{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T04:18:21Z","timestamp":1744777101284,"version":"3.40.4"},"reference-count":35,"publisher":"Wiley","issue":"S2","license":[{"start":{"date-parts":[[2025,2,19]],"date-time":"2025-02-19T00:00:00Z","timestamp":1739923200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2702500"],"award-info":[{"award-number":["2022YFC2702500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82271654","82070565"],"award-info":[{"award-number":["82271654","82070565"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["obgyn.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["BJOG"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>To clarify the protective effects of gonadotropin\u2010releasing hormone analogues (GnRHas) on cyclophosphamide (CTX)\u2010induced oocyte number loss and development of potential damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Design<\/jats:title><jats:p>Mice model study.<\/jats:p><\/jats:sec><jats:sec><jats:title>Setting<\/jats:title><jats:p>Laboratory\u2010based animal study conducted in controlled research facilities.<\/jats:p><\/jats:sec><jats:sec><jats:title>Population<\/jats:title><jats:p>Female C57\/BL6 mice subjected to CTX\u2010induced ovarian damage.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>The effects of GnRHa on CTX mice were evaluated in terms of hormones, oocyte count on slices, oocyte count in established three\u2010dimensional\u2013constructed ovaries, in\u00a0vitro fertilisation, RNA sequencing and microinjection.<\/jats:p><\/jats:sec><jats:sec><jats:title>Main Outcome Measures<\/jats:title><jats:p>The main outcome measures were the number of oocytes in intact mouse ovaries and oocyte quality, evaluated using three\u2010dimensional (3D) tissue\u2010clearing methods, oxidative stress markers (reactive oxygen species [ROS] and malondialdehyde [MDT]), mitochondrial function (ATP levels), and embryogenesis rates at the two\u2010cell, four\u2010cell and blastocyst stages.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In CTX mice, GnRHa pretreatment did not protect endocrine hormone changes, but protected loss of oocyte number on slice counting. A tissue\u2010clearing technique, CUBIC (Clear, Unobstructed Body Imaging Cocktails), was a suitable method for ovaries clearing, and a 3D method for oocyte counting was validated with accuracy of 105.22%\u2009\u00b1\u20093.48%. By this method, GnRHa was also found to protect the loss of oocyte number (597\u2009\u00b1\u200928 vs. 222\u2009\u00b1\u200915, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), which may be mediated by upregulated anti\u2010M\u00fcllerian hormone (AMH) levels inhibiting primordial follicle development approved by in\u00a0vitro culture of ovaries. GnRHa also increased the number of retrieved oocytes in CTX mice (19.4\u2009\u00b1\u20092.1 vs. 15.0\u2009\u00b1\u20091.6, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) and developmental ability of oocytes (65.0\u2009\u00b1\u20094.6 vs. 48.1\u2009\u00b1\u20094.2 for blastocyst, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001). RNA sequencing revealed GnRHa pretreatment downregulated pathways of exogenous drug metabolism, oxidative stress and cytochrome P450, validated by detection of adenosine triphosphate (ATP), MDA and ROS levels. The up\u2010expression of <jats:italic>Cox17<\/jats:italic> (cytochrome c oxidase copper chaperone 17) after GnRHa pretreatment was confirmed by PCR and microinjection of si<jats:italic>Cox17<\/jats:italic> increased the embryogenesis from CTX mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>GnRHa was associated with reduced oocyte loss and improved embryogenesis, likely mediated by AMH and Cox17 upregulation.<\/jats:p><\/jats:sec>","DOI":"10.1111\/1471-0528.18098","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T06:39:19Z","timestamp":1740033559000},"page":"107-119","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Effects of Gonadotropin\u2010Releasing Hormone Analogues on Ovarian Function and Embryogenesis: A Cyclophosphamide\u2010Induced Mouse Model Study"],"prefix":"10.1111","volume":"132","author":[{"given":"Qiwang","family":"Lin","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Center for Reproductive Medicine, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Guangdong Provincial Clinical Research Center for Obstetrics and Gynecology, Guangdong Hong Kong Macao Greater Bay Area Higher Education Joint Laboratory of Maternal\u2010Fetal Medicine The Third Affiliated Hospital of Guangzhou Medical University  Guangzhou China"},{"name":"Department of Gynecology, Obstetrics &amp; 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