{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T04:01:43Z","timestamp":1792036903626,"version":"4.4.0"},"reference-count":51,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T00:00:00Z","timestamp":1556582400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T00:00:00Z","timestamp":1556582400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Mechanical and inflammatory signals in the fetal membrane play an important role in extracellular matrix (ECM) remodelling in order to dictate the timing of birth. We developed a mechanical model that mimics repetitive stretching of the amniotic membrane (AM) isolated from regions over the placenta (PAM) or cervix (CAM) and examined the effect of cyclic tensile strain (CTS) on mediators involved in mechanotransduction (Cx43, AKT), tissue remodelling (GAGs, elastin, collagen) and inflammation (PGE<jats:sub>2<\/jats:sub>, MMPs). In CAM and PAM specimens, the application of CTS increased GAG synthesis, PGE<jats:sub>2<\/jats:sub> release and MMP activity, with concomitant reduction in collagen and elastin content. Co-stimulation with CTS and pharmacological agents that inhibit either Cx43 or AKT, differentially influenced collagen, GAG and elastin in a tissue-dependent manner. SHG confocal imaging of collagen fibres revealed a reduction in SHG intensity after CTS, with regions of disorganisation dependent on tissue location. CTS increased Cx43 and AKT protein and gene expression and the response could be reversed with either CTS, the Cx43 antisense or AKT inhibitor. We demonstrate that targeting Cx43 and AKT prevents strain-induced ECM damage and promotes tissue remodelling mechanisms in the AM. We speculate that a combination of inflammatory and mechanical factors could perturb typical mechanotransduction processes mediated by Cx43 signalling. Cx43 could therefore be a potential therapeutic target to prevent inflammation and preterm premature rupture of the fetal membranes.<\/jats:p>","DOI":"10.1038\/s41598-019-42379-4","type":"journal-article","created":{"date-parts":[[2019,4,30]],"date-time":"2019-04-30T10:04:20Z","timestamp":1556618660000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Targeting mechanotransduction mechanisms and tissue weakening signals in the human amniotic membrane"],"prefix":"10.1038","volume":"9","author":[{"given":"David W.","family":"Barrett","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca K.","family":"John","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9425-8624","authenticated-orcid":false,"given":"Christopher","family":"Thrasivoulou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alvaro","family":"Mata","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan A.","family":"Deprest","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David L.","family":"Becker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0199-6140","authenticated-orcid":false,"given":"Anna L.","family":"David","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tina T.","family":"Chowdhury","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,4,30]]},"reference":[{"key":"42379_CR1","doi-asserted-by":"publisher","first-page":"2162","DOI":"10.1016\/S0140-6736(12)60820-4","volume":"379","author":"H Blencowe","year":"2012","unstructured":"Blencowe, H. et al. National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications. Lancet 379, 2162\u201372 (2012).","journal-title":"Lancet"},{"key":"42379_CR2","doi-asserted-by":"crossref","unstructured":"Malak, T. M., & Bell, S. C. Structural characteristics of term human fetal membranes: a novel zone of extreme morphological alteration within the rupture site. Br J Obstet. Gynaecol 101, 375\u201386 (199).","DOI":"10.1111\/j.1471-0528.1994.tb11908.x"},{"key":"42379_CR3","first-page":"178","volume":"101","author":"BM Mercer","year":"2003","unstructured":"Mercer, B. M. Preterm premature rupture of the membranes. Obstet Gynecol 101, 178\u201393 (2003).","journal-title":"Obstet Gynecol"},{"key":"42379_CR4","doi-asserted-by":"publisher","first-page":"140","DOI":"10.1177\/1933719111424454","volume":"20","author":"JF Strauss","year":"2013","unstructured":"Strauss, J. F. Extracellular matrix dynamics and fetal membrane rupture. Reprod Sci 20, 140\u201353 (2013).","journal-title":"Reprod Sci"},{"key":"42379_CR5","doi-asserted-by":"publisher","first-page":"830.e1","DOI":"10.1016\/j.ajog.2015.08.028","volume":"213","author":"A Waldorf","year":"2015","unstructured":"Waldorf, A. et al. Uterine overdistention induces preterm labor mediated by inflammation: observations in pregnant women and nonhuman primates. Am J Obstet Gynecol 213, 830.e1\u2013830.e19 (2015).","journal-title":"Am J Obstet Gynecol"},{"key":"42379_CR6","doi-asserted-by":"publisher","first-page":"1047","DOI":"10.1016\/S0002-9378(96)80051-2","volume":"175","author":"RL Goldenberg","year":"1996","unstructured":"Goldenberg, R. L. et al. The preterm prediction study: risk factors in twin gestations. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. Am J Obstet Gynecol 175, 1047\u201353 (1996).","journal-title":"Am J Obstet Gynecol"},{"key":"42379_CR7","first-page":"117","volume":"67","author":"P Kirkinen","year":"1978","unstructured":"Kirkinen, P. & Jouppila, P. Polyhydramnion. A clinical study. Ann Chir Gynaecol 67, 117\u201322 (1978).","journal-title":"Ann Chir Gynaecol"},{"key":"42379_CR8","doi-asserted-by":"publisher","first-page":"224","DOI":"10.1016\/S0015-0282(97)81506-3","volume":"68","author":"PK Heinonen","year":"1997","unstructured":"Heinonen, P. K. Unicornuate uterus and rudimentary horn. Fertil Steril 68, 224\u201330 (1997).","journal-title":"Fertil Steril"},{"key":"42379_CR9","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1016\/j.placenta.2015.12.011","volume":"38","author":"EM Joyce","year":"2016","unstructured":"Joyce, E. M. et al. In-vivo stretch of term human fetal membranes. Placenta 38, 57\u201366 (2016).","journal-title":"Placenta"},{"key":"42379_CR10","doi-asserted-by":"publisher","first-page":"967","DOI":"10.2353\/ajpath.2006.050207","volume":"169","author":"X Wang","year":"2006","unstructured":"Wang, X. et al. Disruption of IL-18, but not IL1, increases vulnerability to preterm delivery and fetal mortality after intrauterine inflammation. Am J Pathol 169, 967\u201376 (2006).","journal-title":"Am J Pathol"},{"key":"42379_CR11","doi-asserted-by":"publisher","first-page":"1215","DOI":"10.1177\/1933719114534535","volume":"21","author":"SM Lannon","year":"2014","unstructured":"Lannon, S. M., Vanderhoeven, J. P., Eschenbach, D. A., Gravett, M. G. & Adams Waldorf, K. M. Synergy and interactions among biological pathways leading to preterm premature rupture of membranes. Reprod Sci 21, 1215\u201327 (2014).","journal-title":"Reprod Sci"},{"key":"42379_CR12","doi-asserted-by":"publisher","first-page":"517","DOI":"10.1093\/humupd\/3.5.517","volume":"3","author":"SM Cox","year":"1997","unstructured":"Cox, S. M., Casey, M. L. & MacDonald, P. C. Accumulation of IL-1\u03b2 and IL-6 in amniotic fluid: a sequela of labour at term and preterm. Hum Reprod Update 3, 517\u201327 (1997).","journal-title":"Hum Reprod Update"},{"key":"42379_CR13","doi-asserted-by":"publisher","first-page":"1142","DOI":"10.1016\/S0002-9378(99)70097-9","volume":"181","author":"E Maymon","year":"1999","unstructured":"Maymon, E. et al. The TNF\u03b1 and its soluble receptor profile in term and preterm parturition. Am J Obstet Gynecol 181, 1142\u20138 (1999).","journal-title":"Am J