Dataset Information

GSTO2 Isoforms Participate in the Oxidative Regulation of the Plasmalemma in Eutherian Spermatozoa during Capacitation.

ABSTRACT: In addition to perinuclear theca anchored glutathione-s-transferase omega 2 (GSTO2), whose function is to participate in sperm nuclear decondensation during fertilization (Biol Reprod. 2019, 101:368-376), we herein provide evidence that GSTO2 is acquired on the sperm plasmalemma during epididymal maturation. This novel membrane localization was reinforced by the isolation and identification of biotin-conjugated surface proteins from ejaculated and capacitated boar and mouse spermatozoa, prompting us to hypothesize that GSTO2 has an oxidative/reductive role in regulating sperm function during capacitation. Utilizing an inhibitor specific to the active site of GSTO2 in spermatozoa, inhibition of this enzyme led to a decrease in tyrosine phosphorylation late in the capacitation process, followed by an expected decrease in acrosome exocytosis and motility. These changes were accompanied by an increase in reactive oxygen species (ROS) levels and membrane lipid peroxidation and culminated in a significant decrease in the percentage of oocytes successfully penetrated by sperm during in vitro fertilization. We conclude that GSTO2 participates in the regulation of sperm function during capacitation, most likely through protection against oxidative stress on the sperm surface.

SUBMITTER: Hamilton LE

PROVIDER: S-EPMC6943649 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature

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GSTO2 Isoforms Participate in the Oxidative Regulation of the Plasmalemma in Eutherian Spermatozoa during Capacitation.

Hamilton Lauren E LE Zigo Michal M Mao Jiude J Xu Wei W Sutovsky Peter P O'Flaherty Cristian C Oko Richard R

Antioxidants (Basel, Switzerland) 20191129 12

In addition to perinuclear theca anchored glutathione-s-transferase omega 2 (GSTO2), whose function is to participate in sperm nuclear decondensation during fertilization (Biol Reprod. 2019, 101:368-376), we herein provide evidence that GSTO2 is acquired on the sperm plasmalemma during epididymal maturation. This novel membrane localization was reinforced by the isolation and identification of biotin-conjugated surface proteins from ejaculated and capacitated boar and mouse spermatozoa, promptin ...[more]

PMID: 31795389

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Project description:BACKGROUND: There has been an ongoing debate in the reproductive field about whether mammalian spermatozoa rely on glycolysis, oxidative phosphorylation or both for their energy production. Recent studies have proposed that human spermatozoa depend mainly on glucose for motility and fertilization but the mechanism behind an efficient glycolysis in human spermatozoa is not well understood. Here, we demonstrate how human spermatozoa utilize exogenous pyruvate to enhance glycolytic ATP production, motility, hyperactivation and capacitation, events that are crucial for male fertility. METHODS: Purified human spermatozoa from healthy donors were incubated under capacitating conditions (including albumin, bicarbonate and glucose) and tested for changes in ATP levels, motility, hyperactivation and tyrosine phosphorylation after treatment with pyruvate. The experiments were repeated in the presence of sodium cyanide in order to assess the contribution from mitochondrial respiration. The metabolism of (13)C labeled glucose and pyruvate was traced by a combination of liquid chromatography and mass spectrometry. RESULTS: The treatment of human spermatozoa with exogenous pyruvate increased intracellular ATP levels, progressive motility and hyperactivation by 56, 21 and 130%, respectively. In addition, added pyruvate induced a significant increase in tyrosine phosphorylation levels. Blocking of the electron transport chain did not markedly affect the results, indicating that the mechanism is independent of oxidative phosphorylation. However, the observed effects could be counteracted by oxamate, an inhibitor of lactate dehydrogenase (LDH). Metabolic tracing experiments revealed that the observed rise in ATP concentration resulted from an enhanced glycolytic flux, which was increased by more than 50% in the presence of exogenous pyruvate. Moreover, all consumed (13)C labeled pyruvate added was converted to lactate rather than oxidized in the tricarboxylic acid cycle. CONCLUSIONS: Human spermatozoa seem to rely mainly, if not entirely, on glycolysis as the source of ATP fueling the energy-demanding processes of motility and capacitation. The efficient glycolysis is dependent on exogenous pyruvate, which indirectly feeds the accelerated glycolysis with NAD(+) through the LDH-mediated conversion of pyruvate to lactate. Pyruvate is present in the human female reproductive tract at concentrations in accordance with our results. As seen in other mammals, the motility and fertility of human spermatozoa seem to be dictated by the available energy substrates present in the conspecific female.

Dataset Information

GSTO2 Isoforms Participate in the Oxidative Regulation of the Plasmalemma in Eutherian Spermatozoa during Capacitation.

Publications

GSTO2 Isoforms Participate in the Oxidative Regulation of the Plasmalemma in Eutherian Spermatozoa during Capacitation.

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