Department DiBEST (Biologia, Ecologia, Scienze della Terra) Unit of Biochemistry and Molecular Biotechnology, University of Calabria, Via P. Bucci 4C, Arcavacata di Rende 87036, Italy.
CNR Institute of Biomembranes, Bioenergetics and Molecular Biotechnology (IBIOM), via Amendola 122/O, Bari 70126, Italy.
Biochem Pharmacol. 2024 Dec;230(Pt 1):116565. doi: 10.1016/j.bcp.2024.116565. Epub 2024 Oct 3.
Carnitine is a vital molecule in human metabolism, prominently involved in fatty acid β-oxidation within mitochondria. Predominantly sourced from dietary intake, carnitine also derives from endogenous synthesis. This review delves into the complex network of carnitine transport and distribution, emphasizing its pivotal role in human fertility. Together with its role in fatty acid oxidation, carnitine modulates the acety-CoA/CoA ratio, influencing carbohydrate metabolism, lipid biosynthesis, and gene expression. The intricate regulation of carnitine homeostasis involves a network of membrane transporters, notably OCTN2, which is central in its absorption, reabsorption, and distribution. OCTN2 dysfunction, results in Primary Carnitine Deficiency (PCD), characterized by systemic carnitine depletion and severe clinical manifestations, including fertility issues. In the male reproductive system, carnitine is crucial for sperm maturation and motility. In the female reproductive system, carnitine supports mitochondrial function necessary for oocyte quality, folliculogenesis, and embryonic development. Indeed, deficiencies in carnitine or its transporters have been linked to asthenozoospermia, reduced sperm quality, and suboptimal fertility outcomes in couples. Moreover, the antioxidant properties of carnitine protect spermatozoa from oxidative stress and help in managing conditions like polycystic ovary syndrome (PCOS) and endometriosis, enhancing sperm viability and fertilization potential of oocytes. This review summarizes the key role of membrane transporters in guaranteeing carnitine homeostasis with a special focus on the implications in fertility and possible treatments of infertility and other related disorders.
肉碱是人体代谢中的重要分子，主要参与线粒体中的脂肪酸β氧化。肉碱主要来源于饮食摄入，也可以通过内源性合成获得。本综述深入探讨了肉碱的运输和分布的复杂网络，强调了它在人类生育中的关键作用。除了在脂肪酸氧化中的作用外，肉碱还调节乙酰-CoA/CoA 比率，影响碳水化合物代谢、脂质生物合成和基因表达。肉碱动态平衡的复杂调节涉及膜转运体网络，特别是 OCTN2，它在肉碱的吸收、重吸收和分布中起着核心作用。OCTN2 功能障碍会导致原发性肉碱缺乏症（PCD），其特征是全身肉碱耗竭和严重的临床表现，包括生育问题。在男性生殖系统中，肉碱对于精子成熟和活力至关重要。在女性生殖系统中，肉碱支持卵母细胞质量、卵泡发生和胚胎发育所需的线粒体功能。事实上，肉碱或其转运体的缺乏与弱精症、精子质量下降以及夫妇的生育结局不佳有关。此外，肉碱的抗氧化特性可以保护精子免受氧化应激的伤害，并有助于管理多囊卵巢综合征（PCOS）和子宫内膜异位症等情况，提高精子的活力和卵母细胞的受精能力。本综述总结了膜转运体在保证肉碱动态平衡中的关键作用，特别关注其在生育中的意义以及治疗不孕和其他相关疾病的可能性。
