Normotensive rats with PCOS exhibit the hypertensive pattern: focus on oxidative stress

Abstract

Numerous evidence implies complex interrelations between polycystic ovary syndrome (PCOS) and hypertension (HT) in reproductive-age women. We aimed to investigate the potential strain differences in ovarian morphology, hemodynamic and biochemical characteristics in an androgen-induced PCOS rat model. A total of 3 weeks old 24 rats (12 Wistar Kyoto - WK and 12 Spontaneously Hypertensive Rats – SHR) were divided into four groups: WK, WK PCOS, SHR, and SHR PCOS. PCOS was induced by daily subcutaneous injections of testosterone-enanthate (1 mg/100 g body weight (BW)) administered for 5 weeks. PCOS induction led to estrus cyclicity cessation, cystic ovarian appearance, and sex hormones disturbances in both strains. The morphometric parameters in ovaries were altered in a manner of PCOS-related changes in both strains (higher number in preantral, atretic and cystic follicles). Ultrasonographycally, a significant decrease in ovarian volume (OV) was registered in PCOS groups, but also in SHR compared to WK rats. All blood pressure parameters were higher in SHR compared to WK. PCOS modeling increased systolic, mean arterial and pulse pressure in WK strain, while in SHR, only mean arterial and pulse pressure were higher. Alterations in oxidative stress parameters could provide a molecular basis for PCOS-related changes: in PCOS groups, TBARS and O2- were higher in both strains, while SOD and GSH were significantly lowered.

High Fat Diet Exaggerate Metabolic and Reproductive PCOS Features by Promoting Oxidative Stress: An Improved EV Model in Rats

“…Furthermore, levels of nitrites were higher, and alterations were in the same manner as TBARS. Similar results were also confirmed in the previous reports on male rats [ 80 , 81 ], as well as in PCOS rat models investigated in our previous studies [ 12 , 26 , 27 ]. However, our previous investigations regarding PCOS considered different methodology (androgens such as testosterone-enanthate and DHEA), while here for the first time, we evaluated the EV protocol combined with HFD.…”

“…Ovaries were measured in three dimensions to determine their volume, as well as longitudinal (D1), transverse (D2), and antero- posterior (D3) diameters. Ovarian volume was calculated by the following formula [volume = π/6 (LOD × TOD × APOD)] [ 26 ].…”

“…Three sections of the ovaries were used to monitor the evaluation of ovarian histomorphology, the number of follicular cysts, and the number of corpora lutea. Analysis was performed using an Olympus BX-51, Olympus Europa GmbH, Hamburg, Germany [ 26 ].…”

Sex differences in preclinical models of hypertension

“…Moreover, women with increased levels of testosterone e.g., women with polycystic ovary syndrome (PCOS) have an increased prevalence of cardiovascular disease risk factors, including high blood pressure and metabolic abnormalities, compared to healthy women [ 82 ], which further highlights the role of male hormones in hypertension and supports the results of testosterone administration experiments in female and castrated male animal models. Relevant in vivo models of PCOS evidencing the role of sex hormones in the development of hypertension include the oestradiol valerate (EV)-induced PCOS rat model [ 83 ], the peripubertal testosterone exposure mouse model [ 84 ], and the testosterone enanthate-induced rat model [ 85 ]. Each of these models demonstrates elevated blood pressure alongside other cardiovascular complications (Table 1 ).…”

“…↑ BP [24] ↓ NO production ↑ proinflammatory cytokines and↓ GFR in males [25] Genetic hypertensive models SHR ↑BP ↑ proteinuria and ↓ GFR in males [28] ↑ NO bioavailability in females? [40] Sex hormones [28,29] SHR-derived Y chromosome loci [34,35] Increased vascular collagen accumulation in males [37] Altered NO signalling [40] Improved renal anti-inflammatory mechanism in females [42] SHRSP ↑BP ↑ stroke incidence [46] ↑ inflammation and ↑ kidney dysfunction in males [47,48] ↓ NO bioavailability in males [47] SHRSP-derived Y chromosome loci [49,50] ↑ inflammatory state in males [54,55] Impaired NO-induced relaxation in males [47] DSS rat ↑ BP ↑ kidney damage [61] Sex hormones [58,59,61] ↑ Sympathetic activation in males [57,60] and ↑ vasodilatory prostaglandins in females [60] Hormone-induced PCOS rodent models (EV)-induced PCOS rat model [83] ↑ BP compared to female controls [83] ↑ Sympathetic activity in PCOS females [83] Peripubertal testosterone exposure mouse model [84] ↑ BP and ↑ dyslipidaemia compared to female controls [84] Testosterone enanthate-induced rat model [85] ↑ BP compared to female controls [85] Oxidative stress dysregulation in PCOS females [85] adults whose blood pressure levels are up to 6% higher in men compared to women [79]. It is important to note that these marked differences diminish after menopause: women have an increase in blood pressure which peaks at >70 years-old when the prevalence of hypertension is highe...…”