Paternal effects on early embryogenesis

  • Laszlo Nanassy
  • Douglas T Carrell
Open Access


Historically, less attention has been paid to paternal effects on early embryogenesis than maternal effects. However, it is now apparent that certain male factor infertility phenotypes are associated with increased DNA fragmentation and/or chromosome aneuploidies that may compromise early embryonic development. In addition, there is a growing body of evidence that the fertilizing sperm has more function than just carrying an intact, haploid genome. The paternally inherited centrosome is essential for normal fertilization, and the success of higher order chromatin packaging may impact embryogenesis. Epigenetic modifications of sperm chromatin may contribute to the reprogramming of the genome, and sperm delivered mRNA has also been hythesized to be necessary for embryogenesis. There is less information about the epigenetic factors affecting embryogenesis than genetic factors, but the epigenetics of gamete and early embryogenesis is a rapidly advancing field.


  1. 1.
    Emery BR, Carrell DT: The effect of epigenetic sperm abnormalities on early embryogenesis. Asian J Androl. 2006, 8: 131-142.PubMedGoogle Scholar
  2. 2.
    Minor A, Wong EC, Harmer K, Ma S: Molecular and cytogenetic investigation of Y chromosome deletions over three generations facilitated by intracytoplasmic sperm injection. Prenat Diagn. 2007, 27: 743-747.PubMedGoogle Scholar
  3. 3.
    Cox GF, Burger J, Lip V, Mau UA, Sperling K, Wu BL, Horsthemke B: Intracytoplasmic sperm injection may increase the risk of imprinting defects. Am J Hum Genet. 2002, 71: 162-164.PubMedPubMedCentralGoogle Scholar
  4. 4.
    DeBaun MR, Niemitz EL, Feinberg AP: Association of in vitro fertilization with Beckwith-Wiedemann syndrome and epigenetic alterations of LIT1 and H19. Am J Hum Genet. 2003, 72: 156-160.PubMedGoogle Scholar
  5. 5.
    Gosden R, Trasler J, Lucifero D, Faddy M: Rare congenital disorders, imprinted genes, and assisted reproductive technology. Lancet. 2003, 361: 1975-1977.PubMedGoogle Scholar
  6. 6.
    Kidd SA, Eskenazi B, Wyrobek AJ: Effects of male age on semen quality and fertility: a review of the literature. Fertil Steril. 2001, 75: 237-248.PubMedPubMedCentralGoogle Scholar
  7. 7.
    Hassold T, Hunt P: To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet. 2001, 2: 280-291.PubMedGoogle Scholar
  8. 8.
    Ng KK, Donat R, Chan L, Lalak A, Di Pierro I, Handelsman DJ: Sperm output of older men. Hum Reprod. 2004, 19: 1811-1815.PubMedGoogle Scholar
  9. 9.
    Eskenazi B, Wyrobek AJ, Sloter E, Kidd SA, Moore L, Young S, Moore D: The association of age and semen quality in healthy men. Hum Reprod. 2003, 18: 447-454.PubMedGoogle Scholar
  10. 10.
    Kuhnert B, Nieschlag E: Reproductive functions of the ageing male. Hum Reprod Update. 2004, 10: 327-339.PubMedGoogle Scholar
  11. 11.
    Frattarelli JL, Miller KA, Miller BT, Elkind-Hirsch K, Scott RT: Male age negatively impacts embryo development and reproductive outcome in donor oocyte assisted reproductive technology cycles. Fertil Steril. 2007Google Scholar
  12. 12.
    Watanabe Y, Cornet D, Merviel P, Mandelbaum J, Antoine J, Uzan S: Influence of husband's age on outcome of a shared oocyte donation program. Fertil Steril. 2000, 74: S78-S79.Google Scholar
  13. 13.
    Gallardo E, Simon C, Levy M, Guanes PP, Remohi J, Pellicer A: Effect of age on sperm fertility potential: oocyte donation as a model. Fertil Steril. 1996, 66: 260-264.PubMedGoogle Scholar
  14. 14.
