L-Carnitine improves endocrine function and folliculogenesis by reducing inflammation, oxidative stress and apoptosis in mice following induction of polycystic ovary syndrome

Abstract

Polycystic ovary syndrome (PCOS) is related to low levels of serum l-carnitine, which has antioxidant, anti-inflammatory and antiapoptotic properties. The aim of this study was to investigate the effect of l-carnitine on folliculogenesis in mice following induction of PCOS. PCOS was induced by daily injections of testosterone enanthate (1mg per 100g, s.c., for 35 days). NMRI mice (21 days old) were divided into four groups (n=6 per group): Control, Control+l-carnitine, PCOS and PCOS+l-carnitine. Mice were treated with 500mgkg−1, i.p., l-carnitine every second day for 28 days. Ovaries were studied stereologically and serum concentrations of FSH, LH, testosterone, interleukin (IL)-6 and tumour necrosis factor (TNF)-α were determined using ELISA kits. Serum concentrations of malondialdehyde (MDA) and the ferric ion reducing antioxidant power (FRAP) were also analysed. Apoptosis of follicles was evaluated by terminal deoxyribonucleotidyl transferase-mediated dUTP–digoxigenin nick end-labelling (TUNEL). CD31 was assessed immunohistochemically. Data were analysed using one-way analysis of variance (ANOVA) and Tukey’s test, differences considered significant at P<0.05.The total volume of the ovary, cortex volume, oocyte volume, zona pellucida thickness and the number of antral follicles increased significantly, whereas the number of primary and preantral follicles decreased significantly, in the PCOS+l-carnitine versus PCOS group. In the PCOS+l-carnitine group, serum concentrations of FSH and FRAP increased significantly, whereas there were significant decreases in serum concentrations of testosterone, LH, MDA, IL-6 and TNF-α, as well as in the percentage of TUNEL-positive apoptotic cells, compared with the PCOS group. l-Carnitine improves folliculogenesis and is therefore suggested as a therapeutic supplement in the treatment of PCOS.

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

“…Regarding LC and ALC, our results are in line with previous observations on humans and mouse model. Numerous studies report that LC supplementation counteracts metabolic and hormonal PCOS symptoms and positively affects folliculogenesis, ovulation and pregnancy rate [4,9,[23][24][25][26][27][28][29], possibly in relation to favorable influence on serum biomarkers of oxidative stress [40]. Samimi et al [10] observed that PCOS patients receiving both ALC and LC presented the reduction of body weight and insulin resistance.…”

“…In two different studies, LC administration has improved menstrual cycle regularity, ovulation and pregnancy rates [9,23]. At the ovarian level, Kalhori et al [29] observed in a PCOS mouse model alterations in ovarian volume and folliculogenesis that were partially prevented by LC administration. Genazzani et al [30] administered ALC in association with LC in PCOS women, demonstrating its beneficial effects on insulin resistance.…”

Biological roles of l‐carnitine in oocyte and early embryo development

“…They showed that oral administration of L-carnitine and ALC counteracted the detrimental effect on oocyte quality and ovulation rate, thus improving ovarian environment (Di Emidio et al, 2020). A similar research on folliculogenesis has also been reported (Kalhori et al, 2019). An experiment in superovulated mice revealed that dietary L-carnitine (0.4 mg per mouse) and ALC (0.12 mg per mouse) contributed to higher oocyte formation rates, less oocyte degradation, and increased number of live births in 8-week-old female CD1 mice (Virmani, 2015).…”

The Role of l-Carnitine in Mitochondria, Prevention of Metabolic Inflexibility and Disease Initiation

“…The neuroendocrine system is closely linked to l -carnitine synthesis and utilization, and the release of GnRH by the hypothalamus is improved by supplementation with l -carnitine [ 66 ]. Preclinical studies demonstrated that l -carnitine improves β-oxidation in mitochondria resulting in improved fertilization rate and blastocyte development [ 67 , 68 , 69 ].…”