Carnitines as Mitochondrial Modulators of Oocyte and Embryo Bioenergetics

Abstract

Recently, the importance of bioenergetics in the reproductive process has emerged. For its energetic demand, the oocyte relies on numerous mitochondria, whose activity increases during embryo development under a fine regulation to limit ROS production. Healthy oocyte mitochondria require a balance of pyruvate and fatty acid oxidation. Transport of activated fatty acids into mitochondria requires carnitine. In this regard, the interest in the role of carnitines as mitochondrial modulators in oocyte and embryos is increasing. Carnitine pool includes the un-esterified l-carnitine (LC) and carnitine esters, such as acetyl-l-carnitine (ALC) and propionyl-l-carnitine (PLC). In this review, carnitine medium supplementation for counteracting energetic and redox unbalance during in vitro culture and cryopreservation is reported. Although most studies have focused on LC, there is new evidence that the addition of ALC and/or PLC may boost LC effects. Pathways activated by carnitines include antiapoptotic, antiglycative, antioxidant, and antiinflammatory signaling. Nevertheless, the potential of carnitine to improve energetic metabolism and oocyte and embryo competence remains poorly investigated. The importance of carnitine as a mitochondrial modulator may suggest that this molecule may exert a beneficial role in ovarian disfunctions associated with metabolic and mitochondrial alterations, including PCOS and reproductive aging.

Mitochondria Biology in Reproductive Function

“…This enzyme drives the transport of acyl-L-carnitines to the inner mitochondrial membrane, where they enter the β-oxidation process, suggesting that beneficial effects of resveratrol are mediated by increased mitochondrial lipid metabolism in the aged ovarian microenvironment. As reported by Placidi and colleagues [ 13 ], acyl-L-carnitines activate antiapoptotic, antiglycative, antioxidant, and anti-inflammatory signaling in the female germ cell and reproductive system. Indeed, these authors highlighted the importance of acyl L-carnitine and the mechanisms by which these molecules may represent promising culture medium supplements to counteract altered energy and redox homeostasis associated with oocyte and embryo in vitro culture and cryopreservation in ART [ 13 ].…”

“…As reported by Placidi and colleagues [ 13 ], acyl-L-carnitines activate antiapoptotic, antiglycative, antioxidant, and anti-inflammatory signaling in the female germ cell and reproductive system. Indeed, these authors highlighted the importance of acyl L-carnitine and the mechanisms by which these molecules may represent promising culture medium supplements to counteract altered energy and redox homeostasis associated with oocyte and embryo in vitro culture and cryopreservation in ART [ 13 ]. These reviews further sustain the hypothesis that mitochondria are the main targets of carnitine supplementation in PCOS mice diet, probably due to the activation of a SIRT1 pathway [ 5 , 14 , 15 ].…”

“…This is not surprising, since miR-132 is known to be deregulated with aging and stressing conditions in the mammalian oocyte, and Sirt1 is one of the most studied targets of its activity [ 16 ]. Therefore, resveratrol may improve follicular microenvironment by transcriptomic and proteomic modifications in granulosa cells [ 12 ], positively affecting oocyte competence by regulating lipid utilization and energetic metabolism [ 13 ]. Nevertheless, granulosa/cumulus cells are not always necessary for proper oocyte functioning and metabolism.…”

The Importance of Natural Antioxidants in Female Reproduction

“…They play an important role in intermediate metabolism as they act as a cofactor in the transport of free fatty acids from the cytosol to the mitochondrial matrix [ 66 , 67 , 68 ]. The supplementation of L-carnitine in oocytes and embryos increases energy production by β-oxidation of fatty acids, scavenges ROS, has anti-apoptotic and anti-inflammatory effects, and results in an increased pregnancy rate, as well as enhanced cryo-tolerance [ 99 ]. L-carnitine is converted to ALC in the mitochondria.…”

The effects of L-carnitine-loaded solid lipid nanoparticles on performance, antioxidant parameters, and expression of genes associated with cholesterol metabolism in laying hens

“…LC treatment can also decrease serum cholesterol and triglycerides in rats and domestic fowls ( Eskandari et al, 2004 ; Malaguarnera et al, 2009 ; Adabi et al, 2011 ; Jang et al, 2014 ; Fallah and Mirzaei, 2016 ; Rehman et al, 2017 ). The addition of LC to the laying hen diet reduced egg yolk cholesterol and triglycerides for unknown reasons ( Adabi et al, 2006 ; Rehman et al, 2017 ; Placidi et al, 2022 ).…”