    Paulson RJ, Milligan RC, Sokol RZ: The lack of influence of age on male fertility. Am J Obstet Gynecol. 2001, 184: 818-822. discussion 822-814PubMedPubMedCentralGoogle Scholar
  15. 15.
    Slama R, Bouyer J, Windham G, Fenster L, Werwatz A, Swan SH: Influence of paternal age on the risk of spontaneous abortion. Am J Epidemiol. 2005, 161: 816-823.PubMedGoogle Scholar
  16. 16.
    Kleinhaus K, Perrin M, Friedlander Y, Paltiel O, Malaspina D, Harlap S: Paternal age and spontaneous abortion. Obstet Gynecol. 2006, 108: 369-377.PubMedGoogle Scholar
  17. 17.
    Klonoff-Cohen HS, Natarajan L: The effect of advancing paternal age on pregnancy and live birth rates in couples undergoing in vitro fertilization or gamete intrafallopian transfer. Am J Obstet Gynecol. 2004, 191: 507-514.PubMedGoogle Scholar
  18. 18.
    de La Rochebrochard E, de Mouzon J, Thepot F, Thonneau P: Fathers over 40 and increased failure to conceive: the lessons of in vitro fertilization in France. Fertil Steril. 2006, 85: 1420-1424.PubMedGoogle Scholar
  19. 19.
    Spandorfer SD, Avrech OM, Colombero LT, Palermo GD, Rosenwaks Z: Effect of parental age on fertilization and pregnancy characteristics in couples treated by intracytoplasmic sperm injection. Hum Reprod. 1998, 13: 334-338.PubMedGoogle Scholar
  20. 20.
    Aboulghar M, Mansour R, Al-Inany H, Abou-Setta AM, Aboulghar M, Mourad L, Serour G: Paternal age and outcome of intracytoplasmic sperm injection. Reprod Biomed Online. 2007, 14: 588-592.PubMedGoogle Scholar
  21. 21.
    Schwarzer JU, Fiedler K, Hertwig I, Krusmann G, Wurfel W, Muhlen B, Pickl U, Lochner-Ernst D, Schleyer M, Ovens-Rader A, Hennig M: Male factors determining the outcome of intracytoplasmic sperm injection with epididymal and testicular spermatozoa. Andrologia. 2003, 35: 220-226.PubMedGoogle Scholar
  22. 22.
    Wyrobek AJ, Eskenazi B, Young S, Arnheim N, Tiemann-Boege I, Jabs EW, Glaser RL, Pearson FS, Evenson D: Advancing age has differential effects on DNA damage, chromatin integrity, gene mutations, and aneuploidies in sperm. Proc Natl Acad Sci USA. 2006, 103: 9601-9606.PubMedPubMedCentralGoogle Scholar
  23. 23.
    Singh NP, Muller CH, Berger RE: Effects of age on DNA double-strand breaks and apoptosis in human sperm. Fertil Steril. 2003, 80: 1420-1430.PubMedGoogle Scholar
  24. 24.
    Puscheck EE, Jeyendran RS: The impact of male factor on recurrent pregnancy loss. Curr Opin Obstet Gynecol. 2007, 19: 222-228.PubMedGoogle Scholar
  25. 25.
    Sartorelli EM, Mazzucatto LF, de Pina-Neto JM: Effect of paternal age on human sperm chromosomes. Fertil Steril. 2001, 76: 1119-1123.PubMedGoogle Scholar
  26. 26.
    Lambert SM, Masson P, Fisch H: The male biological clock. World J Urol. 2006, 24: 611-617.PubMedGoogle Scholar
  27. 27.
    Nagy Z, Liu J, Cecile J, Silber S, Devroey P, Van Steirteghem A: Using ejaculated, fresh, and frozen-thawed epididymal and testicular spermatozoa gives rise to comparable results after intracytoplasmic sperm injection. Fertil Steril. 1995, 63: 808-815.PubMedGoogle Scholar
  28. 28.
