Deleterious effects of polynuclear aromatic hydrocarbon on blood vascular system of the rat fetus.
BACKGROUND
Polynuclear aromatic hydrocarbons (PAH), benzo[alpha]pyrene (B[alpha]P) and 7,12-dimethylbenz[alpha]anthracene (DMBA) are toxic environmental agents distributed widely. The relative deleterious effects of these agents on growth and blood vasculature of fetus and placental tissues of the rat were studied.


METHODS
Pregnant rats (Day 1 sperm positive) with implantation sites confirmed by laparotomy were treated intraperitoneally (i.p.) on Pregnancy Days 10, 12, and 14 with these agents dissolved in corn oil at cumulated total doses 50, 100, and 200 mg/kg/rat, and control with corn oil only (3-20 dams/group). Fetal growth, tissue hemorrhage, and placental pathology were evaluated by different parameters on Pregnancy Day (PD) 20 in treated and control rats.


RESULTS
DMBA was relatively more deleterious compared to B[alpha]P indicated by increased lethality and progressive reduction of body weight of the mother with increasing doses. At 200 mg/kg/rat doses of these agents, maternal survival was 45% and 100% and body weight reduced 24% and 52% of controls, respectively. The fetal survival rates in live mothers were similar to that of controls. They induced marked fetal growth retardation and necrosis of placental tissues. B[alpha]P and DMBA produced significant toxicity to differentiating fetal blood vascular system as exhibited by rupture of blood vessels and hemorrhage, especially in the skin, cranial, and brain tissues.


CONCLUSIONS
Maternal PAH exposure induced placental toxicity and associated adverse fetal development and hemorrhage in different parts of the fetal body, in particular, marked intradermal and cranial hemorrhage, showing that developing fetal blood vasculature is a target of PAH toxicity.
Sanyal
Mrinal K
MK
Department of Obstetrics and Gynecology, Yale University Medical School, New Haven, CT, USA. sanyal.mmsj@att.net
Li
You-Lan
YL
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000008:administration & dosage / Q000633:toxicity; D000818:Animals; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity; D001808:Blood Vessels / Q000002:abnormalities* / Q000187:drug effects* / Q000196:embryology / Q000473:pathology; D005260:Female; D047109:Fetal Development / Q000187:drug effects; D005317:Fetal Growth Retardation / Q000139:chemically induced; D005865:Gestational Age; D006470:Hemorrhage / Q000139:chemically induced; D010920:Placenta / Q000187:drug effects / Q000473:pathology; D011084:Polycyclic Aromatic Hydrocarbons / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D017207:Rats, Sprague-Dawley
D011084:Polycyclic Aromatic Hydrocarbons; D001564:Benzo(a)pyrene; D015127:9,10-Dimethyl-1,2-benzanthracene