1. 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
- Author
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Carla Tatone, Domenica Cocciolone, Giulia Rossi, Anna Maria D'Alessandro, Martina Placidi, Giovanna Di Emidio, Ashraf Virmani, Guido Macchiarelli, Maria Grazia Palmerini, Francesco Rea, and Paolo Giovanni Artini
- Subjects
0301 basic medicine ,medicine.medical_specialty ,endocrine system ,endocrine system diseases ,L-carnitine (LC) ,Physiology ,Propionyl-L-carnitine (PLC) ,Clinical Biochemistry ,SOD2 ,Dehydroepiandrosterone ,Acetyl-L-carnitine (ALC) ,Biochemistry ,Article ,Superoxide dismutase ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,PCOS ,acetyl-L-carnitine (ALC) ,propionyl-L-carnitine (PLC) ,mitochondria ,advanced glycation end-products ,sirtuins ,oocyte quality oxidative stress ,glycative stress ,Internal medicine ,medicine ,Sirtuins ,Carnitine ,Ovarian follicle ,Advanced glycation end-products ,Molecular Biology ,Oocyte quality oxidative stress ,030219 obstetrics & reproductive medicine ,biology ,Glycative stress ,Mitochondria ,Chemistry ,lcsh:RM1-950 ,Methylglyoxal ,Cell Biology ,TFAM ,Polycystic ovary ,lcsh:Therapeutics. Pharmacology ,030104 developmental biology ,medicine.anatomical_structure ,Endocrinology ,biology.protein ,medicine.drug - Abstract
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.
- Published
- 2020