Impact of genistein on maturation of mouse oocytes, fertilization, and fetal development

Department of Bioscience Technology and Center for Nanotechnology, Chung Yuan Christian University, 200, Chung Pei Road, Chung Li 32023, Taiwan.
Reproductive Toxicology (Impact Factor: 3.23). 08/2009; 28(1):52-8. DOI: 10.1016/j.reprotox.2009.03.014
Source: PubMed


Genistein (GNT), a natural isoflavone compound found in soy products, affects diverse cell functions, including proliferation, differentiation and cell death. An earlier study by our group showed that GNT has cytotoxic effects on mouse blastocysts and is associated with defects in their subsequent development in vitro. Here, we further investigate the effects of GNT on oocyte maturation, and subsequent pre- and postimplantation development, both in vitro and in vivo. GNT induced a significant reduction in the rate of oocyte maturation, fertilization, and in vitro embryo development. Treatment of oocytes with GNT during in vitro maturation (IVM) led to increased resorption of postimplantation embryos, and decreased placental and fetal weights. With the aid of an in vivo mouse model, we showed that consumption of drinking water containing GNT led to decreased oocyte maturation and in vitro fertilization, as well as early embryonic developmental injury. Moreover, our findings support a degree of selective inhibition of retinoic acid receptors in blastocysts treated with GNT during oocyte maturation. To our knowledge, this is the first study investigating the impact of GNT on maturation of mouse oocytes, fertilization, and sequential embryonic development.

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    • "Additionally, studies have been conducted for evaluating the effects of various compounds on embryonic development: 3-hydroxyflavone [6] has been shown to have a beneficial effect on embryonic development, whereas studies suggest that flavonoids such as genistein [7], ginkgolides [8], and daidzein [9] may be toxic. "
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    ABSTRACT: Treatment with resveratrol at concentrations greater than 0.5 μmol/L resulted in the arrest of mouse embryo development at the two-cell stage. Resveratrol-induced cytotoxicity was investigated in embryos by evaluating morphologic features by using the bromodeoxyuridine assay and acridine orange and ethidium bromide double staining. Resveratrol was found to significantly increase the expressions of p53, p21, Atf3, smac/Diablo, Bax, Bak1, Bok, and Noxa mRNA in the embryos, whereas Cullin 3 and Cdk1 expressions were decreased. Furthermore, active p53 positive signal in embryos arrested at the two-cell stage was localized in the nucleus, whereas no active p53 signal was observed in control embryos. Pretreatment with pifithrin-α, a p53 inhibitor, downregulated active p53 in two-cell embryo nuclei and ameliorated approximately 50% of the embryonic developmental defect caused by resveratrol. The findings of the present study, therefore, suggest that pifithrin-α could be used as an effective cytoprotective agent against a reproductive toxin such as resveratrol. Copyright © 2015 Elsevier Inc. All rights reserved.
    Theriogenology 11/2014; 83(5). DOI:10.1016/j.theriogenology.2014.11.023 · 1.80 Impact Factor
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    • "Studies have been performed investigating the effect at low concentration of genistein (Chan 2009) on mouse, and daidzein (Galeati et al. 2010) on pig IVM, fertilization and development, but using cumulus-oocyte complexes (COCs), although in the present study, cumulus-oophorous complexes were completely removed to eliminate the possibility that cumulus cells might be responsible for the buffering of cytotoxicity. In these earlier studies, Genistein produced a slight decrease in IVM in a dose dependent manner between 1 and 10 lM (Chan 2009). As there was no significant difference between control and 5 lM genistein in our system (Fig. 2a), this discrepancy may indeed have occurred due to the buffering effect of cumulus cells, rather than due to a direct effect on oocytes. "
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    ABSTRACT: Phytoestrogens are a group of naturally occurring compounds that have weak estrogenic activity. Genistein and daidzein are major phytoestrogens produced by soybeans. It has been reported previously that at high concentration, some phytoestrogens inhibit cell cycle progression of mouse germinal vesicle (GV) oocytes, but the environmentally relevant level is much lower. Here we show the effects of low concentrations of the isoflavones genistein, daidzein and the daidzein metabolite, equol, on mouse oocyte maturation. GV oocytes denuded of cumulus cells were cultured in TaM medium containing low levels (5 μM) of genistein, daidzein. or equol. In all cases, the oocytes underwent normal GV break down, first polar body extrusion and became arrested at metaphase II (mII). As judged by fluorescence microscopy, the treated mII oocytes exhibited normal distributions of actin microfilaments, cortical granules and metaphase spindle formation with condensed metaphase chromatin. Moreover, mRNA expression levels of the cytostatic factors Emi2 and Mos were similar to those of their respective controls. These data suggest that exposure of maturing GV oocytes to environmental levels of genistein, daidzein or equol in vitro do not cause negative effects on maturation to produce mII oocytes.
    Cytotechnology 06/2011; 64(3):241-7. DOI:10.1007/s10616-011-9369-2 · 1.75 Impact Factor
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    ABSTRACT: The mechanisms of prolactin signal transduction in generative and somatic cells of mammalian ovarian follicles are poorly understood. In this work, participation of tyrosine kinases and protein kinase C in mediation of the previously revealed modulating effects of prolactin on the nuclear maturation of bovine oocytes and the morphologic and functional state of surrounding cumulus cells in vitro has been investigated. It was found that a tyrosine kinase inhibitor genistein suppresses the stimulating action of prolactin on the completion of oocyte nuclear maturation and cumulus expansion, whereas a protein kinase C inhibitor calpostin C does not affect the hormonal effect. Furthermore, both genistein and calpostin C inhibited the inducing influence of prolactin on the proliferative activity of cumulus cells. At the same time, the retarding action of prolactin on destructive processes in cumulus cells was blocked only in the presence of calpostin C. These results show that the stimulating influence of prolactin on oocyte nuclear maturation accompanied by cumulus expansion is achieved with participation of tyrosine kinases, whereas the modulating action of the hormone on the functional state of cumulus cells depends on activation both of tyrosine kinases and protein kinase C.
    Cell and Tissue Biology 12/2011; 5(6). DOI:10.1134/S1990519X11060071
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