Regulatory Functions of L Carnitine, Acetyl, and Propionyl L Carnitine in a PCOS Mouse Model: Focus on Antioxidant/Antiglycative Molecular Pathways in the Ovarian Microenvironment
Polycystic ovary syndrome (PCOS) is a complex metabolic disorder associated with female infertility. Based on energy and antioxidant regulatory functions of carnitines, we investigated whether acyl L carnitines improve PCOS phenotype in a mouse model induced by dehydroepiandrosterone (DHEA) CD1 mice received DHEA for 20 days along with two different carnitine formulations: one containing L carnitine (LC) and acetyl L carnitine (ALC) and the other one containing also propionyl L carnitine (PLC) We evaluated estrous cyclicity, testosterone level, ovarian follicle health, ovulation rate and oocyte quality, collagen deposition, lipid droplets, and 17ss HSD IV (17 beta hydroxysteroid dehydrogenase type IV) expression. Moreover, we analyzed protein expression of SIRT1, SIRT3, SOD2 (superoxide dismutase 2) mitochondrial transcriptional factor A (mtTFA) RAGE (receptor for AGEs) GLO2 (glyoxalase 2) and ovarian accumulation of MG AGEs (advanced glycation end products formed by methylglyoxal) Both carnitine formulations ameliorated ovarian PCOS phenotype and positively modulated antioxidant molecular pathways in the ovarian microenvironment. Addition of PLC to LC ALC formulation mitigated intraovarian MG AGE accumulation and increased mtTFA expression. In conclusion, our study supports the hypothesis that oral administration of acyl L carnitines alleviates ovarian dysfunctions associated with this syndrome and that co administration of PLC provides better activity. Molecular mechanisms underlying these effects include anti oxidant/glycative activity and potentiation of mitochondria.
Antioxidants