{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,29]],"date-time":"2026-08-29T02:08:56Z","timestamp":1787969336420,"version":"build-2784847793"},"reference-count":40,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2023,12,21]],"date-time":"2023-12-21T00:00:00Z","timestamp":1703116800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM121334"],"award-info":[{"award-number":["P20GM121334"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["American J Rep Immunol"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Preeclampsia (PE) is a multisystem disorder characterized by new onset hypertension in mid\u2010late gestation and can include multi\u2010organ dysfunction with or without proteinuria. It affects 5%\u20137% of all pregnancies in the U.S., making PE a major contributor to maternal and fetal morbidity and mortality. Currently, there is no cure for this pregnancy complication except for early delivery of the placenta and fetus. Moreover, the therapeutic options to treat PE are very limited. One potential trigger for the development of PE is progesterone deficiency\u2010induced imbalance between T Helper 1(Th1)\/Th2 cells, an increase in cytolytic natural killer (NK) cells and inflammatory cytokines that in turn leads to endothelial dysfunction, intrauterine growth restriction (IUGR) and hypertension. Importantly, progesterone signals the synthesis of progesterone\u2010induced blocking factor (PIBF) which has anti\u2010inflammatory effects and could promote the regulation of inflammation balance during pregnancy. However, the role of progesterone and PIBF in the pathophysiology of PE is still not fully understood. Thus, this current study was designed to test the hypothesis that inhibition of PIBF causes signs of PE in pregnant Sprague Dawley rats. In order to address our hypothesis, rabbit anti\u2010PIBF IgG (0.25, low dose\u2010LD or 0.50\u00a0mg\/mL, high dose\u2010HD) was administered intraperitoneally on gestation day (GD) 15 to normal pregnant Sprague Dawley (NP) rats. On GD 18, carotid catheters were inserted and on GD 19 mean blood pressure (MAP) and samples were collected for further analysis. MAP in normal pregnant rats (NP) rats (<jats:italic>n<\/jats:italic>\u00a0=\u00a07) was 99\u00a0\u00b1\u00a03\u00a0mmHg, which increased to 116\u00a0\u00b1\u00a02 mmHg in NP+ anti\u2010PIBF LD (<jats:italic>n<\/jats:italic>\u00a0=\u00a010) and 113\u00a0\u00b1\u00a04\u00a0mmHg in NP+ anti\u2010PIBF HD (<jats:italic>n<\/jats:italic>\u00a0=\u00a04), <jats:italic>p<\/jats:italic>\u00a0&lt;0\u00a0.05. Plasma TNF\u2010alpha levels were 35\u00a0\u00b1\u00a08 pg\/mL in NP rats and increased to 84\u00a0\u00b1\u00a021 pg\/mL in NP+ Anti\u2010PIBF HD (<jats:italic>n<\/jats:italic>\u00a0=\u00a04), <jats:italic>p<\/jats:italic>\u00a0&lt;0\u00a0.05. Plasma IL\u20104 and IL\u201010 levels were 22\u00a0\u00b1\u00a05 and 25+6 pg\/mL in NP (<jats:italic>n<\/jats:italic>\u00a0=\u00a05), which decreased to 6\u00a0\u00b1\u00a01 and 8\u00a0\u00b1\u00a01 pg\/mL in NP+ Anti\u2010PIBF LD (<jats:italic>n<\/jats:italic>\u00a0=\u00a06, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.05) and 16\u00a0\u00b1\u00a04 and 15\u00a0\u00b1\u00a05 pg\/mL in NP+ Anti\u2010PIBF HD (<jats:italic>n<\/jats:italic>\u00a0=\u00a04). Circulating total NK cells were 67\u00a0\u00b1\u00a011 % gate\u00a0in NP rats (<jats:italic>n<\/jats:italic>\u00a0=\u00a03), which decreased to 28\u00a0\u00b1\u00a07% gate in NP+ Anti\u2010PIBF LD and 45\u00a0\u00b1\u00a06% gate in NP+ Anti\u2010PIBF HD. Cytolytic NK cells were increased in NP+ Anti\u2010PIBF HD, <jats:italic>p<\/jats:italic>\u00a0&lt;0\u00a0.05. Moreover, circulating NO levels were significantly decreased while renal cortex PPET\u20101 levels increased NP+ Anti\u2010PIBF HD. Our study demonstrates that PIBF blockade causes hypertension, inflammation and signs of endothelial dysfunction, all of which are associated with PE, thus indicating the importance of progesterone signalling pathways during a healthy pregnancy.<\/jats:p>","DOI":"10.1111\/aji.13805","type":"journal-article","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T05:14:21Z","timestamp":1703222061000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Progesterone\u2010induced blocking factor blockade causes hypertension in pregnant rats"],"prefix":"10.1111","volume":"91","author":[{"given":"Alexis","family":"Meadors","sequence":"first","affiliation":[{"name":"Pharmacology &amp; Toxicology University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyleigh","family":"Comley","sequence":"additional","affiliation":[{"name":"Pharmacology &amp; Toxicology University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesse N.","family":"Cottrell","sequence":"additional","affiliation":[{"name":"Marshall