Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens

Boberg, Julie; Mandrup, Karen; Jacobsen, Peter; Isling, Louise Krag; Hadrup, Niels; Berthelsen, Line Olrik; Elleby, Anders; Kiersgaard, Maria Kristina; Vinggaard, Anne Marie; Hass, Ulla; Nellemann, Christine

doi:10.1016/j.reprotox.2013.05.014

Cited by 30 publications

(16 citation statements)

References 47 publications

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“…Plants appear as a therapeutic option, since some of their constituents have the ability to bind to estrogen receptors and to act in preventing the discomfort caused by the hormonal imbalance associated with menopause. These constituents are also related to the reduction of cancer incidence, particularly estrogen-dependent cancers, such as breast cancer, cardiovascular diseases and osteoporosis [11-14]. …”

Section: Introductionmentioning

confidence: 99%

Estrogenic and mutagenic activities of Crotalaria pallida measured by recombinant yeast assay and Ames test

Boldrin

Resende

Höhne

et al. 2013

BMC Complement Altern Med

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BackgroundCrotalaria pallida Ailton is a plant belonging to the Fabaceae family, popularly known as “rattle or rattlesnake” and used in traditional medicine to treat swelling of the joints and as a vermifuge. Previous pharmacological studies have also reported anti-inflammatory, antimicrobial and antifungal activities. Nevertheless, scientific information regarding this species is scarce, and there are no reports related to its possible estrogenic and mutagenic effects. Thus, the purpose of the present study was to investigate the estrogenic potential of C. pallida leaves by means of the Recombinant Yeast Assay (RYA), seeking an alternative for estrogen replacement therapy during menopause; and to reflect on the safe use of natural products to assess the mutagenic activity of the crude extract from C. pallida leaves, the dichloromethane fraction and stigmasterol by means of the Ames test.MethodsThe recombinant yeast assay with the strain BY4741 of Saccharomyces cerevisiae, was performed with the ethanolic extract, dichloromethane fraction and stigmasterol isolated from the leaves of C. pallida. Mutagenic activity was evaluated by the Salmonella/microsome assay (Ames test), using the Salmonella typhimurium tester strains TA100, TA98, TA97 and TA102, with (+S9) and without (-S9) metabolization, by the preincubation method.ResultsAll samples showed estrogenic activity, mainly stigmasterol. The ethanolic extract from C. pallida leaves showed mutagenic activity in the TA98 strain (-S9), whereas dichloromethane fraction and stigmasterol were found devoid of activity.ConclusionConsidering the excellent estrogenic activity performed by stigmasterol in the RYA associated with the absence of mutagenic activity when evaluated by the Ames test, stigmasterol becomes a strong candidate to be used in hormone replacement therapy during menopause.

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Section: Introductionmentioning

confidence: 99%

Estrogenic and mutagenic activities of Crotalaria pallida measured by recombinant yeast assay and Ames test

Boldrin

Resende

Höhne

et al. 2013

BMC Complement Altern Med

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“…Flaxseed lignans are structurally similar to soybean isoflavones and endogenous estrogens and despite their benefits, can exert endocrine imbalances, affecting the male reproductive system (Duncan et al 2003, Boberg et al 2013. Therefore, the concentrations of lignans and its derivatives have gained attention because of the possibility of them affecting the gonadal morphology and hormone metabolism at certain administration doses and duration (Tou et al 1999(Tou et al , 1998.…”

Section: Discussionmentioning

confidence: 99%

“…Current studies have focused on soybean isoflavones and their effects on reproductive health. Because of their similarity to these phytoestrogens, flaxseeds have been suggested to affect reproductive development (Boberg et al 2013). Therefore, the present study aims at evaluating the changes in the testicular and epididymal morphology of rats whose mothers were administered flaxseed diets, from lactation to offspring adulthood (i.e., after 250 days of ingestion).…”

