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.

Giovanna Di Emidio,Giulia Rossi,Paolo Giovanni Artini,Guido Macchiarelli,Francesco Rea,Domenica Cocciolone,Maria Grazia Palmerini,Carla Tatone,Ashraf Virmani,Anna Maria D’Alessandro,Martina Placidi

doi:10.3390/antiox9090867

Giovanna Di Emidio, Giulia Rossi + Show 9 more

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https://doi.org/10.3390/antiox9090867

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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.

Highlights

The polycystic ovarian syndrome (PCOS) is a metabolic and endocrine condition affecting 4–21% of women in reproductive age [1,2]
Administration of carnitines formulation 1 did not prevent loss of estrous cyclicity induced by DHEA in 80% of mice during the whole length of treatment (Figure 1D)
Contrast, ovaries from mice receiving administration of acyl-L-carnitines alleviates ovarian dysfunctions associated with this syndrome carnitine formulation 1 and 2 presented lower levels of RAGE in comparison to DHEA (Figure 5)

Summary

Introduction

The polycystic ovarian syndrome (PCOS) is a metabolic and endocrine condition affecting 4–21% of women in reproductive age [1,2]. Antioxidants 2020, 9, 867 and polycystic ovaries [3] This syndrome is usually associated with insulin resistance, metabolic disorders, and infertility [3], and in the long run with diabetes and cardiovascular disease. Many studies have suggested a central role for oxidative and glycative stresses in the pathogenesis of the PCOS and a decreased antioxidant capacity in patients with PCOS [4,5,6,7]. It has been demonstrated that PCOS patients consuming antioxidants present an amelioration of ovarian function and morphology, with a reduction of oxidative stress [8]

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