Article(id=1210676790662664321, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1210676785113600955, articleNumber=null, orderNo=null, doi=10.11855/j.issn.0577-7402.2021.05.05, pmid=null, cstr=null, oa=null, hot=null, price=null, onlineType=0, articleFormat=0, articleType=null, articleTypeStr=research-article, receivedDate=1609171200000, receivedDateStr=2020-12-29, revisedDate=1614441600000, revisedDateStr=2021-02-28, acceptedDate=null, acceptedDateStr=null, onlineDate=1766577440181, onlineDateStr=2025-12-24, pubDate=1622131200000, pubDateStr=2021-05-28, doiRegisterDate=null, doiRegisterDateStr=null, onlineIssueDate=1766577440181, onlineIssueDateStr=2025-12-24, onlineJustAcceptDate=null, onlineJustAcceptDateStr=null, onlineFirstDate=null, onlineFirstDateStr=null, sourceXml=null, magXml=null, createTime=1766577440181, creator=13701087609, updateTime=1766577440181, updator=13701087609, issue=Issue{id=1210676785113600955, tenantId=1146029695717560320, journalId=1189873630562394117, year='2021', volume='46', issue='5', pageStart='425', pageEnd='530', issueExtLink='null', onlineDate='null', pubDate='null', beforeIssueId=null, nextIssueId=null, price=null, status=1, issueComplete=1, articleOrder=1, issueType=-1, specialIssue=0, createTime=1766577438858, creator=13701087609, updateTime=1766718730270, updator=13701087609, preIssue=null, nextIssue=null, ext={EN=IssueExt(id=1211269404306838321, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1210676785113600955, language=EN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=), CN=IssueExt(id=1211269404306838322, tenantId=1146029695717560320, journalId=1189873630562394117, issueId=1210676785113600955, language=CN, specialIssueTitle=, coverIllustrator=null, specialIssueEditor=, specialIssueAbout=)}, issueFiles=null}, startPage=456, endPage=461, ext={EN=ArticleExt(id=1210676791019180183, articleId=1210676790662664321, tenantId=1146029695717560320, journalId=1189873630562394117, language=EN, title=Effect of advanced pregnancy on DNA methylation level of hippocampus of the offspring rats, columnId=1190310110212751762, journalTitle=Medical Journal of Chinese People’s Liberation Army, columnName=Basic Research, runingTitle=null, highlight=null, articleAbstract=

Objective To investigate the effects of advanced pregnancy on DNA methylation level of hippocampus in the offspring rats. Methods 12- and 3-month-old female SD rats were mated with 3-month-old male SD rats. The offspring(s)from older mother were marked as AMA group, and those from younger mother were marked as control group. The brain and hippocampus samples of the offsprings were taken at the 7th, 14th and 28th day after birth. The mRNA levels of DNA methyltransferase (Dnmt)1, Dnmt3A and Dnmt3B were detected by real-time fluorescent quantitative PCR (RT-PCR). The protein expression levels of Dnmt1, Dnmt3A and Dnmt3B were measured by Western blotting. Immunofluorescence and ELISA were used to detect the localization and expression level of 5-methylcytosine (5-mC) in hippocampus. Results RT-PCR showed the Dnmt1 mRNA level was markedly lower in hippocampus of AMA group than that in control group on day 28 after birth (P<0.05); Western blotting analysis showed the expression level of Dnmt3A protein was obviously higher in hippocampus of the AMA group than that in control group on day 7 after birth (P<0.05), while the expression levels of Dnmt1 and Dnmt3A were lower in AMA group than those in control group on day 28 after birth (P<0.05). Immunofluorescence test showed that the 5-mC level in hippocampus was significantly higher in AMA group than that in control group on day 7 and 14 after birth (P<0.05). ELISA showed that the 5-mC level in hippocampus increased slightly but without statistical significance in AMA group than that in control group on day 7, 14 and 28 after birth (P>0.05). Conclusion Advanced pregnancy may lead to the expression disorder of Dnmts and the increased DNA methylation level in offspring's hippocampus, which may be one of the potential mechanisms of offspring's brain dysfunction.