Obstet Gynecol"},{"key":"42379_CR14","doi-asserted-by":"publisher","first-page":"147","DOI":"10.1016\/j.ejogrb.2009.10.027","volume":"148","author":"N Thomakos","year":"2010","unstructured":"Thomakos, N. et al. Amniotic fluid IL-6 and TNFa at mid-trimester genetic amniocentesis: relationship to intra-amniotic microbial invasion and preterm delivery. Eur J Obstet Gynecol Reprod Biol 148, 147\u201351 (2010).","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"42379_CR15","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1186\/1477-7827-8-121","volume":"15","author":"MF Miller","year":"2010","unstructured":"Miller, M. F. & Loch-Caruso, R. Comparison of LPS-stimulated release of cytokines in punch versus transwell tissue culture systems of human gestational membranes. Reprod Biol Endocrinol 15, 121\u20139 (2010).","journal-title":"Reprod Biol Endocrinol"},{"key":"42379_CR16","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1016\/j.ejogrb.2011.12.026","volume":"161","author":"J Polettini","year":"2012","unstructured":"Polettini, J. et al. IL-18 messenger RNA and proIL-18 protein expression in chorioamniotic membranes from pregnant women with preterm prelabor rupture of membranes. Eur J Obstet Gynecol Reprod Biol 161, 134\u20139 (2012).","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"42379_CR17","doi-asserted-by":"publisher","first-page":"194","DOI":"10.1016\/j.cyto.2017.07.005","volume":"99","author":"LM Scott","year":"2017","unstructured":"Scott, L. M. et al. Production and regulation of interleukin-1 family cytokines at the materno-fetal interface. Cytokine 99, 194\u2013202 (2017).","journal-title":"Cytokine"},{"key":"42379_CR18","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1515\/JPM.1999.049","volume":"27","author":"SJ Fortunato","year":"1999","unstructured":"Fortunato, S. J., Menon, R. & Lombardi, S. J. MMP\/TIMP imbalance in amniotic fluid during PROM: an indirect support for endogenous pathway to membrane rupture. J Perinat Med 27, 362\u20138 (1999).","journal-title":"J Perinat Med"},{"key":"42379_CR19","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1093\/molehr\/8.5.494","volume":"8","author":"PE Ferrand","year":"2002","unstructured":"Ferrand, P. E. et al. A polymorphism in the matrix metalloproteinase-9 promoter is associated with increased risk of preterm premature rupture of membranes in African Americans. Mol Hum Reprod 8, 494\u2013501 (2002).","journal-title":"Mol Hum Reprod"},{"key":"42379_CR20","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1016\/0002-9378(95)90085-3","volume":"172","author":"GD Bryant-Greenwood","year":"1995","unstructured":"Bryant-Greenwood, G. D. & Yamamoto, S. Y. Control of peripartal collagenolysis in the human chorion-decidua. Am J Obstet Gynecol 172, 63\u201370 (1995).","journal-title":"Am J Obstet Gynecol"},{"key":"42379_CR21","doi-asserted-by":"publisher","first-page":"59","DOI":"10.3109\/03008208309005612","volume":"12","author":"MG Dunn","year":"1983","unstructured":"Dunn, M. G. & Silver, F. H. Viscoelastic behavior of human connective tissues: relative contribution of viscous and elastic components. Connect Tissue Res 12, 59\u201370 (1983).","journal-title":"Connect Tissue Res"},{"key":"42379_CR22","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1095\/biolreprod.105.045328","volume":"74","author":"D Kumar","year":"2006","unstructured":"Kumar, D. et al. Proinflammatory cytokines found in amniotic fluid induce collagen remodeling, apoptosis, and biophysical weakening of cultured human fetal membranes. Biol Reprod 74, 29\u201334 (2006).","journal-title":"Biol Reprod"},{"key":"42379_CR23","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1016\/j.jsgi.2004.04.001","volume":"11","author":"R