Reproductive safety studies with genistein in rats

McClain, R.M.; Wolz, E.; Davidovich, A.; Edwards, John S.; Bausch, Jochen

doi:10.1016/j.fct.2007.01.009

Cited by 71 publications

(48 citation statements)

References 43 publications

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“…There has only been a limited number of reproductive safety studies conducted, which would shed light on the potential teratogenicity of those compounds that one might hypothesize because of their cyclopamine-like effects. Genistein did not cause any fetal malformations when fed to pregnant rats up to 1,000 mg/kg/d (47). Resveratrol has been reported to act as an antiteratogenic compound (48), as has curcumin (49).…”

Section: Discussionmentioning

confidence: 96%

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

et al. 2010

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Many botanical compounds have been proposed to prevent cancer. We investigated the cancer treatment and prevention abilities of apigenin, baicalein, curcumin, epigallocatechin 3-gallate (EGCG), genistein, quercetin, and resveratrol both in vivo in transgenic adenocarcinoma of the mouse prostate (TRAMP) mice as well as in vitro in prostate cancer cell lines. In our experiments, these seven compounds act similarly to the Hedgehog antagonist cyclopamine, a teratogenic plant alkaloid, which had been previously shown to "cure" prostate cancer in a mouse xenograft model. With IC 50 values ranging from <1 to 25 μmol/L, these compounds can inhibit Gli1 mRNA concentration by up to 95% and downregulate Gli reporter activity by 80%. We show that four compounds, genistein, curcumin, EGCG, and resveratrol, inhibit Hedgehog signaling as monitored by real-time reverse transcription-PCR analysis of Gli1 mRNA concentration or by Gli reporter activity. Three compounds, apigenin, baicalein, and quercetin, decreased Gli1 mRNA concentration but not Gli reporter activity. Our results show that these compounds are also able to reduce or delay prostate cancer in vivo in TRAMP mice. All seven compounds, when fed in combination as pure compounds or as crude plant extracts, inhibit well-differentiated carcinoma of the prostate by 58% and 81%, respectively. In vitro, we show that all seven compounds also inhibit growth in human and mouse prostate cancer cell lines. Mechanistically, we propose the Hedgehog signaling pathway to be a direct or indirect target of these compounds. These botanicals at pharmacologic concentrations are potentially safer and less expensive alternatives to cyclopamine and its pharmaceutical analogues for cancer therapy. Cancer Res; 70(8); 3382-90. ©2010 AACR.

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Section: Discussionmentioning

confidence: 96%

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

et al. 2010

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“…Serum concentration of phytoestrogen under a classical Asian diet is equivalent to that of a rat at the dose of 40-50 mg/kg (H et al, 1993;KS et al, 2001) and the no observed adverse eff ect level (NOAEL) of genistein is considered to be 50 mg/kg/ day (Michael et al, 2006). No treatment-related teratogenic eff ects were noted in body weight, normalized anogenital distance, serum testosterone or sperm concentration in the male offspring after exposure to GEN 300 mg /kg bw/ day (Wisniewski et al, 2005) and GEN 500 mg /kg bw/day (McClain et al, 2007) during pregnancy.…”

Section: Chemicals and F0 Treatmentmentioning

confidence: 99%

Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein

et al. 2013

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Studies of developmental eff ects of mixtures of endocrine disrupters on the male reproductive system are of great concern. In this study, the reproductive eff ects of the co-administration of di-2-(ethylhexyl) phthalate (DEHP) and genistein (GEN) during pregnancy and lactation were studied in male rat off spring. Pregnant Sprague-Dawley rats were gavaged from gestation day 3 to postnatal day 21 with vehicle control, DEHP 250 mg⁄kg body weight (bw)⁄day, GEN 50 mg⁄kg bw⁄day, GEN 400 mg⁄kg bw⁄day, and two combinations of the two compounds (DEHP 250 mg⁄kg bw⁄day + GEN 50 mg⁄kg bw⁄day, DEHP 250 mg⁄kg bw⁄day + GEN 400 mg⁄kg bw⁄day). The outcomes studied were general morphometry (weight, AGD), testicular histology, testosterone levels, and expression at the mRNA level of genes involved in steroidogenesis. Organ coeffi cient, AGD / body weight 1 / 3 , serum testosterone concentration and genes involved in steroidogenic pathway expression when exposed to DEHP (250mg/kg bw⁄day), GEN(50mg/kg bw⁄day) or GEN(400mg/kg bw⁄day) alone were not signifi cantly diff erent from the control group. When exposed to (DEHP 250mg/kg bw⁄day +GEN 50mg/kg bw⁄day) together during pregnancy and lactation, serum testosterone concentration, epididymis coeffi cient and Cypal17a1,Scarb1 m RNA expression signifi cantly decreased compared to the control and GEN(50mg/kg bw⁄day). When exposed to (DEHP 250mg/kg bw⁄day +GEN 400mg/kg bw⁄day) together during pregnancy and lactation, AGD / body weight 1 / 3 , serum testosterone concentration, testis and epididymis coeffi cient and Star, Cypal17a1 mRNA expression appeared signifi cantly decreased compared to the control and DEHP/GEN single exposure, together with developmental impairment of seminiferous tubules and seminiferous epithelium. Overall, co-administration of DEHP and GEN during gestation and lactation seem to acts in a cumulative manner to induce the most signifi cant alterations in the neonate, especially with GEN at high dose, although the eff ect of the DEHP-GEN mixture on adult off spring should be observed further.

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“…Nesse mesmo estudo, avaliou-se o potencial teratogênico da genisteína por via oral, e não se observou nenhum feto malformado na avaliação macroscópica externa. Na avaliação esquelética, observaram-se anomalias no esterno e costelas e ossificação incompleta (McClain et al, 2007).…”

Section: Discussionunclassified

Desenvolvimento pós-natal e potencial teratogênico da prole de ratos Wistar no estudo da toxicidade reprodutiva de duas preparações fitoterápicas contendo soja Glycine max (L.) Merr

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Bortolini

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et al. 2010

Arq. Bras. Med. Vet. Zootec.

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Reproductive safety studies with genistein in rats

Cited by 71 publications

References 43 publications

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

Common Botanical Compounds Inhibit the Hedgehog Signaling Pathway in Prostate Cancer

Disruption of reproductive development in male rat offspring following gestational and lactational exposure to di-(2-ethylhexyl) phthalate and genistein

Desenvolvimento pós-natal e potencial teratogênico da prole de ratos Wistar no estudo da toxicidade reprodutiva de duas preparações fitoterápicas contendo soja Glycine max (L.) Merr

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