{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T13:19:57Z","timestamp":1787318397515,"version":"build-2736575974"},"reference-count":51,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T00:00:00Z","timestamp":1702512000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>\n                    Preterm birth is the leading cause of infant morbidity and mortality. There has been an interest in developing prostaglandin F\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    (PGF\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    ) antagonists as a new treatment for preterm birth, although much of the rationale for their use is based on studies in rodents where PGF\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    initiates labour by regressing the corpus luteum and reducing systemic progesterone concentrations. How PGF\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    antagonism would act in humans who do not have a fall in systemic progesterone remains unclear. One possibility, in addition to an acute stimulation of contractions, is a direct alteration of the myometrial smooth muscle cell state towards a pro-labour phenotype. In this study, we developed an immortalised myometrial cell line, MYLA, derived from myometrial tissue obtained from a pregnant, non-labouring patient, as well as a novel class of PGF\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    receptor (FP) antagonist. We verified the functionality of the cell line by stimulation with PGF\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    , resulting in G\u03b1\n                    <jats:sub>q<\/jats:sub>\n                    -specific coupling and Ca\n                    <jats:sup>2+<\/jats:sup>\n                    release, which were inhibited by FP antagonism. Compared to four published FP receptor antagonists, the novel FP antagonist N582707 was the most potent compound [F\n                    <jats:sub>max<\/jats:sub>\n                    7.67 \u00b1 0.63 (IC\n                    <jats:sub>50<\/jats:sub>\n                    21.26\u00a0nM), AUC 7.30 \u00b1 0.32 (IC\n                    <jats:sub>50<\/jats:sub>\n                    50.43\u00a0nM), and frequency of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    oscillations 7.66 \u00b1 0.41 (IC\n                    <jats:sub>50<\/jats:sub>\n                    22.15\u00a0nM)]. RNA-sequencing of the MYLA cell line at 1, 3, 6, 12, 24, and 48\u00a0h post PGF\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    treatment revealed a transforming phenotype from a fibroblastic to smooth muscle mRNA profile. PGF\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    treatment increased the expression of\n                    <jats:italic>MYLK<\/jats:italic>\n                    ,\n                    <jats:italic>CALD1<\/jats:italic>\n                    , and\n                    <jats:italic>CNN1<\/jats:italic>\n                    as well as the pro-labour genes\n                    <jats:italic>OXTR<\/jats:italic>\n                    ,\n                    <jats:italic>IL6<\/jats:italic>\n                    , and\n                    <jats:italic>IL11<\/jats:italic>\n                    , which were inhibited by FP antagonism. Concomitant with the inhibition of a smooth muscle, pro-labour transition, FP antagonism increased the expression of the fibroblast marker genes\n                    <jats:italic>DCN<\/jats:italic>\n                    ,\n                    <jats:italic>FBLN1<\/jats:italic>\n                    , and\n                    <jats:italic>PDGFRA<\/jats:italic>\n                    . Our findings suggest that in addition to the well-described acute contractile effect, PGF\n                    <jats:sub>2\u03b1<\/jats:sub>\n                    transforms myometrial smooth muscle cells from a myofibroblast to a smooth muscle, pro-labour\u2013like state and that the novel compound N582707 has the potential for prophylactic use in preterm labour management beyond its use as an acute tocolytic drug.\n                  <\/jats:p>","DOI":"10.3389\/fphar.2023.1285779","type":"journal-article","created":{"date-parts":[[2023,12,14]],"date-time":"2023-12-14T09:59:46Z","timestamp":1702547986000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["PGF2\u03b1 induces a pro-labour phenotypical switch in human myometrial cells that can be inhibited with PGF2\u03b1 receptor antagonists"],"prefix":"10.3389","volume":"14","author":[{"given":"Isabel","family":"Hamshaw","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Straube","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Stark","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Baxter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad T.","family":"Alam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Walter J.","family":"Wever","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong","family":"Yue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Pinton","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aritro","family":"Sen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory D.","family":"Ferguson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew M.","family":"Blanks","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,12,14]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"285","DOI":"10.1016\/s1388-1981(99)00164-x","article-title":"The utilization of recombinant prostanoid receptors to determine the affinities and selectivities of prostaglandins and related analogs","volume":"1483","author":"Abramovitz","year":"2000","journal-title":"Biochimica Biophysica Acta (BBA)-Molecular Cell Biol. 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