Menon","year":"2004","unstructured":"Menon, R. & Fortunato, S. J. The role of matrix degrading enzymes and apoptosis in rupture of membranes. J Soc Gynecol Investig 11, 427\u201337 (2004).","journal-title":"J Soc Gynecol Investig"},{"key":"42379_CR24","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1016\/j.placenta.2011.01.006","volume":"32","author":"D Kumar","year":"2011","unstructured":"Kumar, D. et al. The effects of thrombin and cytokines upon the biomechanics and remodeling of isolated amnion membrane, in vitro. Placenta 32, 206\u201313 (2011).","journal-title":"Placenta"},{"key":"42379_CR25","doi-asserted-by":"publisher","first-page":"781","DOI":"10.1095\/biolreprod.108.073205","volume":"80","author":"RM Moore","year":"2009","unstructured":"Moore, R. M. et al. Alpha-lipoic acid inhibits tumor necrosis factor-induced remodeling and weakening of human fetal membranes. Biol Reprod 80, 781\u20137 (2009).","journal-title":"Biol Reprod"},{"key":"42379_CR26","doi-asserted-by":"publisher","first-page":"573","DOI":"10.1016\/j.placenta.2003.12.005","volume":"25","author":"D Kumar","year":"2004","unstructured":"Kumar, D., Moore, R. M., Elkhwad, M., Silver, R. J. & Moore, J. J. Vitamin C exacerbates hydrogen peroxide induced apoptosis and concomitant PGE2 release in amnion epithelial and mesenchymal cells and in intact amnion. Placenta 25, 573\u20139 (2004).","journal-title":"Placenta"},{"key":"42379_CR27","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1016\/j.placenta.2018.01.009","volume":"63","author":"J Polettini","year":"2018","unstructured":"Polettini, J., Richardson, L. S. & Menon, R. Oxidative stress induces senescence and sterile inflammation in murine amniotic cavity. Placenta 63, 26\u201331 (2018).","journal-title":"Placenta"},{"key":"42379_CR28","doi-asserted-by":"publisher","first-page":"176","DOI":"10.1095\/biolreprod60.1.176","volume":"60","author":"H Lei","year":"1999","unstructured":"Lei, H., Kalluri, R., Furth, E. E., Baker, A. H. & Strauss, J. F. Rat amnion type IV collagen composition and metabolism: implications for membrane breakdown. Biol Reprod 60, 176\u201382 (1999).","journal-title":"Biol Reprod"},{"key":"42379_CR29","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1023\/B:JMSM.0000026102.85071.1f","volume":"15","author":"ML Oyen","year":"2004","unstructured":"Oyen, M. L., Calvin, S. E. & Cook, R. F. Uniaxial stress-relaxation and stress-strain responses of human amnion. J Mater Sci Mater Med 15, 619\u201324 (2004).","journal-title":"J Mater Sci Mater Med"},{"key":"42379_CR30","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1023\/B:JMSM.0000030205.62668.90","volume":"15","author":"ML Oyen","year":"2004","unstructured":"Oyen, M. L., Cook, R. F. & Calvin, S. E. Mechanical failure of human fetal membrane tissues. J Mater Sci Mater Med 15, 651\u20138 (2004).","journal-title":"J Mater Sci Mater Med"},{"key":"42379_CR31","first-page":"87","volume":"60","author":"JP Lavery","year":"1982","unstructured":"Lavery, J. P., Miller, C. E. & Knight, R. D. The effect of labor on the rheologic response of chorioamniotic membranes. Obstet Gynecol 60, 87\u201392 (1982).","journal-title":"Obstet Gynecol"},{"key":"42379_CR32","doi-asserted-by":"crossref","unstructured":"Pandey, V. et al. The force required to rupture fetal membranes paradoxically increases with acute in vitro repeated stretching. 