Genistein exerts estrogen-like effects in male mouse reproductive tract

Strauss, Leena; Mäkelä, Sari; Joshi, S. C.; Huhtaniemi, Ilpo; Santti, Risto

doi:10.1016/s0303-7207(98)00152-x

Cited by 105 publications

(82 citation statements)

References 30 publications

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“…In previous studies, neonatal exposure to genistein has been reported to induce structural changes in the urethroprostatic complex of rats [10] and inhibition of the growth and proliferation of testicular cells in mouse [1 1 ] . On the other hand, it has also been reported that neonatal treatment with genistein does not alter adult testis weight and most males exhibit normal mating and fertility, though a minority is infertile [29].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, coumestrol causes infertility of sheep (clover disease) [8], and daizein significantly decreases ERa and androgen receptor (AR) mRNAs in rat uterus [9]. Also for the male reproductive system, neonatal exposure to high doses of genistein induced structural changes in the urethroprostatic complex of rats [10], and inhibited the growth and proliferation of testicular cells [11]. Further, maternal vegetarianism in pregnancy was associated with fetal hypospadias [12].…”

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confidence: 99%

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Neonatal Exposure to Genistein Reduces Expression of Estrogen Receptor Alpha and Androgen Receptor in Testes of Adult Mice.

Shibayama

Fukata²,

Sakurai

et al. 2001

Endocr J

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Abstract.We investigated the long-term estrogenic influence of genistein on the male reproductive system in mice. Newborn ICR male mice were treated with genistein (10, 100, or 1000 , tg/mouse) for neonatal 5 days. As positive control, administration of diethylstilbestrol (0.5-50 pg/mouse) was carried out. In mice exposed to genistein,we examined weight of testes, sperm counts, sperm motility, and mRNA expression levels of estrogen receptor a (ERa) and androgen receptor (AR) at 4, 8 or 12 weeks after birth. Moreover, at 12 weeks of age, we evaluated protein level of ERa. In our conventional reproductive-toxicological study (weight of testes, sperm counts and sperm motility), neonatal transient exposure to genistein did not show adverse effects on the male reproductive system in 4, 8 or 12 week old mice. However, in mice treated with genistein mRNA expression levels of ERa and AR were reduced at 8 weeks. This reduction was recovered at 12 weeks in mice treated with a lower dose (10 ICg) of genistein but not in those with higher doses (100 pg and 1000 rig). In addition, ERa protein levels tended to decrease in 12 weeks of adulthood.Our results exhibited that the disruption of gene expression continued for long term such as 3 months after administration of genistein, even if no effect was found at conventional reproductive-toxicological level. We have shown that neonatal administration of weak estrogenic compound (genistein) affects male reproductive organs at molecular levels in adulthood.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Neonatal Exposure to Genistein Reduces Expression of Estrogen Receptor Alpha and Androgen Receptor in Testes of Adult Mice.

Shibayama

Fukata²,

Sakurai

et al. 2001

Endocr J

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“…There is evidence for estrogenic action of isoflavones in the prostate. Isoflavonoids induce c-fos expression in the murine prostate at doses of 0.025-2.5 mg/kg/day sc (GEN) and 5 mg/kg/day (COM, DAI) (125,126). Ten days of treatment with GEN (2.5 mg/kg/day sc) induced neoplastic transformation in neonatally estrogenized mice, whereas a sc dose of 1.2 mg/kg/day had no effect (125).…”

Section: Prostate and Testesmentioning

confidence: 99%

Cross-species and interassay comparisons of phytoestrogen action.

Whitten

Patisaul

2001

Environ Health Perspect

174

105

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This paper compiles animal and human data on the biologic effects and exposure levels of phytoestrogens in order to identify areas of research in which direct species comparisons can be made. In vitro and in vivo assays of phytoestrogen action and potency are reviewed and compared to actions, dose-response relationships, and estimates of exposure in human subjects. Binding studies show that the isoflavonoid phytoestrogens are high-affinity ligands for estrogen receptors (ERs), especially ER beta, but have lower potency in whole-cell assays, perhaps because of interactions with binding proteins. Many other enzymatic actions require concentrations higher than those normally seen in plasma. In vivo data show that phytoestrogens have a wide range of biologic effects at doses and plasma concentrations seen with normal human diets. Significant in vivoresponses have been observed in animal and human tests for bone, breast, ovary, pituitary, vasculature, prostate, and serum lipids. The doses reported to be biologically active in humans (0.4--10 mg/kg body weight/day) are lower than the doses generally reported to be active in rodents (10--100 mg/kg body weight/day), although some studies have reported rodent responses at lower doses. However, available estimates of bioavailability and peak plasma levels in rodents and humans are more similar. Steroidogenesis and the hypothalamic-pituitary-gonadal axis appear to be important loci of phytoestrogen actions, but these inferences must be tentative because good dose-response data are not available for many end points. The similarity of reported proliferative and antiproliferative doses illustrates the need for fuller examination of dose-response relationships and multiple end points in assessing phytoestrogen actions.

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“…A myriad of experimental studies were performed to explore effects of phytoestrogens on the structures and functions of the reproductive system and related mechanisms. To date, there is evidence that phytoestrogens (such as genistein, coumestrol, quercetin), given in high doses or at critical stages of development in experi-mental animals can result in severe reproductive tract disorders (Lamartiniere et al, 1995;Strauss et al, 1998;Tou et al, 1999), and temporary infertility syndromes in domestic animals have been related to high phytoestrogens consumption in grazing (Adams, 1995).…”

Section: Introductionmentioning

confidence: 99%