Section: Introductionmentioning

confidence: 99%

Influence of prolonged flaxseed ( Linum usitatissimum ) consumption over epididymis and testicle histoarchitecture of Wistar rats

et al. 2017

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Flaxseed is considered a functional food with several health benefits. However, because of its high phytoestrogen content, flaxseed influences hormone metabolism and affects the gonadal biomorphology. In this study, computerized histomorphometry was used to evaluate seminiferous and epididymal tubules, considering the different regions of the epididymis (head, body and tail) of rats subjected to a prolonged diet of flaxseed. Young adult male Wistar rats (n=20) were divided into 2 groups during their lactation period: Control Group (CG), fed casein-based meals and Flaxseed Group (FG), fed a 25% flaxseed meal. After 250 days of continuous ingestion, the animals were euthanized and a blood sample was collected. The testicles and epididymis were removed and fixed in buffered formalin solution. The samples were subjected to routine histological paraffin techniques and stained with hematoxilin and eosin. Immunostaining was performed using an antivimentin antibody for Sertoli cell identification. For morphometry, images of the slides were scanned and analyzed using Image J to determine the epithelial height, tubular and luminal diameter and tubular and luminal area. In the hormonal evaluation, FG had a higher serum concentration of estrogen (P=0.001), but no change was observed in the concentration of testosterone. The morphometric assay of seminiferous tubules and epididymal regions revealed no significant differences between the analyzed groups. Similarly, Sertoli cell quantification showed no significant differences in the FG (P=0.98). These results revealed that the continuous and prolonged intake of 25% flaxseed meals from gestation to 250 days of age, even with a significant increase in serum levels of estradiol, does not exert adverse effects on the testicular and epididymal structure or on the cells participating in the spermatogenesis of rats. seu elevado teor de fitoestrógenos, esta semente pode influenciar no metabolismo hormonal e interferir na biomorfologia gonadal. Neste estudo, utilizamos a histomorfometria computadorizada para avaliar os túbulos seminíferos e epididimários, considerando as diferentes regiões do epiPesq. Vet. Bras. 37(6):650-656, junho 2017 651 Influence of prolonged flaxseed (Linum usitatissimum) consumption over epididymis and testicle histoarchitecture of Wistar rats dídimo (cabeça, corpo e cauda) de ratos submetidos a uma dieta prolongada de semente de linhaça. Foram utilizados ratos Wistar machos adultos jovens (n=20) divididos em 2 grupos, durante o período de lactação: Grupo Controle (GC) a base de caseína e Grupo Linhaça (GL) alimentados com 25% de semente de linhaça. Ao final de 250 dias de ingestão contínua, os animais foram sacrificados e amostra de sangue foi coletada. Os testículos e epidídimos foram retirados e fixados em formol tamponado. As amostras foram submetidas ao processamento histológico de rotina para parafina e coradas em hematoxilina e eosina. Foi feita a imunomarcação com anticorpo antivimentina para identificação das células de Sertoli. Para morfometria, as im...

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“…A range of studies [113,[123][124][125] indicate that the male rat MG is very sensitive to estrogen and may serve as a model for investigating the effects of EDs, although relevance for the female MG would have to be established [113,126].…”

Section: Other Tools To Improve Testingmentioning

confidence: 99%

Evaluating chemical effects on mammary gland development: A critical need in disease prevention

Osborne¹,

Rudel

Schwarzman³

2015

Reproductive Toxicology

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Although understanding the environmental factors that contribute to breast cancer could improve disease prevention, standard chemical testing protocols do not adequately evaluate chemicals' effects on breast development. Evidence suggests: (1) mammary gland (MG) development is a complex process that extends from gestation through fetal and neonatal growth, puberty, and pregnancy; (2) altered MG development can increase the risk of breast cancer and other adverse outcomes; and (3) chemical exposures during susceptible windows of development may alter the MG in ways that increase risk for later disease. Together, these highlight the need to better understand the complex relationship between exposure to endocrine disrupting compounds (EDCs) and the alterations in MG morphology and gene expression that ultimately increase disease risk. Changing guideline toxicity testing studies to incorporate perinatal exposures and MG whole mounts would generate critical knowledge about the effects of EDCs on the MG and could ultimately inform disease prevention.

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Endocrine disrupting effects in rats perinatally exposed to a dietary relevant mixture of phytoestrogens

Cited by 30 publications

References 47 publications

Estrogenic and mutagenic activities of Crotalaria pallida measured by recombinant yeast assay and Ames test

Estrogenic and mutagenic activities of Crotalaria pallida measured by recombinant yeast assay and Ames test

Influence of prolonged flaxseed ( Linum usitatissimum ) consumption over epididymis and testicle histoarchitecture of Wistar rats

Evaluating chemical effects on mammary gland development: A critical need in disease prevention

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