INFLUENCE OF BENZO(A)PYRENE ON OVARIAN FUNCTION

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 背景 多环芳烃（PAH）家族包括100种不同的化合物。 这些化合物是由涉及高温热解过程的天然和合成来源形成的，然而，就环境分布而言，来自合成来源的多环芳烃在数量上更为重要。 人类对多环芳烃的接触归因于家庭取暖和使用煤炭或木材烹饪、吸烟、汽车尾气排放、食用受污染的食品、焦炭、石墨电极和碳阳极制造业的职业接触等。多环芳烃的毒性已经在体外条件下进行了研究，并没有试图在亚慢性方案中研究多环芳烃的毒性。 对于风险评估，动物长期暴露于常见的多环芳烃是必不可少的。 由于缺乏足够的动物研究数据集，多环芳烃的定量风险评估受到阻碍。 通过摄入受多环芳烃污染的水、食物或土壤进行急性和亚慢性接触的相关信息对于评估危险废物场地周围地区居民的风险至关重要。 由于多环芳烃在环境中的广泛可用性和人类接触的相当大的可能性，这种化合物的潜在不利影响值得调查。对于这个试点项目，我们评估了苯并（a）芘（BaP），一种典型的PAH，对卵巢功能的影响，具体目标如下。 具体目标 1. 测定苯并（a）芘在雌性大鼠体内的生物利用度和毒代动力学。 2. 确定苯并（a）芘处理对大鼠动情周期期间性腺类固醇和调节这些类固醇的垂体激素的血浆浓度的影响。 3. 探讨苯并（a）芘（BaP）对卵巢外分泌功能及黄体维持的影响。 4. 确定苯并（a）芘对受精和着床前发育的影响。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. BACKGROUND The polycyclic aromatic hydrocarbon (PAH) family includes 100 different compounds. These compounds are formed from natural and synthetic sources that involve high-temperature pyrolytic processes, however, PAHs originating from synthetic sources are quantitatively more important in terms of environmental distribution. Human exposure to PAHs has been attributed to home heating and cooking using coal or wood, cigarette smoking, automobile exhaust emissions, consumption of ontaminated foods, occupational exposure in coke, graphite-electrode and carbon-anode manufacturing industries to mention a few. The toxicity of PAHs has been studied by a number of investigators under in vitro conditions and there have been no attempts to study PAH toxicity in a subchronic regimen. For risk estimation, long-term animal exposure to commonly occurring PAHs is essential. Quantitative risk assessment of PAHs has been hampered by lack of sufficient data sets from animal studies. Information relative to acute and subchronic exposures through ingestion of PAH-contaminated water, food, or soil is vital in assessing the risk to individuals living in areas surrounding hazardous waste sites. Because of the widespread availability of PAHs in the environment and the considerable probability of human exposure, the potential adverse effects of this compound merit investigation. For this pilot project, we assessed the effects of benzo(a)pyrene (BaP), a prototypical PAH, on ovarian function with the following specific aims. SPECIFIC AIMS 1. To determine the bioavailability and toxicokinetics of benzo(a)pyrene in female rats. 2. To determine the effect of BaP treatment on plasma concentrations of gonadal steroids and the pituitary hormones that regulate these steroids during the rat estrous cycle. 3. To determine the effect of BaP on ovarian exocrine function and luteal maintenance. 4. To determine the effect of BaP on fertilization and pre-implantation development.