Molecular insights into mammalian sperm physiology: a comparative study of glutathione S-transferases in male reproduction

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Male infertility is a global health problem affecting one in four infertile couples. This also has a negative repercussion on the animal breeding industry, where infertility has a detrimental impact on their balance sheets. Sperm preservation is a common strategy used together with assisted reproduction techniques in humans and other animals. While sperm conservation methods, both liquid storage and cryopreservation, can lead to sperm damage, they are extensively used. Traditional semen analysis through the seminogram has a limited capacity to predict male infertility disorders and the resilience of sperm to preservation, that is why novel markers to assess sperm quality are needed. This Doctoral Thesis investigated the role of glutathione S-transferases (GSTs), a group of antioxidant proteins, in sperm physiology and male infertility in mammals. The results evidenced the presence of GSTs in reproductive tissues, seminal plasma and sperm of pigs, cattle and humans. The study also uncovered the role of these antioxidant enzymes in sperm detoxification, thus maintaining their basic cellular functions. Moreover, the tight association between sperm function and the presence of GSTs encouraged interrogating whether the quantification of one of these proteins (GSTM3) could serve as an indicator of sperm quality and male infertility. Data supported that the levels of GSTM3 in sperm are associated to their quality and fertility in pigs, cattle and humans. It was also worth investigating the putative use of this protein to predict the capacity of sperm to withstand liquid storage and cryopreservation, with GSTM3 being confirmed to be associated to the sperm resilience to preservation. The findings of this Dissertation warrant the use of these antioxidant proteins as novel biomarkers of sperm quality, fertility and capacity of conservation. The implementation of these biomarkers in fertility clinics and the animal breeding industry may be translated into cost-effective and accurate approaches to diagnose male infertility disorders and anticipate the resilience of sperm to liquid storage and cryopreservation ​
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