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Comparative effects of 17β-estradiol and phytoestrogens in the regulation of endometrial functions in the rodent uterus

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Abstract

The present study aimed at improving our understanding of the effects of 17β-estradiol and phytoestrogens on the uterine tissue, by evaluating tissue-specific modulation of molecules related to cell-cycle control and angiogenesis. Specifically, the uterine expression of Ki67, peroxisome proliferator-activated receptor γ (PPARγ), and vascular endothelial growth factor receptor-2 (VEGFR-2), was examined by immunohistochemical analysis. Ovariectomized (OVX) rats were treated with either the vehicle, a phytoestrogen-containing soy extract (SSE) (100 mg/kg/day pos), or 17β-estradiol (0.5 mg/kg/day pos); a sham control group (SHAM) was also included in the study. At necropsy, uteri were weighed, collected, and subsequently processed for histopathology or immunohistochemistry. SSE-treated rats did not show any significant change either in the weight or in histological features of the uterus when compared to OVX controls; the epithelial expression of proliferation marker Ki67 was seen to be significantly reduced, in comparison to both SHAM and OVX rats. Conversely, 17β-estradiol significantly increased uterine weight, induced hyperplasia in the majority of rats, and enhanced Ki67 epithelial expression. The regulation of PPARγ expression, reduced after ovariectomy, was similar in SSE- and 17β-estradiol-treated rats, showing a further significant decrease in stromal immunostaining, in comparison to OVX controls. VEGFR-2 epithelial immunostaining, slightly reduced following ovariectomy, was highly increased on 17β-estradiol treatment, while following SSE, the pattern of staining observed was similar to that of OVX controls. Data from this study show that PPARy and VEGFR-2 represent additional targets by which sex steroid estrogen and plant-derived phytoestrogens may, at certain doses, differentially regulate endometrial functions.

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, L.go A. Gemelli 8, 00168, Rome, Italy

    D. Gallo, M. Fabrizi, I. De Stefano, E. Mantuano & G. Scambia MD, PhD

  2. Department of Histopathology, Catholic University of the Sacred Heart, Rome

    G. F. Zannoni

  3. Department of Oncology, Catholic University of the Sacred Heart, Campobasso, Italy

    G. Scambia MD, PhD

Authors
  1. D. Gallo
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  2. G. F. Zannoni
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  3. M. Fabrizi
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  4. I. De Stefano
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  5. E. Mantuano
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  6. G. Scambia MD, PhD
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Correspondence to G. Scambia MD, PhD.

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Gallo, D., Zannoni, G.F., Fabrizi, M. et al. Comparative effects of 17β-estradiol and phytoestrogens in the regulation of endometrial functions in the rodent uterus. J Endocrinol Invest 31, 48–56 (2008). https://doi.org/10.1007/BF03345566

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