    Aboulghar MA, Mansour RT, Serour GI, Fahmy I, Kamal A, Tawab NA, Amin YM: Fertilization and pregnancy rates after intracytoplasmic sperm injection using ejaculate semen and surgically retrieved sperm. Fertil Steril. 1997, 68: 108-111.PubMedGoogle Scholar
  29. 29.
    Hourvitz A, Shulman A, Madjar I, Levron J, Levran D, Mashiach S, Dor J: In vitro fertilization treatment for severe male factor: a comparative study of intracytoplasmic sperm injection with testicular sperm extraction and with spermatozoa from ejaculate. J Assist Reprod Genet. 1998, 15: 386-389.PubMedPubMedCentralGoogle Scholar
  30. 30.
    Vernaeve V, Tournaye H, Osmanagaoglu K, Verheyen G, Van Steirteghem A, Devroey P: Intracytoplasmic sperm injection with testicular spermatozoa is less successful in men with nonobstructive azoospermia than in men with obstructive azoospermia. Fertil Steril. 2003, 79: 529-533.PubMedGoogle Scholar
  31. 31.
    Ghanem M, Bakr NI, Elgayaar MA, El Mongy S, Fathy H, Ibrahim AH: Comparison of the outcome of intracytoplasmic sperm injection in obstructive and non-obstructive azoospermia in the first cycle: a report of case series and meta-analysis. Int J Androl. 2005, 28: 16-21.PubMedGoogle Scholar
  32. 32.
    Pasqualotto FF, Rossi-Ferragut LM, Rocha CC, Iaconelli A, Borges E: Outcome of in vitro fertilization and intracytoplasmic injection of epididymal and testicular sperm obtained from patients with obstructive and nonobstructive azoospermia. J Urol. 2002, 167: 1753-1756.PubMedGoogle Scholar
  33. 33.
    Bernardini L, Gianaroli L, Fortini D, Conte N, Magli C, Cavani S, Gaggero G, Tindiglia C, Ragni N, Venturini PL: Frequency of hyper-, hypohaploidy and diploidy in ejaculate, epididymal and testicular germ cells of infertile patients. Hum Reprod. 2000, 15: 2165-2172.PubMedGoogle Scholar
  34. 34.
    Burrello N, Vicari E, Calogero AE: Chromosome abnormalities in spermatozoa of patients with azoospermia and normal somatic karyotype. Cytogenet Genome Res. 2005, 111: 363-365.PubMedGoogle Scholar
  35. 35.
    Levron J, Aviram-Goldring A, Madgar I, Raviv G, Barkai G, Dor J: Sperm chromosome abnormalities in men with severe male factor infertility who are undergoing in vitro fertilization with intracytoplasmic sperm injection. Fertil Steril. 2001, 76: 479-484.PubMedGoogle Scholar
  36. 36.
    Carrell DT, Wilcox AL, Lowy L, Peterson CM, Jones KP, Erickson L, Campbell B, Branch DW, Hatasaka HH: Elevated sperm chromosome aneuploidy and apoptosis in patients with unexplained recurrent pregnancy loss. Obstet Gynecol. 2003, 101: 1229-1235.PubMedGoogle Scholar
  37. 37.
    Dozortsev D, Neme R, Diamond MP, Abdelmassih S, Abdelmassih V, Oliveira F, Abdelmassih R: Embryos generated using testicular spermatozoa have higher developmental potential than those obtained using epididymal spermatozoa in men with obstructive azoospermia. Fertil Steril. 2006, 86: 606-611.PubMedGoogle Scholar
  38. 38.
    Buffat C, Patrat C, Merlet F, Guibert J, Epelboin S, Thiounn N, Vieillefond A, Adda-Lievin A, Lebon C, Jouannet P: ICSI outcomes in obstructive azoospermia: influence of the origin of surgically retrieved spermatozoa and the cause of obstruction. Hum Reprod. 2006, 21: 1018-1024.PubMedGoogle Scholar
  39. 39.
