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Maternal high estradiol exposure alters CDKN1C and IGF2 expression in human placenta.
Chen, Xi-Jing; Chen, Feng; Lv, Ping-Ping; Zhang, Dan; Ding, Guo-Lian; Hu, Xiao-Ling; Feng, Chun; Sheng, Jian-Zhong; Huang, He-Feng.
Afiliação
  • Chen XJ; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Chen F; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Lv PP; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Zhang D; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Ding GL; Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310058, China; International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Diseases
  • Hu XL; Department of Reproductive Endocrinology, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310006, China; Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Feng C; Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310058, China; The Center of Reproductive Medicine, The 2nd Afliated Hospital of Medical School, Zhejiang University, Hangzhou, Zhejiang 310006, China.
  • Sheng JZ; Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310058, China.
  • Huang HF; Key Laboratory of Reproductive Genetics, Ministry of Education, Zhejiang University, Hangzhou, Zhejiang 310058, China; International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai 200030, China; Institute of Embryo-Fetal Original Adult Diseases
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.
Assuntos
Inibidor de Quinase Dependente de Ciclina p57/agonistas; Metilação de DNA/efeitos dos fármacos; Estradiol/efeitos adversos; Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos; Fator de Crescimento Insulin-Like II/agonistas; Indução da Ovulação/efeitos adversos; Placenta/efeitos dos fármacos; Adulto; Linhagem Celular; China/epidemiologia; Inibidor de Quinase Dependente de Ciclina p57/química; Inibidor de Quinase Dependente de Ciclina p57/genética; Inibidor de Quinase Dependente de Ciclina p57/metabolismo; Transferência Embrionária/efeitos adversos; Estradiol/sangue; Estradiol/farmacocinética; Estradiol/farmacologia; Estrogênios/efeitos adversos; Estrogênios/sangue; Estrogênios/farmacocinética; Estrogênios/farmacologia; Feminino; Fármacos para a Fertilidade Feminina/efeitos adversos; Fármacos para a Fertilidade Feminina/sangue; Fármacos para a Fertilidade Feminina/farmacocinética; Fármacos para a Fertilidade Feminina/farmacologia; Desenvolvimento Fetal/efeitos dos fármacos; Retardo do Crescimento Fetal/induzido quimicamente; Retardo do Crescimento Fetal/epidemiologia; Retardo do Crescimento Fetal/etiologia; Humanos; Infertilidade Feminina/sangue; Infertilidade Feminina/metabolismo; Infertilidade Feminina/terapia; Fator de Crescimento Insulin-Like II/química; Fator de Crescimento Insulin-Like II/genética; Fator de Crescimento Insulin-Like II/metabolismo; Placenta/metabolismo; Gravidez; Risco; Trofoblastos/efeitos dos fármacos; Trofoblastos/metabolismo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Indução da Ovulação / Placenta / Fator de Crescimento Insulin-Like II / Regulação da Expressão Gênica no Desenvolvimento / Metilação de DNA / Estradiol / 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
Texto completo
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Indução da Ovulação / Placenta / Fator de Crescimento Insulin-Like II / Regulação da Expressão Gênica no Desenvolvimento / Metilação de DNA / Estradiol / 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