Genetic and microscopic assessment of the human chemotherapy-exposed placenta reveals possible pathways contributive to fetal growth restriction

Result code in IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F00216208%3A11120%2F18%3A43916552" target="_blank" >RIV/00216208:11120/18:43916552 - isvavai.cz</a>

Alternative codes found

RIV/00064173:_____/18:N0000093

Result on the web

<a href="https://doi.org/10.1016/j.placenta.2018.03.002" target="_blank" >https://doi.org/10.1016/j.placenta.2018.03.002</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1016/j.placenta.2018.03.002" target="_blank" >10.1016/j.placenta.2018.03.002</a>

Result language

angličtina

Original language name

Genetic and microscopic assessment of the human chemotherapy-exposed placenta reveals possible pathways contributive to fetal growth restriction

Original language description

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.

Czech name

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Czech description

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Type

J_imp - Article in a specialist periodical, which is included in the Web of Science database

CEP classification

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OECD FORD branch

30214 - Obstetrics and gynaecology

Project

—

Continuities

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Publication year

2018

Confidentiality

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Name of the periodical

Placenta

ISSN

0143-4004

e-ISSN

—

Volume of the periodical

64

Issue of the periodical within the volume

April

Country of publishing house

GB - UNITED KINGDOM

Number of pages

10

Pages from-to

61-70

UT code for WoS article

000429556800008

EID of the result in the Scopus database

2-s2.0-85043976595