Hypoxia-inducible factor and vascular endothelial growth factor are targets of dietary soy during acute stroke in female rats.

Dietary soy and soy isoflavones are neuroprotective in experimental cerebral ischemia. Because these isoflavones have estrogenic properties, we hypothesized that, like estrogens, they would inhibit acute vascular injury and the detrimental acute increase in hypoxia-induced vascular endothelial growth factor (VEGF) that leads to cerebral edema after stroke. Mature ovariectomized female Sprague Dawley rats were fed soy-free or soy-containing diets for 4 weeks followed by 90 minutes of transient middle cerebral artery occlusion.

Effect of high soy diet on the cerebrovasculature and endothelial nitric oxide synthase in the ovariectomized rat.

High soy (HS) diets are neuroprotective and promote vascular dilatation in the periphery. We hypothesized that an HS diet would promote vascular dilatation in the cerebrovasculature by mimicking estradiol's actions on the endothelial nitric oxide synthase (eNOS) system including increasing eNOS expression and decreasing caveolin-1 expression to increase nitric oxide (NO) production. Ovariectomized rats were fed HS or a soy-free diet (SF)+/-low physiological estradiol (E2) for 4weeks.

Protective effect of estrogen in endothelin-induced middle cerebral artery occlusion in female rats.

Estrogen is a powerful endogenous and exogenous neuroprotective agent in animal models of brain injury, including focal cerebral ischemia. Although this protection has been demonstrated in several different treatment and injury paradigms, it has not been demonstrated in focal cerebral ischemia induced by intraparenchymal endothelin-1 injection, a model with many advantages over other models of experimental focal ischemia. Reproductively mature female Sprague-Dawley rats were ovariectomized and divided into placebo and estradiol-treated groups.

A high soy diet enhances neurotropin receptor and Bcl-XL gene expression in the brains of ovariectomized female rats.

Estrogen is a powerful neuroprotective agent with the ability to induce trophic and antiapoptotic genes. However, concerns about negative overall health consequences of estrogen replacement after menopause have led to the adoption of other strategies to obtain estrogen's benefits in the brain, including the use of selective estrogen receptor modulators, high soy diets, or isoflavone supplements. This study sought to determine the ability of a high soy diet to induce neuroprotective gene expression in the female rat brain and compare the actions of soy with estrogen.

Granulosa cell expression of G1/S phase cyclins and cyclin-dependent kinases in PMSG-induced follicle growth.

Follicular development involves a complex orchestration of granulosa cell proliferation and differentiation. It is becoming increasingly apparent that the rate of granulosa cell proliferation declines as follicles reach the large antral status, prior to an ovulatory gonadotropin stimulus, although a precise time course and mechanism for this decline has not been described. The goal of the present study was to characterize granulosa cell proliferation following the onset of antral follicle growth in PMSG-primed immature rats, with emphasis on G1/S phase cyclins and cyclin-dependent kinases.

The peroxisome proliferator-activated receptor gamma ligand troglitazone induces apoptosis and p53 in rat granulosa cells.

PPARgamma is expressed in both the rodent and human ovary, but the endogenous activation state of PPARgamma in the ovary and its normal role in ovarian function remain unclear. Here, we investigated mRNA and protein expression as well as DNA-binding activity of PPARgamma during follicle growth and luteinization in the immature, gonadotropin-primed rat model. Gel shift analysis demonstrated binding of ovarian PPAR to a consensus peroxisome proliferator response element (PPRE) that was supershifted with an antibody specific for PPARgamma, but not with antibodies specific for PPARalpha or beta/delta.

Dual activation of PPARalpha and PPARgamma by mono-(2-ethylhexyl) phthalate in rat ovarian granulosa cells.

Peroxisome proliferator-activated receptors (PPARs) are key regulators of lipid metabolism and cell differentiation. The plasticizer di-(2-ethylhexyl) phthalate is a peroxisome proliferator, and its active metabolite mono-(2-ethylhexyl) phthalate (MEHP) activates PPARalpha and PPARgamma in cell transactivation assays. MEHP is a female reproductive toxicant and decreases activity, mRNA, and protein levels of aromatase, the rate-limiting enzyme that converts testosterone to estradiol in ovarian granulosa cells.

Mechanisms of phthalate ester toxicity in the female reproductive system.

Phthalates are high-production-volume synthetic chemicals with ubiquitous human exposures because of their use in plastics and other common consumer products. Recent epidemiologic evidence suggests that women have a unique exposure profile to phthalates, which raises concern about the potential health hazards posed by such exposures. Research in our laboratory examines how phthalates interact with the female reproductive system in animal models to provide insights into the potential health effects of these chemicals in women.