    Borges E, Rossi-Ferragut LM, Pasqualotto FF, dos Santos DR, Rocha CC, Iaconelli A: Testicular sperm results in elevated miscarriage rates compared to epididymal sperm in azoospermic patients. Sao Paulo Med J. 2002, 120: 122-126.PubMedGoogle Scholar
  40. 40.
    Tarozzi N, Bizzaro D, Flamigni C, Borini A: Clinical relevance of sperm DNA damage in assisted reproduction. Reprod Biomed Online. 2007, 14: 746-757.PubMedGoogle Scholar
  41. 41.
    Aitken RJ, Krausz C: Oxidative stress, DNA damage and the Y chromosome. Reproduction. 2001, 122: 497-506.PubMedGoogle Scholar
  42. 42.
    Seli E, Sakkas D: Spermatozoal nuclear determinants of reproductive outcome: implications for ART. Hum Reprod Update. 2005, 11: 337-349.PubMedGoogle Scholar
  43. 43.
    Carrell DT, Emery BR, Hammoud S: Altered protamine expression and diminished spermatogenesis: what is the link?. Hum Reprod Update. 2007, 13: 313-327.PubMedGoogle Scholar
  44. 44.
    Aitken RJ, Marshall Graves JA: The future of sex. Nature. 2002, 415: 963-PubMedGoogle Scholar
  45. 45.
    Aoki VW, Emery BR, Liu L, Carrell DT: Protamine levels vary between individual sperm cells of infertile human males and correlate with viability and DNA integrity. J Androl. 2006, 27: 890-898.PubMedGoogle Scholar
  46. 46.
    Angelopoulou R, Plastira K, Msaouel P: Spermatozoal sensitive biomarkers to defective protaminosis and fragmented DNA. Reprod Biol Endocrinol. 2007, 5: 36-PubMedPubMedCentralGoogle Scholar
  47. 47.
    Lewis SE, Aitken RJ: DNA damage to spermatozoa has impacts on fertilization and pregnancy. Cell Tissue Res. 2005, 322: 33-41.PubMedGoogle Scholar
  48. 48.
    Aoki VW, Moskovtsev SI, Willis J, Liu L, Mullen JB, Carrell DT: DNA integrity is compromised in protamine-deficient human sperm. J Androl. 2005, 26: 741-748.PubMedGoogle Scholar
  49. 49.
    Benchaib M, Braun V, Lornage J, Hadj S, Salle B, Lejeune H, Guerin JF: Sperm DNA fragmentation decreases the pregnancy rate in an assisted reproductive technique. Hum Reprod. 2003, 18: 1023-1028.PubMedGoogle Scholar
  50. 50.
    Seli E, Gardner DK, Schoolcraft WB, Moffatt O, Sakkas D: Extent of nuclear DNA damage in ejaculated spermatozoa impacts on blastocyst development after in vitro fertilization. Fertil Steril. 2004, 82: 378-383.PubMedGoogle Scholar
  51. 51.
    Lin MH, Kuo-Kuang Lee R, Li SH, Lu CH, Sun FJ, Hwu YM: Sperm chromatin structure assay parameters are not related to fertilization rates, embryo quality, and pregnancy rates in in vitro fertilization and intracytoplasmic sperm injection, but might be related to spontaneous abortion rates. Fertil Steril. 2007Google Scholar
  52. 52.
    Carrell DT, Liu L, Peterson CM, Jones KP, Hatasaka HH, Erickson L, Campbell B: Sperm DNA fragmentation is increased in couples with unexplained recurrent pregnancy loss. Arch Androl. 2003, 49: 49-55.PubMedGoogle Scholar
  53. 53.
    Borini A, Tarozzi N, Bizzaro D, Bonu MA, Fava L, Flamigni C, Coticchio G: Sperm DNA fragmentation: paternal effect on early post-implantation embryo development in ART. Hum Reprod. 2006, 21: 2876-2881.PubMedGoogle Scholar
  54. 54.
    Morris ID, Ilott S, Dixon L, Brison DR: The spectrum of DNA damage in human sperm assessed by single cell gel electrophoresis (Comet assay) and its relationship to fertilization and embryo development. Hum Reprod. 2002, 17: 990-998.PubMedGoogle Scholar
  55. 55.
