{"doi":"10.32604/biocell.2023.029644","title":"Reversal of maternal obesity attenuates hypoxia and improves placental development in the preeclamptic-like BPH/5 mouse model","abstract":"<b>Background:</b> Women with obesity have higher risk of adverse pregnancy outcomes, including preeclampsia (PE). Late-gestational hypertension, aberrant fetoplacental development, and fetal growth restriction (FGR), hallmarks of PE, are observed spontaneously in BPH/5 mice. Similar to obese preeclamptic women, BPH/5 mice have higher visceral white adipose tissue (WAT) and circulating leptin. We hypothesized that attenuation of maternal obesity and serum leptin in pregnant BPH/5 mice will improve fetoplacental development by decreasing hypoxia markers and leptin expression at the maternal-fetal interface. <b>Methods:</b> To test this hypothesis, BPH/5 mice were fed <i>ad libitum</i> (lib) and pair-fed (PF) to C57 ad lib controls beginning at embryonic day (e) 0.5. Hypoxia-related genes, hypoxia inducible factor (Hif) 1α, stem cell factor (Scf), heme oxygenase-1 (Ho-1), leptin (Lep), and leptin receptor (LepR) were assessed in e7.5 implantation sites. <b>Results:</b> BPH/5 ad lib had 1.5 to 2-fold increase in <i>Hif1α</i>, <i>Scf</i>, and <i>Ho-1</i> mRNA and a greater than 3-fold increase in leptin mRNA <i>vs</i>. C57 that was attenuated with PF. Exogenous leptin promoted Hif1α and Ho-1 mRNA expression in e7.5 decidua <i>in vitro</i>. While hypoxic conditions <i>in vitro</i> did not change decidual leptin mRNA. Furthermore, BPH/5 PF mice demonstrated improved fetal and placental outcomes later in gestation, with greater placental vascular area by e18.5 and attenuation of FGR. <b>Conclusion:</b> In conclusion, pair-feeding BPH/5 mice beginning at conception may improve placental vasculature formation via decreased leptin and hypoxia-associated markers in this model. Future investigations are needed to better determine the effect of hypoxia and leptin on pregnancy outcomes in obese pregnant women.","journal":"Biocell","year":2023,"id":362909,"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":8,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9544,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":763965,"name":"Kalie F. Beckers","orcid":null,"position":1,"is_corresponding":false},{"id":940624,"name":"Juliet P. Flanagan","orcid":null,"position":2,"is_corresponding":false},{"id":427839,"name":"Viviane C. L. Gomes","orcid":"0000-0002-4352-3798","position":3,"is_corresponding":false},{"id":427840,"name":"Chin‐Chi Liu","orcid":"0000-0003-0723-8313","position":4,"is_corresponding":false},{"id":745018,"name":"Jenny L. Sones","orcid":"0000-0002-5360-1243","position":5,"is_corresponding":false},{"id":763967,"name":"Daniella M. Adams","orcid":null,"position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T01:14:23.749325Z","pmid":"37829603","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":[]}