Journal
FERTILITY AND STERILITY
Volume 94, Issue 5, Pages 1728-1733Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.fertnstert.2009.09.010
Keywords
Imprinting; Beckwith-Wiedemann syndrome and epigenetic alterations; Angelman syndrome; chromatin; assisted reproductive technology; IVF; ICSI; oligozoospermic; protamines
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Objective: To evaluate the associations between proper protamine incorporation and DNA methylation at imprinted loci. Design: Experimental research study. Setting: Research laboratory. Patient(s): Three populations were tested-abnormal protamine patients, oligozoospermic patients, and fertile donors. Intervention(s): The CpG methylation patterns were examined at seven imprinted loci sequenced: LIT1, MEST, SNRPN, PLAGL1, PEG3, H19, and IGF2. Main Outcome Measure(s): The DNA methylation patterns were analyzed using bisulfite sequencing. The percentage of methylation was compared between fertile and infertile patients displaying abnormal protamination. Result(s): At six of the seven imprinted genes, the overall DNA methylation patterns at their respective differentially methylated regions were significantly altered in both infertile patient populations. When comparing the severity of methylation alterations among infertile patients, the oligozoospermic patients were significantly affected at mesoderm-specific transcript (MEST), whereas abnormal protamine patients were affected at KCNQ1, overlapping transcript 1 (LIT1), and at small nuclear ribonucleoprotein polypeptide N (SNRPN). Conclusion(s): Patients with male factor infertility had significantly increased methylation alteration at six of seven imprinted loci tested, with differences in significance observed between oligozoospermic and abnormal protamine patients. This could suggest that risk of transmission of epigenetic alterations may be different with diagnoses. However, this study does not provide a causal link for epigenetic inheritance of imprinting diseases, but does show significant association between male factor infertility and alterations in sperm DNA methylation at imprinted loci. (Fertil Steril (R) 2010;94:1728-33. (C)2010 by American Society for Reproductive Medicine.)
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