:263–274PubMedCrossRefGoogle Scholar
  43. Lauressergues D, Couzigou J-M, Clemente HS, Martinez Y, Dunand C, Becard G, Combier J-P (2015) Primary transcripts of microRNAs encode regulatory peptides. Nature 520:90–93PubMedCrossRefGoogle Scholar
  44. Law JA, Jacobsen SE (2010) Establishing, maintaining and modifying DNA methylation patterns in plants and animals. Nat Rev Genet 11:204–220PubMedPubMedCentralCrossRefGoogle Scholar
  45. Lefievre L, Jha KN, de Lamirande E, Visconti PE, Gagnon C (2002) Activation of protein kinase A during human sperm capacitation and acrosome reaction. J Androl 23:709–716PubMedGoogle Scholar
  46. Li Y-F, He W, Jha KN, Klotz K, Kim Y-H, Mandal A, Pulido S, Digilio L, Flickinger CJ, Herr JC (2007) FSCB, a novel protein kinase A-phosphorylated calcium-binding protein, is a CABYR-binding partner involved in late steps of fibrous sheath biogenesis. J Biol Chem 282:34104–34119PubMedCrossRefGoogle Scholar
  47. Liebers R, Rassoulzadegan M, Lyko F (2014) Epigenetic regulation by heritable RNA. PLoS Genet 10:e1004296PubMedPubMedCentralCrossRefGoogle Scholar
  48. Lin YN, Roy A, Yan W, Burns KH, Matzuk MM (2007) Loss of zona pellucida binding proteins in the acrosomal matrix disrupts acrosome biogenesis and sperm morphogenesis. Mol Cell Biol 27:6794–6805PubMedPubMedCentralCrossRefGoogle Scholar
  49. Linschooten JO, Verhofstad N, Gutzkow K, Olsen A-K, Yauk C, Oligschlager Y, Brunborg G, van Schooten FJ, Godschalk RWL (2013) Paternal lifestyle as a potential source of germline mutations transmitted to offspring. FASEB J Off Publ Fed Am Soc Exp Biol 27:2873–2879Google Scholar
  50. Liu WM, Pang RT, Chiu PC, Wong BP, Lao K, Lee KF, Yeung WS (2012) Sperm-borne microRNA-34c is required for the first cleavage division in mouse. Proc Natl Acad Sci U S A 109:490–494PubMedPubMedCentralCrossRefGoogle Scholar
  51. Lopez Rodriguez A, Rijsselaere T, Beek J, Vyt P, Van Soom A, Maes D (2013) Boar seminal plasma components and their relation with semen quality. Syst Biol Reprod Med 59:5–12PubMedCrossRefGoogle Scholar
  52. Manandhar G, Schatten H, Sutovsky P (2005) Centrosome reduction during gametogenesis and its significance. Biol Reprod 72:2–13PubMedCrossRefGoogle Scholar
  53. Mao S, Goodrich RJ, Hauser R, Schrader SM, Chen Z, Krawetz SA (2013) Evaluation of the effectiveness of semen storage and sperm purification methods for spermatozoa transcript profiling. Syst Biol Reprod MedGoogle Scholar
  54. Martinez-Heredia J, de Mateo S, Vidal-Taboada JM, Ballesca JL, Oliva R (2008) Identification of proteomic differences in asthenozoospermic sperm samples. Hum Reprod 23:783–791PubMedCrossRefGoogle Scholar
  55. Martins RP, Krawetz SA (2007) Nuclear organization of the protamine locus. Soc Reprod Fertil Suppl 64:1–12PubMedGoogle Scholar
  56. Montjean D, De La Grange P, Gentien D, Rapinat A, Belloc S, Cohen-Bacrie P, Menezo Y, Benkhalifa M (2012) Sperm transcriptome profiling in oligozoospermia. J Assist Reprod Genet 29:3–10PubMedPubMedCentralCrossRefGoogle Scholar
  57. Naaby-Hansen S, Diekman A, Shetty J, Flickinger CJ, Westbrook A, Herr JC (2010) Identification of calcium-binding proteins associated with the human sperm plasma membrane. Reprod Biol Endocrinol 8:6PubMedPubMedCentralCrossRefGoogle Scholar
  58. Ng SF, Lin RCY, Laybutt DR, Barres R, Owens JA, Morris MJ (2010) Chronic high-fat diet in fathers programs beta-cell dysfunction in female rat offspring. Nature 467:963–U103PubMedCrossRefGoogle Scholar
