{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T21:20:59Z","timestamp":1787779259870,"version":"build-2784847793"},"reference-count":37,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T00:00:00Z","timestamp":1785196800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Swiss Science National Foundation","award":["310030_185026"],"award-info":[{"award-number":["310030_185026"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>In brief: This study identifies pregnanolone as a previously unrecognized circulating progestogen that emerges during the implantation period following embryonic diapause in roe deer.<\/jats:p>\n                  <jats:p>Abstract: Roe deer (Capreolus capreolus) are seasonal animals with fertilization taking place in summer (July\/August). Thereafter, the embryo enters a 4- to 5-month period of embryonic diapause. This reproductive strategy, displaying a reduced embryonic developmental velocity at the blastocyst stage, leads to reactivation and implantation in late December\u2013January and parturition in spring (May\/June). The endocrine mechanisms governing reactivation, implantation and placentation remain poorly understood. Here, we applied ultra-high-performance liquid chromatography coupled to high-resolution mass spectrometry to profile circulating progestogens from reactivation through late gestation (December\u2013April), and in placental and luteal tissue. Notably, the neurosteroid pregnanolone (3\u03b1,5\u03b2-tetrahydroprogesterone; 3\u03b1,5\u03b2-THP) appeared exclusively in pregnant does from late December\/early January onwards, coinciding with the period of implantation. Pregnanolone was detected in placental but not luteal tissue, pointing to the placenta as a potential source. Our results indicate a previously unrecognized shift in progestogens from reactivation\/early placentation onwards, suggesting that nonclassical progestogens may contribute to the endocrine regulation of implantation and pregnancy maintenance. Further investigation into the origin and functional roles of pregnanolone are needed to elucidate its contribution to pregnancy and reproductive success in roe deer.<\/jats:p>","DOI":"10.1093\/reprod\/xaag091","type":"journal-article","created":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T11:20:03Z","timestamp":1785151203000},"source":"Crossref","is-referenced-by-count":0,"title":["Pregnanolone appearance coincides with the period of implantation following embryonic diapause in the roe deer"],"prefix":"10.1093","volume":"172","author":[{"given":"Sara","family":"Elsafadi","sequence":"first","affiliation":[{"name":"ETH Zurich, Animal Physiology, Institute of Agricultural Sciences , Universitatstrasse 2 , 8092 Zurich,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haolin","family":"Chen","sequence":"additional","affiliation":[{"name":"ETH Zurich, Animal Physiology, Institute of Agricultural Sciences , Universitatstrasse 2 , 8092 Zurich,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reto","family":"Giacometti","sequence":"additional","affiliation":[{"name":"ETH Zurich, Animal Physiology, Institute of Agricultural Sciences , Universitatstrasse 2 , 8092 Zurich,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna-Katharina","family":"Hankele","sequence":"additional","affiliation":[{"name":"ETH Zurich, Animal Physiology, Institute of Agricultural Sciences , Universitatstrasse 2 , 8092 Zurich,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susanne","family":"Holtze","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Zoo and Wildlife Research Department of Reproduction Management, , Alfred-Kowalke-Strasse 17 , Berlin D-10315,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Goeritz","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Zoo and Wildlife Research Department of Reproduction Management, , Alfred-Kowalke-Strasse 17 , Berlin D-10315,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Hildebrandt","sequence":"additional","affiliation":[{"name":"Leibniz Institute for Zoo and Wildlife Research Department of Reproduction Management, , Alfred-Kowalke-Strasse 17 , Berlin D-10315,","place":["Germany"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0355-3869","authenticated-orcid":false,"given":"Susanne E","family":"Ulbrich","sequence":"additional","affiliation":[{"name":"ETH Zurich, Animal Physiology, Institute of Agricultural Sciences , Universitatstrasse 2 , 8092 Zurich,","place":["Switzerland"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,7,28]]},"reference":[{"key":"2026082616514873100_xaag091-B1","doi-asserted-by":"publisher","first-page":"1447","DOI":"10.1021\/ACS.JPROTEOME.9B00640","article-title":"Skyline for small molecules: A unifying software package for quantitative metabolomics","volume":"19","author":"Adams","year":"2020","journal-title":"Journal of Proteome Research"},{"key":"2026082616514873100_xaag091-B2","doi-asserted-by":"publisher","first-page":"1349","DOI":"10.1210\/endo-81-6-1349","article-title":"Steroid hormone transformations by endocrine organs from pregnant mammals. II. Formation and metabolism of progesterone by bovine and sheep placental