The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) production
Abstract Background The syncytiotrophoblast (STB) layer of the placenta is formed by cell fusion of cytotrophoblasts, acts as a feto-maternal barrier, is required for the production of pregnancy hormones such as chorionic gonadotropin, estradiol and progesterone and is also responsible for feto-mate...
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BMC
2025-03-01
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| Series: | Reproductive Biology and Endocrinology |
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| Online Access: | https://doi.org/10.1186/s12958-025-01362-7 |
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| author | Anna-Lena Gehl Daniel Klawitter Ulrich Wissenbach Marnie Cole Christine Wesely Heidi Löhr Petra Weissgerber Adela Sota Markus R. Meyer Claudia Fecher-Trost |
| author_facet | Anna-Lena Gehl Daniel Klawitter Ulrich Wissenbach Marnie Cole Christine Wesely Heidi Löhr Petra Weissgerber Adela Sota Markus R. Meyer Claudia Fecher-Trost |
| author_sort | Anna-Lena Gehl |
| collection | DOAJ |
| description | Abstract Background The syncytiotrophoblast (STB) layer of the placenta is formed by cell fusion of cytotrophoblasts, acts as a feto-maternal barrier, is required for the production of pregnancy hormones such as chorionic gonadotropin, estradiol and progesterone and is also responsible for feto-maternal mineral exchange such as calcium. Adequate mineral supply and placental hormone production are essential for the maintenance of pregnancy, and disturbances in trophoblast integrity are associated with pregnancy complications. Since knowledge about the identity and expression levels of proteins in trophoblast and syncytiotrophoblast cells is limited so far, we analyzed the proteomes of trophoblast-like and syncytiotrophoblast-like BeWo cells under different calcium conditions. The investigation of protein expression profiles in combination with hormone assays can provide a better understanding of calcium-dependent cellular processes in trophoblasts and syncytiotrophoblasts. Methods Here, we combine human trophoblast model cell cultures, hormone assays, antibody-based detection methods and high-resolution mass spectrometry analyzes to assess changes in cellular processes during syncytialization. Results We monitored the changes in protein expression profiles during forskolin induced syncytialization of trophoblast-like cells in an unbiased manner and show that the expression of numerous proteins is strongly altered. Among them are enzymes of the glucocorticoid and sex hormones synthesis pathways such as cytochrome P450 (CYP) 19A1, CYP11A1, adrenodoxin (FDX1), hydroxysteroid dehydrogenase (HSD) 11β2 and HSD17β1, whose expression is strongly induced by syncytialization. The production of beta human chorionic gonadotropin (ß-hCG), progesterone and estradiol increase during syncytialization, while the secretion and synthesis of ß-hCG and the expression of several protein syncytiotrophoblast markers show a clear calcium dependence. Conclusion The broad applicability of semi-quantitative proteome profiling of cytotrophoblast- and syncytiotrophoblast-like cells provides new insights into signaling processes that occur in cytotrophoblasts /syncytiotrophoblasts during pregnancy. |
| format | Article |
| id | doaj-art-93bc3d28d2124ce1959c5fc5ac80a5d4 |
| institution | Kabale University |
| issn | 1477-7827 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
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| series | Reproductive Biology and Endocrinology |
| spelling | doaj-art-93bc3d28d2124ce1959c5fc5ac80a5d42025-08-20T03:55:24ZengBMCReproductive Biology and Endocrinology1477-78272025-03-0123111910.1186/s12958-025-01362-7The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) productionAnna-Lena Gehl0Daniel Klawitter1Ulrich Wissenbach2Marnie Cole3Christine Wesely4Heidi Löhr5Petra Weissgerber6Adela Sota7Markus R. Meyer8Claudia Fecher-Trost9Experimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityExperimental and Clinical Pharmacology and Toxicology, Center for Molecular Signaling (PZMS), Saarland UniversityAbstract Background The syncytiotrophoblast (STB) layer of the placenta is formed by cell fusion of cytotrophoblasts, acts as a feto-maternal barrier, is required for the production of pregnancy hormones such as chorionic gonadotropin, estradiol and progesterone and is also responsible for feto-maternal mineral exchange such as calcium. Adequate mineral supply and placental hormone production are essential for the maintenance of pregnancy, and disturbances in trophoblast integrity are associated with pregnancy complications. Since knowledge about the identity and expression levels of proteins in trophoblast and syncytiotrophoblast cells is limited so far, we analyzed the proteomes of trophoblast-like and syncytiotrophoblast-like BeWo cells under different calcium conditions. The investigation of protein expression profiles in combination with hormone assays can provide a better understanding of calcium-dependent cellular processes in trophoblasts and syncytiotrophoblasts. Methods Here, we combine human trophoblast model cell cultures, hormone assays, antibody-based detection methods and high-resolution mass spectrometry analyzes to assess changes in cellular processes during syncytialization. Results We monitored the changes in protein expression profiles during forskolin induced syncytialization of trophoblast-like cells in an unbiased manner and show that the expression of numerous proteins is strongly altered. Among them are enzymes of the glucocorticoid and sex hormones synthesis pathways such as cytochrome P450 (CYP) 19A1, CYP11A1, adrenodoxin (FDX1), hydroxysteroid dehydrogenase (HSD) 11β2 and HSD17β1, whose expression is strongly induced by syncytialization. The production of beta human chorionic gonadotropin (ß-hCG), progesterone and estradiol increase during syncytialization, while the secretion and synthesis of ß-hCG and the expression of several protein syncytiotrophoblast markers show a clear calcium dependence. Conclusion The broad applicability of semi-quantitative proteome profiling of cytotrophoblast- and syncytiotrophoblast-like cells provides new insights into signaling processes that occur in cytotrophoblasts /syncytiotrophoblasts during pregnancy.https://doi.org/10.1186/s12958-025-01362-7PlacentaTrophoblastBeWo cellsSyncytializationHormone synthesisCalcium |
| spellingShingle | Anna-Lena Gehl Daniel Klawitter Ulrich Wissenbach Marnie Cole Christine Wesely Heidi Löhr Petra Weissgerber Adela Sota Markus R. Meyer Claudia Fecher-Trost The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) production Reproductive Biology and Endocrinology Placenta Trophoblast BeWo cells Syncytialization Hormone synthesis Calcium |
| title | The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) production |
| title_full | The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) production |
| title_fullStr | The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) production |
| title_full_unstemmed | The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) production |
| title_short | The proteomic landscape of trophoblasts unravels calcium-dependent syncytialization processes and beta-chorionic gonadotropin (ß-hCG) production |
| title_sort | proteomic landscape of trophoblasts unravels calcium dependent syncytialization processes and beta chorionic gonadotropin ss hcg production |
| topic | Placenta Trophoblast BeWo cells Syncytialization Hormone synthesis Calcium |
| url | https://doi.org/10.1186/s12958-025-01362-7 |
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