{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T02:46:26Z","timestamp":1785379586141,"version":"3.55.0"},"reference-count":53,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T00:00:00Z","timestamp":1727913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"name":"Qinghai Provincial Government"},{"DOI":"10.13039\/501100002367","name":"Chinese Academy of Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002367","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Natural Science Foundation of Qinghai","award":["2020-ZJ-902"],"award-info":[{"award-number":["2020-ZJ-902"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U22A20447"],"award-info":[{"award-number":["U22A20447"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,12,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Environmental hypoxia adversely impacts the reproduction of humans and animals. Previously, we showed that fetal hypoxia exposure led to granulosa cell (GC) autophagic cell death via the Foxo1\/Pi3k\/Akt pathway. However, the upstream regulatory mechanisms underlying GC dysfunction remain largely unexplored. Here, we tested the hypothesis that fetal hypoxia exposure altered gene expression programs in adult GCs and impaired ovarian function. We established a fetal hypoxia model in which pregnant mice were maintained in a high-plateau hypoxic environment from gestation day (E) 0\u201316.5 to study the impact of hypoxia exposure on the ovarian development and subsequent fertility of offspring. Compared with the unexposed control, fetal hypoxia impaired fertility by disordering ovarian function. Specifically, fetal hypoxia caused mitochondrial dysfunction, oxidant stress, and autophagy in GCs in the adult ovary. RNA sequencing analysis revealed that 437 genes were differentially expressed in the adult GCs of exposed animals. Western blotting results also revealed that fetal exposure induced high levels of hypoxia-inducible factor 1-alpha (Hif1a) expression in adult GCs. We then treated granulosa cells isolated from exposed mice with PX-478, a specific pharmacological inhibitor of Hif1a, and found that autophagy and apoptosis were effectively alleviated. Finally, by using a human ovarian granulosa-like tumor cell line (KGN) to simulate hypoxia in vitro, we showed that Hif1a regulated autophagic cell death in GCs through the Pi3k\/Akt pathway. Together, these findings suggest that fetal hypoxia exposure induced persistent Hif1a expression, which impaired mitochondrial function and led to autophagic cell death in the GCs of the adult ovary.<\/jats:p>","DOI":"10.1093\/biolre\/ioae141","type":"journal-article","created":{"date-parts":[[2024,10,3]],"date-time":"2024-10-03T19:46:21Z","timestamp":1727984781000},"page":"1220-1234","source":"Crossref","is-referenced-by-count":8,"title":["Fetal hypoxia exposure induces Hif1a activation and autophagy in adult ovarian granulosa cells"],"prefix":"10.1093","volume":"111","author":[{"given":"Lu-Yao","family":"Zhang","sequence":"first","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]},{"name":"Chinese Academy of Sciences , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]},{"name":"Chinese Academy of Sciences , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xi","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Animal Science , College of Animal Science, , Urumqi ,","place":["China"]},{"name":"Xinjiang Agricultural University , College of Animal Science, , Urumqi ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hai-Ping","family":"Tao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]},{"name":"Chinese Academy of Sciences , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gong-Xue","family":"Jia","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]},{"name":"Chinese Academy of Sciences , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"You-Gui","family":"Fang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]},{"name":"Chinese Academy of Sciences , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yun-Peng","family":"Hou","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Animal Biotech Breeding , College of Biological Sciences, , Beijing ,","place":["China"]},{"name":"China Agricultural University , College of Biological Sciences, , Beijing ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi-En","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Adaptation and Evolution of Plateau Biota , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]},{"name":"Chinese Academy of Sciences , Northwest Institute of Plateau Biology, , Qinghai ,","place":["China"]},{"name":"University of Chinese Academy of Sciences , Beijing ,","place":["China"]},{"name":"Qinghai Key Laboratory of Animal Ecological Genomics , Northwest Institute of Plateau Biology, , Xining, Qinghai ,","place":["China"]},{"name":"Chinese Academy of Sciences , Northwest Institute of Plateau Biology, , Xining, Qinghai ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,10,3]]},"reference":[{"key":"2024121609352628500_ref1","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1186\/s13059-023-02894-0","article-title":"Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects","volume":"24","author":"Li","year":"2023","journal-title":"Genome Biol"},{"key":"2024121609352628500_ref2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41419-021-03842-1","article-title":"HDAC6 regulates primordial follicle activation through mTOR signaling pathway","volume":"12","author":"Zhang","year":"2021","journal-title":"Cell