Influence of Vitamin D on the Vasoactive Effect of Estradiol in a Rat Model of Polycystic Ovary Syndrome

Abstract

We examined the vasoactive effect of estradiol in a rat model of early PCOS and the influence of vitamin D deficiency (VDD). We created a model of chronic hyperandrogenism and VDD in adolescent female Wistar rats (N = 46) with four experimental groups: vitamin D supplemented (T-D+), VDD (T-D-), hyperandrogenic and vitamin D supplemented (T+D+), and hyperandrogenic and VDD (T+D-). T+ groups received an 8-week-long transdermal Androgel treatment, D- animals were on vitamin D-reduced diet and D+ rats were supplemented orally with vitamin D3. Estrogen-induced vasorelaxation of thoracic aorta segments were measured with a wire myograph system with or without the inhibition of endothelial nitric oxide synthase (eNOS) or cyclooxygenase-2 (COX-2). The distribution of estrogen receptor (ER), eNOS and COX-2 in the aortic wall was assessed by immunohistochemistry. VDD aortas showed significantly lower estradiol-induced relaxation independently of androgenic status that was further decreased by COX-2 inhibition. COX-2 inhibition failed to alter vessel function in D+ rats. Inhibition of eNOS abolished the estradiol-induced relaxation in all groups. Changes in vascular function in VDD were accompanied by significantly decreased ER and eNOS staining. Short-term chronic hyperandrogenism failed to, but VDD induced vascular dysfunction, compromised estrogen-dependent vasodilatation and changes in ER and eNOS immunostaining.

Effects of Gender and Vitamin D on Vascular Reactivity of the Carotid Artery on a Testosterone-Induced PCOS Model

“…There has been less research in the literature on how estrogen receptor levels change under the influence of PCOS outside the ovaries and endometrium. Estrogen receptor optical density increased in aortic endothelium after chronic Androgel treatment [25]. In our myographic measurements, we did not see any change in estrogen-induced relaxation in our PCOS animals, which could be explained by the fact that we did not see any difference in estrogen receptor density.…”

“…PCOS is also often associated with vitamin D deficiency [24], so both the hyperandrogenic state and vitamin D deficiency can have adverse cardiovascular effects in PCOS women. Previous literature has investigated how vascular function is impaired in animals with PCOS compared with healthy females [25,26]. However, whether the vascular function of PCOS female animals differs from that of healthy males has been less investigated.…”

“…The originality of the research concept is that we analyzed the effects of testosterone and vitamin D according to gender. We used a hyperandrogenic female PCOS model as described before [25,28].…”

The effect of human menstrual blood-derived stem cells on ovarian folliculogenesis, angiogenesis and collagen volume in female rats affected by the polycystic ovary syndrome

“…PCOS is one of the most common endocrine-related metabolic disorders in women with high-level androgens, anovulation, and polycystic ovaries. It affects 5-20 percent of women of reproductive age (3), with complications including menstrual irregularities, infertility, hirsutism and cardiovascular diseases (CVD) (4). Women with PCOS have a large number of small antral follicles (more than twice the number of normal ovaries) at the periphery of the ovary but many do not proceed in the physiological growth leading to ovulation disorders or anovulation (5).…”

The effect of human menstrual blood-derived stem cells on ovarian folliculogenesis, angiogenesis and collagen volume in female rats affected by the polycystic ovary syndrome

“…PCOS is one of the most common endocrine-related metabolic disorders in women with high-level androgens, anovulation, and polycystic ovaries. It affects 5–20% of women of reproductive age [ 3 ], with complications including menstrual irregularities, infertility, hirsutism and cardiovascular diseases (CVD) [ 4 ].…”