196, 165 (2007).","DOI":"10.1016\/j.ajog.2006.10.861"},{"key":"42379_CR33","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1159\/000293546","volume":"28","author":"N Kanayama","year":"1989","unstructured":"Kanayama, N. & Fukamizu, H. Mechanical stretching increases prostaglandin E2 in cultured human amnion cells. Gynecol Obstet Invest 28, 123\u201326 (1989).","journal-title":"Gynecol Obstet Invest"},{"key":"42379_CR34","doi-asserted-by":"publisher","first-page":"1850","DOI":"10.1210\/en.2006-1289","volume":"148","author":"AR Mohan","year":"2007","unstructured":"Mohan, A. R., Sooranna, S. R., Lindstrom, T. M., Johnson, M. R. & Bennett, P. R. The effect of mechanical stretch on COX2 expression and AP-1 and NFkB activity in human amnion cells. Endocrinology 148, 1850\u20137 (2007).","journal-title":"Endocrinology"},{"key":"42379_CR35","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/S0301-2115(95)02602-9","volume":"27","author":"K Maehara","year":"1996","unstructured":"Maehara, K. et al. Mechanical stretching induces interleukin-8 gene expression in fetal membranes: a possible role for the initiation of human parturition. Eur J Obstet Gynecol Reprod Biol 27, 191\u20136 (1996).","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"42379_CR36","doi-asserted-by":"publisher","first-page":"5398","DOI":"10.1210\/endo.138.12.5624","volume":"138","author":"CW Ou","year":"1997","unstructured":"Ou, C. W., Orsino, A. & Lye, S. J. Expression of connexin-43 and connexin-26 in the rat myometrium during pregnancy and labor is differentially regulated by mechanical and hormonal signals. Endocrinology 138, 5398\u2013407 (1997).","journal-title":"Endocrinology"},{"key":"42379_CR37","doi-asserted-by":"publisher","first-page":"35","DOI":"10.1177\/1933719107310763","volume":"14","author":"CE Kendal-Wright","year":"2007","unstructured":"Kendal-Wright, C. E. Stretching, mechanotransduction, and proinflammatory cytokines in the fetal membranes. Reprod Sci 14, 35\u201341 (2007).","journal-title":"Reprod Sci"},{"key":"42379_CR38","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1016\/j.placenta.2014.09.006","volume":"35","author":"B Chowdhury","year":"2014","unstructured":"Chowdhury, B. et al. Tensile strain increased COX-2 expression and PGE2 release leading to weakening of the human amniotic membrane. Placenta 35, 1057\u201364 (2014).","journal-title":"Placenta"},{"key":"42379_CR39","doi-asserted-by":"publisher","first-page":"061010","DOI":"10.1115\/1.4030054","volume":"137","author":"M Perrini","year":"2015","unstructured":"Perrini, M. et al. Mechanical and microstructural investigation of the cyclic behavior of human amnion. J Biomech Eng 137, 061010 (2015).","journal-title":"J Biomech Eng"},{"key":"42379_CR40","doi-asserted-by":"publisher","first-page":"2600","DOI":"10.1074\/jbc.M111.276261","volume":"287","author":"C Dunn","year":"2012","unstructured":"Dunn, C., Su, A., Lau, V. & Lampe, A. F. P. D. Activation of Akt, not connexin 43 protein ubiquitination, regulates gap junction stability. J Biol Chem 287, 2600\u20137 (2012).","journal-title":"J Biol Chem"},{"key":"42379_CR41","doi-asserted-by":"publisher","first-page":"10582","DOI":"10.1074\/jbc.M114.550608","volume":"289","author":"N Batra","year":"2014","unstructured":"Batra, N. et al. Direct regulation of osteocytic connexin 43 hemichannels through AKT kinase activated by mechanical stimulation. J Biol Chem 289, 10582\u201391 (2014).","journal-title":"J Biol Chem"},{"key":"42379_CR42","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1091\/mbc.e04-10-0912","volume":"16","author":"PP Cherian","year":"2005","unstructured":"Cherian, P. P. et al. Mechanical strain opens connexin 43 hemichannels in osteocytes: a novel mechanism for the release of prostaglandin. Mol Biol Cell 16, 3100\u20136 (2005).","journal-title":"Mol Biol Cell"},{"key":"42379_CR43","doi-asserted-by":"publisher","first-page":"1205","DOI":"10.1111\/bjd.14064","volume":"173","author":"JE Sutcliffe","year":"2015","unstructured":"Sutcliffe, J. E. et al. Abnormal connexin expression in human chronic wounds. Br J Dermatol 173, 1205\u201315 (2015).","journal-title":"Br J Dermatol"},{"key":"42379_CR44","doi-asserted-by":"crossref","unstructured":"Sutcliffe, J. E. S. et al. Changes in the extracellular matrix surrounding human chronic wounds revealed by 2-photon imaging. 