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Still, HLA<\/jats:styled-content><\/jats:italic> connections to other infertility phenotypes such as semen hyperviscosity (SHV<\/jats:styled-content>), asthenozoospermia (AST<\/jats:styled-content>), and oligozoospermia (OLI<\/jats:styled-content>) have been often neglected.<\/jats:p><\/jats:sec>Objectives<\/jats:title>In this work, we aimed to evaluate the association of HLA<\/jats:styled-content><\/jats:italic> class I and II<\/jats:styled-content> genes with SHV<\/jats:styled-content>, AST<\/jats:styled-content>, and OLI<\/jats:styled-content> phenotypes while exploring a possible role in an adaptive immune response to sexually transmitted diseases (STD<\/jats:styled-content>).<\/jats:p><\/jats:sec>Materials and methods<\/jats:title>Whole\u2010exome sequencing was performed in a Portuguese cohort of 71 infertility cases and 68 controls, followed by HLA<\/jats:styled-content><\/jats:italic> typing using a specific software\u2014HLA<\/jats:styled-content>*PRG<\/jats:styled-content>:LA<\/jats:styled-content> tool. Molecular screenings of seven STD<\/jats:styled-content> were carried out in a subset of 72 samples (30 cases and 42 controls).<\/jats:p><\/jats:sec>Results<\/jats:title>Statistical tests uncovered three protective alleles: HLA<\/jats:styled-content>\u2010A*11:01,<\/jats:italic> associated with all forms of male infertility (p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0006); HLA<\/jats:styled-content>\u2010DQB<\/jats:styled-content>1*03:02<\/jats:italic> with SHV<\/jats:styled-content> and OLI<\/jats:styled-content> (P<\/jats:italic>SHV<\/jats:sub><\/jats:styled-content>\u00a0<\/jats:sub>=\u00a00.0303, P<\/jats:italic>OLI<\/jats:sub><\/jats:styled-content>\u00a0<\/jats:sub>=\u00a00.0153); and HLA<\/jats:styled-content>\u2010A*29:02<\/jats:italic> with OLI<\/jats:styled-content> (p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0355), which was found to interfere in sperm number together with HPV<\/jats:styled-content> (p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0313). Five risk alleles were also identified: two linked with SHV<\/jats:styled-content> (HLA<\/jats:styled-content>\u2010B*50:01, p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0278; and HLA<\/jats:styled-content>\u2010C*06:02<\/jats:italic>, p\u00a0=\u00a0<\/jats:italic>0.0461), another one with both SHV<\/jats:styled-content> and OLI<\/jats:styled-content> (HLA<\/jats:styled-content>\u2010DQA<\/jats:styled-content>1*05:01<\/jats:italic>, P<\/jats:italic>SHV<\/jats:sub><\/jats:styled-content>\u00a0<\/jats:sub>=\u00a00.0444 and P<\/jats:italic>OLI<\/jats:sub><\/jats:styled-content>=0.0265), and two with OLI<\/jats:styled-content> (HLA<\/jats:styled-content>\u2010C*03:03<\/jats:italic>, p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0480; and HLA<\/jats:styled-content>\u2010DQB<\/jats:styled-content>1*03:<\/jats:italic>01, p\u00a0<\/jats:italic>=\u00a0<\/jats:italic>0.0499). Here, HLA<\/jats:styled-content>\u2010C*03:03<\/jats:italic> carriers tend to be HPV<\/jats:styled-content> infected.<\/jats:p><\/jats:sec>Conclusions<\/jats:title>The application of HLA<\/jats:styled-content>*PRG<\/jats:styled-content>:LA<\/jats:styled-content> tool to the study of male infertility provided novel insights for an HLA<\/jats:styled-content><\/jats:italic> correlation with semen quality, namely among SHV<\/jats:styled-content> and OLI<\/jats:styled-content> phenotypes. The discovery of an HLA<\/jats:styled-content>\u2010A*29:02<\/jats:italic>\/HPV<\/jats:styled-content> crosstalk, together with former reports of HLA<\/jats:styled-content><\/jats:italic> alleles conferring resistance\u2013susceptibility to diverse human pathogens, raises the hypothesis of a mechanistic link between male infertility, HLA<\/jats:styled-content><\/jats:italic> polymorphism, and host response to STD<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.12625","type":"journal-article","created":{"date-parts":[[2019,4,19]],"date-time":"2019-04-19T16:50:02Z","timestamp":1555692602000},"page":"867-877","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Semen quality is affected by HLA<\/scp><\/i> class I alleles together with sexually transmitted diseases"],"prefix":"10.1111","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6050-628X","authenticated-orcid":false,"given":"P. 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