Sanyal Mrinal K, Li You-Lan
Department of Obstetrics and Gynecology, Yale University Medical School, New Haven, CT, USA.
Birth Defects Res B Dev Reprod Toxicol. 2007 Oct;80(5):367-73. doi: 10.1002/bdrb.20122.
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.
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.
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.
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.
多环芳烃（PAH）、苯并[a]芘（B[a]P）和7,12-二甲基苯并[a]蒽（DMBA）是广泛分布的有毒环境因子。研究了这些因子对大鼠胎儿及胎盘组织生长和血管系统的相对有害影响。
通过剖腹术确认有着床部位的怀孕大鼠（精子阳性第1天）在妊娠第10、12和14天腹腔注射（i.p.）溶解于玉米油中的这些试剂，累积总剂量分别为50、100和200 mg/kg/大鼠，对照组仅注射玉米油（每组3 - 20只母鼠）。在妊娠第20天，通过不同参数评估处理组和对照组大鼠的胎儿生长、组织出血和胎盘病理学情况。
与B[a]P相比，DMBA的危害相对更大，表现为随着剂量增加，母鼠致死率增加且体重逐渐减轻。在这些试剂剂量为200 mg/kg/大鼠时，母鼠存活率分别为45%和100%，体重分别减轻至对照组的24%和52%。存活母鼠的胎儿存活率与对照组相似。它们导致明显的胎儿生长迟缓以及胎盘组织坏死。B[a]P和DMBA对分化中的胎儿血管系统产生显著毒性，表现为血管破裂和出血，尤其是在皮肤、颅骨和脑组织中。
母体暴露于PAH会导致胎盘毒性以及相关的胎儿发育不良和胎儿身体不同部位出血，特别是明显的皮内和颅骨内出血，表明发育中的胎儿血管系统是PAH毒性的靶点。
