title: Epigenetic Alterations in Density Selected Human Spermatozoa for Assisted Reproduction.
abstract: Epidemiological evidence indicates that assisted reproductive technologies (ART) may be associated with several epigenetic diseases such as Beckwith-Wiedemann syndrome (BWS) or Silver-Russell syndrome (SRS). Selection of sperm by density-gradients in ART has improved DNA integrity and sperm quality; however, epigenetic alterations associated with this approach are largely unknown. In the present study, we investigated DNA methylation and histone retention profiles in raw sperm and selected sperm derived from the same individual and separated by using density-gradients. Results from a study group consisting of 93 males demonstrated that both global DNA methylation and histone retention levels decreased in density selected sperm. Compared to unselected raw sperm, histone transition rates decreased by an average of 27.2% in selected sperm, and the global methylation rate was 3.8% in unselected sperm and 3.3% in the selected sperm. DNA methylation and histone retention location profiling analyses suggested that these alterations displayed specific location patterns in the human genome. Changes in the pattern of hypomethylation largely occurred in transcriptional factor gene families such as HOX, FOX, and GATA. Histone retention increased in 67 genes, whereas it was significantly clustered in neural development-related gene families, particularly the olfactory sensor gene family. Although a causative relationship could not be established, the results of the present study suggest the possibility that sperm with good density also possess unique epigenetic profiles, particularly for genes involved in neural and olfactory development. As increasing evidence demonstrates that epigenetics plays a key role in embryonic development and offspring growth characteristics, the specific epigenetic alterations we observed in selected sperm may influence the transcriptional process and neural development in embryos.
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Bolan
authors.initials: B
authors.lastname: Yu
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Hua
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Min
authors.initials: M
authors.lastname: Liu
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Ting
authors.initials: T
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.|Key Laboratory for Major Obstetric Diseases of Guangdong Province, Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510150, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education in China, Guangzhou 510080, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education in China, Guangzhou 510080, China.
authors.forename: Xiaoxie
authors.initials: X
authors.lastname: Xu
authors.affiliation: Institute of Human Virology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Department of Biochemistry, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.|Key Laboratory of Tropical Diseases Control (Sun Yat-sen University), Ministry of Education in China, Guangzhou 510080, China.
authors.forename: Zhaofeng
authors.initials: Z
authors.lastname: Huang
mesh_terms: D000328:Adult; D053627:Asthenozoospermia / Q000235:genetics / Q000473:pathology / Q000628:therapy; D001506:Beckwith-Wiedemann Syndrome / Q000209:etiology / Q000235:genetics; D016022:Case-Control Studies; D002469:Cell Separation; D002499:Centrifugation, Density Gradient; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D018392:Genomic Imprinting; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D005810:Multigene Family; D027724:Reproductive Techniques, Assisted / Q000009:adverse effects*; D056730:Silver-Russell Syndrome / Q000209:etiology / Q000235:genetics; D013094:Spermatozoa / Q000166:cytology* / Q000378:metabolism*
chemical_list: D006657:Histones