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1 July 2002 Placental Endocrine Disruption Induced by Cadmium: Effects on P450 Cholesterol Side-Chain Cleavage and 3β-Hydroxysteroid Dehydrogenase Enzymes in Cultured Human Trophoblasts
Motoyuki Kawai, Kenneth F. Swan, Amy E. Green, Deborah E. Edwards, Mary B. Anderson, Michael C. Henson
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Abstract

We previously suggested that cadmium (Cd), an environmental toxicant and constituent of tobacco smoke, inhibits progesterone secretion in cultured human placental trophoblasts by inhibiting low-density lipoprotein receptor mRNA expression. In the current study, we investigated whether Cd also disrupts progesterone synthesis via P450 cholesterol side-chain cleavage (P450scc) and 3β-hydroxysteroid dehydrogenase (3β-HSD), enzymes that play important roles in placental steroidogenesis. Human cytotrophoblasts were purified by density gradient centrifugation and incubated in Dulbecco modified Eagle medium 10% fetal bovine serum with 0, 5, 10, or 20 μM CdCl2 for 96 h. Cells progressed to syncytiotrophoblastic maturity regardless of treatment. No differences (P > 0.05) in cell protein and lactate dehydrogenase activity were observed between untreated trophoblasts and those treated with CdCl2. However, P450scc and 3β-HSD mRNA transcript levels declined in a dose-dependent manner (P <0.05) in trophoblasts cocultured with 5, 10, or 20 μM CdCl2. P450scc activity was similarly inhibited (P < 0.05) by CdCl2 treatment, although 3β-HSD activity was not significantly affected. Coculture with 8-bromo-cAMP enhanced progesterone secretion in untreated cultures but did not reverse the decline in progesterone secretion induced by CdCl2 treatment. CdCl2 failed to influence cAMP content in cultured cells. Collectively, results suggest that P450scc enzyme is another site at which Cd interferes with placental progesterone production. However, it is unlikely that an inhibition of cAMP is involved with the inhibition of progesterone biosynthesis by Cd in human trophoblasts.

Motoyuki Kawai, Kenneth F. Swan, Amy E. Green, Deborah E. Edwards, Mary B. Anderson, and Michael C. Henson "Placental Endocrine Disruption Induced by Cadmium: Effects on P450 Cholesterol Side-Chain Cleavage and 3β-Hydroxysteroid Dehydrogenase Enzymes in Cultured Human Trophoblasts," Biology of Reproduction 67(1), 178-183, (1 July 2002). https://doi.org/10.1095/biolreprod67.1.178
Received: 25 October 2001; Accepted: 1 January 2002; Published: 1 July 2002
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