Naslov
The potential for cadmium to act as a placental steroid disruptor in humans: ex vivo and in vitro data

Autori
Piasek, Martina ; Henson, Michael C. ; Stasenko, Sandra ; Kušec, Vesna

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Abstract for the Forthcoming International Federation of Placenta Associations Meeting IFPA 2008/12th EPG Conference ; u: Placenta 29 (2008) (A.1-A.102) / - : Elsevier, 2008

Skup
IFPA Meeting 2008

Mjesto i datum
Leibnitz, Austrija, 10.09.2008. - 13.09.2008

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
cadmium; ex vivo studies; in vitro studies; human placenta; steroid disruptors

Sažetak
Objectives: Toxic metals can interfere with the maintenance of pregnancy and fetal viability. However, human placenta can be used to monitor metal effects in both the maternal and internal fetal environments when information concerning the specimen’ s history, endocrine milieu, and patient demographics (maternal age, medical history, professional history, sources of environmental exposure, active and passive smoking, and diet) is carefully evaluated. Cadmium has recently been suggested to act as an endocrine disrupting chemical and metalloestrogen in mammals. Work in our laboratories has validated this concept with respect to steroid disruption in human placenta via exposure to the metal as a constituent of tobacco smoke. Methods: In ex vivo studies on placentas, data on health condition, lifestyle and exposure sources were collected from parturients (healthy urban women with normal pregnancies and deliveries at term ; two cohorts N=56 and N=208, non-smokers and smokers/previous smokers, average age 28 years) by a questionnaire. Representative paired placental tissue samples (central and peripheral sampling sites) were dissected from each placenta and subjected to metal (cadmium, iron, zinc, and copper) analysis by atomic absorption spectrometry and steroid hormone (progesterone and estradiol) analysis by specific immunoassays (RIA and IEMA). Results were grouped according to tobacco smoke exposure. For in vitro studies, human cytotrophoblasts were purified by density gradient centrifugation and incubated in Dulbecco modified Eagle medium plus 10% fetal bovine serum with 5, 10, or 20 mM CdCl2 for 96 h. To assess enzymatic (P450scc and 3beta- HSD) activities, trophoblast cells were cultured under conditions (with or without pregnenolone and with or without 25-hydroxycholesterol or aminoglutethimide) to assess their respective steps in the progesterone biosynthetic pathway. Results: The results showed that increases in placental cadmium concentrations were commensurate with a decrease in placental progesterone concentrations in women exposed to tobacco smoke during pregnancy. Cadmium ions readily accumulated in human placental (trophoblast) cells where they suppressed progesterone release without apparent inhibition of syncytial development. This suppression in cultured human trophoblast cells represented a direct effect of cadmium on the progesterone biosynthetic pathway. The effect may have been attributed, at least in part, to a deleterious effect on low-density lipoprotein receptor. Another site at which cadmium interfered with placental progesterone production was the P450scc enzyme, although it is unlikely that an inhibition of cAMP was involved. The possibility still exists, however, that the cadmium ion may interfere with the downstream cascade of the cAMP-protein kinase A-dependent pathway. Conclusion: The human placenta offers a unique opportunity to study the mechanisms regulating endocrine disruption by toxic metals, with steroid disruption serving as a useful tool in assessing placental function and as a post hoc indicator of fetal distress in utero.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti, Javno zdravstvo i zdravstvena zaštita

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