    Boe-Hansen GB, Fedder J, Ersboll AK, Christensen P: The sperm chromatin structure assay as a diagnostic tool in the human fertility clinic. Hum Reprod. 2006, 21: 1576-1582.PubMedGoogle Scholar
  56. 56.
    Bungum M, Humaidan P, Spano M, Jepson K, Bungum L, Giwercman A: The predictive value of sperm chromatin structure assay (SCSA) parameters for the outcome of intrauterine insemination, IVF and ICSI. Hum Reprod. 2004, 19: 1401-1408.PubMedGoogle Scholar
  57. 57.
    Bungum M, Spano M, Humaidan P, Eleuteri P, Rescia M, Giwercman A: Sperm chromatin structure assay parameters measured after density gradient centrifugation are not predictive for the outcome of ART. Hum Reprod. 2008, 23: 4-10.PubMedGoogle Scholar
  58. 58.
    Martin RH: Mechanisms of nondisjunction in human spermatogenesis. Cytogenet Genome Res. 2005, 111: 245-249.PubMedGoogle Scholar
  59. 59.
    Hassold T, Hall H, Hunt P: The origin of human aneuploidy: where we have been, where we are going. Hum Mol Genet. 2007, 16 (Spec No 2): R203-208.PubMedGoogle Scholar
  60. 60.
    Sun F, Ko E, Martin RH: Is there a relationship between sperm chromosome abnormalities and sperm morphology?. Reprod Biol Endocrinol. 2006, 4: 1-PubMedPubMedCentralGoogle Scholar
  61. 61.
    Calogero AE, De Palma A, Grazioso C, Barone N, Burrello N, Palermo I, Gulisano A, Pafumi C, D'Agata R: High sperm aneuploidy rate in unselected infertile patients and its relationship with intracytoplasmic sperm injection outcome. Hum Reprod. 2001, 16: 1433-1439.PubMedGoogle Scholar
  62. 62.
    Calogero AE, De Palma A, Grazioso C, Barone N, Romeo R, Rappazzo G, D'Agata R: Aneuploidy rate in spermatozoa of selected men with abnormal semen parameters. Hum Reprod. 2001, 16: 1172-1179.PubMedGoogle Scholar
  63. 63.
    Calogero AE, Burrello N, De Palma A, Barone N, D'Agata R, Vicari E: Sperm aneuploidy in infertile men. Reprod Biomed Online. 2003, 6: 310-317.PubMedGoogle Scholar
  64. 64.
    Perrin A, Morel F, Moy L, Colleu D, Amice V, Braekeleer MD: Study of aneuploidy in large-headed, multiple-tailed spermatozoa: case report and review of the literature. Fertil Steril. 2007Google Scholar
  65. 65.
    Nagvenkar P, Zaveri K, Hinduja I: Comparison of the sperm aneuploidy rate in severe oligozoospermic and oligozoospermic men and its relation to intracytoplasmic sperm injection outcome. Fertil Steril. 2005, 84: 925-931.PubMedGoogle Scholar
  66. 66.
    Carrell DT, Wilcox AL, Udoff LC, Thorp C, Campbell B: Chromosome 15 aneuploidy in the sperm and conceptus of a sibling with variable familial expression of round-headed sperm syndrome. Fertil Steril. 2001, 76: 1258-1260.PubMedGoogle Scholar
  67. 67.
    Tomascik-Cheeseman LM, Lowe XR, Eskenazi B, Kidd S, Nath J, Moore D, Wyrobek AJ: A father of four consecutive trisomic pregnancies with elevated frequencies of associated aneuploid sperm. Am J Med Genet A. 2006, 140: 1840-1845.Google Scholar
  68. 68.
    Van Dyk Q, Lanzendorf S, Kolm P, Hodgen GD, Mahony MC: Incidence of aneuploid spermatozoa from subfertile men: selected with motility versus hemizona-bound. Hum Reprod. 2000, 15: 1529-1536.PubMedGoogle Scholar
  69. 69.
