Widespread Epigenetic Abnormalities Suggest a Broad DNA Methylation Erasure Defect in Abnormal Human Sperm

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2007 Dec 13

PMID 18074014

Citations 96

Authors

Sahar Houshdaran

Victoria K Cortessis

Kimberly Siegmund

Allen Yang

Peter W Laird

Rebecca Z Sokol

Affiliations

Soon will be listed here.

Abstract

Background: Male-factor infertility is a common condition, and etiology is unknown for a high proportion of cases. Abnormal epigenetic programming of the germline is proposed as a possible mechanism compromising spermatogenesis of some men currently diagnosed with idiopathic infertility. During germ cell maturation and gametogenesis, cells of the germ line undergo extensive epigenetic reprogramming. This process involves widespread erasure of somatic-like patterns of DNA methylation followed by establishment of sex-specific patterns by de novo DNA methylation. Incomplete reprogramming of the male germ line could, in theory, result in both altered sperm DNA methylation and compromised spermatogenesis.

Methodology/principal Finding: We determined concentration, motility and morphology of sperm in semen samples collected by male members of couples attending an infertility clinic. Using MethyLight and Illumina assays we measured methylation of DNA isolated from purified sperm from the same samples. Methylation at numerous sequences was elevated in DNA from poor quality sperm.

Conclusions: This is the first report of a broad epigenetic defect associated with abnormal semen parameters. Our results suggest that the underlying mechanism for these epigenetic changes may be improper erasure of DNA methylation during epigenetic reprogramming of the male germ line.

Citing Articles

Sperm epigenetics and male infertility: unraveling the molecular puzzle.

Hosseini M, Khalafiyan A, Zare M, Karimzadeh H, Bahrami B, Hammami B Hum Genomics. 2024; 18(1):57.

PMID: 38835100 PMC: 11149391. DOI: 10.1186/s40246-024-00626-4.

Genome and Epigenome Disorders and Male Infertility: Feedback from 15 Years of Clinical and Research Experience.

Montjean D, Beaumont M, Natiq A, Louanjli N, Hazout A, Miron P Genes (Basel). 2024; 15(3).

PMID: 38540436 PMC: 10970370. DOI: 10.3390/genes15030377.

Methylation Status of cAMP-responsive Element Modulator (CREM) Gene in Infertile Men and Its Association with Sperm Parameters.

Hezarcheshmeh F, Yaghmaei P, Roodbari N, Yari K Reprod Sci. 2024; 31(7):2001-2008.

PMID: 38499948 DOI: 10.1007/s43032-024-01510-1.

Genomic aspects in reproductive medicine.

Go M, Shim S Clin Exp Reprod Med. 2024; 51(2):91-101.

PMID: 38263590 PMC: 11140259. DOI: 10.5653/cerm.2023.06303.

Etiology of Male Infertility: an Update.

Bhattacharya I, Sharma S, Majumdar S Reprod Sci. 2023; 31(4):942-965.

PMID: 38036863 DOI: 10.1007/s43032-023-01401-x.

References

Sullivan M, Taniguchi T, Jhee A, Kerr N, Reeve A . Relaxation of IGF2 imprinting in Wilms tumours associated with specific changes in IGF2 methylation. Oncogene. 1999; 18(52):7527-34. DOI: 10.1038/sj.onc.1203096. View

Szabo P, Hubner K, Scholer H, Mann J . Allele-specific expression of imprinted genes in mouse migratory primordial germ cells. Mech Dev. 2002; 115(1-2):157-60. DOI: 10.1016/s0925-4773(02)00087-4. View

Chang H, Anway M, Rekow S, Skinner M . Transgenerational epigenetic imprinting of the male germline by endocrine disruptor exposure during gonadal sex determination. Endocrinology. 2006; 147(12):5524-41. DOI: 10.1210/en.2006-0987. View

Runte M, Huttenhofer A, Gross S, Kiefmann M, Horsthemke B, Buiting K . The IC-SNURF-SNRPN transcript serves as a host for multiple small nucleolar RNA species and as an antisense RNA for UBE3A. Hum Mol Genet. 2001; 10(23):2687-700. DOI: 10.1093/hmg/10.23.2687. View

de la Puente A, Hall J, Wu Y, Leone G, Peters J, Yoon B . Structural characterization of Rasgrf1 and a novel linked imprinted locus. Gene. 2002; 291(1-2):287-97. DOI: 10.1016/s0378-1119(02)00601-7. View

