Maternal high estradiol exposure alters CDKN1C and IGF2 expression in human placenta.
Placenta
; 61: 72-79, 2018 01.
Article
em En
| MEDLINE
| ID: mdl-29277274
ABSTRACT
INTRODUCTION:
The increased maternal estradiol (E2) concentrations induced by assisted reproductive technology (ART) result in lower birth weight of offspring, which is associated with increased risk of adult diseases. However, the exact mechanism remains unknown. The present study investigated the effect of high E2 exposure on the expression of imprinted genes CDKN1C and IGF2 in human placentas and the DNA methylation status of their differential methylation regions (DMRs).METHODS:
The mRNA expression of CDKN1C and IGF2 in human placentas and the human trophoblast cells (HTR8) treated with E2 were investigated by reverse transcription-real time polymerase chain reaction (PCR). The DNA methylation of their DMRs were investigated by sodium bisulfite sequencing.RESULTS:
CDKN1C and IGF2 were significantly up-regulated in ART conceived placentas. The mean birth weight of ART singletons was significantly lower than that of naturally conceived (NC) ones, with the increased percentage of small-for-gestational-age (SGA) birth. The DNA methylation was significantly down-regulated in the DMR of CDKN1C (KvDMR1) and up-regulated in the DMR of IGF2 (H19 DMR) in ART placentas. The treatment of E2 altered the expression of the two genes and the DNA methylation of their DMRs in HTR8 to a similar tendency as in vivo.DISCUSSION:
The maternal high E2 levels after ART up-regulate the expression of imprinted genes in human placentas through epigenetic modifications, which influences the growth potential of the offspring. Further studies are needed to follow up the growth and development of the ART offspring.Palavras-chave
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Indução da Ovulação
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Placenta
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Fator de Crescimento Insulin-Like II
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Regulação da Expressão Gênica no Desenvolvimento
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Metilação de DNA
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Estradiol
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Inibidor de Quinase Dependente de Ciclina p57
Tipo de estudo:
Etiology_studies
/
Risk_factors_studies
País como assunto:
Asia
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article