Ourlad Alzeus G Tantengco1,2, Lauren S Richardson1,3, Ramkumar Menon1. 1. Division of Maternal-Fetal Medicine and Perinatal Research, Department of Obstetrics and Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA. 2. College of Medicine, University of the Philippines Manila, Manila, Philippines. 3. Department of Electrical and Computer Engineering, Department of Biomedical Engineering, Texas A&M University, College Station, TX, USA.
Abstract
PROBLEM: Estrogen (E2) is one of the main steroid hormones associated with pregnancy and parturition. High levels of E2 increase uterine contractions, promote fetal membrane weakening, and induce degradation of the cervical extracellular matrix (ECM). Current evidence supports the role of E2 in epithelial-to-mesenchymal transition (EMT) and inflammation in different cell types; however, its effects on the cellular components of the cervix are still unknown. METHOD OF STUDY: In this study, we assessed the effects of gestational levels of E2 in: (a) the cellular transition of endocervical epithelial cells (EEC) and cervical stromal cells (CSC) in vitro using immunocytochemical staining and Western blot analyses for EMT markers (cytokeratin-18, E-cadherin, N-cadherin, SNAIL, and vimentin); (b) cell migration using in vitro scratch assays; (c) inflammatory cytokine (interleukin 1β and TNF-α) and MMP9 production under untreated and lipopolysaccharide (LPS)-treated conditions using immunoassays. RESULTS: E2 treatment and co-treatment with LPS as a proxy for infection maintained the metastate of EEC (expression of both cytokeratin and vimentin) and the mesenchymal state of CSC. E2 delayed wound healing, which mimics the tissue remodeling process, in EEC and CSC. E2 led to persistently elevated levels of vimentin throughout the EEC wound healing process. E2 did not affect inflammatory cytokine production by EEC and CSC but increased MMP9 production by EEC. CONCLUSION: Collectively, these results show that third trimester levels of E2 may permit localized inflammation, increase MMP-9 production, and cause an EMT-mediated impairment of the remodeling process in the cervix in vitro. These data suggest a potential contribution of E2 in cervical ripening.
PROBLEM: Estrogen (E2) is one of the main steroid hormones associated with pregnancy and parturition. High levels of E2 increase uterine contractions, promote fetal membrane weakening, and induce degradation of the cervical extracellular matrix (ECM). Current evidence supports the role of E2 in epithelial-to-mesenchymal transition (EMT) and inflammation in different cell types; however, its effects on the cellular components of the cervix are still unknown. METHOD OF STUDY: In this study, we assessed the effects of gestational levels of E2 in: (a) the cellular transition of endocervical epithelial cells (EEC) and cervical stromal cells (CSC) in vitro using immunocytochemical staining and Western blot analyses for EMT markers (cytokeratin-18, E-cadherin, N-cadherin, SNAIL, and vimentin); (b) cell migration using in vitro scratch assays; (c) inflammatory cytokine (interleukin 1β and TNF-α) and MMP9 production under untreated and lipopolysaccharide (LPS)-treated conditions using immunoassays. RESULTS: E2 treatment and co-treatment with LPS as a proxy for infection maintained the metastate of EEC (expression of both cytokeratin and vimentin) and the mesenchymal state of CSC. E2 delayed wound healing, which mimics the tissue remodeling process, in EEC and CSC. E2 led to persistently elevated levels of vimentin throughout the EEC wound healing process. E2 did not affect inflammatory cytokine production by EEC and CSC but increased MMP9 production by EEC. CONCLUSION: Collectively, these results show that third trimester levels of E2 may permit localized inflammation, increase MMP-9 production, and cause an EMT-mediated impairment of the remodeling process in the cervix in vitro. These data suggest a potential contribution of E2 in cervical ripening.
Authors: Ourlad Alzeus G Tantengco; Lauren S Richardson; Joy Vink; Talar Kechichian; Paul Mark B Medina; Richard B Pyles; Ramkumar Menon Journal: Mol Cell Endocrinol Date: 2021-04-03 Impact factor: 4.369
Authors: Ourlad Alzeus G Tantengco; Talar Kechichian; Kathleen L Vincent; Richard B Pyles; Paul Mark B Medina; Ramkumar Menon Journal: Reproduction Date: 2021-12-09 Impact factor: 3.906
Authors: Ourlad Alzeus G Tantengco; Lauren S Richardson; Joy Vink; Talar Kechichian; Paul Mark B Medina; Richard B Pyles; Ramkumar Menon Journal: Mol Cell Endocrinol Date: 2021-04-03 Impact factor: 4.369
Authors: Ourlad Alzeus G Tantengco; Lauren S Richardson; Enkhtuya Radnaa; Ananth Kumar Kammala; Sungjin Kim; Paul Mark B Medina; Arum Han; Ramkumar Menon Journal: Front Cell Dev Biol Date: 2022-08-15
Authors: Ourlad Alzeus G Tantengco; Lauren S Richardson; Paul Mark B Medina; Arum Han; Ramkumar Menon Journal: FASEB J Date: 2021-04 Impact factor: 5.191