, correspAuthors=Li Jiang, authorNote=null, correspAuthorsNote=, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=null, magXml=null, pdfUrl=null, pdf=null, pdfFileSize=null, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=null, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=null, mapNumber=null, authorCompany=null, fund=null, authors=null, authorsList=Ya-Nan Pan, Wei Han, Jing Yang, Li Cheng, Li Jiang), CN=ArticleExt(id=1210676791916761284, articleId=1210676790662664321, tenantId=1146029695717560320, journalId=1189873630562394117, language=CN, title=高龄妊娠对子代大鼠海马甲基化水平的影响, columnId=1190310110472798614, journalTitle=解放军医学杂志, columnName=基础研究, runingTitle=null, highlight=null, articleAbstract=

目的 探讨高龄妊娠对子代大鼠海马甲基化水平的影响。方法 将12月龄及3月龄SD雌性大鼠分别与3月龄SD雄性大鼠合笼，将其子代分为高龄子代组(AMA组)和适龄子代组(对照组)，留取子代生后第7、14、28天的大脑及海马标本。实时荧光定量PCR检测两组子代海马DNA甲基转移酶(Dnmt)1、Dnmt3A、Dnmt3B mRNA表达水平，Western blotting检测两组子代海马Dnmt1、Dnmt3A、Dnmt3B蛋白表达水平，免疫荧光及ELISA法检测两组子代海马5-甲基胞嘧啶(5-mC)的定位及表达水平。结果 实时荧光定量PCR检测结果显示，AMA组生后第28天海马Dnmt1 mRNA表达水平明显低于对照组(P<0.05)。Western blotting检测结果显示，AMA组生后第7天海马Dnmt3A蛋白表达水平明显高于对照组(P<0.05)，第28天海马Dnmt1、Dnmt3A蛋白表达水平明显低于对照组(P<0.05)。免疫荧光检测结果显示，5-mC表达于海马DG、CA1、CA3区的细胞核内，AMA组生后第7、14天海马5-mC表达水平明显高于对照组(P<0.05)。ELISA检测结果显示，AMA组生后第7、14、28天海马5-mC表达水平较对照组升高，但差异无统计学意义(P>0.05)。结论 高龄妊娠可导致子代海马Dnmts表达紊乱，海马整体甲基化水平升高，可能是高龄妊娠子代脑功能障碍的潜在机制之一。

, correspAuthors=蒋莉, authorNote=null, correspAuthorsNote=, copyrightStatement=null, copyrightOwner=null, extLink=null, articleAbsUrl=null, sourceXml=IpUI4N7wFHRslY4R8R3d3Q==, magXml=aV4ZaHhb+k7qxV0/FGadAQ==, pdfUrl=null, pdf=RCQk6x1Y1yQRsi7y5tvqOQ==, pdfFileSize=3168944, pdfExtLink=null, richHtmlUrl=null, mobilePdfUrl=null, reviewReport=null, pdfFirstPage=null, abstractGraph=8qlaSeWQThQ+q3L76dragQ==, abstractGraphContent=null, abstractVideo=null, citation=null, cebUrl=null, magXmlContent=L9LXHZuTAP6HllpG406wtg==, mapNumber=null, authorCompany=null, fund=null, authors=, authorsList=潘亚男, 韩慰, 杨静, 程莉, 蒋莉)}, authors=[Author(id=1210676792470409447, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, orderNo=0, firstName=null, middleName=null, lastName=null, nameCn=null, orcid=null, stid=null, country=null, authorPic=null, dead=0, email=null, emailSecond=null, emailThird=null, correspondingAuthor=0, authorType=1, ext={EN=AuthorExt(id=1210676792583655662, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, authorId=1210676792470409447, language=EN, stringName=Ya-Nan Pan, firstName=Ya-Nan, middleName=null, lastName=Pan, prefix=null, suffix=null, authorComment=null, nameInitials=null, affiliation=null, department=null, xref=^{1, 2}, address=¹Department of Neurology, Children's Hospital of Chongqing Medical University/National Clinical Research Center for Children's Health and Disease/Ministry of Education Key Laboratory of Developmental Diseases in Children, Chongqing 400014, China
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潘亚男，硕士研究生，主要从事高龄妊娠子代发育认知方面的研究

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潘亚男，硕士研究生，主要从事高龄妊娠子代发育认知方面的研究

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A、B、C. 生后第7、14、28天；与对照组比较，(1)P<0.05。

