{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T15:25:23Z","timestamp":1787066723336,"version":"build-2736575974"},"reference-count":60,"publisher":"MDPI AG","issue":"16","license":[{"start":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T00:00:00Z","timestamp":1628467200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Epigenetics play a vital role in early embryo development. Offspring conceived via assisted reproductive technologies (ARTs) have a three times higher risk of epigenetic diseases than naturally conceived children. However, investigations into ART-associated placental histone modifications or sex-stratified analyses of ART-associated histone modifications remain limited. In the current study, we carried out immunohistochemistry, chip-sequence analysis, and a series of in vitro experiments. Our results demonstrated that placentas from intra-cytoplasmic sperm injection (ICSI), but not in vitro fertilization (IVF), showed global tri-methylated-histone-H3-lysine-4 (H3K4me3) alteration compared to those from natural conception. However, for acetylated-histone-H3-lysine-9 (H3K9ac) and acetylated-histone-H3-lysine-27 (H3K27ac), no significant differences between groups could be found. Further, sex -stratified analysis found that, compared with the same-gender newborn cord blood mononuclear cell (CBMC) from natural conceptions, CBMC from ICSI-boys presented more genes with differentially enriched H3K4me3 (n = 198) than those from ICSI-girls (n = 79), IVF-girls (n = 5), and IVF-boys (n = 2). We also found that varying oxygen conditions, RNA polymerase II subunit A (Polr2A), and lysine demethylase 5A (KDM5A) regulated H3K4me3. These findings revealed a difference between IVF and ICSI and a difference between boys and girls in H3K4me3 modification, providing greater insight into ART-associated epigenetic alteration.<\/jats:p>","DOI":"10.3390\/ijms22168574","type":"journal-article","created":{"date-parts":[[2021,8,9]],"date-time":"2021-08-09T21:41:46Z","timestamp":1628545306000},"page":"8574","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Comparison of Histone H3K4me3 between IVF and ICSI Technologies and between Boy and Girl Offspring"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8165-621X","authenticated-orcid":false,"given":"Huixia","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0182-7854","authenticated-orcid":false,"given":"Zhi","family":"Ma","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Kuhn","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337 Munich, Germany"},{"name":"Department of Obstetrics and Gynecology, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Rahmeh","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Mahner","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2623-3235","authenticated-orcid":false,"given":"Udo","family":"Jeschke","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337 Munich, Germany"},{"name":"Department of Obstetrics and Gynecology, University Hospital Augsburg, 86156 Augsburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viktoria","family":"von Sch\u00f6nfeldt","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, University Hospital, LMU Munich, 80337 Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,8,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1975","DOI":"10.1016\/S0140-6736(03)13592-1","article-title":"Rare congenital disorders, imprinted genes, and assisted reproductive technology","volume":"361","author":"Gosden","year":"2003","journal-title":"Lancet"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12885-019-6455-x","article-title":"An analysis about heterogeneity among cancers based on the DNA methylation patterns","volume":"19","author":"Liu","year":"2019","journal-title":"BMC Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"5052","DOI":"10.1172\/JCI68943","article-title":"Mice generated by in vitro fertilization exhibit vascular dysfunction and shortened life span","volume":"123","author":"Rexhaj","year":"2013","journal-title":"J. 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