Genetic and microscopic assessment of the human chemotherapy-exposed placenta reveals possible pathways contributive to fetal growth restriction
Language English Country Netherlands Media print-electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
29626982
DOI
10.1016/j.placenta.2018.03.002
PII: S0143-4004(18)30069-9
Knihovny.cz E-resources
- Keywords
- Chemotherapy, Fetal growth restriction, Oxidative damage, Placenta, Proliferation,
- MeSH
- Antineoplastic Agents adverse effects MeSH
- Adult MeSH
- Immunohistochemistry MeSH
- Real-Time Polymerase Chain Reaction MeSH
- Humans MeSH
- Young Adult MeSH
- Pregnancy Complications, Neoplastic drug therapy metabolism pathology MeSH
- Placenta metabolism pathology MeSH
- Prospective Studies MeSH
- Fetal Growth Retardation chemically induced metabolism pathology MeSH
- Exome Sequencing MeSH
- Case-Control Studies MeSH
- Pregnancy MeSH
- Check Tag
- Adult MeSH
- Humans MeSH
- Young Adult MeSH
- Pregnancy MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- Antineoplastic Agents 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
References provided by Crossref.org
Pregnancy and Cancer: the INCIP Project
