title: Assessment of steroid disruption using cultures of whole ovary and/or placenta in rat and in human placental tissue.
abstract: OBJECTIVE
  The paper presents results of collaborative research on cadmium as an endocrine disruptor. To detect steroidogenic alterations in cycling and pregnant rats following cadmium exposures in vivo (at 3 or 5 mg/kg as a single s.c. dose) and in vitro (from 0 through 2000 microM Cd(2+)) whole-ovary culture was used. To evaluate steroid productions in rats fed low iron (10 ppm) and concomitantly exposed to cadmium (5 mg/kg total dose by s.c.-implanted osmotic pumps) during 19 days of pregnancy whole-placenta culture was also used. In human placental tissue cadmium and progesterone concentrations were assessed in relation to cigarette smoking.
  
  
  METHODS
  Cultures of minced ovaries were evaluated for 1-h basal steroid production and following 1-h production stimulated with either human chorionic gonadotropin (hCG) or hCG and pregnenolone. Placental cultures were evaluated for average 1-h progesterone production following 3 h of unstimulated production. Steroid hormones were evaluated by specific radioimmunoassay. Placental cadmium concentrations were analyzed by atomic absorption spectrometry.
  
  
  RESULTS
  In-vivo cadmium exposure interfered with normal steroidogenesis in cycling rats and in early pregnancy, with ovarian estradiol production the most affected. Under in-vitro cadmium exposure the most affected was ovarian production of progesterone and testosterone in cycling (proestrous) rats with medial inhibitory concentrations under 500 micro M Cd(2+). Cadmium interfered with the steroidogenic pathway at more than one site. Linear and additive effects of low-iron feeding and concomitant cadmium exposure during pregnancy on placental progesterone production were found. In humans, we found that the placentas of smoking mothers contained twice as much cadmium and approximately half the amount of progesterone than did the placentas of non-smoking mothers.
  
  
  CONCLUSIONS
  Results of the research on cadmium-induced steroidogenic effects using cultures of whole rat ovary and/or placenta as well as human placental tissues point to cadmium as an endocrine disruptor that may compromise pregnancy outcome and fetal viability.
authors.affiliation: Institute for Medical Research and Occupational Health, Mineral Metabolism Unit, P O Box 291, HR-10001 Zagreb, Republic of Croatia. mpiasek@imi.hr
authors.forename: Martina
authors.initials: M
authors.lastname: Piasek
authors.forename: John W
authors.initials: JW
authors.lastname: Laskey
authors.forename: Krista
authors.initials: K
authors.lastname: Kostial
authors.forename: Maja
authors.initials: M
authors.lastname: Blanusa
mesh_terms: D000328:Adult; D000818:Animals; D002104:Cadmium / Q000009:adverse effects* / Q000493:pharmacokinetics; D046508:Culture Techniques; D004703:Endocrine System / Q000187:drug effects*; D005260:Female; D006801:Humans; D007279:Injections, Subcutaneous; D010053:Ovary / Q000473:pathology* / Q000502:physiology; D010920:Placenta / Q000473:pathology* / Q000502:physiology; D011247:Pregnancy; D011256:Pregnancy Outcome; D011374:Progesterone / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012907:Smoking / Q000009:adverse effects*
chemical_list: D002104:Cadmium; D011374:Progesterone