title: Fetal rat hearts do not display acute cardiotoxicity in response to maternal Doxorubicin treatment.
abstract: Anthracyclines are used to treat cancers during the second and third trimester of pregnancy. The chemotherapeutic effect of anthracyclines is associated with a dose- and time-dependent cardiotoxicity that is well described for infants and adults. However, data regarding fetal anthracycline-related cardiotoxicity after administration of chemotherapeutics during pregnancy are limited. In this study, we analyzed the acute effect of doxorubicin, an anthracycline derivative, on fetal and maternal rat myocardium. We injected 10 or 20 mg/kg i.v. doxorubicin to pregnant Wistar rats at day 18 of pregnancy; age-matched pregnant rats injected with physiologic saline served as controls. Maternal echocardiography and fetal Doppler scanning were performed before the injection and before sacrifice. Cesarean operation was performed at day 19 or 20, and maternal and fetal blood samples and heart biopsies were collected to measure apoptosis, the impact on cell proliferation, and structural cardiac damage. Acute maternal cardiotoxicity is associated with loss of body weight, moderately deteriorated left ventricular function, induction of apoptosis, and a decrease in cell turnover. Despite a 30% lower fetal body weight and elevated plasma B-type natriuretic peptide concentrations after doxorubicin administration, the fetal hearts had intact microstructure, an unaltered number of apoptotic cells, and preserved cell proliferation compared with controls. Our study suggests that acute treatment using anthracyclines during pregnancy impairs maternal cardiac function, whereas fetal hearts are protected.
authors.affiliation: Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, University Hospital Leuven, Katholieke Universiteit Leuven, Leuven, Belgium.
authors.forename: Mina Mhallem
authors.initials: MM
authors.lastname: Gziri
authors.forename: Peter
authors.initials: P
authors.lastname: Pokreisz
authors.forename: Rita
authors.initials: R
authors.lastname: De Vos
authors.forename: Eric
authors.initials: E
authors.lastname: Verbeken
authors.forename: Frédéric
authors.initials: F
authors.lastname: Debiève
authors.forename: Luc
authors.initials: L
authors.lastname: Mertens
authors.forename: Stefan P
authors.initials: SP
authors.lastname: Janssens
authors.forename: Frédéric
authors.initials: F
authors.lastname: Amant
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics* / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects; D009320:Atrial Natriuretic Factor / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004317:Doxorubicin / Q000493:pharmacokinetics* / Q000633:toxicity*; D004452:Echocardiography; D005260:Female; D005318:Fetal Heart / Q000187:drug effects*; D006331:Heart Diseases / Q000139:chemically induced* / Q000000981:diagnostic imaging; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D008431:Maternal-Fetal Exchange; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000378:metabolism; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012313:RNA / Q000096:biosynthesis / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000903:Antibiotics, Antineoplastic; D012313:RNA; D004317:Doxorubicin; D009320:Atrial Natriuretic Factor; D009218:Myosins