| Title | The combination of DNA methylome and transcriptome revealed the intergenerational inheritance on the influence of advanced maternal age |
| Authors | Hua, Lingyue Chen, Wei Meng, Yan Qin, Meng Yan, Zhiqiang Yang, Rui Liu, Qiang Wei, Yuan Zhao, Yangyu Yan, Liying Qiao, Jie |
| Affiliation | Peking Univ Third Hosp, Ctr Reprod Med, Dept Obstet & Gynecol, Beijing 100191, Peoples R China Peking Univ Third Hosp, Natl Clin Res Ctr Obstet & Gynecol, Beijing, Peoples R China Peking Univ, Key Lab Assisted Reprod, Minist Educ, Beijing, Peoples R China Beijing Key Lab Reprod Endocrinol & Assisted Repr, Beijing, Peoples R China Peking Univ, Dept Obstet & Gynecol, Beijing Jishuitan Hosp, Clin Coll 4, Beijing, Peoples R China Peking Univ Third Hosp, Dept Obstet & Gynecol, Beijing, Peoples R China Natl Ctr Healthcare Qual Management Obstet, Beijing, Peoples R China Beijing Adv Innovat Ctr Genom, Beijing, Peoples R China Peking Univ, Peking Tsinghua Ctr Life Sci, Beijing, Peoples R China Chinese Acad Med Sci, Res Units Comprehens Diag & Treatment Oocyte Matu, Beijing, Peoples R China |
| Keywords | EXPRESSION PROFILES GENE-EXPRESSION HUMAN OOCYTES PARENTAL AGE METHYLATION PREGNANCY MICE BLASTOCYSTS LANDSCAPES EXPOSURE |
| Issue Date | Sep-2022 |
| Publisher | CLINICAL AND TRANSLATIONAL MEDICINE |
| Abstract | Background The number of women delivering at advanced maternal age (AMA; > = 35) continuously increases in developed and high-income countries. Large cohort studies have associated AMA with increased risks of various pregnancy complications and adverse pregnancy outcomes, which raises great concerns about the adverse effect of AMA on the long-term health of offspring. Specific acquired characteristics of parents can be passed on to descendants through certain molecular mechanisms, yet the underlying connection between AMA-related alterations in parents and that in offspring remains largely uncharted. Methods We profiled the DNA methylomes of paired parental peripheral bloods and cord bloods from 20 nuclear families, including 10 AMA and 10 Young, and additional transcriptomes of 10 paired maternal peripheral bloods and cord bloods. Results We revealed that AMA induced aging-like changes in DNA methylome and gene expression in both parents and offspring. The expression changes in several genes, such as SLC28A3, were highly relevant to the disorder in DNA methylation. In addition, AMA-related differentially methylated regions (DMRs) identified in mother and offspring groups showed remarkable similarities in both genomic locations and biological functions, mainly involving neuron differentiation, metabolism, and histone modification pathways. AMA-related differentially expressed genes (DEGs) shared by mother and offspring groups were highly enriched in the processes of immune cell activation and mitotic nuclear division. We further uncovered developmental-dependent dynamics for the DNA methylation of intergenerationally correlated DMRs during pre-implantation embryonic development, as well as diverse gene expression patterns during gametogenesis and early embryonic development for those common AMA-related DEGs presenting intergenerational correlation, such as CD24. Moreover, some intergenerational DEGs, typified by HTRA3, also showed the same significant alterations in AMA MII oocyte or blastocyst. Conclusions Our results reveal potential intergenerational inheritance of both AMA-related DNA methylome and transcriptome and provide new insights to understand health problems in AMA offspring. |
| URI | http://hdl.handle.net/20.500.11897/654552 |
| ISSN | 2001-1326 |
| DOI | 10.1002/ctm2.990 |
| Indexed | SCI(E) |
| Appears in Collections: | 第三医院 北京积水潭医院 生命科学学院 |
