Effect of co‐administration of retinoids on rat embryo development in vitro

Ritchie, Helen E.; Brown‐Woodman, P. D. C.; Korabelnikoff, A

doi:10.1002/bdra.10054

Cited by 14 publications

(5 citation statements)

References 46 publications

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“…By contrast, ligands of RARs are known as potential teratogens in developing vertebrate embryos. Previous studies have demonstrated that excess RAs cause a spectrum of teratogenesis in many animals, including fish 3, 4, amphibians 5–7, and mammals 8, 9. Accordingly, the environmental occurrence of RAR agonists that disrupt RAR signaling may cause detrimental effects in humans and wild animals.…”

Section: Introductionmentioning

confidence: 99%

Detection of retinoic acid receptor agonistic activity and identification of causative compounds in municipal wastewater treatment plants in Japan

Sawada

Inoue

Wada

et al. 2011

Environmental Toxicology and Chemistry

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Retinoic acid (RA) receptor (RAR) agonists are potential toxicants that can cause teratogenesis in vertebrates. To determine the occurrence of RAR agonists in municipal wastewater treatment plants (WWTPs), we examined the RARα agonistic activities of influent and effluent samples from several municipal WWTPs in Osaka, Japan, using a yeast two-hybrid assay. Significant RARα agonistic activity was detected in all the influent samples investigated, suggesting that municipal wastewater consistently contains RAR agonists. Fractionations using high-performance liquid chromatography, directed by the bioassay, found several bioactive peaks from influent samples. The RAR agonists, all-trans RA (atRA), 13-cis RA (13cRA), 4-oxo-atRA, and 4-oxo-13cRA, possibly arising from human urine, were identified by liquid chromatography ion trap time-of-flight mass spectrometry. Quantification of the identified compounds in municipal WWTPs confirmed that they were responsible for the majority of RARα agonistic activity in WWTP influents, and also revealed they were readily removed from wastewater by activated sludge treatment. Simultaneous measurement of the RARα agonistic activity revealed that although total activity typically declined concomitant with the reduction of the four identified compounds, it remained high after the decline of RAs and 4-oxo-RAs in one WWTP, suggesting the occurrence of unidentified RAR agonists during the activated sludge treatment.

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Section: Introductionmentioning

confidence: 99%

Detection of retinoic acid receptor agonistic activity and identification of causative compounds in municipal wastewater treatment plants in Japan

Sawada

Inoue

Wada

et al. 2011

Environmental Toxicology and Chemistry

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“…However, both deficiency and excess of RAs and related retinoids during pregnancy cause abnormal morphological development (teratogenesis) of various organs and tissues, such as the eye, brain, heart, segment and limbs in the offspring (Collins and Mao, 1999;Zile, 2001). Teratogenesis by excess RAs has been observed in various vertebrates including fish (Herrmann, 1995;Haga et al, 2002), amphibians (Degitz et al, 2000(Degitz et al, , 2003Alsop et al, 2004) and mammals (Lee et al, 1995;Ritchie et al, 2003). It has also been reported that high dietary intake of vitamin A by pregnant women can cause birth defects (Rothman et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Contamination with retinoic acid receptor agonists in two rivers in the Kinki region of Japan

et al. 2010

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RARa agonistic activityRiver Surface water Yeast two-hybrid assay a b s t r a c t This study was conducted to investigate the agonistic activity against human retinoic acid receptor (RAR) a in the Lake Biwa-Yodo River and the Ina River in the Kinki region of Japan.To accomplish this, a yeast two-hybrid assay was used to elucidate the spatial and temporal variations and potential sources of RARa agonist contamination in the river basins. RARa agonistic activity was commonly detected in the surface water samples collected along two rivers at different periods, with maximum all-trans retinoic acid (atRA) equivalents of 47.6 ng-atRA/L and 23.5 ng-atRA/L being observed in Lake Biwa-Yodo River and Ina River, respectively. The results indicated that RARa agonists are always present and widespread in the rivers. Comparative investigation of RARa and estrogen receptor a agonistic activities at 20 stations along each river revealed that the spatial variation pattern of RARa agonist contamination was entirely different from that of the estrogenic compound contamination.This suggests that the effluent from municipal wastewater treatment plants, a primary source of estrogenic compounds, seemed not to be the cause of RARa agonist contamination in the rivers. Fractionation using high performance liquid chromatography (HPLC) directed by the bioassay found two bioactive fractions from river water samples, suggesting the presence of at least two RARa agonists in the rivers. Although a trial conducted to identify RARa agonists in the major bioactive fraction was not completed as part of this study, comparison of retention times in HPLC analysis and quantification with liquid chromatography-mass spectrometry analysis revealed that the major causative contaminants responsible for the RARa agonistic activity were not RAs (natural RAR ligands) and 4-oxoRAs, while 4-oxo-RAs were identified as the major RAR agonists in sewage in Beijing, China.These findings suggest that there are unknown RARa agonists with high activity in the rivers. A v a i l a b l e a t w w w . s c i e n c e d i r e c t . c o m j o u r n a l h o m e p a g e : w w w . e l s e v i e r . c o m / l o c a t e / w a t r e s w a t e r r e s e a r c h 4 4 ( 2 0 1 0 ) 2 4 0 9 -2 4 1 80043-1354/$ -see front matter ª

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“…Most importantly, when mice were exposed to subthreshold doses of CdCl 2 (0.5 mg/kg) and RA (1 mg/kg), the combined treatment exceeded the threshold, with forelimb ectrodactyly in 19% of fetuses as opposed to 0% if the response were additive. The concept that combined doses of 2 agents that are administered below the threshold can exceed the threshold was previously demonstrated by Wilson et al (1969) for 5‐fluorouracil and either uracil or thymine, by Shiota et al (1988) for ethanol and hyperthermia, and recently by Ritchie et al (2003) for active retinoids in embryo culture.…”

Section: Discussionmentioning

confidence: 91%

Interactive effects of cadmium and all-trans-retinoic acid on the induction of forelimb ectrodactyly in C57BL/6 mice

et al. 2006

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Effect of co‐administration of retinoids on rat embryo development in vitro

Abstract: Knowledge of the way in which retinyl palmitate metabolites interact should refine our ability to predict risk from a potentially teratogenic event e.g., accidental overdose with RP during human pregnancy.

Cited by 14 publications

References 46 publications

Detection of retinoic acid receptor agonistic activity and identification of causative compounds in municipal wastewater treatment plants in Japan

Detection of retinoic acid receptor agonistic activity and identification of causative compounds in municipal wastewater treatment plants in Japan

Contamination with retinoic acid receptor agonists in two rivers in the Kinki region of Japan

Interactive effects of cadmium and all-trans-retinoic acid on the induction of forelimb ectrodactyly in C57BL/6 mice

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