    Burrello N, Vicari E, Shin P, Agarwal A, De Palma A, Grazioso C, D'Agata R, Calogero AE: Lower sperm aneuploidy frequency is associated with high pregnancy rates in ICSI programmes. Hum Reprod. 2003, 18: 1371-1376.PubMedGoogle Scholar
  70. 70.
    Carrell DT: The Clinical Implementation of Sperm Chromosome Aneuploidy Testing: Pitfalls and Promises. J Androl. 2007Google Scholar
  71. 71.
    Topping D, Brown P, Hassold T: The immunocytogenetics of human male meiosis: a progress report. The genetics of male infertility. Edited by: Carrell DT. 2007, New Jersey: Humana Press, 115-128.Google Scholar
  72. 72.
    Martin RH: The clinical relevance of sperm aneuploidy. The genetics of male infertility. Edited by: Carrell DT. 2007, New Jersey: Humana Press, 129-144.Google Scholar
  73. 73.
    Sanderson ML, Hassold TJ, Carrell DT: Proteins involved in meiotic recombination: a role in male infertility?. Syst Biol Reprod Med. 2008, 54: 57-74.PubMedGoogle Scholar
  74. 74.
    Gonsalves J, Sun F, Schlegel PN, Turek PJ, Hopps CV, Greene C, Martin RH, Pera RA: Defective recombination in infertile men. Hum Mol Genet. 2004, 13: 2875-2883.PubMedGoogle Scholar
  75. 75.
    Sun F, Greene C, Turek PJ, Ko E, Rademaker A, Martin RH: Immunofluorescent synaptonemal complex analysis in azoospermic men. Cytogenet Genome Res. 2005, 111: 366-370.PubMedGoogle Scholar
  76. 76.
    Ferguson KA, Wong EC, Chow V, Nigro M, Ma S: Abnormal meiotic recombination in infertile men and its association with sperm aneuploidy. Hum Mol Genet. 2007Google Scholar
  77. 77.
    Carrell DT, Emery BR: Use of automated imaging and analysis technology for the detection of aneuploidy in human sperm. Fertil Steril. 2007Google Scholar
  78. 78.
    Palermo GD, Colombero LT, Rosenwaks Z: The human sperm centrosome is responsible for normal syngamy and early embryonic development. Rev Reprod. 1997, 2: 19-27.PubMedGoogle Scholar
  79. 79.
    Manandhar G, Schatten H, Sutovsky P: Centrosome reduction during gametogenesis and its significance. Biol Reprod. 2005, 72: 2-13.PubMedGoogle Scholar
  80. 80.
    Schatten G: The centrosome and its mode of inheritance: the reduction of the centrosome during gametogenesis and its restoration during fertilization. Dev Biol. 1994, 165: 299-335.PubMedGoogle Scholar
  81. 81.
    Sathananthan AH: Paternal centrosomal dynamics in early human development and infertility. J Assist Reprod Genet. 1998, 15: 129-139.PubMedPubMedCentralGoogle Scholar
  82. 82.
    Terada Y: Functional analyses of the sperm centrosome in human reproduction: implications for assisted reproductive technique. Soc Reprod Fertil Suppl. 2007, 63: 507-513.PubMedGoogle Scholar
  83. 83.
    Rawe VY, Terada Y, Nakamura S, Chillik CF, Olmedo SB, Chemes HE: A pathology of the sperm centriole responsible for defective sperm aster formation, syngamy and cleavage. Hum Reprod. 2002, 17: 2344-2349.PubMedGoogle Scholar
  84. 84.
    Palermo G, Munne S, Cohen J: The human zygote inherits its mitotic potential from the male gamete. Hum Reprod. 1994, 9: 1220-1225.PubMedGoogle Scholar
  85. 85.
    Obasaju M, Kadam A, Sultan K, Fateh M, Munne S: Sperm quality may adversely affect the chromosome constitution of embryos that result from intracytoplasmic sperm injection. Fertil Steril. 1999, 72: 1113-1115.PubMedGoogle Scholar
  86. 86.
