Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid
Abstract Background Successful pregnancy is supported by a healthy maternal–fetal interface (i.e., the decidual tissues) which holds the conceptus and safeguards it against stressors from the beginning of pregnancy. Any disturbance of this interface can presumably lead to the loss of pregnancy. The...
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| Format: | Article |
| Language: | English |
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BMC
2021-01-01
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| Series: | Journal of Biomedical Science |
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| Online Access: | https://doi.org/10.1186/s12929-020-00704-4 |
| _version_ | 1818580122055213056 |
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| author | Paz de la Torre Miguel Fernández-de la Torre Ana I. Flores |
| author_facet | Paz de la Torre Miguel Fernández-de la Torre Ana I. Flores |
| author_sort | Paz de la Torre |
| collection | DOAJ |
| description | Abstract Background Successful pregnancy is supported by a healthy maternal–fetal interface (i.e., the decidual tissues) which holds the conceptus and safeguards it against stressors from the beginning of pregnancy. Any disturbance of this interface can presumably lead to the loss of pregnancy. The use of the immunosuppressive drug mycophenolic acid (MPA) should be discontinued in pregnancy given its abortive and embryotoxic effects. Direct teratogenic effects have been observed in mammalian embryos cultured in MPA, but the underlying mechanisms of abortion by MPA are less understood. Methods Decidual stromal cells isolated from human placentas are cultured in the presence of clinically relevant doses of MPA. Data regarding the effects of MPA on the proliferation and viability of decidua cultures are first analysed and then, molecular pathways contributing to these effects are unravelled. Results MPA treatment of decidual stromal cells results in loss of proliferation capacity and a decrease in the viability of decidua cultures. The molecular pathways involved in the effects of MPA on decidual stromal cells are a reduction in pre-rRNA synthesis and subsequent disruption of the nucleolus. The nucleolar stress stabilizes p53, which in turn, leads to a p21–mediated cell cycle arrest in late S and G2 phases, preventing the progression of the decidua cells into the mitosis. Furthermore, MPA does not induce apoptosis but activate mechanisms of autophagy and senescence in decidual stromal cells. Conclusion The irreversible growth arrest of decidua cells, whose role in the maintenance of the pregnancy microenvironment is known, may be one cause of miscarriage in MPA treated pregnant women. |
| first_indexed | 2024-12-16T07:12:34Z |
| format | Article |
| id | doaj.art-9215b6fe9f6e4b4a91224d395c141485 |
| institution | Directory Open Access Journal |
| issn | 1423-0127 |
| language | English |
| last_indexed | 2024-12-16T07:12:34Z |
| publishDate | 2021-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Journal of Biomedical Science |
| spelling | doaj.art-9215b6fe9f6e4b4a91224d395c1414852022-12-21T22:39:52ZengBMCJournal of Biomedical Science1423-01272021-01-0128111410.1186/s12929-020-00704-4Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acidPaz de la Torre0Miguel Fernández-de la Torre1Ana I. Flores2Grupo de Medicina Regenerativa, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12)Grupo de Enfermedades Raras, Mitocondriales y Neuromusculares, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12)Grupo de Medicina Regenerativa, Instituto de Investigación Sanitaria Hospital 12 de Octubre (imas12)Abstract Background Successful pregnancy is supported by a healthy maternal–fetal interface (i.e., the decidual tissues) which holds the conceptus and safeguards it against stressors from the beginning of pregnancy. Any disturbance of this interface can presumably lead to the loss of pregnancy. The use of the immunosuppressive drug mycophenolic acid (MPA) should be discontinued in pregnancy given its abortive and embryotoxic effects. Direct teratogenic effects have been observed in mammalian embryos cultured in MPA, but the underlying mechanisms of abortion by MPA are less understood. Methods Decidual stromal cells isolated from human placentas are cultured in the presence of clinically relevant doses of MPA. Data regarding the effects of MPA on the proliferation and viability of decidua cultures are first analysed and then, molecular pathways contributing to these effects are unravelled. Results MPA treatment of decidual stromal cells results in loss of proliferation capacity and a decrease in the viability of decidua cultures. The molecular pathways involved in the effects of MPA on decidual stromal cells are a reduction in pre-rRNA synthesis and subsequent disruption of the nucleolus. The nucleolar stress stabilizes p53, which in turn, leads to a p21–mediated cell cycle arrest in late S and G2 phases, preventing the progression of the decidua cells into the mitosis. Furthermore, MPA does not induce apoptosis but activate mechanisms of autophagy and senescence in decidual stromal cells. Conclusion The irreversible growth arrest of decidua cells, whose role in the maintenance of the pregnancy microenvironment is known, may be one cause of miscarriage in MPA treated pregnant women.https://doi.org/10.1186/s12929-020-00704-4PlacentaDeciduaMiscarriageMycophenolic acidImmunosuppressionCell cycle |
| spellingShingle | Paz de la Torre Miguel Fernández-de la Torre Ana I. Flores Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid Journal of Biomedical Science Placenta Decidua Miscarriage Mycophenolic acid Immunosuppression Cell cycle |
| title | Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid |
| title_full | Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid |
| title_fullStr | Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid |
| title_full_unstemmed | Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid |
| title_short | Premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid |
| title_sort | premature senescence of placental decidua cells as a possible cause of miscarriage produced by mycophenolic acid |
| topic | Placenta Decidua Miscarriage Mycophenolic acid Immunosuppression Cell cycle |
| url | https://doi.org/10.1186/s12929-020-00704-4 |
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