{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T18:57:45Z","timestamp":1787597865115,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T00:00:00Z","timestamp":1701043200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003977","name":"Israel Science Foundation","doi-asserted-by":"publisher","award":["1252\/19"],"award-info":[{"award-number":["1252\/19"]}],"id":[{"id":"10.13039\/501100003977","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Einstein Kaye Foundation","award":["1252\/19"],"award-info":[{"award-number":["1252\/19"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Parturition is the final and essential step for mammalian reproduction. While the uterus is quiescent during pregnancy, fundamental changes arise in the myometrial contractility, inducing fetal expulsion. Extracellular matrix (ECM) remodeling is fundamental for these events. The gelatinases subgroup of matrix metalloproteinases (MMPs), MMP2 and MMP9, participate in uterine ECM remodeling throughout pregnancy and parturition. However, their loss-of-function effect is unknown. Here, we determined the result of eliminating Mmp2 and\/or Mmp9 on parturition in vivo, using single- and double-knockout (dKO) mice. The dystocia rates were measured in each genotype, and uterine tissue was collected from nulliparous synchronized females at the ages of 2, 4, 9 and 12 months. Very high percentages of dystocia (40\u201355%) were found in the Mmp2\u2212\/\u2212 and dKO females, contrary to the Mmp9\u2212\/\u2212 and wild-type females. The histological analysis of the uterus and cervix revealed that Mmp2\u2212\/\u2212 tissues undergo marked structural alterations, including highly enlarged myometrial, endometrial and luminal cavity. Increased collagen deposition was also demonstrated, suggesting a mechanism of extensive fibrosis in the Mmp2\u2212\/\u2212 myometrium, which may result in dystocia. Overall, this study describes a new role for MMP2 in myometrium remodeling during mammalian parturition process, highlighting a novel cause for dystocia due to a loss in MMP2 activity in the uterine tissue.<\/jats:p>","DOI":"10.3390\/ijms242316822","type":"journal-article","created":{"date-parts":[[2023,11,27]],"date-time":"2023-11-27T07:56:10Z","timestamp":1701071770000},"page":"16822","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Mmp2 Deficiency Leads to Defective Parturition and High Dystocia Rates in Mice"],"prefix":"10.3390","volume":"24","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9298-5537","authenticated-orcid":false,"given":"Rotem","family":"Kalev-Altman","sequence":"first","affiliation":[{"name":"The Koret School of Veterinary Medicine, The RH Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel"},{"name":"The Institute of Biochemistry, Food Science and Nutrition, The RH Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gal","family":"Becker","sequence":"additional","affiliation":[{"name":"The Institute of Biochemistry, Food Science and Nutrition, The RH Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamar","family":"Levy","sequence":"additional","affiliation":[{"name":"The Koret School of Veterinary Medicine, The RH Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Svetlana","family":"Penn","sequence":"additional","affiliation":[{"name":"The Institute of Biochemistry, Food Science and Nutrition, The RH Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2560-3783","authenticated-orcid":false,"given":"Nahum Y.","family":"Shpigel","sequence":"additional","affiliation":[{"name":"The Koret School of Veterinary Medicine, The RH Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7023-5065","authenticated-orcid":false,"given":"Efrat","family":"Monsonego-Ornan","sequence":"additional","affiliation":[{"name":"The Institute of Biochemistry, Food Science and Nutrition, The RH Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7498-061X","authenticated-orcid":false,"given":"Dalit","family":"Sela-Donenfeld","sequence":"additional","affiliation":[{"name":"The Koret School of Veterinary Medicine, The RH Smith Faculty of Agriculture, Food and Environment, The Hebrew University of Jerusalem, Rehovot 7610001, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,11,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1101\/cshperspect.a023069","article-title":"Molecular regulation of parturition: A myometrial perspective","volume":"5","author":"Renthal","year":"2015","journal-title":"Cold Spring Harb. 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