preparations in vitro","volume":"81","author":"Ainsworth","year":"1967","journal-title":"Endocrinology"},{"key":"2026082616514873100_xaag091-B3","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1530\/JRF.0.0390225","article-title":"Delayed implantation in roe deer (Capreolus capreolus)","volume":"39","author":"Aitken","year":"1974","journal-title":"Journal of Reproduction and Fertility"},{"key":"2026082616514873100_xaag091-B4","first-page":"83","article-title":"Aspects of delayed implantation in the roe deer (Capreolus capreolus)","volume":"29","author":"Aitken","year":"1981","journal-title":"Journal of Reproduction and Fertility. Supplement"},{"key":"2026082616514873100_xaag091-B5","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/0248-4900(91)90045-O","article-title":"Neurosteroids: A new function in the brain","volume":"71","author":"Baulieu","year":"1991","journal-title":"Biology of the Cell"},{"key":"2026082616514873100_xaag091-B6","author":"Bischoff","year":"1854"},{"key":"2026082616514873100_xaag091-B7","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.pneurobio.2013.08.005","article-title":"Allopregnanolone in the brain: Protecting pregnancy and birth outcomes","volume":"113","author":"Brunton","year":"2014","journal-title":"Progress in Neurobiology"},{"key":"2026082616514873100_xaag091-B71449784","author":"Chen","year":"2026"},{"key":"2026082616514873100_xaag091-B8","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1111\/j.1365-2435.2010.01812.x","article-title":"Gestation length variation in a wild ungulate","volume":"25","author":"Clements","year":"2011","journal-title":"Functional Ecology"},{"key":"2026082616514873100_xaag091-B9","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1016\/J.REPBIO.2019.04.003","article-title":"Do ovarian steroid hormones control the resumption of embryonic growth following the period of diapause in roe deer (Capreolus capreolus)?","volume":"19","author":"Drews","year":"2019","journal-title":"Reproductive Biology"},{"key":"2026082616514873100_xaag091-B10","doi-asserted-by":"publisher","first-page":"804","DOI":"10.1095\/BIOLREPROD28.4.804","article-title":"Steroid metabolism by the bovine uterine endometrium and conceptus","volume":"28","author":"Eley","year":"1983","journal-title":"Biology of Reproduction"},{"key":"2026082616514873100_xaag091-B11","doi-asserted-by":"publisher","first-page":"100136","DOI":"10.1016\/J.THERWI.2025.100136","article-title":"First successful cervical artificial insemination in the European roe deer (Capreolus capreolus)","volume":"7","author":"Elsafadi","year":"2025","journal-title":"Theriogenology Wild"},{"key":"2026082616514873100_xaag091-B12","doi-asserted-by":"publisher","first-page":"559","DOI":"10.4098\/AT.ARCH.00-54","article-title":"Ultrasonography of the ovaries and uterus and grey scale analysis of the endometrium during embryonic diapause in European roe deer","volume":"45","author":"Hermes","year":"2000","journal-title":"Acta Theriologica"},{"key":"2026082616514873100_xaag091-B13","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1016\/S0960-0760(01)00073-5","article-title":"Neuroactive steroids, their precursors and polar conjugates during parturition and postpartum in maternal blood: 2. 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Identification and simultaneous determination of pregnanolone isomers","volume":"75","author":"Hill","year":"2000","journal-title":"The Journal of Steroid Biochemistry and Molecular Biology"},{"key":"2026082616514873100_xaag091-B15","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1016\/J.JSBMB.2013.03.008","article-title":"Steroid profiling in pregnancy: A focus on the human fetus","volume":"139","author":"Hill","year":"2014","journal-title":"The Journal of Steroid Biochemistry and Molecular Biology"},{"key":"2026082616514873100_xaag091-B16","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1016\/S0378-4320(98)00123-7","article-title":"Endocrinology of the ovarian cycle and pregnancy in the Asian (Elephas maximus) and African (Loxodonta africana) elephant","volume":"53","author":"Hodges","year":"1998","journal-title":"Animal Reproduction 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Development"}],"container-title":["Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/reproduction\/advance-article-pdf\/doi\/10.1093\/reprod\/xaag091\/70263923\/xaag091.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/172\/2\/xaag091\/70263923\/xaag091.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/172\/2\/xaag091\/70263923\/xaag091.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T20:51:53Z","timestamp":1787777513000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/reproduction\/article\/doi\/10.1093\/reprod\/xaag091\/8744105"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,28]]},"references-count":37,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,8,4]]}},"URL":"https:\/\/doi.org\/10.1093\/reprod\/xaag091","relation":{},"ISSN":["1470-1626","1741-7899"],"issn-type":[{"value":"1470-1626","type":"print"},{"value":"1741-7899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,7,28]]},"article-number":"xaag091"}}