Cadmium-induced Alteration in Morphology and Progesterone Production
of Human Ovarian Granulosa Cells in vitro
K. Paksy, Zs. Forgács, K. Rajczy*, I. Gáti*
National Institute of Occupational Health, Budapest, Hungary
* Kaáli Institute, Budapest, Hungary
CEJOEM 1997, Vol.3. No.4.:335
Cadmium (Cd) has been reported to be found as a contaminant in food, alcoholic
beverages and cigarette tobacco. As to experimental evidence this toxic
metal is able to reduce preovulatory luteinizing hormone (LH) levels in
blood and inhibit ovulation in rats. The present study deals with direct
effect of Cd on steroidogenesis of human granulosa cells in culture. Cells
were obtained from ovarian follicular aspirates of women undergoing in
vitro fertilization following ovarian hyperstimulation with clomiphen
citrate, human menopausal gonadotropin or buserelin acetate. Cells cultured
for 48 h formed a semiconfluent monolayer. Morphological alteration of
cells and progesterone (P) production by them were determined after exposure
to concentrations of 8, 16, 32 and 64 µM CdCl2 for 2, 4, 8, 24 and
48 hr in the presence or absence of follicle-stimulating hormone (FSH).
Cd 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. Cd diminished P production in unstimulated
and FSH-supported cells depending on its concentration and the exposure
time. FSH (1,000 ng/l) protected against Cd-induced suppression of P production.
Retraction of cytoplasmic extensions occurred at a lower dose and within
a shorter exposure than a decrease in P production.
In conclusion: Cd exerted a direct effect on both
granulosa cell morphology and on steroid biosynthesis. The lowest Cd concentration
(16 µM) which was able to reduce P production was about 3.5 times
higher than tissue levels reported in the ovary of female smokers. The
present data help to define environmental, occupational and lifestyle (smoking)
risk factors in gonadal function during the preconception period of female
reproductive lifespan.
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