Loggia Diego, O'Flaherty Cristian
Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 1Y6, Canada.
Department of Surgery, Urology Division, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H4A 3J1, Canada.
Antioxidants (Basel). 2024 Jul 23;13(8):885. doi: 10.3390/antiox13080885.
Sperm capacitation is a complex process essential for the spermatozoon to recognize and fertilize the oocyte. For capacitation to occur, human spermatozoa require low levels of reactive oxygen species (ROS), increased protein tyrosine phosphorylation, and sufficient levels of energy metabolites such as citrate. Human spermatozoa are exposed to high concentrations of citrate from the seminal plasma, yet the role of citrate in sperm capacitation is largely unknown. We report that citrate can support capacitation in human spermatozoa incubated with no other energy metabolites in the capacitation medium. Reduced capacitation levels were observed in spermatozoa incubated with inhibitors of mitochondrial citrate transporter (CIC), cytosolic ATP-citrate lyase (ACLY), malic enzyme (ME), and nitric oxide synthase (NOS). The role of citrate metabolism in ROS production was further elucidated as citrate increased NO production in capacitated spermatozoa, whereas inhibition of ACLY reduced NO production. This research characterizes a novel metabolic pathway for citrate to produce NO in the process of human sperm capacitation.
精子获能是精子识别并使卵母细胞受精所必需的复杂过程。为了实现获能，人类精子需要低水平的活性氧（ROS）、增加的蛋白质酪氨酸磷酸化以及足够水平的能量代谢物，如柠檬酸盐。人类精子暴露于来自精浆的高浓度柠檬酸盐中，然而柠檬酸盐在精子获能中的作用在很大程度上尚不清楚。我们报告称，在获能培养基中没有其他能量代谢物的情况下孵育时，柠檬酸盐可以支持人类精子的获能。在用线粒体柠檬酸盐转运体（CIC）、胞质ATP - 柠檬酸裂解酶（ACLY）、苹果酸酶（ME）和一氧化氮合酶（NOS）抑制剂孵育的精子中观察到获能水平降低。由于柠檬酸盐增加了获能精子中的一氧化氮产生，而抑制ACLY则减少了一氧化氮产生，因此进一步阐明了柠檬酸盐代谢在ROS产生中的作用。这项研究描述了一种新的代谢途径，即柠檬酸盐在人类精子获能过程中产生一氧化氮。
