Cardiovascular-Renal and Metabolic Characterization of a Rat Model of Polycystic Ovary Syndrome

Abstract

Background Polycystic ovary syndrome (PCOS) is the most common reproductive dysfunction in premenopausal women. PCOS is also associated with increased risk of cardiovascular disease at the time of PCOS and later in life. Hypertension, a common finding in women with PCOS, is a leading risk factor for cardiovascular disease. The mechanisms responsible for hypertension in women with PCOS has not been elucidated. Objectives To characterize the cardiovascular-renal consequences of hyperandrogenemia in a female rat model. Methods Female Sprague Dawley rats, aged 4–6 weeks, were implanted with DHT or placebo pellets lasting 90 days. Following 10–12 weeks, blood pressure (by radiotelemetry), renal function (glomerular filtration rate, morphology, protein and albumin excretion), metabolic parameters (plasma insulin, glucose, leptin, cholesterol, oral glucose tolerance test), inflammation (plasma TNF-α), oxidative stress (mRNA expression of NADPH oxidase subunits, p22phox, p47phox, gp91phox, and NOX4, nitrate/nitrite excretion), and mRNA expression of components of the renin-angiotensin system (RAS) (angiotensinogen, angiotensin-I-converting enzyme (ACE), AT1 receptor) were determined. Results Plasma DHT was increased 3-fold in hyperandrogenemic female 1 rats, whereas plasma estradiol levels were not different compared to control females. HAF rats exhibited estrus cycle dysfunction. They also had increased food intake and body weight, increased visceral fat, glomerular filtration rate, renal injury, insulin resistance and metabolic dysfunction, oxidative stress, and increased expression of angiotensinogen and ACE and reduced AT1 receptor expression. Conclusions The HAF rat is a unique model that exhibits many of the characteristics of PCOS in women and is a useful model in order to study the mechanisms responsible for hypertension.

Arteriolar insulin resistance in a rat model of polycystic ovary syndrome

“…As a model of human polycystic ovary syndrome, 10 weeks of DHT treatment starting during adolescence in female rats (13,14) induced significant arteriole alterations in our studies. We observed an increase in vascular diameter, a reduction of the Note: The 120-minute postload insulin level in the DHT group was significantly higher than in the control group (*P< .01).…”

“…It has been shown that an 8-12-week DHT treatment identical to the one that we used induces PCOS and significantly, approximately threefold, increases androgen levels in female rats (13). Yanes has detected several metabolic abnormalities (14). Despite normal E 2 levels, DHT-treated animals exhibited estrus cycle dysfunction.…”

“…The experimental model used in the present study has been proven to be an adequate rat PCOS model (13,14). It has been shown that an 8-12-week DHT treatment identical to the one that we used induces PCOS and significantly, approximately threefold, increases androgen levels in female rats (13).…”

“…We detected polycystic morphology in the DHT-treated groups and normal ovaries in the control groups, as published earlier in Manneras and Yanes (13,14). Morphometric measurements were made using the Pannoramic Viewer software (3D Histech).…”

“…After 90 days, this treatment altered ovarian morphology and vital parameters; early impairment of glucose metabolism was also found. The authors suggested that the DHT model is suitable for studies of the metabolic and ovarian features of the syndrome (13,14).…”