Bibikova M, Lin Z, Zhou L, Chudin E, Garcia E, Wu B . High-throughput DNA methylation profiling using universal bead arrays. Genome Res. 2006; 16(3):383-93. PMC: 1415217. DOI: 10.1101/gr.4410706. View

Kerjean A, Dupont J, Vasseur C, Le Tessier D, Cuisset L, Paldi A . Establishment of the paternal methylation imprint of the human H19 and MEST/PEG1 genes during spermatogenesis. Hum Mol Genet. 2000; 9(14):2183-7. DOI: 10.1093/hmg/9.14.2183. View

Murphy S, Wylie A, Jirtle R . Imprinting of PEG3, the human homologue of a mouse gene involved in nurturing behavior. Genomics. 2001; 71(1):110-7. DOI: 10.1006/geno.2000.6419. View

Kearns M, Preis J, McDonald M, Morris C, Whitelaw E . Complex patterns of inheritance of an imprinted murine transgene suggest incomplete germline erasure. Nucleic Acids Res. 2000; 28(17):3301-9. PMC: 110704. DOI: 10.1093/nar/28.17.3301. View

10.

Abma J, Chandra A, Mosher W, Peterson L, Piccinino L . Fertility, family planning, and women's health: new data from the 1995 National Survey of Family Growth. Vital Health Stat 23. 1997; (19):1-114. View

11.

Schaefer C, Ooi S, Bestor T, Bourchis D . Epigenetic decisions in mammalian germ cells. Science. 2007; 316(5823):398-9. DOI: 10.1126/science.1137544. View

12.

Thonneau P, Marchand S, Tallec A, Ferial M, Ducot B, Lansac J . Incidence and main causes of infertility in a resident population (1,850,000) of three French regions (1988-1989). Hum Reprod. 1991; 6(6):811-6. DOI: 10.1093/oxfordjournals.humrep.a137433. View

13.

Guzick D, Overstreet J, Factor-Litvak P, Brazil C, Nakajima S, Coutifaris C . Sperm morphology, motility, and concentration in fertile and infertile men. N Engl J Med. 2002; 345(19):1388-93. DOI: 10.1056/NEJMoa003005. View

14.

Ariel M, Cedar H, McCarrey J . Developmental changes in methylation of spermatogenesis-specific genes include reprogramming in the epididymis. Nat Genet. 1994; 7(1):59-63. DOI: 10.1038/ng0594-59. View

15.

Trasler J . Origin and roles of genomic methylation patterns in male germ cells. Semin Cell Dev Biol. 1998; 9(4):467-74. DOI: 10.1006/scdb.1998.0225. View

16.

Cui H, Onyango P, Brandenburg S, Wu Y, Hsieh C, Feinberg A . Loss of imprinting in colorectal cancer linked to hypomethylation of H19 and IGF2. Cancer Res. 2002; 62(22):6442-6. View

17.

Li E . Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet. 2002; 3(9):662-73. DOI: 10.1038/nrg887. View

18.

Lane N, Dean W, Erhardt S, Hajkova P, Surani A, Walter J . Resistance of IAPs to methylation reprogramming may provide a mechanism for epigenetic inheritance in the mouse. Genesis. 2003; 35(2):88-93. DOI: 10.1002/gene.10168. View

19.

Yamazaki Y, Mann M, Lee S, Marh J, McCarrey J, Yanagimachi R . Reprogramming of primordial germ cells begins before migration into the genital ridge, making these cells inadequate donors for reproductive cloning. Proc Natl Acad Sci U S A. 2003; 100(21):12207-12. PMC: 218737. DOI: 10.1073/pnas.2035119100. View

20.

Yun J, Park C, Lee Y, Chung J . Allele-specific methylation at the promoter-associated CpG island of mouse Copg2. Mamm Genome. 2003; 14(6):376-82. DOI: 10.1007/s00335-002-2252-x. View