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Cadmium as an endocrine disruptor in women's reproduction: Dual effect and specific action in different steroidogenic cells?

Introduction: Cadmium is present in certain occupations (welding, soldering or oxy-cutting ; paints ; plastics ; textile work ; battery manufacture) and in today’ s environment, including food and tobacco smoke. It bioaccumulates in internal organs over a lifetime. Due to its capacity to alter ovarian and placental steroidogenesis and affect normal ovarian cyclicity, the maintenance of pregnancy, and fetal growth and development, cadmium has been acknowledged as an endocrine disrupting chemical. Methods: We studied cadmium-related steroid disruption in mammalian ovary and placenta. Human placentas were used for ex vivo (epidemiological) and in vitro studies of cadmium effect(s) on placental progesterone production (1, 2). In experiments in laboratory rats in vivo and in vitro (ref1) and using the stable porcine granulosa cell line JC-410 (ref2, 3), steroidogenesis was assessed in placental and ovarian steroidogenic cells. Results: In either human or rat placenta and in ovary of laboratory rats, increased cadmium concentrations in steroidogenic tissue were associated with decreased progesterone production. Direct cadmium effects on specific components of the steroidogenic pathway, including the low-density lipoprotein (LDL)-cholesterol receptor and P450 side chain cleavage enzyme were found. In cultured porcine granulosa cells, cadmium had the potential to stimulate ovarian progesterone synthesis through a mechanisms involving activation of P450 side chain cleavage gene expression. Discussion: Cadmium has the potential to disrupt steroidogenesis in placenta. In the ovary it may display paradoxical dual effects. Depending on exposure level, cadmium may either inhibit or enhance the biosynthesis of progesterone and may inhibit or mimic estrogen, acting as metalloestrogen. Sites of cadmium direct effects on specific components of the steroid biosynthetic pathway are multifaceted. It is possible that cadmium’ s effects are "tissue-specific" in different steroidogenic cells. (References: 1) Int. Arch. Occup. Environ. Health 2002 ; 75:S36. 2) Exp. Biol. Med. 2004 ; 229:383. 3) Immun. Endoc. Metab. Agents Med. Chem. 2006 ; 6:27)

cadmium; dual effect; ovary; placenta; steroid disruption;

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