{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:21:19Z","timestamp":1790173279846,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"4","funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"crossref","award":["APP1120356"],"award-info":[{"award-number":["APP1120356"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["rep.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,2,24]]},"abstract":"<jats:sec>\n                    <jats:title>In brief<\/jats:title>\n                    <jats:p>\n                      <jats:italic>Hsc70Cb<\/jats:italic>\n                      is essential for spermatogonia survival and sperm individualisation in\n                      <jats:italic>Drosophila<\/jats:italic>\n                      . This study highlights the conserved roles of the HSPA4 family across animals and the utility of flies as a model organism for male fertility research.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Abstract<\/jats:title>\n                    <jats:p>\n                      Heat shock proteins play essential roles as molecular chaperones, enacting protein folding and preventing protein aggregation. In a previous study, a homozygous non-synonymous genetic variant that was predicted to be damaging was detected in an infertile man in the heat shock protein gene\n                      <jats:italic>HSPA4L<\/jats:italic>\n                      . Here, we used RNA interference in\n                      <jats:italic>Drosophila melanogaster<\/jats:italic>\n                      to explore the role of the heat shock protein A member 4 family (HSPA4) family in male fertility. Expression of the fly orthologue of the mammalian\n                      <jats:italic>HSPA4<\/jats:italic>\n                      and\n                      <jats:italic>HSPA4L<\/jats:italic>\n                      genes,\n                      <jats:italic>Hsc70Cb<\/jats:italic>\n                      , was reduced in the male germline using two RNAi lines driven by\n                      <jats:italic>Nanos<\/jats:italic>\n                      -Gal4. Robust knockdown of\n                      <jats:italic>Hsc70Cb<\/jats:italic>\n                      in male germ cells resulted in male sterility, characterised by the absence of germ cells in testes and the overproliferation of the testis soma. A less robust knockdown of\n                      <jats:italic>Hsc70Cb<\/jats:italic>\n                      in the male germline resulted in a sperm individualisation defect and a failure of sperm release into the seminal vesicle (analogous to the epididymis). When human\n                      <jats:italic>HSPA4<\/jats:italic>\n                      or\n                      <jats:italic>HSPA4L<\/jats:italic>\n                      cDNA was introduced into infertile\n                      <jats:italic>Hsc70Cb<\/jats:italic>\n                      mutant flies, a partial rescue was observed, whereby in the robust\n                      <jats:italic>Hsc70Cb<\/jats:italic>\n                      knockdown setting, germ cells progressed to the spermatocyte stage before undergoing cell death. The absence of sperm in\n                      <jats:italic>Hsc70Cb<\/jats:italic>\n                      mutant (line 1) is consistent with the clinical presentation of the infertile man harbouring a homozygous\n                      <jats:italic>HSPA4L<\/jats:italic>\n                      genetic variant, supporting the hypothesis that\n                      <jats:italic>HSPA4L<\/jats:italic>\n                      is required for male fertility in humans and flies. This study also highlights the utility of the fly as a model of human spermatogenesis.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1530\/rep-24-0458","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T08:09:12Z","timestamp":1740384552000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-11","source":"Crossref","is-referenced-by-count":2,"title":["Mammalian heat shock protein A4 family ortholog Hsc70Cb is required for two phases of spermatogenesis in D. melanogaster"],"prefix":"10.1093","volume":"169","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1078-756X","authenticated-orcid":true,"given":"Brendan J","family":"Houston","sequence":"first","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Parkville, Australia"},{"name":"Bio21 Molecular Sciences and Biotechnology Institute, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Nguyen","sequence":"additional","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Parkville, Australia"},{"name":"Bio21 Molecular Sciences and Biotechnology Institute, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Burke","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Monash University, Clayton, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Nogueira Alves","sequence":"additional","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary R","family":"Hime","sequence":"additional","affiliation":[{"name":"Department of Anatomy and Physiology, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Moira K","family":"O\u2019Bryan","sequence":"additional","affiliation":[{"name":"School of BioSciences, The University of Melbourne, Parkville, Australia"},{"name":"Bio21 Molecular Sciences and Biotechnology Institute, The University of Melbourne, Parkville, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","reference":[{"key":"bib1","series-title":"Fertil Steril","first-page":"1475","article-title":"Hsp90beta1 knockout targeted to male germline: a mouse model for globozoospermia","volume":"95","author":"Audouard C","year":"2011","unstructured":"Audouard C\n & \nChristians E\n\n 2011 Hsp90beta1 knockout targeted to male germline: a mouse model for globozoospermia. 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