{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T03:07:09Z","timestamp":1788145629652,"version":"build-2803163510"},"reference-count":90,"publisher":"Bioscientifica","issue":"1","content-domain":{"domain":["joe.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2018,1]]},"abstract":"<jats:p>\n                    A clinical association between thyroid dysfunction and pregnancy complications has been extensively reported; however, the molecular mechanisms through which TH might regulate key events of pregnancy have not been elucidated yet. In this respect, we performed\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies in MMI-induced hypothyroid pregnant mice, evaluating the effect of hypothyroidism on the number of implantation sites, developing embryos\/resorptions and pups per litter, at 4.5, 10.5, 18.5 days post-coitum (dpc) and at birth. We also studied the expression of major molecules involved in implantation and placentation, such as the proteases ISPs, MMPs, TIMPs and Notch pathway-related genes. Our results demonstrate that hypothyroidism may have a dual effect on pregnancy, by initially influencing implantation and by regulating placental development at later stages of gestation. To further elucidate the role of TH in implantation, we performed\n                    <jats:italic>in vitro<\/jats:italic>\n                    studies by culturing 3.5 dpc blastocysts in the presence of TH, with or without endometrial cells used as the feeder layer, and studied their ability to undergo hatching and outgrowth. We observed that, in the presence of endometrial feeder cells, TH is able to anticipate blastocyst hatching by upregulating the expression of blastocyst-produced ISPs, and to enhance blastocyst outgrowth by upregulating endometrial ISPs and MMPs. These results clearly indicate that TH is involved in the bidirectional crosstalk between the competent blastocyst and the receptive endometrium at the time of implantation.\n                  <\/jats:p>","DOI":"10.1530\/joe-17-0436","type":"journal-article","created":{"date-parts":[[2017,10,9]],"date-time":"2017-10-09T20:40:33Z","timestamp":1507581633000},"page":"1-12","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-5","source":"Crossref","is-referenced-by-count":27,"title":["Thyroid hormone regulates protease expression and activation of Notch signaling in implantation and embryo development"],"prefix":"10.1530","volume":"236","author":[{"given":"Diletta","family":"Piccirilli","sequence":"first","affiliation":[{"name":"1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enke","family":"Baldini","sequence":"additional","affiliation":[{"name":"2Department of Surgical Sciences, \u2018Sapienza\u2019 University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Micol","family":"Massimiani","sequence":"additional","affiliation":[{"name":"1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonella","family":"Camaioni","sequence":"additional","affiliation":[{"name":"1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonietta","family":"Salustri","sequence":"additional","affiliation":[{"name":"1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bernardini","sequence":"additional","affiliation":[{"name":"3Department of Biology, NSTA, II University of Rome, Tor Vergata, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Centanni","sequence":"additional","affiliation":[{"name":"4Department of Medico-Surgical Sciences and Biotechnologies, \u2018Sapienza\u2019 University of Rome, Latina, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salvatore","family":"Ulisse","sequence":"additional","affiliation":[{"name":"2Department of Surgical Sciences, \u2018Sapienza\u2019 University of Rome, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Costanzo","family":"Moretti","sequence":"additional","affiliation":[{"name":"5Department of Systems\u2019 Medicine University of Rome Tor Vergata, UOC of Endocrinology and Diabetes, Section of Reproductive Endocrinology Fatebenefratelli Hospital, \u2018Isola Tiberina\u2019, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luisa","family":"Campagnolo","sequence":"additional","affiliation":[{"name":"1Department of Biomedicine and Prevention, University of Rome Tor Vergata, Rome, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"416","reference":[{"key":"ref561","first-page":"1719","article-title":"Detection of thyroid hormones in human embryonic cavities during the first trimester of pregnancy","volume":"77","year":"1993","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"ref471","first-page":"57","article-title":"Tissue interactions in the control of trophoblast invasion","volume":"55","year":"2000","journal-title":"Journal of Reproduction and Fertility: Supplement"},{"key":"ref601","doi-asserted-by":"crossref","first-page":"2687","DOI":"10.1210\/jc.2013-1302","article-title":"Thyroid testing and management of hypothyroidism during pregnancy: a population-based study","volume":"98","year":"2013","journal-title":"Journal of Clinical Endocrinology and 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