Altered Production and Cellular Levels of Hydrogen Sulfide (H<sub>2</sub>S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia
Background/Objectives: Hydrogen sulfide (H<sub>2</sub>S) is a vasorelaxant gas and exerts anti-oxidative, anti-inflammatory, and cytoprotective effects. H<sub>2</sub>S has been implicated in regulating placental vaso-activity and angiogenesis. It is believed that abnormal tro...
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2025-03-01
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| author | Xiaodan Chu Jie Xu Xinggui Shen Wenji Sheng Jingxia Sun Yang Gu David F. Lewis Danielle Cooper Dani Zoorob Yuping Wang |
| author_facet | Xiaodan Chu Jie Xu Xinggui Shen Wenji Sheng Jingxia Sun Yang Gu David F. Lewis Danielle Cooper Dani Zoorob Yuping Wang |
| author_sort | Xiaodan Chu |
| collection | DOAJ |
| description | Background/Objectives: Hydrogen sulfide (H<sub>2</sub>S) is a vasorelaxant gas and exerts anti-oxidative, anti-inflammatory, and cytoprotective effects. H<sub>2</sub>S 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 H<sub>2</sub>S 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 H<sub>2</sub>S in the culture medium and the cellular levels of H<sub>2</sub>S were analyzed by reversed phase high-performance liquid chromatography (RP-HPLC). Expression levels of the three key H<sub>2</sub>S converting enzymes, cystathionine-β-synthase (CBS), cystathionine-γ-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 H<sub>2</sub>S were significantly reduced in cells from pre-eclamptic vs. normal placentas; (2) free H<sub>2</sub>S 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 H<sub>2</sub>S production and decreased cellular H<sub>2</sub>S levels in pre-eclamptic placentas. Our data provide further evidence that expression of 3-MST in placental trophoblasts is likely gestational age (developmental)-dependent. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-03-01 |
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| spelling | doaj-art-d0058bc05b6e4d4baa45f036a544af472025-08-20T03:43:20ZengMDPI AGPathophysiology1873-149X2025-03-013211010.3390/pathophysiology32010010Altered Production and Cellular Levels of Hydrogen Sulfide (H<sub>2</sub>S) in Placental Trophoblasts from Pregnancies Affected by Pre-EclampsiaXiaodan Chu0Jie Xu1Xinggui Shen2Wenji Sheng3Jingxia Sun4Yang Gu5David F. Lewis6Danielle Cooper7Dani Zoorob8Yuping Wang9Department of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USADepartment of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USADepartment of Pathology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USADepartment of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USADepartment of Obstetrics and Gynecology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, ChinaDepartment of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USADepartment of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USADepartment of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USADepartment of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USADepartment of Obstetrics and Gynecology, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USABackground/Objectives: Hydrogen sulfide (H<sub>2</sub>S) is a vasorelaxant gas and exerts anti-oxidative, anti-inflammatory, and cytoprotective effects. H<sub>2</sub>S 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 H<sub>2</sub>S 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 H<sub>2</sub>S in the culture medium and the cellular levels of H<sub>2</sub>S were analyzed by reversed phase high-performance liquid chromatography (RP-HPLC). Expression levels of the three key H<sub>2</sub>S converting enzymes, cystathionine-β-synthase (CBS), cystathionine-γ-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 H<sub>2</sub>S were significantly reduced in cells from pre-eclamptic vs. normal placentas; (2) free H<sub>2</sub>S 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 H<sub>2</sub>S production and decreased cellular H<sub>2</sub>S levels in pre-eclamptic placentas. Our data provide further evidence that expression of 3-MST in placental trophoblasts is likely gestational age (developmental)-dependent.https://www.mdpi.com/1873-149X/32/1/10H<sub>2</sub>SCBSCSE3-MSTtrophoblastplacenta |
| spellingShingle | Xiaodan Chu Jie Xu Xinggui Shen Wenji Sheng Jingxia Sun Yang Gu David F. Lewis Danielle Cooper Dani Zoorob Yuping Wang Altered Production and Cellular Levels of Hydrogen Sulfide (H<sub>2</sub>S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia Pathophysiology H<sub>2</sub>S CBS CSE 3-MST trophoblast placenta |
| title | Altered Production and Cellular Levels of Hydrogen Sulfide (H<sub>2</sub>S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia |
| title_full | Altered Production and Cellular Levels of Hydrogen Sulfide (H<sub>2</sub>S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia |
| title_fullStr | Altered Production and Cellular Levels of Hydrogen Sulfide (H<sub>2</sub>S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia |
| title_full_unstemmed | Altered Production and Cellular Levels of Hydrogen Sulfide (H<sub>2</sub>S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia |
| title_short | Altered Production and Cellular Levels of Hydrogen Sulfide (H<sub>2</sub>S) in Placental Trophoblasts from Pregnancies Affected by Pre-Eclampsia |
| title_sort | altered production and cellular levels of hydrogen sulfide h sub 2 sub s in placental trophoblasts from pregnancies affected by pre eclampsia |
| topic | H<sub>2</sub>S CBS CSE 3-MST trophoblast placenta |
| url | https://www.mdpi.com/1873-149X/32/1/10 |
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