{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,7]],"date-time":"2025-11-07T19:18:14Z","timestamp":1762543094681,"version":"build-2065373602"},"reference-count":61,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T00:00:00Z","timestamp":1563321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K08287","16H05107"],"award-info":[{"award-number":["17K08287","16H05107"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Elevated plasma homocysteine levels are considered as a risk factor for cardiovascular diseases as well as preeclampsia\u2014a pregnancy disorder characterized by hypertension and proteinuria. We previously generated mice lacking cystathionine \u03b3-lyase (Cth) as cystathioninuria models and found them to be with cystathioninemia\/homocysteinemia. We investigated whether Cth-deficient (Cth\u2212\/\u2212) pregnant mice display any features of preeclampsia. Cth\u2212\/\u2212 females developed normally but showed mild hypertension (~10 mmHg systolic blood pressure elevation) in late pregnancy and mild proteinuria throughout development\/pregnancy. Cth\u2212\/\u2212 dams had normal numbers of pups and exhibited normal maternal behavior except slightly lower breastfeeding activity. However, half of them could not raise their pups owing to defective lactation; they could produce\/store the first milk in their mammary glands but not often provide milk to their pups after the first ejection. The serum oxytocin levels and oxytocin receptor expression in the mammary glands were comparable between wild-type and Cth\u2212\/\u2212 dams, but the contraction responses of mammary gland myoepithelial cells to oxytocin were significantly lower in Cth\u2212\/\u2212 dams. The contraction responses to oxytocin were lower in uteruses isolated from Cth\u2212\/\u2212 mice. Our results suggest that elevated homocysteine or other unknown factors in preeclampsia-like Cth\u2212\/\u2212 dams interfere with oxytocin that regulates milk ejection reflex.<\/jats:p>","DOI":"10.3390\/ijms20143507","type":"journal-article","created":{"date-parts":[[2019,7,17]],"date-time":"2019-07-17T11:25:12Z","timestamp":1563362712000},"page":"3507","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Preeclampsia-Like Features and Partial Lactation Failure in Mice Lacking Cystathionine \u03b3-Lyase\u2014An Animal Model of Cystathioninuria"],"prefix":"10.3390","volume":"20","author":[{"given":"Noriyuki","family":"Akahoshi","sequence":"first","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hiroki","family":"Handa","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rintaro","family":"Takemoto","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shotaro","family":"Kamata","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masahide","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jichi Medical University, Tochigi 329-0498, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatsushi","family":"Onaka","sequence":"additional","affiliation":[{"name":"Department of Physiology, Jichi Medical University, Tochigi 329-0498, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5367-205X","authenticated-orcid":false,"given":"Isao","family":"Ishii","sequence":"additional","affiliation":[{"name":"Department of Health Chemistry, Showa Pharmaceutical University, Tokyo 194-8543, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,7,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2213","DOI":"10.1515\/cclm-2012-0078","article-title":"Plasma homocysteine and the risk of venous thromboembolism: Insights from the FIELD study","volume":"50","author":"Herrmann","year":"2012","journal-title":"Clin. 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