Paksy K, Rajczy K, Forgács Z, Lázár P, Bernard A, Gáti I, Kaáli G S
National Institute of Occupational Health, Budapest, Hungary.
J Appl Toxicol. 1997 Sep-Oct;17(5):321-7. doi: 10.1002/(sici)1099-1263(199709)17:5<321::aid-jat443>3.0.co;2-e.
Cadmium (Cd) is able to decrease preovulatory luteinizing hormone (LH) levels in blood and inhibit ovulation in rats. In this study the direct effects of Cd on steroidogenesis in granulosa cells were investigated. The cells obtained from ovarian follicular aspirates of 41 women undergoing in vitro fertilization (IVF) were cultured. Cadmium-induced alterations in the cellular morphology and in the production of progesterone by the cells was determined after exposure to concentrations of 8, 16, 32 and 64 microM CdCl2 for 2, 4, 8, 24 and 48 h. Progesterone secretion by granulosa cells could be stimulated with increasing concentrations of follicle-stimulating hormone (FSH). Combined effects of Cd and FSH were also studied. Cadmium diminished progesterone production in unstimulated and FSH-supported cells depending on its concentration and the exposure time. Follicle-stimulating hormone (100 ng ml[-1]) protected against Cd-induced suppression of progesterone production. Cadmium interfered with cell-cell junctions and the adherence of cells. No protective effect of FSH on Cd-induced alteration in cell morphology could be observed. Retraction of cytoplasmic extensions occurred at a lower dose and within a shorter exposure than a decrease in progesterone production. In conclusion, Cd exerted a direct effect on both granulosa cell morphology and on steroid biosynthesis. The lowest Cd concentration (16 microM) that was able to reduce progesterone production was about 3.5 times higher than levels reported in the ovary of a female smoker. The presented data can help to define environmental, occupational and life-style (smoking) risk factors in gonadal function during the preconception period of the female reproductive lifespan.
镉（Cd）能够降低大鼠血液中排卵前促黄体生成素（LH）的水平并抑制排卵。在本研究中，对镉对颗粒细胞类固醇生成的直接影响进行了调查。从41名接受体外受精（IVF）的女性的卵泡抽吸物中获取细胞并进行培养。在暴露于8、16、32和64微摩尔/升氯化镉2、4、8、24和48小时后，测定镉诱导的细胞形态变化以及细胞孕酮生成情况。颗粒细胞的孕酮分泌可随卵泡刺激素（FSH）浓度增加而受到刺激。还研究了镉与FSH的联合作用。镉会根据其浓度和暴露时间减少未受刺激和FSH支持的细胞中的孕酮生成。卵泡刺激素（100纳克/毫升）可防止镉诱导的孕酮生成抑制。镉会干扰细胞间连接和细胞黏附。未观察到FSH对镉诱导的细胞形态改变有保护作用。细胞质延伸的回缩在比孕酮生成减少更低的剂量和更短的暴露时间内发生。总之，镉对颗粒细胞形态和类固醇生物合成均有直接影响。能够降低孕酮生成的最低镉浓度（16微摩尔/升）比女性吸烟者卵巢中报道的水平高约3.5倍。所呈现的数据有助于确定女性生殖寿命孕前阶段性腺功能中的环境、职业和生活方式（吸烟）风险因素。