Obstetrics &amp; Gynecology Marshall University Medical Center  Huntington West Virginia USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Ibhahim","sequence":"additional","affiliation":[{"name":"Pharmacology &amp; Toxicology University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"Jr.","given":"Mark W.","family":"Cunningham","sequence":"additional","affiliation":[{"name":"Physiology and Anatomy School of Biomedical Sciences The University of North Texas Health Science Center at Forth Worth  Fort Worth Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7581-9182","authenticated-orcid":false,"given":"Lorena M.","family":"Amaral","sequence":"additional","affiliation":[{"name":"Pharmacology &amp; Toxicology University of Mississippi Medical Center  Jackson Mississippi USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,12,21]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1097\/01.AOG.0000437382.03963.88"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1097\/AOG.0000000000003018"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(10)60518-1"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.01113.2007"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20150702"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2010.00852.x"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)17987-2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2011.01.049"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2012.01120.x"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1097\/MD.0000000000015080"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(02)08778-0"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3109\/10641950902875772"},{"key":"e_1_2_10_14_1","article-title":"Drugs for treatment of very high blood pressure during pregnancy","volume":"7","author":"Duley L","year":"2013","journal-title":"Cochrane Database Syst Rev"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2013.03.032"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0167-5699(97)01127-4"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2010.00833.x"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00152.2020"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod.104.030437"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2016.07.003"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajog.2021.11.844"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-0528.2005.00633.x"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1006\/cimm.1997.1090"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.117.09969"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jlb.63.2.209"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1042\/CS20171118"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2019.11.005"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00167.2018"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.preghy.2019.11.005"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.107.108837"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000175476.26719.36"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.genm.2008.03.013"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.HYP.0000169152.59854.36"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1161\/HYPERTENSIONAHA.110.167569"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-020-59452-y"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.171.11.5956"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1111\/aji.13693"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jri.2009.01.004"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.176.2.819"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.2005.00261.x"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0897.1996.tb00492.x"}],"container-title":["American Journal of Reproductive Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/aji.13805","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,2,7]],"date-time":"2024-02-07T10:36:58Z","timestamp":1707302218000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/aji.13805"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,21]]},"references-count":40,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1]]}},"alternative-id":["10.1111\/aji.13805"],"URL":"https:\/\/doi.org\/10.1111\/aji.13805","archive":["Portico"],"relation":{},"ISSN":["1046-7408","1600-0897"],"issn-type":[{"value":"1046-7408","type":"print"},{"value":"1600-0897","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,12,21]]},"assertion":[{"value":"2023-05-12","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-11-29","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-12-21","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e13805"}}