Effect of cadmium on morphology and steroidogenesis of cultured human ovarian granulosa cells.
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.
Paksy
K
K
National Institute of Occupational Health, Budapest, Hungary.
Rajczy
K
K
Forgács
Z
Z
Lázár
P
P
Bernard
A
A
Gáti
I
I
Kaáli
G S
GS
D000328:Adult; D002104:Cadmium / Q000633:toxicity*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005640:Follicle Stimulating Hormone / Q000008:administration & dosage; D006107:Granulosa Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007986:Luteinizing Hormone / Q000096:biosynthesis; D008597:Menstrual Cycle / Q000187:drug effects; D011374:Progesterone / Q000096:biosynthesis*; D012307:Risk Factors
D002104:Cadmium; D011374:Progesterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone