Acyl-Carnitines Exert Positive Effects on Mitochondrial Activity under Oxidative Stress in Mouse Oocytes: A Potential Mechanism Underlying Carnitine Efficacy on PCOS

Abstract

Carnitines play a key physiological role in oocyte metabolism and redox homeostasis. In clinical and animal studies, carnitine administration alleviated metabolic and reproductive dysfunction associated with polycystic ovarian syndrome (PCOS). Oxidative stress (OS) at systemic, intraovarian, and intrafollicular levels is one of the main factors involved in the pathogenesis of PCOS. We investigated the ability of different acyl-carnitines to act at the oocyte level by counteracting the effects of OS on carnitine shuttle system and mitochondrial activity in mouse oocytes. Germinal vesicle (GV) oocytes were exposed to hydrogen peroxide and propionyl-l-carnitine (PLC) alone or in association with l-carnitine (LC) and acetyl-l-carnitine (ALC) under different conditions. Expression of carnitine palmitoyltransferase-1 (Cpt1) was monitored by RT-PCR. In in vitro matured oocytes, metaphase II (MII) apparatus was assessed by immunofluorescence. Oocyte mitochondrial respiration was evaluated by Seahorse Cell Mito Stress Test. We found that Cpt1a and Cpt1c isoforms increased under prooxidant conditions. PLC alone significantly improved meiosis completion and oocyte quality with a synergistic effect when combined with LC + ALC. Acyl-carnitines prevented Cpt1c increased expression, modifications of oocyte respiration, and ATP production observed upon OS. Specific effects of PLC on spare respiratory capacity were observed. Therefore, carnitine supplementation modulated the intramitochondrial transfer of fatty acids with positive effects on mitochondrial activity under OS. This knowledge contributes to defining molecular mechanism underlying carnitine efficacy on PCOS.

Ovarian aging: energy metabolism of oocytes

“…It is worth noting that although carnitine expression overall decreases, the age-dependent expression of butyryl carnitine and acetylcarnitine increases in oocytes [7]. Carnitine treatment contributes to the preservation of oocyte quality and the enhancement of embryo development [85][86][87][88][89]. Specifically, it decreases oocyte lipid content, boosts cellular energy supply, enhances antioxidant capacity, and actively modulates mitochondrial activity during oxidative stress [85][86][87][88][89].…”

“…Carnitine treatment contributes to the preservation of oocyte quality and the enhancement of embryo development [85][86][87][88][89]. Specifically, it decreases oocyte lipid content, boosts cellular energy supply, enhances antioxidant capacity, and actively modulates mitochondrial activity during oxidative stress [85][86][87][88][89]. This, to some extent, prevents abnormal changes in phospholipid and sphingolipid content as oocytes develop into blastocysts [85][86][87][88][89].…”

“…Specifically, it decreases oocyte lipid content, boosts cellular energy supply, enhances antioxidant capacity, and actively modulates mitochondrial activity during oxidative stress [85][86][87][88][89]. This, to some extent, prevents abnormal changes in phospholipid and sphingolipid content as oocytes develop into blastocysts [85][86][87][88][89]. However, the specific changes in acylcarnitine spectrum in oocytes with age and its potential clinical value have not been well explored.…”