{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,6,27]],"date-time":"2025-06-27T18:02:18Z","timestamp":1751047338908},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"12","license":[{"start":{"date-parts":[[2020,12,1]],"date-time":"2020-12-01T00:00:00Z","timestamp":1606780800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Globozoospermia is a rare form of male infertility where men produce round-headed sperm that are incapable of fertilizing an oocyte naturally. In a previous study where we undertook a whole exome screen to define novel genetic causes of globozoospermia, we identified homozygous mutations in the gene PDCD2L. Two brothers carried a p.(Leu225Val) variant predicted to introduce a novel splice donor site, thus presenting PDCD2L as a potential regulator of male fertility. In this study, we generated a Pdcd2l knockout mouse to test its role in male fertility. Contrary to the phenotype predicted from its testis-enriched expression pattern, Pdcd2l null mice died during embryogenesis. Specifically, we identified that Pdcd2l is essential for post-implantation embryonic development. Pdcd2l\u2212\/\u2212 embryos were resorbed at embryonic days 12.5-17.5 and no knockout pups were born, while adult heterozygous Pdcd2l males had comparable fertility to wildtype males. To specifically investigate the role of PDCD2L in germ cells, we employed Drosophila melanogaster as a model system. Consistent with the mouse data, global knockdown of trus, the fly ortholog of PDCD2L, resulted in lethality in flies at the third instar larval stage. However, germ cell-specific knockdown with two germ cell drivers did not affect male fertility. Collectively, these data suggest that PDCD2L is not essential for male fertility. By contrast, our results demonstrate an evolutionarily conserved role of PDCD2L in development.<\/jats:p>","DOI":"10.1534\/g3.120.401714","type":"journal-article","created":{"date-parts":[[2020,10,15]],"date-time":"2020-10-15T05:30:11Z","timestamp":1602739811000},"page":"4449-4457","source":"Crossref","is-referenced-by-count":5,"title":["Programmed Cell Death 2-Like (<i>Pdcd2l<\/i>) Is Required for Mouse Embryonic Development"],"prefix":"10.1093","volume":"10","author":[{"given":"Brendan J","family":"Houston","sequence":"first","affiliation":[{"name":"School of Biological Sciences, Monash University, Clayton, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manon S","family":"Oud","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel M","family":"Aguirre","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Monash University, Clayton, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D Jo","family":"Merriner","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Monash University, Clayton, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne E","family":"O\u2019Connor","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Monash University, Clayton, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ozlem","family":"Okutman","sequence":"additional","affiliation":[{"name":"Laboratoire de Diagnostic G\u00e9n\u00e9tique, UF3472-g\u00e9n\u00e9tique de l\u2019infertilit\u00e9, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"},{"name":"Institut de Parasitologie et Pathologie Tropicale, EA 7292, Universit\u00e9 de Strasbourg, 3 rue Koeberl\u00e9, Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"St\u00e9phane","family":"Viville","sequence":"additional","affiliation":[{"name":"Laboratoire de Diagnostic G\u00e9n\u00e9tique, UF3472-g\u00e9n\u00e9tique de l\u2019infertilit\u00e9, H\u00f4pitaux Universitaires de Strasbourg, Strasbourg, France"},{"name":"Institut de Parasitologie et Pathologie Tropicale, EA 7292, Universit\u00e9 de Strasbourg, 3 rue Koeberl\u00e9, Strasbourg, France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard","family":"Burke","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Monash University, Clayton, Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joris A","family":"Veltman","sequence":"additional","affiliation":[{"name":"Department of Human Genetics, Radboud University Medical Center, Nijmegen, The Netherlands"},{"name":"Centre for Life, Newcastle University, Newcastle Upon Tyne, UK"},{"name":"International Male Infertility Genomics Consortium"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moira K","family":"O\u2019Bryan","sequence":"additional","affiliation":[{"name":"School of Biological Sciences, Monash University, Clayton, Australia"},{"name":"International Male Infertility Genomics Consortium"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2020,12,1]]},"reference":[{"key":"2021042011145271800_bib1","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1016\/S0015-0282(16)53833-3","article-title":"Analysis of sperm function in globozoospermia: implications for the mechanism of sperm-zona interaction.","volume":"54","author":"Aitken","year":"1990","journal-title":"Fertil. 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