    Sathananthan AH, Ratnasooriya WD, de Silva PK, Menezes J: Characterization of human gamete centrosomes for assisted reproduction. Ital J Anat Embryol. 2001, 106: 61-73.PubMedGoogle Scholar
  87. 87.
    Terada Y, Nakamura S, Simerly C, Hewitson L, Murakami T, Yaegashi N, Okamura K, Schatten G: Centrosomal function assessment in human sperm using heterologous ICSI with rabbit eggs: a new male factor infertility assay. Mol Reprod Dev. 2004, 67: 360-365.PubMedGoogle Scholar
  88. 88.
    Nakamura S, Terada Y, Horiuchi T, Emuta C, Murakami T, Yaegashi N, Okamura K: Human sperm aster formation and pronuclear decondensation in bovine eggs following intracytoplasmic sperm injection using a Piezo-driven pipette: a novel assay for human sperm centrosomal function. Biol Reprod. 2001, 65: 1359-1363.PubMedGoogle Scholar
  89. 89.
    Terada Y, Nakamura S, Morita J, Tachibana M, Morito Y, Ito K, Murakami T, Yaegashi N, Okamura K: Use of Mammalian eggs for assessment of human sperm function: molecular and cellular analyses of fertilization by intracytoplasmic sperm injection. Am J Reprod Immunol. 2004, 51: 290-293.PubMedGoogle Scholar
  90. 90.
    Aoki VW, Carrell DT: Human protamines and the developing spermatid: their structure, function, expression and relationship with male infertility. Asian J Androl. 2003, 5: 315-324.PubMedGoogle Scholar
  91. 91.
    Oliva R: Protamines and male infertility. Hum Reprod Update. 2006, 12: 417-435.PubMedGoogle Scholar
  92. 92.
    Carrell DT, Liu L: Altered protamine 2 expression is uncommon in donors of known fertility, but common among men with poor fertilizing capacity, and may reflect other abnormalities of spermiogenesis. J Androl. 2001, 22: 604-610.PubMedGoogle Scholar
  93. 93.
    Aoki VW, Liu L, Carrell DT: Identification and evaluation of a novel sperm protamine abnormality in a population of infertile males. Hum Reprod. 2005, 20: 1298-1306.PubMedGoogle Scholar
  94. 94.
    Nasr-Esfahani MH, Razavi S, Mardani M, Shirazi R, Javanmardi S: Effects of failed oocyte activation and sperm protamine deficiency on fertilization post-ICSI. Reprod Biomed Online. 2007, 14: 422-429.PubMedGoogle Scholar
  95. 95.
    Aoki VW, Liu L, Jones KP, Hatasaka HH, Gibson M, Peterson CM, Carrell DT: Sperm protamine 1/protamine 2 ratios are related to in vitro fertilization pregnancy rates and predictive of fertilization ability. Fertil Steril. 2006, 86: 1408-1415.PubMedGoogle Scholar
  96. 96.
    Ooi SL, Henikoff S: Germline histone dynamics and epigenetics. Curr Opin Cell Biol. 2007, 19: 257-265.PubMedGoogle Scholar
  97. 97.
    Ito T: Role of histone modification in chromatin dynamics. J Biochem (Tokyo). 2007, 141: 609-614.Google Scholar
  98. 98.
    Martin C, Zhang Y: Mechanisms of epigenetic inheritance. Curr Opin Cell Biol. 2007, 19: 266-272.PubMedGoogle Scholar
  99. 99.
    Biermann K, Steger K: Epigenetics in male germ cells. J Androl. 2007, 28: 466-480.PubMedGoogle Scholar
  100. 100.
    Li E: Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet. 2002, 3: 662-673.PubMedGoogle Scholar
  101. 101.
    Reik W, Dean W, Walter J: Epigenetic reprogramming in mammalian development. Science. 2001, 293: 1089-1093.PubMedGoogle Scholar
  102. 102.