14, 1225\u20131236 (2017).","DOI":"10.1111\/iwj.12789"},{"key":"42379_CR45","doi-asserted-by":"publisher","first-page":"263","DOI":"10.1016\/S0950-3552(05)80226-3","volume":"4","author":"N Uldbjerg","year":"1990","unstructured":"Uldbjerg, N. & Ulmsten, U. The physiology of cervical ripening and cervical dilatation and the effect of abortifacient drugs. Baillieres Clin Obstet Gynaecol 4, 263\u201382 (1990).","journal-title":"Baillieres Clin Obstet Gynaecol"},{"key":"42379_CR46","first-page":"1013","volume":"82","author":"M Norman","year":"1993","unstructured":"Norman, M., Ekman, G. & Malmstrom, A. PGE2-induced ripening of the human cervix involves changes in proteoglycan metabolism. Obstet Gynecol 82, 1013\u201320 (1993).","journal-title":"Obstet Gynecol"},{"key":"42379_CR47","first-page":"217","volume":"81","author":"N Norman","year":"1993","unstructured":"Norman, N., Ekman, G. & Malmstrom, A. Changed proteoglycan metabolism in human cervix immediately after spontaneous vaginal delivery. Obstet Gynecol 81, 217\u201323 (1993).","journal-title":"Obstet Gynecol"},{"key":"42379_CR48","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1016\/j.placenta.2014.10.001","volume":"35","author":"D Kumar","year":"2014","unstructured":"Kumar, D. et al. Decidual GM-CSF is a critical common intermediate necessary for thrombin and TNF induced in vitro fetal membrane weakening. Placenta 35, 1049\u201356 (2014).","journal-title":"Placenta"},{"key":"42379_CR49","doi-asserted-by":"publisher","first-page":"520.e1","DOI":"10.1016\/j.ajog.2015.06.014","volume":"213","author":"D Kumar","year":"2015","unstructured":"Kumar, D. et al. Progesterone inhibits in vitro fetal membrane weakening. Am J Obstet Gynecol 213, 520.e1\u20139 (2015).","journal-title":"Am J Obstet Gynecol"},{"key":"42379_CR50","doi-asserted-by":"publisher","first-page":"695.e1","DOI":"10.1016\/j.ajog.2017.10.004","volume":"217","author":"D Kumar","year":"2017","unstructured":"Kumar, D. et al. In an in-vitro model using human fetal membranes, 17-alpha hydroxyprogesterone caproate is not an optimal progestogen for inhibition of fetal membrane weakening. Am J Obstet Gynecol 217, 695.e1\u2013695.e14 (2017).","journal-title":"Am J Obstet Gynecol"},{"key":"42379_CR51","doi-asserted-by":"publisher","first-page":"2809","DOI":"10.2337\/db07-0613","volume":"56","author":"CM Wang","year":"2007","unstructured":"Wang, C. M., Lincoln, J., Cook, J. E. & Becker, D. L. Abnormal connexin expression underlies delayed wound healing in diabetic skin. Diabetes 56, 2809\u201317 (2007).","journal-title":"Diabetes"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42379-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42379-4","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42379-4.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,17]],"date-time":"2022-12-17T09:11:57Z","timestamp":1671268317000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-019-42379-4"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,30]]},"references-count":51,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2019,12]]}},"alternative-id":["42379"],"URL":"https:\/\/doi.org\/10.1038\/s41598-019-42379-4","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,30]]},"assertion":[{"value":"24 July 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"29 March 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"30 April 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing Interests"}}],"article-number":"6718"}}