{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T10:35:20Z","timestamp":1791974120914,"version":"4.4.0"},"reference-count":28,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T00:00:00Z","timestamp":1741046400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathophysiology"],"abstract":"<jats:p>Background\/Objectives: Hydrogen sulfide (H2S) is a vasorelaxant gas and exerts anti-oxidative, anti-inflammatory, and cytoprotective effects. H2S has been implicated in regulating placental vaso-activity and angiogenesis. It is believed that abnormal trophoblast production of vasodilators and angiogenic factors contributes to pre-eclampsia development. However, little is known about whether aberrant H2S production is present in placental trophoblasts from pre-eclamptic pregnancies. Methods: Trophoblasts were isolated from normal and pre-eclamptic placentas. After incubation, cell production of H2S in the culture medium and the cellular levels of H2S were analyzed by reversed phase high-performance liquid chromatography (RP-HPLC). Expression levels of the three key H2S converting enzymes, cystathionine-\u03b2-synthase (CBS), cystathionine-\u03b3-lyase (CSE), and 3-mercaptopyruvate sulfurtransferase (3-MST), were determined by immunohistochemistry. The protein expression of CBS and CSE was assessed by Western blot analysis. Results: (1) Trophoblast production and cellular levels of H2S were significantly reduced in cells from pre-eclamptic vs. normal placentas; (2) free H2S production was increased in a time-dependent manner in cultured trophoblasts from normal, but not from pre-eclamptic, placentas; and (3) strong CBS and CSE expression was seen in trophoblasts from normal, as opposed to pre-eclamptic, placentas. Reduced CBS and CSE expression in trophoblasts from pre-eclamptic vs. normal placentas were confirmed by Western blot analysis; and (4) 3-MST expression was undetachable in both normal and pre-eclamptic placentas, but 3-MST expression was strongly expressed in the first and second trimester placentas. Conclusions: These data provide plausible evidence that downregulation of CBS and CSE, but not 3-MST, expression may be responsible for reduced free H2S production and decreased cellular H2S levels in pre-eclamptic placentas. Our data provide further evidence that expression of 3-MST in placental trophoblasts is likely gestational age (developmental)-dependent.<\/jats:p>","DOI":"10.3390\/pathophysiology32010010","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T07:47:37Z","timestamp":1741074457000},"page":"10","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Altered Production and Cellular Levels of Hydrogen Sulfide (H2S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia"],"prefix":"10.3390","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6295-6487","authenticated-orcid":false,"given":"Xiaodan","family":"Chu","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"},{"name":"Department of Obstetrics and Gynecology, The Second Affiliated Hospital, Harbin Medical University, Harbin 150086, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8183-9526","authenticated-orcid":false,"given":"Jie","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4002-9671","authenticated-orcid":false,"given":"Xinggui","family":"Shen","sequence":"additional","affiliation":[{"name":"Department of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2152-2118","authenticated-orcid":false,"given":"Wenji","family":"Sheng","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"},{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-3043-7516","authenticated-orcid":false,"given":"Jingxia","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7348-1528","authenticated-orcid":false,"given":"Yang","family":"Gu","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Lewis","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9616-7555","authenticated-orcid":false,"given":"Danielle","family":"Cooper","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6471-1528","authenticated-orcid":false,"given":"Dani","family":"Zoorob","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8676-7549","authenticated-orcid":false,"given":"Yuping","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"S32","DOI":"10.1016\/j.placenta.2008.11.009","article-title":"The two stage model of preeclampsia: Variations on the theme","volume":"30","author":"Roberts","year":"2009","journal-title":"Placenta"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"946","DOI":"10.1016\/S0002-9378(12)80017-2","article-title":"Placental lipid peroxides and thromboxane are increased and prostacyclin is decreased in women with preeclampsia","volume":"167","author":"Wang","year":"1992","journal-title":"Am. 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