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The triple role of glutathione S-transferases in mammalian male fertility

Abstract

Male idiopathic infertility accounts for 15–25% of reproductive failure. One of the factors that has been linked to this condition is oxidative stress (OS), defined as the imbalance between antioxidants and reactive oxygen species. Amongst the different factors that protect the cell against OS, the members of the glutathione S-transferase (GST) superfamily play an important role. Interestingly, reduction or lack of some GSTs has been associated to infertility in men. Therefore, and to clarify the relationship between GSTs and male fertility, the aim of this work is to describe the role that GSTs play in the male reproductive tract and in sperm physiology. To that end, the present review provides a novel perspective on the triple role of GSTs (detoxification, regulation of cell signalling and fertilisation), and reports their localisation in sperm, seminal plasma and the male reproductive tract. Furthermore, we also tackle the existing correlation between some GST classes and male fertility. Due to the considerable impact of GSTs in human pathology and their tight relationship with fertility, future research should address the specific role of these proteins in male fertility, which could result in new approaches for the diagnosis and/or treatment of male infertility.

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Acknowledgements

The authors acknowledge the support from the European Commission (H2020-MSCA-IF-79212); the Ministry of Science, Innovation and Universities, Spain (Grants RYC-2014-15581, AGL2016-81890-REDT, AGL2017-88329-R and FJCI-2017-31689); and Regional Government of Catalonia, Spain (2017-SGR-1229). The authors would also like to thank Servier Medical Art for their image bank used to create all figures.

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Supplementary Figure 1

Confirmed transcript variants of GSTA1-GSTA5. Boxes represent exons and lines represent introns. In all family members, the first transcript variant corresponds to the canonical variant. Information was retrieved from RefSeq (https://www.ncbi.nlm.nih.gov/refseq/) [30] and Uniprot (https://www.uniprot.org/) [31] databases (TIFF 96 kb)

Supplementary Figure 2

Confirmed transcript variants of GSTM1-GSTM5. Boxes represent exons and lines represent introns. In all family members, the first transcript variant corresponds to the canonical variant. The red transcript variants do not codify for any isoform. Information was retrieved from RefSeq (https://www.ncbi.nlm.nih.gov/refseq/) [30] and Uniprot (https://www.uniprot.org/) [31] databases (TIFF 128 kb)

Supplementary Figure 3

Confirmed transcript variants of GSTO1, GSTO2, GSTP1 and GSTS1. Boxes represent exons and lines represent introns. In all family members, the first transcript variant corresponds to the canonical variant. Information was retrieved from RefSeq (https://www.ncbi.nlm.nih.gov/refseq/) [30] and Uniprot (https://www.uniprot.org/) [31] databases. (TIFF 101 kb)

Supplementary Figure 4

Confirmed transcript variants of GSTT1, GSTT2 and GSTZ1. Boxes represent exons and lines represent introns. In all family members, the first transcript variant corresponds to the canonical variant. Information was retrieved from RefSeq (https://www.ncbi.nlm.nih.gov/refseq/) [30] and Uniprot (https://www.uniprot.org/) [31] databases (TIFF 155 kb)

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Llavanera, M., Mateo-Otero, Y., Bonet, S. et al. The triple role of glutathione S-transferases in mammalian male fertility. Cell. Mol. Life Sci. 77, 2331–2342 (2020). https://doi.org/10.1007/s00018-019-03405-w

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Keywords

  • GSTs
  • Infertility
  • Detoxification
  • Cell signaling
  • Fertilisation