The Phytoestrogen Quercetin Impairs Steroidogenesis and Angiogenesis in Swine Granulosa Cells In Vitro

Abstract

Experimental evidence documents that nutritional phytoestrogens may interact with reproductive functions but the exact mechanism of action is still controversial. Since quercetin is one of the main flavonoids in livestock nutrition, we evaluated its possible effects on cultured swine granulosa cell proliferation, steroidogenesis, and redox status. Moreover, since angiogenesis is essential for follicle development, the effect of the flavonoid on Vascular Endothelial Growth Factor output by granulosa cells was also taken into account. Our data evidence that quercetin does not affect granulosa cell growth while it inhibits progesterone production and modifies estradiol 17β production in a dose-related manner. Additionally, the flavonoid interferes with the angiogenic process by inhibiting VEGF production as well as by altering redox status. Since steroidogenesis and angiogenesis are strictly involved in follicular development, these findings appear particularly relevant, pointing out a possible negative influence of quercetin on ovarian physiology. Therefore, the possible reproductive impact of the flavonoid should be carefully considered in animal nutrition.

Quercetin Improves In Vitro Development of Porcine Oocytes by Decreasing Reactive Oxygen Species Levels.

“…Furthermore, parthenogenetic activation is relevant to cloning research because artificial oocyte activation is an essential component of nuclear transfer protocols [19]. The concentrations of quercetin used in this study (1,10, and 50 μg/mL) were selected based on previous results from a study of porcine granulosa cells [28]. In this study, 50 μg/mL quercetin was found to inhibit progesterone production, modify estradiol-17β production, and interfere with angiogenesis in granulosa cells by inhibiting vascular endothelial growth factor production, implying that quercetin may have a negative influence on ovarian physiology.…”

Changes in antioxidant status of porcine ovarian granulosa cells after quercetin and T-2 toxin treatment

“…[27,29] Natural antioxidants as quercetin or resveratrol can modulate ovarian function, interfering with porcine granulosa cell steroidogenic activity. [12,28] Activity of SOD and GPx were significantly decreased by T-2 toxin in the rat ovarian granulosa cells. [16] In our study T-2 toxin decreased the activity of SOD, but only slightly at the dose of 100 ng/mL.…”

“…Quercetin has been found to exhibit both estrogenic and antiestrogenic actions in vitro thus suggesting different potential effects on reproductive function. [11,12] T-2 toxin, cytotoxic fungal metabolite, belongs to the trichothecene mycotoxin family, type A. It is produced by various species of Fusarium.…”

Nitric oxide in follicle development and oocyte competence

“…Physiological hypoxia taking place during follicle growth could be an important factor inhibiting NO synthesis in swine granulosa cells (Basini et al 2004). In addition, it has been demonstrated that NO production by swine granulosa cells is modulated by physiological peptides (Basini et al 2011(Basini et al , 2014 as well as by endocrine disruptors (Santini et al 2009, Basini et al 2012.…”