  59. Nixon B, Mitchell LA, Anderson AL, McLaughlin EA, O’Bryan MK, Aitken RJ (2011) Proteomic and functional analysis of human sperm detergent resistant membranes. J Cell Physiol 226:2651–2665PubMedCrossRefGoogle Scholar
  60. Nixon B, Bromfield EG, Dun MD, Redgrove KA, McLaughlin EA, Aitken RJ (2015) The role of the molecular chaperone heat shock protein A2 (HSPA2) in regulating human sperm-egg recognition. Asian J AndrolGoogle Scholar
  61. Oliva R, Mezquita J, Mezquita C, Dixon GH (1988) Haploid expression of the rooster protamine mRNA in the postmeiotic stages of spermatogenesis. Dev Biol 125:332–340PubMedCrossRefGoogle Scholar
  62. Ostermeier GC, Dix DJ, Miller D, Khatri P, Krawetz SA (2002) Spermatozoal RNA profiles of normal fertile men. Lancet 360:772–777PubMedCrossRefGoogle Scholar
  63. Owen DH, Katz DF (2005) A review of the physical and chemical properties of human semen and the formulation of a semen simulant. J Androl 26:459–469PubMedCrossRefGoogle Scholar
  64. Palacios MJ, Joshi HC, Simerly C, Schatten G (1993) Gamma-tubulin reorganization during mouse fertilization and early development. J Cell Sci 104(Pt 2):383–389PubMedGoogle Scholar
  65. Pantano L, Jodar M, Bak M, Ballesca JL, Tommerup N, Oliva R, Vavouri T (2015) The small RNA content of human sperm reveals pseudogene-derived piRNAs complementary to protein-coding genes. RNAGoogle Scholar
  66. Pilch B, Mann M (2006) Large-scale and high-confidence proteomic analysis of human seminal plasma. Genome Biol 7:R40PubMedPubMedCentralCrossRefGoogle Scholar
  67. Platts AE, Dix DJ, Chemes HE, Thompson KE, Goodrich R, Rockett JC, Rawe VY, Quintana S, Diamond MP, Strader LF, Krawetz SA (2007) Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs. Hum Mol Genet 16:763–773PubMedCrossRefGoogle Scholar
  68. Rando OJ (2012) Daddy issues: paternal effects on phenotype. Cell 151:702–708PubMedPubMedCentralCrossRefGoogle Scholar
  69. Rassoulzadegan M, Grandjean V, Gounon P, Vincent S, Gillot I, Cuzin F (2006) RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441:469–474PubMedCrossRefGoogle Scholar
  70. Rengan AK, Agarwal A, van der Linde M, du Plessis SS (2012) An investigation of excess residual cytoplasm in human spermatozoa and its distinction from the cytoplasmic droplet. Reprod Biol Endocrinol 10:92PubMedPubMedCentralCrossRefGoogle Scholar
  71. Rettie EC, Dorus S (2012) Drosophila sperm proteome evolution: Insights from comparative genomic approaches. Spermatogenesis 2:213–223PubMedPubMedCentralCrossRefGoogle Scholar
  72. Robertson SA (2005) Seminal plasma and male factor signalling in the female reproductive tract. Cell Tissue Res 322:43–52PubMedCrossRefGoogle Scholar
  73. Robertson SA, Prins JR, Sharkey DJ, Moldenhauer LM (2013) Seminal fluid and the generation of regulatory T cells for embryo implantation. Am J Reprod Immunol 69:315–330PubMedCrossRefGoogle Scholar
  74. Ruddock NT, Wilson KJ, Cooney MA, Korfiatis NA, Tecirlioglu RT, French AJ (2004) Analysis of imprinted messenger RNA expression during bovine preimplantation development. Biol Reprod 70:1131–1135PubMedCrossRefGoogle Scholar
  75. Sassone-Corsi P (2002) Unique chromatin remodeling and transcriptional regulation in spermatogenesis. Science 296:2176–2178PubMedCrossRefGoogle Scholar
