{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:24:21Z","timestamp":1790958261645,"version":"4.1.0"},"reference-count":13,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T00:00:00Z","timestamp":1706832000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> During early development in most male mammals the testes move from a position near the kidneys through the abdomen to eventually reside in the scrotum. The transabdominal phase of this migration is driven by insulin-like peptide 3 (INSL3) which stimulates growth of the gubernaculum, a key ligament connecting the testes with the abdominal wall. While all marsupials, except the marsupial mole (<jats:italic>Notoryctes typhlops<\/jats:italic>), have a scrotum and fully descended testes, it is unclear if <jats:italic>INSL3<\/jats:italic> drives this process in marsupials especially given that marsupials have a different mechanism of scrotum determination and position relative to the phallus compared to eutherian mammals.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> To understand if INSL3 plays a role in marsupial testicular descent we have sequenced and curated the <jats:italic>INSL3<\/jats:italic> gene and its receptor (<jats:italic>RXFP2<\/jats:italic>) in a range of marsupials representing every order. Furthermore, we looked at single cell RNA-seq and qPCR analysis of INSL3 in the fat-tailed dunnart testis (<jats:italic>Sminthopsis crassicaudata<\/jats:italic>) to understand the location and timing of expression during development.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> These data show a strong phylogenetic similarity between marsupial and eutherian orthologues, but not with monotreme INSL3s which were more similar to the ancestral RLN3 gene. We have also shown the genomic location of <jats:italic>INSL3<\/jats:italic>, and surrounding genes is conserved in a range of marsupials and eutherians. Single cell RNA-seq and qPCR data show that <jats:italic>INSL3<\/jats:italic> mRNA is expressed specifically in Leydig cells and expressed at higher levels during the testicular descent phase in developing marsupials.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Together, these data argue strongly for a therian origin of INSL3 mediated testicular descent in mammals and suggests that a coordinated movement of the testes to the abdominal wall may have preceded externalization in marsupials and therian mammals.<\/jats:p>","DOI":"10.3389\/fcell.2024.1353598","type":"journal-article","created":{"date-parts":[[2024,2,2]],"date-time":"2024-02-02T04:52:10Z","timestamp":1706849530000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Therian origin of INSL3\/RXFP2-driven testicular descent in mammals"],"prefix":"10.3389","volume":"12","author":[{"given":"Brandon R.","family":"Menzies","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gerard A.","family":"Tarulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen R.","family":"Frankenberg","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew J.","family":"Pask","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,2,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"244","DOI":"10.1210\/mend.16.2.0772","article-title":"The overexpression of the insl3 in female mice causes descent of the ovaries","volume":"16","author":"Adham","year":"2002","journal-title":"Mol. 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