{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,27]],"date-time":"2026-08-27T16:19:21Z","timestamp":1787847561815,"version":"build-2784847793"},"reference-count":74,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T00:00:00Z","timestamp":1677024000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100006377","name":"Purdue University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006377","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>To understand the effect of fetal thyroid gland disruption on development in swine, we evaluated thyroid hormone levels, growth and developmental characteristics, and gene expression associated with thyroid hormone metabolism in late gestation fetuses exposed to methimazole (MMI). Pregnant gilts were given either oral MMI or equivalent sham from gestation day 85\u2013106 (n\u00a0=\u20094\/group), followed by intensive phenotyping of all fetuses (n\u00a0=\u2009120). Samples of liver (LVR), kidney (KID), fetal placenta (PLC), and the corresponding maternal endometrium (END) were collected from a subset of fetuses (n\u00a0=\u200932). Fetuses exposed to MMI in utero were confirmed hypothyroid, with a significant increase in thyroid gland size, goitrous thyroid histology, and dramatically suppressed thyroid hormone in serum. In dams, no differences in temporal measurements of average daily gain, thyroid hormone, or rectal temperatures relative to controls suggests that MMI had little effect on maternal physiology. However, fetuses from MMI-treated gilts exhibited significant increases in body mass, girth, and vital organ weights, but no differences in crown-rump length or bone measurements suggesting non-allometric growth. The PLC and END showed a compensatory decrease in expression of inactivating deiodinase (DIO3). Similar compensatory gene expression was observed in fetal KID and LVR with a downregulation of all deiodinases (DIO1, DIO2, DIO3). Minor alterations in the expression of thyroid hormone transporters (SLC16A2 and SLC16A10) were observed in PLC, KID, and LVR. Collectively, MMI crosses the PLC of the late gestation pig, resulting in congenital hypothyroidism, alterations in fetal growth, and compensatory responses within the maternal fetal interface.<\/jats:p>","DOI":"10.1093\/biolre\/ioad024","type":"journal-article","created":{"date-parts":[[2023,2,22]],"date-time":"2023-02-22T16:23:46Z","timestamp":1677083026000},"page":"731-743","source":"Crossref","is-referenced-by-count":13,"title":["Compensatory mechanisms in response to induced hypothyroidism in the late gestation pig fetus"],"prefix":"10.1093","volume":"108","author":[{"given":"Erin K","family":"Ison","sequence":"first","affiliation":[{"name":"Purdue University Department of Animal Science, , West Lafayette, IN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Coral E","family":"Kent-Dennis","sequence":"additional","affiliation":[{"name":"Postdoctoral fellow, Oak Ridge Institute for Science and Education"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Fazioli","sequence":"additional","affiliation":[{"name":"Purdue University Department of Animal Science, , West Lafayette, IN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margaret K","family":"Mulligan","sequence":"additional","affiliation":[{"name":"Purdue University Department of Animal Science, , West Lafayette, IN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Pham","sequence":"additional","affiliation":[{"name":"Purdue University Department of Animal Science, , West Lafayette, IN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J Alex","family":"Pasternak","sequence":"additional","affiliation":[{"name":"Purdue University Department of Animal Science, , West Lafayette, IN , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2023,2,22]]},"reference":[{"key":"2023051502235877700_ref1","doi-asserted-by":"crossref","first-page":"2534","DOI":"10.2527\/2004.8292534x","article-title":"Growth and compositional changes of fetal tissues in pigs","volume":"82","author":"McPherson","year":"2004","journal-title":"J Anim Sci"},{"key":"2023051502235877700_ref2","doi-asserted-by":"crossref","first-page":"3344","DOI":"10.1210\/en.2005-1328","article-title":"Maternal insulin-like growth factors-I and -II act via different pathways to promote fetal growth","volume":"147","author":"Sferruzzi-Perri","year":"2006","journal-title":"Endocrinology"},{"key":"2023051502235877700_ref3","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1016\/0300-9629(89)90068-6","article-title":"Changes in the levels of growth hormones, insulin, cortisol, thyroxine and somatomedin-C\/IGF-1, with increasing gestational age in the fetal pig, and the effect of thyroidectomy in utero","volume":"93","author":"Spencer","year":"1989","journal-title":"Comp Biochem Physiol A Comp Physiol"},{"key":"2023051502235877700_ref4","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1556\/avet.52.2004.4.1","article-title":"Changes in thyroxine, 3,3\u2032,5-triiodothyronine and 3,3\u20325\u2019-triiodothyronine content in the thyroid gland and in serum to thyroid tissue iodothyronine ratios during ontogenesis in the fetal pig","volume":"52","author":"Brzezi\u0144ska-Slebodzi\u0144ska","year":"2004","journal-title":"Acta Vet Hung"},{"key":"2023051502235877700_ref5","doi-asserted-by":"crossref","first-page":"3267","DOI":"10.2527\/jas.2007-0368","article-title":"Differences in placental structure during gestation associated with large and small pig fetuses","volume":"85","author":"Vallet","year":"2007","journal-title":"J Anim Sci"},{"key":"2023051502235877700_ref6","doi-asserted-by":"crossref","DOI":"10.1186\/2049-1891-5-55","article-title":"Placental accommodations for transport and metabolism during intra-uterine crowding in pigs","volume":"5","author":"Vallet","year":"2014","journal-title":"J Anim Sci Biotechnol"},{"key":"2023051502235877700_ref7","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1293\/tox.2013-0060","article-title":"A comparison of the histological structure of the placenta in experimental animals","volume":"27","author":"Furukawa","year":"2014","journal-title":"J Toxicol Pathol"},{"key":"2023051502235877700_ref8","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1007\/BF00315905","article-title":"The placenta of the pig. 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