Lead Accumulation in Human Ovarian Follicular Fluid, and in Vitro Effect of Lead on Progesterone Production by Cultured Human Ovarian Granulosa Cells

Abstract

Lead content of ovarian follicular fluid obtained from 23 women was determined by atomic absorption spectrophotometry. In an in vitro experiment the direct effect of lead on the morphology and on progesterone (P) production by cultured granulosa cells of six women was investigated. Follicular fluid and granulosa cells were obtained from follicular aspirates of women undergoing in vitro fertilization (IVF) and embryo transfer (ET). Granulosa cells were cultured for 48 h to form monolayers in the presence or absence of lead acetate (100-1,600 microM). The effect of the metal proved to be concentration dependent. While 100-400 microM lead had no effect on the integrity of the monolayer, concentrations as high as 800 microM or higher inhibited cell adhesion and induced detachment of cells. The lead levels found in follicular fluid were 11.29 +/- 1.38 microg/L (0.056 +/- 0.007 microM). With lead in vitro at 1,600 microM (331.5 mg/L) there resulted a significant decrease in P production by granulosa cells. This concentration is very much higher than that measured in follicular fluid of IVF/ET patients, specifically nonexposed to lead, and even higher than mean blood levels reported by others in high exposure groups. In conclusion, lead seems not to exert a specific effect on the steroidogenesis by cultured human granulosa cells. Therefore, the lead levels measured in the ovarian follicular fluid seem not to pose a hazard with respect to progesterone secretion by the ovary.

Associations between toxic metals in follicular fluid and in vitro fertilization (IVF) outcomes

“…The FF concentrations of Hg, Cd and Pb measured in our study are generally lower than reported in the literature [7,12,16,[21][22][23]], a comprehensive comparison of which is provided elsewhere [25]. The lower FF values measured in our study may reflect the highly sensitive ICP-MS method employed, coupled to different exposure patterns.…”

“…It is presumed that FF will provide a closer approximation to the biologically-effective dose of a toxicant to an oocyte than achieved using blood or urine measures. Several groups previously reported Hg, Cd and/or Pb concentrations measured in human FF specimens, although with little methodologic detail [7,12,15,[21][22][23]24]. To facilitate investigation of associations between toxic metals in FF and IVF outcomes, our laboratory recently developed and validated a method for the measurement of elements in FF at trace concentrations [25].…”

Trace element concentrations in follicular fluid of small follicles differ from those in blood serum, and may represent long-term exposure

“…Despite their suspected impact on female reproduction and environmental prevalence (1)(2)(3)(4)(5), the concentration of these elements within the follicular fluid (FF) has not been well characterized. In an earlier study our group focused on the influence of lead concentration in FF on the outcome of pregnancy.…”

The association between cadmium, lead and mercury blood levels and reproductive hormones among healthy, premenopausal women

“…All three metals have been identified in human follicular fluid (Zenzes et al, 1995;Paksy et al, 2001;Al-Saleh et al, 2008) and ovarian tissue (Varga et al, 1993), and have been associated with adverse reproductive outcomes in epidemiologic studies. While the biological mechanisms by which these metals may exert adverse reproductive effects have not been fully elucidated, toxicologic studies have provided some insights.…”