The impact of the phyto-oestrogen genistein on swine granulosa cell function

Dipartimento di Produzioni Animali, Biotecnologie Veterinarie, Qualità e Sicurezza degli Alimenti - Sezione di Fisiologia Veterinaria, Università degli Studi di Parma, Parma, Italy.
J Anim Physiol a Anim Nutr (Impact Factor: 1.41). 12/2010; 94(6):e374-82. DOI: 10.1111/j.1439-0396.2010.01025.x
Source: PubMed


Soya and soybean products used in swine feeding contain genistein, a non-steroidal phyto-oestrogen which has been demonstrated to influence endocrine functions. This observation leads us to design this study to evaluate the effect of genistein on swine granulosa cell steroidogenesis and proliferation. In the attempt to unravel the genistein signal transduction mechanisms, we verified the effect of lavendustin, a Tyrosine Kinase (TK) inhibitor, and the potential involvement of NO/cGMP pathway. Finally, as angiogenesis is essential for follicle development, we tested the effect of the phyto-oestrogen on vascular endothelial growth factor production and on granulosa cell redox status, because free-radical species modulate neovascularization. Our data provide evidence that genistein interferes with granulosa cell steroidogenesis while it does not modulate cell growth: this effect could be at least partially produced by inhibiting TK-dependent signalling systems. On the contrary, NO/cGMP pathway or vascular endothelial growth factor production can be excluded as signalling mechanism involved in phyto-oestrogen effects. Remarkably, genistein stimulates hydrogen peroxide production thus potentially inhibiting follicular angiogenesis. Collectively, these results suggest that genistein consumption could potentially negatively impact swine reproductive function.

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    • "It is possible that because of the different hormonal milieu to which granulosa cells from medium and large follicles had been exposed in vivo, that is, before collection [25], the cells have responded differently to subsequent in vitro treatments . In addition, the high treatment concentrations (18.5 and 185 ␮M) used by the cited authors may be responsible for the observed difference [4]. The high concentrations of both genistein (45 ␮M) and tyrphostin (100 ␮M), another PTK inhibitor, also decreased P 4 production by porcine theca and luteal cells [26]. "
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    ABSTRACT: The use of soy-based products in pig diets had raised concerns regarding the reproductive toxicity of genistein, the predominant isoflavone in soybeans. Genistein was reported to exhibit weak estrogenic activity but its mechanism of action is not fully recognized. The aim of the study was to examine the in vitro effects of genistein on (1) progesterone (P(4)) and estradiol (E(2)) secretion by porcine granulosa cells harvested from medium follicles, (2) the viability of cultured granulosa cells, and (3) the mRNA and protein expression of estrogen receptors α and β (ERα and ERβ) in these cells. In addition, to verify the role of protein tyrosine kinase (PTK)-dependent mechanisms possibly involved in genistein biological action, we tested the effects of lavendustin C, the nonsteroidal PTK inhibitor, on granulosa cell steroidogenesis. We found that genistein inhibited (P < 0.05) basal P(4) secretion by granulosa cells harvested from medium follicles of pigs. In contrast, lavendustin C did not affect basal P(4) secretion by the cells. Moreover, genistein increased (P < 0.05) basal granulosal secretion of E(2). In contrast, lavendustin C did not alter basal E(2) secretion by porcine granulosa cells. In addition, we demonstrated that genistein increased mRNA and protein expression of ERβ (P < 0.05) in the examined cells. The expression of ERα mRNA was not affected by genistein and ERα protein was not detected in the cultured granulosa cells of pigs. In summary, the genistein action on follicular steroidogenesis in pigs involved changes in the granulosal expression of ERβ. However, the genistein action on P(4) and E(2) production by granulosa cells harvested from medium follicles did not seem to be associated with PTK.
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