Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti, Italy.
Domest Anim Endocrinol. 2010 Jul;39(1):34-9. doi: 10.1016/j.domaniend.2010.01.004. Epub 2010 Feb 11.
Because of its widespread use and potential adverse biological effects, bisphenol A (BPA) represents one of the most studied endocrine-disrupting compounds. Within the reproductive system, ovarian granulosa cells have been documented as a target of BPA action, but no consensus has been reached about functional modifications induced by BPA. On these bases, we studied the potential disrupting effects of BPA on the main granulosa cell functional activities, also taking into account a potential interference with the ovarian angiogenic process. Ovarian granulosa cells were isolated from porcine follicles and cultured in the presence or absence of BPA at different concentrations for 48h. Cell proliferation was studied by measuring adenosine triphosphate content. Progesterone (P4) and estradiol 17beta (E2) production was determined by radioimmunoassay. Vascular endothelial growth factor (VEGF) output was quantified by an enzyme-linked immunosorbent assay. Redox status was monitored by measuring superoxide anion and hydrogen peroxide, and by determining the activities of the scavenging enzymes superoxide dismutase, catalase, and peroxidase by colorimetric methods. Granulosa cell proliferation as well as redox status resulted unaffected by BPA. Concentrations of E2 were stimulated by the lower BPA concentration, whereas they were inhibited by the larger doses tested. P4 output was decreased by all BPA concentrations. To the contrary, VEGF production was stimulated. Data indicate that BPA can interfere with reproductive activity by affecting granulosa cell steroidogenesis in vitro; furthermore, BPA can exert a promoting effect on the ovarian angiogenic process by increasing VEGF output in pigs. A disruption of this finely tuned process seems particularly relevant because of the risk of uncontrolled neovascularization.
由于其广泛的应用和潜在的不良生物学效应，双酚 A（BPA）是研究最多的内分泌干扰化合物之一。在生殖系统中，卵巢颗粒细胞已被证明是 BPA 作用的靶细胞，但对于 BPA 引起的功能改变尚未达成共识。基于这些原因，我们研究了 BPA 对主要颗粒细胞功能活动的潜在干扰作用，同时考虑了其对卵巢血管生成过程的潜在干扰作用。从猪卵泡中分离卵巢颗粒细胞，并在存在或不存在不同浓度 BPA 的情况下培养 48 小时。通过测量三磷酸腺苷含量来研究细胞增殖。通过放射免疫测定法测定孕酮（P4）和雌二醇 17β（E2）的产生。通过酶联免疫吸附试验定量测定血管内皮生长因子（VEGF）的产量。通过测量超氧阴离子和过氧化氢，并通过比色法测定清除酶超氧化物歧化酶、过氧化氢酶和过氧化物酶的活性来监测氧化还原状态。BPA 对颗粒细胞增殖和氧化还原状态没有影响。较低浓度的 BPA 刺激 E2 浓度，而较大剂量的 BPA 则抑制 E2 浓度。所有 BPA 浓度均降低 P4 的产生。相反，VEGF 的产生增加。数据表明，BPA 可以通过影响体外颗粒细胞甾体生成来干扰生殖活动；此外，BPA 可以通过增加猪卵巢中的 VEGF 产量来发挥促进卵巢血管生成过程的作用。由于不受控制的新血管生成的风险，这种精细调节过程的破坏似乎尤为重要。
