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Effects of assisted reproduction technology on placental imprinted gene expression.

ABSTRACT: We used placental tissue to compare the imprinted gene expression of IGF2, H19, KCNQ1OT1, and CDKN1C of singletons conceived via assisted reproduction technology (ART) with that of spontaneously conceived (SC) singletons. Of 989 singletons examined (ART n = 65; SC n = 924), neonatal weight was significantly lower (P < .001) in the ART group than in the SC group, but placental weight showed no significant difference. Gene expression analyzed by real-time PCR was similar for both groups with appropriate-for-date (AFD) birth weight. H19 expression was suppressed in fetal growth retardation (FGR) cases in the ART and SC groups compared with AFD cases (P < .02 and P < .05, resp.). In contrast, CDKN1C expression was suppressed in FGR cases in the ART group (P < .01), while KCNQ1OT1 expression was hyperexpressed in FGR cases in the SC group (P < .05). As imprinted gene expression patterns differed between the ART and SC groups, we speculate that ART modifies epigenetic status even though the possibilities always exist.

SUBMITTER: Katagiri Y

PROVIDER: S-EPMC2913850 | biostudies-literature | 2010

REPOSITORIES: biostudies-literature

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Effects of assisted reproduction technology on placental imprinted gene expression.

Katagiri Yukiko Y Aoki Chizu C Tamaki-Ishihara Yuko Y Fukuda Yusuke Y Kitamura Mamoru M Matsue Yoichi Y So Akiko A Morita Mineto M

Obstetrics and gynecology international 20100712

We used placental tissue to compare the imprinted gene expression of IGF2, H19, KCNQ1OT1, and CDKN1C of singletons conceived via assisted reproduction technology (ART) with that of spontaneously conceived (SC) singletons. Of 989 singletons examined (ART n = 65; SC n = 924), neonatal weight was significantly lower (P < .001) in the ART group than in the SC group, but placental weight showed no significant difference. Gene expression analyzed by real-time PCR was similar for both groups with appro ...[more]

PMID: 20706653

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Project description:Assisted reproductive technology (ART) is an important part of reproductive medicine that comprises superovulation, in vitro fertilization (IVF), in vitro culture of embryos, cryopreservation and embryo transfer. Because it occurs in the sensitive period of gametogenesis and early embryonic development, its possible health effects on the offspring have received widespread attention in recent years. Relevant studies, though, are limited to postnatal follow-up and blood sample analysis. In this study, a mouse model was used to explore the effect of ART on gene expression in the organs of the off-spring using next-generation sequencing. The results showed that it caused abnormal expression in 1060 and 179 genes in the heart and spleen, respectively. Differentially expressed genes (DEGs) in the heart are mainly enriched in RNA synthesis and processing, and cardiovascular system development is also enriched. STRING analysis identified Ccl2, Ptgs2, Rock1, MAPK14, Agt, Wnt5a as core interaction factors. DEGs in the spleen are significantly enriched in anti-infection and im-mune responses and in the hematopoiesis-related pathway "hematopoietic cell lineage", which includes the core factors Fos, Jun and Il1r2. Then, we explored the effects of ART on epigenetic modifiers and imprinted genes. The results showed that 42 heart genes and 5 spleen genes were abnormally expressed, most of which were related to histone modification and chromatin remodeling. Imprinted genes are very important for normal fetal and individual growth and development. It was found that the expression of imprinted genes Dhcr7, Igf2, Mest and Smoc1 decreased in the heart of ART offspring, and the DNA methylation levels of Igf2 and Mest imprinting control regions (ICRs) increased abnormally. Therefore, we con-cluded that, in the mouse model, ART can interfere with the gene expression pattern in the heart and spleen of the adult offspring, causing potentially adverse effects on organ function. The results of this study can provide a reference for evaluating the safety of human ART and helping improve the clinical system.

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Effects of assisted reproduction technology on placental imprinted gene expression.

Publications

Effects of assisted reproduction technology on placental imprinted gene expression.

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