{"doi":"10.21203/rs.3.rs-1594481/v2","title":"Glucocorticoid Receptor Regulated KCNA5 Mediates Cell Proliferation in Human Fetal Membranes","abstract":"Abstract Preterm birth is a major public health issue, affecting approximately 10% of pregnancies in the United States. A major identifiable cause of preterm birth is preterm premature rupture of membranes (PPROM). PPROM is a pregnancy complication in which the amnion and chorion weaken and rupture prior to 37 weeks of pregnancy and before contractions have begun. PPROM is responsible for 30–40% of preterm birth cases. Recently, PPROM has been closely linked to maternal stress, leading us to hypothesize that glucocorticoid signaling may contribute to PPROM. We measured the gene expression effects of glucocorticoids in primary amnion cells using RNA-seq. KCNA5 emerged as a potential GR regulated gene. To measure the effects of KCNA5 on cell proliferation in primary amnion epithelial cells, we used siRNA to reduce KCNA5 expression and Cas9-based epigenome editing to increase KCNA5 expression in HEK293T cells; followed by cellular assays to measure effects of proliferation and apoptosis. KCNA5 knockdown significantly increased cell proliferation without appearing to impact apoptosis. CRISPR-mediated over expression of endogenous KCNA5 significantly decreased cell proliferation. Decreases in amnion epithelial proliferation could impair the ability of these cells to repair microfractures in the membrane and lead to overall membrane weakening consistent with PPROM.","journal":"Research Square","year":2022,"id":309153,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.962,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":303894,"name":"Alejandro Barrera","orcid":"0000-0001-9244-9822","position":1,"is_corresponding":false},{"id":1002989,"name":"Laavanya Sankaranarayanan","orcid":"0000-0003-0576-6323","position":2,"is_corresponding":false},{"id":426734,"name":"Terrence K. Allen","orcid":"0000-0003-3904-7618","position":3,"is_corresponding":false},{"id":27827,"name":"Timothy E. Reddy","orcid":"0000-0002-7629-061X","position":4,"is_corresponding":false},{"id":486568,"name":"Sarah J. Cunningham","orcid":"0000-0003-0318-6421","position":0,"is_corresponding":true}],"reference_count":45,"raw_metadata":null,"created_at":"2026-07-19T00:33:11.579763Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}