Alterazioni morfofunzionali indotte dalla sindrome nell’ovaio policistico (PCOS) in un modello murino: effetto protettivo delle carnitine

Polycystic ovarian syndrome (PCOS) is a heterogeneous condition characterized by hyperandrogenism (HA), polycystic ovaries, and dysfunctional ovulation, and it is associated with metabolic problems, such as insulin resistance (IR) and obesity. After having investigated the morphological and antioxidant/antiglycative alterations on the ovaries collected from PCOS mice induced by dehydroepiandrosterone (DHEA), in this PhD thesis the attention was focused on uteri, oviducts, brain and liver using the same experimental model. The modulating effects of the antioxidants L-carnitine (LC) and acetyl-L-carnitine (ALC), as oral supplements in the diet, were also assessed. CD1 mice were administered or not with DHEA (6 mg/100 g body weight) for 20 days, alone or with 0.40 mg of L-carnitine (LC) and 0.20 mg of acetyl-L-carnitine (ALC). Samples were then subjected to histology and immunohistochemistry (IHC) to evaluate morphology, collagen deposition, and steroidogenesis. Oxidative, mitochondrial, and methylglyoxal (MG)-dependent damages were also investigated by IHC. Transmission Electron Microscopy (TEM) was used to detect ultrastructural alterations in the oviducts. PCOS uteri, oviducts and brain were affected by hyperfibrosis, hyperplasia, hypertrophy; altered steroidogenesis, with oxidative alterations associated with MethylGlyoxal-Advanced Glycation End product (MG-AGE) accumulation, were observed. PCOS liver had vacuolated and necrotic cells, with the presence of an inflammatory status, evidenced by IL-1β. LC-ALC administration mitigated most of the PCOS-induced morphofunctional alterations. These results provide evidence for the detrimental action of oxidative and glycative stress in PCOS uteri, oviducts, brain and liver, confirming a protective role of carnitines on the PCOS phenotype.