, figureFileSmall=zxU9RQetiIOrOwBcrFgdRQ==, figureFileBig=8qlaSeWQThQ+q3L76dragQ==, tableContent=null), ArticleFig(id=1210676795196707182, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, language=EN, label=Fig.2, caption=Advanced pregnancy affects the expressions of Dnmt1, Dnmt3A and Dnmt3B mRNA in hippocampus of offspring rats, figureFileSmall=JvPqZL0xCc1yFgoERMbgtw==, figureFileBig=alV4xkfjF/Iy5J/fPOAgZg==, tableContent=null), ArticleFig(id=1210676795326730610, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, language=CN, label=图2, caption=高龄妊娠对子代大鼠海马Dnmt1、Dnmt3A、Dnmt3B mRNA表达的影响

A、B、C. 分别表示Dnmt1、Dnmt3A、Dnmt3B mRNA；与对照组比较，(1)P<0.05。

, figureFileSmall=JvPqZL0xCc1yFgoERMbgtw==, figureFileBig=alV4xkfjF/Iy5J/fPOAgZg==, tableContent=null), ArticleFig(id=1210676795402228084, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, language=EN, label=Fig.3, caption=Advanced pregnancy affects the expression of 5-mC in hippocampus of offspring rats, figureFileSmall=9+aBL3lehMTtD9VIp+FCaA==, figureFileBig=1Kt+i+Av+W0U3stcDPeliQ==, tableContent=null), ArticleFig(id=1210676795494502774, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, language=CN, label=图3, caption=高龄妊娠对子代大鼠海马5-mC表达的影响

A、B、C. 免疫荧光检测生后第7、14、28天两组子代大鼠海马5-mC的表达

, figureFileSmall=9+aBL3lehMTtD9VIp+FCaA==, figureFileBig=1Kt+i+Av+W0U3stcDPeliQ==, tableContent=null), ArticleFig(id=1210676795582583161, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, language=EN, label=Tab.1, caption=

Primer sequence

, figureFileSmall=null, figureFileBig=null, tableContent=

基因	序列
Dnmt1	F：5'-CGACGACGCTAAGGACGATGATG-3'
	R：5'-GCCTTGTTGCTCGCCTCTGTC-3'
Dnmt3A	F：5'-TGCCAGTCATCCGCCACCTC-3'
	R：5'-TCTCCGTCCTCTCGTTCTTGGTG-3'
Dnmt3B	F：5'-GAGATGGAGATGGTGAAGCGGATG-3'
	R：5'-ACTGTTGCTGTTTCGGGTTCGG-3'
β-actin	F：5'-CCCATCTATGAGGGTTACGC-3'
	R：5'-TTTAATGTCACGCACGATTTC-3'

), ArticleFig(id=1210676795662274941, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, language=CN, label=表1, caption=

引物序列

, figureFileSmall=null, figureFileBig=null, tableContent=

基因	序列
Dnmt1	F：5'-CGACGACGCTAAGGACGATGATG-3'
	R：5'-GCCTTGTTGCTCGCCTCTGTC-3'
Dnmt3A	F：5'-TGCCAGTCATCCGCCACCTC-3'
	R：5'-TCTCCGTCCTCTCGTTCTTGGTG-3'
Dnmt3B	F：5'-GAGATGGAGATGGTGAAGCGGATG-3'
	R：5'-ACTGTTGCTGTTTCGGGTTCGG-3'
β-actin	F：5'-CCCATCTATGAGGGTTACGC-3'
	R：5'-TTTAATGTCACGCACGATTTC-3'

), ArticleFig(id=1210676795733578111, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, language=EN, label=Tab.2, caption=

Comparison of the 5-mC expression levels in hippocampus of offspring rats (%,$\bar{x}±s$, n=5)

, figureFileSmall=null, figureFileBig=null, tableContent=

组别	第7天	第14天	第28天
对照组	1.34±0.32	1.34±0.13	1.42±0.24
AMA组	1.57±0.19	1.45±0.21	1.81±0.33
t	1.3580	0.9847	2.1570
P	0.2115	0.3536	0.0631

), ArticleFig(id=1210676795809075585, tenantId=1146029695717560320, journalId=1189873630562394117, articleId=1210676790662664321, language=CN, label=表2, caption=

两组子代大鼠海马5-mC表达水平比较(%,$\bar{x}±s$, n=5)

, figureFileSmall=null, figureFileBig=null, tableContent=

组别	第7天	第14天	第28天
对照组	1.34±0.32	1.34±0.13	1.42±0.24
AMA组	1.57±0.19	1.45±0.21	1.81±0.33
t	1.3580	0.9847	2.1570
P	0.2115	0.3536	0.0631

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