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These multifunctional proteins contribute to disulfide bond formation, proper folding, and protein modifications, and may act as hormone\u2010binding proteins (e.g., steroids), influencing hormone biology. The interplay between ER proteostasis, PDIs, and epididymis\u2014a crucial site for sperm maturation\u2014remains largely understudied.<\/jats:p><\/jats:sec><jats:sec><jats:title>Objectives<\/jats:title><jats:p>This study characterizes transcriptional signatures of <jats:italic>Pdi<\/jats:italic> genes in the epididymis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Material and methods<\/jats:title><jats:p>Transcriptional profiles of selected <jats:italic>Pdi<\/jats:italic> genes were assessed in adult Wistar rat tissues, and epididymis under different experimental conditions (developmental stages, surgical castration, and efferent ductules ligation [EDL]). In silico bioinformatic analyses identified expression trends of this gene family in human epididymal segments.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p><jats:italic>P4hb<\/jats:italic>, <jats:italic>Pdia3<\/jats:italic>, <jats:italic>Pdia5<\/jats:italic>, <jats:italic>Pdia6<\/jats:italic>, <jats:italic>Erp44<\/jats:italic>, <jats:italic>Erp29<\/jats:italic>, and <jats:italic>Casq1<\/jats:italic> transcripts were detected in both reproductive and non\u2010reproductive tissues, while <jats:italic>Casq2<\/jats:italic> exhibited higher abundance in vas deferens, prostate, and heart. <jats:italic>Pdilt<\/jats:italic>, highly expressed in testis, and <jats:italic>Pdia2<\/jats:italic>, highly expressed in heart, showed minimal mRNA levels in the epididymis. In the mesonephric duct, epididymal embryonic precursor, <jats:italic>P4hb<\/jats:italic>, <jats:italic>Pdia3<\/jats:italic>, <jats:italic>Pdia5<\/jats:italic>, <jats:italic>Pdia6<\/jats:italic>, and <jats:italic>Erp29<\/jats:italic> mRNAs were found at gestational day (GD) 17.5. Except for <jats:italic>Erp29<\/jats:italic>, which remained stable, these <jats:italic>Pdi<\/jats:italic> transcript levels increased from GD17.5 to GD20.5, when epididymal morphogenesis occurs, and were maintained to varying degrees in the epididymis during postnatal development. Surgical castration downregulated <jats:italic>P4hb<\/jats:italic>, <jats:italic>Pdia3<\/jats:italic>, <jats:italic>Pdia5<\/jats:italic>, <jats:italic>Pdia6<\/jats:italic>, <jats:italic>Pdilt<\/jats:italic> and <jats:italic>Erp29<\/jats:italic> transcripts, an effect reversed by testosterone replacement. Conversely, transcript levels remained unaffected by EDL, except <jats:italic>P4hb<\/jats:italic>, which was reduced in caput epididymis. All 21 <jats:italic>PDI<\/jats:italic> genes exhibited diverse transcriptional profiles across the human epididymis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion and conclusion<\/jats:title><jats:p>The findings lay the foundations to explore <jats:italic>Pdi<\/jats:italic> genes in epididymal biology. As a considerable proportion of male infertility cases are idiopathic, targeting hormonal regulation of protein quality control in epididymis represents a route to address male infertility and advance therapeutic interventions in this domain.<\/jats:p><\/jats:sec>","DOI":"10.1111\/andr.13700","type":"journal-article","created":{"date-parts":[[2024,8,1]],"date-time":"2024-08-01T12:54:07Z","timestamp":1722516847000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Epididymal mRNA expression profiles for the protein disulfide isomerase gene family: Modulation by development and androgens"],"prefix":"10.1111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1605-376X","authenticated-orcid":false,"given":"Samuel G.","family":"Fernandes","sequence":"first","affiliation":[{"name":"Laboratory of Molecular, Endocrine and Reproductive Pharmacology, Department of Pharmacology Universidade Federal de S\u00e3o Paulo \u2013 Escola Paulista de Medicina  S\u00e3o Paulo Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1043-6900","authenticated-orcid":false,"given":"Lucas G. 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