Genetic and microscopic assessment of the human chemotherapy-exposed placenta reveals possible pathways contributive to fetal growth restriction
Jazyk angličtina Země Nizozemsko Médium print-electronic
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
29626982
DOI
10.1016/j.placenta.2018.03.002
PII: S0143-4004(18)30069-9
Knihovny.cz E-zdroje
- Klíčová slova
- Chemotherapy, Fetal growth restriction, Oxidative damage, Placenta, Proliferation,
- MeSH
- antitumorózní látky škodlivé účinky MeSH
- dospělí MeSH
- imunohistochemie MeSH
- kvantitativní polymerázová řetězová reakce MeSH
- lidé MeSH
- mladý dospělý MeSH
- nádorové komplikace v těhotenství farmakoterapie metabolismus patologie MeSH
- placenta metabolismus patologie MeSH
- prospektivní studie MeSH
- růstová retardace plodu chemicky indukované metabolismus patologie MeSH
- sekvenování exomu MeSH
- studie případů a kontrol MeSH
- těhotenství MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladý dospělý MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- antitumorózní látky MeSH
INTRODUCTION: Fetal growth restriction (FGR) carries an increased risk of perinatal mortality and morbidity. A major cause of FGR is placental insufficiency. After in utero chemotherapy-exposure, an increased incidence of FGR has been reported. In a prospective cohort study we aimed to explore which pathways may contribute to chemotherapy-associated FGR. METHODS: Placental biopsies were collected from 25 cancer patients treated with chemotherapy during pregnancy, and from 66 control patients. Differentially expressed pathways between chemotherapy-exposed patients and controls were examined by whole transcriptome shotgun sequencing (WTSS) and Ingenuity Pathway Analysis (IPA). Immunohistochemical studies for 8-OHdG and eNOS (oxidative DNA damage), proliferation (PCNA) and apoptosis (Cleaved Caspase 3) were performed. The expression level of eNOS, PCNA and IGFBP6 was verified by real-time quantitative Reverse Transcription Polymerase Chain Reaction (RT-qPCR). RESULTS: Most differential expressed genes between chemotherapy-exposed patients and controls were related to growth, developmental processes, and radical scavenging networks. The duration of chemotherapy exposure had an additional impact on the expression of genes related to the superoxide radicals degeneration network. Immunohistochemical analyses showed a significantly increased expression of 8-OHdG (P = 0.003) and a decreased expression of eNOS (P=0.015) in the syncytiotrophoblast of the placenta of cancer patients. A decreased expression of PCNA was detected by immunohistochemistry as RT-qPCR (NS). CONCLUSION: Chemotherapy exposure during pregnancy results in an increase of oxidative DNA damage and might impact the placental cellular growth and development, resulting in an increased incidence of FGR in this specific population. Further large prospective cohort studies and longitudinal statistical analyses are needed.
Department of Oncology KU Leuven Herestraat 49 3000 Leuven Belgium
Department of Reproduction and Regeneration KU Leuven Herestraat 49 3000 Leuven Belgium
Citace poskytuje Crossref.org
Pregnancy and Cancer: the INCIP Project