    Morgan HD, Santos F, Green K, Dean W, Reik W: Epigenetic reprogramming in mammals. Hum Mol Genet. 2005, 14 (Spec No 1): R47-58.PubMedGoogle Scholar
  103. 103.
    Santos F, Dean W: Epigenetic reprogramming during early development in mammals. Reproduction. 2004, 127: 643-651.PubMedGoogle Scholar
  104. 104.
    Dolinoy DC, Das R, Weidman JR, Jirtle RL: Metastable epialleles, imprinting, and the fetal origins of adult diseases. Pediatr Res. 2007, 61: 30R-37R.PubMedGoogle Scholar
  105. 105.
    Schaefer CB, Ooi SK, Bestor TH, Bourc'his D: Epigenetic decisions in mammalian germ cells. Science. 2007, 316: 398-399.PubMedGoogle Scholar
  106. 106.
    Benchaib M, Ajina M, Lornage J, Niveleau A, Durand P, Guerin JF: Quantitation by image analysis of global DNA methylation in human spermatozoa and its prognostic value in in vitro fertilization: a preliminary study. Fertil Steril. 2003, 80: 947-953.PubMedGoogle Scholar
  107. 107.
    Benchaib M, Braun V, Ressnikof D, Lornage J, Durand P, Niveleau A, Guerin JF: Influence of global sperm DNA methylation on IVF results. Hum Reprod. 2005, 20: 768-773.PubMedGoogle Scholar
  108. 108.
    Aoki VW, Emery BR, Carrell DT: Global sperm deoxyribonucleic acid methylation is unaffected in protamine-deficient infertile males. Fertil Steril. 2006, 86: 1541-1543.PubMedGoogle Scholar
  109. 109.
    Costa FF: Non-coding RNAs: new players in eukaryotic biology. Gene. 2005, 357: 83-94.PubMedGoogle Scholar
  110. 110.
    Ostermeier GC, Goodrich RJ, Moldenhauer JS, Diamond MP, Krawetz SA: A suite of novel human spermatozoal RNAs. J Androl. 2005, 26: 70-74.PubMedGoogle Scholar
  111. 111.
    Boerke A, Dieleman SJ, Gadella BM: A possible role for sperm RNA in early embryo development. Theriogenology. 2007, 68 (Suppl 1): S147-155.PubMedGoogle Scholar
  112. 112.
    Miller D, Ostermeier GC: Towards a better understanding of RNA carriage by ejaculate spermatozoa. Hum Reprod Update. 2006, 12: 757-767.PubMedGoogle Scholar
  113. 113.
    Martins RP, Krawetz SA: RNA in human sperm. Asian J Androl. 2005, 7: 115-120.PubMedGoogle Scholar
  114. 114.
    Krawetz SA: Paternal contribution: new insights and future challenges. Nat Rev Genet. 2005, 6: 633-642.PubMedGoogle Scholar
  115. 115.
    Ostermeier GC, Miller D, Huntriss JD, Diamond MP, Krawetz SA: Reproductive biology: delivering spermatozoan RNA to the oocyte. Nature. 2004, 429: 154-PubMedGoogle Scholar
  116. 116.
    Ostermeier GC, Dix DJ, Miller D, Khatri P, Krawetz SA: Spermatozoal RNA profiles of normal fertile men. Lancet. 2002, 360: 772-777.PubMedGoogle Scholar
  117. 117.
    Platts AE, Dix DJ, Chemes HE, Thompson KE, Goodrich R, Rockett JC, Rawe VY, Quintana S, Diamond MP, Strader LF, Krawetz SA: Success and failure in human spermatogenesis as revealed by teratozoospermic RNAs. Hum Mol Genet. 2007, 16: 763-773.PubMedGoogle Scholar

Copyright information

© Nanassy and Carrell; licensee BioMed Central Ltd. 2008

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Authors and Affiliations

  1. 1.Andrology and IVF LaboratoriesUniversity of Utah School of MedicineSalt Lake CityUSA

Personalised recommendations