DNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility

Children conceived through intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of many abnormalities and disorders, including autism and intellectual disability, which may be due to bypassing of the natural sperm selection process during ICSI. Zona pellucida (ZP)-bound s...

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Autores principales:	Longda Wang, Mengxiang Chen, Gaofeng Yan, Shuhua Zhao
Formato:	article
Lenguaje:	EN
Publicado:	Frontiers Media S.A. 2021
Materias:	sperm DNA methylation autism zona pellucida binding assay ICSI Diseases of the endocrine glands. Clinical endocrinology RC648-665
Acceso en línea:	https://doaj.org/article/7d306d70609f40d18cc8e0472566d9d5
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spelling	oai:doaj.org-article:7d306d70609f40d18cc8e0472566d9d52021-11-09T06:17:20ZDNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility1664-239210.3389/fendo.2021.774260https://doaj.org/article/7d306d70609f40d18cc8e0472566d9d52021-11-01T00:00:00Zhttps://www.frontiersin.org/articles/10.3389/fendo.2021.774260/fullhttps://doaj.org/toc/1664-2392Children conceived through intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of many abnormalities and disorders, including autism and intellectual disability, which may be due to bypassing of the natural sperm selection process during ICSI. Zona pellucida (ZP)-bound spermatozoa (ZPBS) have normal morphology and nuclear DNA. Using these spermatozoa for ICSI results in better outcomes compared with conventional ICSI. However, differences besides morphology that exist between sperm selected by ZP and by an embryologist and whether these differences affect the risk of autism in offspring after ICSI are unclear. To explore these questions, we compared genome-wide DNA methylation profiles between ZPBS and manually selected spermatozoa (MSS)using single-cell bisulfite sequencing. Global DNA methylation levels were significantly lower in ZPBS than in MSS. Using gene ontology (GO) analysis, genes overlapping differentially methylated regions (DMRs) were enriched in biological processes involving neurogenesis. Furthermore, we found that 47.8% of autism candidate genes were associated with DMRs, compared with 37.1% of matched background genes (P<0.001). This was mainly because of the high proportion of autism candidate genes with bivalent chromatin structure. In conclusion, bivalent chromatin structure results in large differences in the methylation of autism genes between MSS and ZPBS. ICSI using MSS, which increases the risk of methylation mutations compared with ZPBS, may lead to a higher risk of autism in offspring.Longda WangMengxiang ChenGaofeng YanShuhua ZhaoFrontiers Media S.A.articlespermDNA methylationautismzona pellucida binding assayICSIDiseases of the endocrine glands. Clinical endocrinologyRC648-665ENFrontiers in Endocrinology, Vol 12 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	sperm DNA methylation autism zona pellucida binding assay ICSI Diseases of the endocrine glands. Clinical endocrinology RC648-665
spellingShingle	sperm DNA methylation autism zona pellucida binding assay ICSI Diseases of the endocrine glands. Clinical endocrinology RC648-665 Longda Wang Mengxiang Chen Gaofeng Yan Shuhua Zhao DNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility
description	Children conceived through intracytoplasmic sperm injection (ICSI) have been reported to have a higher risk of many abnormalities and disorders, including autism and intellectual disability, which may be due to bypassing of the natural sperm selection process during ICSI. Zona pellucida (ZP)-bound spermatozoa (ZPBS) have normal morphology and nuclear DNA. Using these spermatozoa for ICSI results in better outcomes compared with conventional ICSI. However, differences besides morphology that exist between sperm selected by ZP and by an embryologist and whether these differences affect the risk of autism in offspring after ICSI are unclear. To explore these questions, we compared genome-wide DNA methylation profiles between ZPBS and manually selected spermatozoa (MSS)using single-cell bisulfite sequencing. Global DNA methylation levels were significantly lower in ZPBS than in MSS. Using gene ontology (GO) analysis, genes overlapping differentially methylated regions (DMRs) were enriched in biological processes involving neurogenesis. Furthermore, we found that 47.8% of autism candidate genes were associated with DMRs, compared with 37.1% of matched background genes (P<0.001). This was mainly because of the high proportion of autism candidate genes with bivalent chromatin structure. In conclusion, bivalent chromatin structure results in large differences in the methylation of autism genes between MSS and ZPBS. ICSI using MSS, which increases the risk of methylation mutations compared with ZPBS, may lead to a higher risk of autism in offspring.
format	article
author	Longda Wang Mengxiang Chen Gaofeng Yan Shuhua Zhao
author_facet	Longda Wang Mengxiang Chen Gaofeng Yan Shuhua Zhao
author_sort	Longda Wang
title	DNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility
title_short	DNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility
title_full	DNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility
title_fullStr	DNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility
title_full_unstemmed	DNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility
title_sort	dna methylation differences between zona pellucida-bound and manually selected spermatozoa are associated with autism susceptibility
publisher	Frontiers Media S.A.
publishDate	2021
url	https://doaj.org/article/7d306d70609f40d18cc8e0472566d9d5
work_keys_str_mv	AT longdawang dnamethylationdifferencesbetweenzonapellucidaboundandmanuallyselectedspermatozoaareassociatedwithautismsusceptibility AT mengxiangchen dnamethylationdifferencesbetweenzonapellucidaboundandmanuallyselectedspermatozoaareassociatedwithautismsusceptibility AT gaofengyan dnamethylationdifferencesbetweenzonapellucidaboundandmanuallyselectedspermatozoaareassociatedwithautismsusceptibility AT shuhuazhao dnamethylationdifferencesbetweenzonapellucidaboundandmanuallyselectedspermatozoaareassociatedwithautismsusceptibility
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DNA Methylation Differences Between Zona Pellucida-Bound and Manually Selected Spermatozoa Are Associated With Autism Susceptibility

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