The Placenta: Relevance to Toxicology

Miller, Richard K.; Ng, Wendy W.; Levin, Arthur A.

doi:10.1007/978-1-4615-9346-1_25

Cited by 11 publications

(5 citation statements)

References 120 publications

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“…Furthermore, the human yolk sac never touches the uterine wall; to reach the yolk sac, materials must diffuse through the chorionic membrane (see discussion and diagrams in Carney et al, 2004). Substances the size of HBOC (250 kD) do not diffuse across intact, nonfenestrated membranes such as those found in the early chorioallantoic placenta (Klaassen, 1980;Miller et al, 1983).…”

Section: Are Key Events In the Animal Moa Plausible In Humans?mentioning

confidence: 97%

Mode of Action: Yolk Sac Poisoning and Impeded Histiotrophic Nutrition—HBOC-Related Congenital Malformations

Holson

Stump

Pearce

et al. 2005

Critical Reviews in Toxicology

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Rodents form an early inverted yolk sac placenta (invYSP) by apposing the yolk sac to the uterine wall. The invYSP supplies nutrients via histiotrophic nutrition involving pinocytosis of materials from uterine gland secretions, lysosomal degradation, and transfer of the products to the embryo. Interference with histiotrophic trafficking through the invYSP by high-molecular-weight molecules (such as trypan blue) causes malformations and resorptions. Later in gestation, rodents form a definitive chorioallantoic placenta (CAP). By contrast, humans and dogs never develop an invYSP, relying exclusively on the CAP. Given their large size (approximately 250 kD), hemoglobin-based oxygen carriers (HBOC), being developed as blood substitutes, could be expected to interfere with histiotrophic trafficking through the invYSP. During initial toxicity testing, intravenous infusions of HBOC caused pronounced developmental toxicity in rats exposed during the pre-CAP period. Assuming that HBOC interfered with invYSP function, we hypothesized that these findings would not apply to humans or dogs, which lack an invYSP. Subsequent extensive developmental toxicity studies in dogs produced no developmental toxicity after intravenous infusion at the maximum tolerated dose. In view of the existing species-specific placental differences and HBOC's demonstrated, exclusive interference with invYSP histiotrophic nutrition, HBOC is not expected to cause abnormal development in humans or other mammals that do not develop an invYSP.

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Section: Are Key Events In the Animal Moa Plausible In Humans?mentioning

confidence: 97%

Mode of Action: Yolk Sac Poisoning and Impeded Histiotrophic Nutrition—HBOC-Related Congenital Malformations

Holson

Stump

Pearce

et al. 2005

Critical Reviews in Toxicology

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“…With the application of current public health regulations, pregnant women can no longer be occupationally exposed to Pb or Cd, but other sources including food and water contamination, wall paint, industrial wastes, automobile exhaust fumes and pesticides are yet to be eliminated. Furthermore, women are generally unaware of the adverse effects of cigarette smoke on the placenta and foetus, due to its toxic constituents, among which is Cd [3][4][5]. Population groups, such as women of childbearing age and infants, with the likelihood of developing nutritional deficiency, are in a more precarious position for toxic effects of Pb or Cd.…”

Section: Significance Of Overall Problemmentioning

confidence: 99%

“…Low Cd concentrations measured in the human foetus indicate that the placenta is not a complete barrier for fetal Cd exposure [9]. Animal studies have shown that transfer of essential trace elements (Fe, Zn) and vitamins may be inhibited by placental Cd accumulation [4].…”

Section: Reproductive Effects Of Lead and Cadmiummentioning

confidence: 99%

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Experimental studies on reproductive and perinatal effects of lead and cadmium

Piasek

Kostial²

1996

Environmental Management and Health

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Lead is a known reproductive toxicant in humans and animals. Data on cadmium reproductive effects in humans are inconclusive, and in female animals are lacking. More information on the toxicokinetics and toxicity of Pb and Cd during the reproductive period and in developing young is needed. Experimental studies on rats conducted in laboratories in Croatia and in the USA separately and as collaborative research show that Pb or Cd have effects on reproductive function. Chronic or subchronic oral Pb or Cd exposure of the dams causes decreased pup weight and survival, and depressed serum progesterone concentration in Cd‐exposed dams at the term. No paternally mediated Pb effects were found in offspring. Organ Pb or Cd accumulation was accompanied by changes in essential element concentrations in both dam and foetus. Acute in vivo and in vitro exposure to Cd had specific effects on gonadal steroidogenesis in both males and females. Proposes possible sites of action of Cd in the steroidogenic pathway.

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“…The potential of chemicals to induce placental injury, thereby compromising placental function, has been described (Juchau 1982;Miller et al 1983). Since the placenta plays a central role in maintaining pregnancy, it seems evident that toxic agents interacting with this organ could have an adverse effect on prenatal development.…”

Section: Introductionmentioning

confidence: 99%

Secretion of human chorionic gonadotropin in superfused young placental tissue exposed to cadmium

et al. 1992

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The effect of various concentrations of cadmium (Cd) in levels ranging from 0.75 to 12 micrograms/ml medium, on the secretion of human chorionic gonadotropin (hCG) in first-trimester placental explants, after 6 or 24 h incubation, employing both static and dynamic systems was examined. Later the unbound Cd was washed for 45 min with fresh medium devoid of Cd, followed by superfusion with the latter medium for 75 min, during which time samples were collected for hCG assay. For the superfusion experiments the parameters used for evaluating the hCG secretion pattern were: mean peak amplitude (MPA), pulse frequency (PF) and the area under the hCG secretion curve (AUC). The results indicate that in the dynamic system the hCG secretion increased significantly, and this increase was dose dependent. There was also a dose-related increase in mean total hCG secreted by the explants exposed to Cd. Maximal hCG secretion was observed after 24 h exposure of explants to 6 micrograms of the metal/ml. Both the MPA and AUC parameters showed a statistically significant increase for this dose level. At 12 micrograms/ml, the pulsatile secretion of hCG decreased, the value for the mean hCG secretion being comparable to that observed for 0.75 micrograms/ml. After 6 h incubation, however, there were no significant changes from the control, as judged by all of the above parameters. The levels of hCG secreted by the explants into the media in the static system were not significantly different from their respective controls, for both incubation periods and Cd levels. These results indicate that Cd may affect the normal placental function, as reflected in its hCG secretion pattern.

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The Placenta: Relevance to Toxicology

Cited by 11 publications

References 120 publications

Mode of Action: Yolk Sac Poisoning and Impeded Histiotrophic Nutrition—HBOC-Related Congenital Malformations

Mode of Action: Yolk Sac Poisoning and Impeded Histiotrophic Nutrition—HBOC-Related Congenital Malformations

Experimental studies on reproductive and perinatal effects of lead and cadmium

Secretion of human chorionic gonadotropin in superfused young placental tissue exposed to cadmium

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