  76. Schjenken JE, Robertson SA (2014) Seminal fluid and immune adaptation for pregnancy–comparative biology in mammalian species. Reprod Domest Anim 49(Suppl 3):27–36PubMedCrossRefGoogle Scholar
  77. Selvaraju S, Jodar M, Krawetz S (2014) The influence of environmental contaminants and lifestyle on testicular damage and male fertility. Methods in Pharmacology and Toxicology. Humana Press, pp 1–19Google Scholar
  78. Sendler E, Johnson GD, Mao S, Goodrich RJ, Diamond MP, Hauser R, Krawetz SA (2013) Stability, delivery and functions of human sperm RNAs at fertilization. Nucleic Acids Res 41:4104–4117PubMedPubMedCentralCrossRefGoogle Scholar
  79. Shen C, Kuang Y, Liu J, Feng J, Chen X, Wu W, Chi J, Tang L, Wang Y, Fei J, Wang Z (2013) Prss37 is required for male fertility in the mouse. Biol Reprod 88:123PubMedCrossRefGoogle Scholar
  80. Skerget S, Rosenow M, Polpitiya A, Petritis K, Dorus S, Karr TL (2013) The Rhesus macaque (Macaca mulatta) sperm proteome. Mol Cell Proteomics 12:3052–3067PubMedPubMedCentralCrossRefGoogle Scholar
  81. Sorensen MB, Bergdahl IA, Hjollund NH, Bonde JP, Stoltenberg M, Ernst E (1999) Zinc, magnesium and calcium in human seminal fluid: relations to other semen parameters and fertility. Mol Hum Reprod 5:331–337PubMedCrossRefGoogle Scholar
  82. Sosnik J, Buffone MG, Visconti PE (2010) Analysis of CAPZA3 localization reveals temporally discrete events during the acrosome reaction. J Cell Physiol 224:575–580PubMedPubMedCentralCrossRefGoogle Scholar
  83. Steger K (1999) Transcriptional and translational regulation of gene expression in haploid spermatids. Anat Embryol (Berl) 199:471–487CrossRefGoogle Scholar
  84. Sullivan R, Saez F, Girouard J, Frenette G (2005) Role of exosomes in sperm maturation during the transit along the male reproductive tract. Blood Cells Mol Dis 35:1–10PubMedCrossRefGoogle Scholar
  85. Suzuki T, Suzuki K, Nakajima K, Otaki N, Yamanaka H (1994) Metallothionein in human seminal plasma. Int J Urol 1:345–348PubMedCrossRefGoogle Scholar
  86. Vojtech L, Woo S, Hughes S, Levy C, Ballweber L, Sauteraud RP, Strobl J, Westerberg K, Gottardo R, Tewari M, Hladik F (2014) Exosomes in human semen carry a distinctive repertoire of small non-coding RNAs with potential regulatory functions. Nucleic Acids Res 42:7290–7304PubMedPubMedCentralCrossRefGoogle Scholar
  87. Wang G, Guo Y, Zhou T, Shi X, Yu J, Yang Y, Wu Y, Wang J, Liu M, Chen X, Tu W, Zeng Y, Jiang M, Li S, Zhang P, Zhou Q, Zheng B, Yu C, Zhou Z, Guo X, Sha J (2013) In-depth proteomic analysis of the human sperm reveals complex protein compositions. J Proteomics 79:114–122PubMedCrossRefGoogle Scholar
  88. Whitaker M (2006) Calcium at fertilization and in early development. Physiol Rev 86:25–88PubMedPubMedCentralCrossRefGoogle Scholar
  89. Yan W (2014) Potential roles of noncoding RNAs in environmental epigenetic transgenerational inheritance. Mol Cell Endocrinol 398:24–30PubMedPubMedCentralCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Berlin Heidelberg 2015

Authors and Affiliations

  • Meritxell Jodar
    • 1
    • 2
  • Edward Sendler
    • 1
    • 2
  • Stephen A. Krawetz
    • 1
    • 2
    Email author
  1. 1.Department of Obstetrics and GynecologyWayne State University School of MedicineDetroitUSA
  2. 2.Center for Molecular Medicine and Genetics, C.S. Mott Center for Human Growth and DevelopmentWayne State University School of MedicineDetroitUSA

Personalised recommendations