Death Dis"},{"key":"2024121609352628500_ref3","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.7150\/thno.89878","article-title":"Polycomb repressive complex 1 modulates granulosa cell proliferation in early folliculogenesis to support female reproduction","volume":"14","author":"Gao","year":"2024","journal-title":"Theranostics"},{"key":"2024121609352628500_ref4","doi-asserted-by":"crossref","first-page":"2501","DOI":"10.1016\/j.cub.2014.09.023","article-title":"Somatic cells initiate primordial follicle activation and govern the development of dormant oocytes in mice","volume":"24","author":"Zhang","year":"2014","journal-title":"Curr Biol"},{"key":"2024121609352628500_ref5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/nrm2815","article-title":"Mechanisms guiding primordial germ cell migration: strategies from different organisms","volume":"11","author":"Richardson","year":"2010","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2024121609352628500_ref6","doi-asserted-by":"crossref","first-page":"e3001025","DOI":"10.1371\/journal.pbio.3001025","article-title":"Single-cell transcriptome landscape of ovarian cells during primordial follicle assembly in mice","volume":"18","author":"Wang","year":"2020","journal-title":"PLoS Biol"},{"key":"2024121609352628500_ref7","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2217\/epi.14.71","article-title":"Lifestyle, pregnancy and epigenetic effects","volume":"7","author":"Barua","year":"2015","journal-title":"Epigenomics"},{"key":"2024121609352628500_ref8","doi-asserted-by":"crossref","first-page":"4999","DOI":"10.1210\/en.2009-0500","article-title":"Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice","volume":"150","author":"Dunn","year":"2009","journal-title":"Endocrinology"},{"key":"2024121609352628500_ref9","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1530\/RAF-20-0073","article-title":"Maternal protein restriction affects fetal ovary development in sheep","volume":"2","author":"Nwachukwu","year":"2021","journal-title":"Reprod Fertil"},{"key":"2024121609352628500_ref10","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1017\/S0967199421000216","article-title":"Paternal hypoxia exposure impairs fertilization process and preimplantation embryo development","volume":"30","author":"Tao","year":"2022","journal-title":"Zygote (Cambridge, England)"},{"key":"2024121609352628500_ref11","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1002\/tox.22883","article-title":"Tea polyphenols alleviate tri-ortho-cresyl phosphate-induced autophagy of mouse ovarian granulosa cells","volume":"35","author":"Yang","year":"2020","journal-title":"Environ Toxicol"},{"key":"2024121609352628500_ref12","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1002\/tox.22846","article-title":"Tri-ortho-cresyl phosphate (TOCP)-induced reproductive toxicity involved in placental apoptosis, autophagy and oxidative stress in pregnant mice","volume":"35","author":"Yang","year":"2020","journal-title":"Environ Toxicol"},{"key":"2024121609352628500_ref13","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/10937400801921320","article-title":"Epidemiologic evidence of relationships between reproductive and child health outcomes and environmental chemical contaminants","volume":"11","author":"Wigle","year":"2008","journal-title":"J Toxicol Environ Health B Crit Rev"},{"key":"2024121609352628500_ref14","doi-asserted-by":"crossref","first-page":"4992","DOI":"10.7150\/thno.55006","article-title":"Single-cell transcriptome dissection of the toxic impact of Di (2-ethylhexyl) phthalate on primordial follicle assembly","volume":"11","author":"Wang","year":"2021","journal-title":"Theranostics"},{"key":"2024121609352628500_ref15","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1126\/science.aat8824","article-title":"The earliest human occupation of the high-altitude Tibetan plateau 40 thousand to 30 thousand years ago","volume":"362","author":"Zhang","year":"2018","journal-title":"Science (New York, NY)"},{"key":"2024121609352628500_ref16","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/s41392-023-01652-9","article-title":"Hypoxia-induced signaling in the cardiovascular system: pathogenesis and therapeutic targets","volume":"8","author":"Zhao","year":"2023","journal-title":"Signal Transduct Target Ther"},{"key":"2024121609352628500_ref17","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1113\/JP280572","article-title":"Regulation of glycolysis by the hypoxia-inducible factor (HIF): implications for cellular physiology","volume":"599","author":"Kierans","year":"2021","journal-title":"J Physiol"},{"key":"2024121609352628500_ref18","doi-asserted-by":"crossref","DOI":"10.1210\/endocr\/bqad169","article-title":"Progesterone activates the histone lactylation-Hif1\u03b1-glycolysis feedback loop to promote decidualization","volume":"165","author":"Zhao","year":"2023","journal-title":"Endocrinology"},{"key":"2024121609352628500_ref19","doi-asserted-by":"crossref","first-page":"587","DOI":"10.1017\/S2040174420000963","article-title":"Prenatal hypoxia increases blood pressure in male rat offspring and affects their response to artificial light at night","volume":"12","author":"Sutovska","year":"2021","journal-title":"J Dev Orig Health Dis"},{"key":"2024121609352628500_ref20","article-title":"Fetal hypoxia expose caused autophagy in ovary granulosa cells via PI3K\/Akt\/FoxO1 pathway and mitigated by melatonin subheading","author":"Zhang","year":"2023","journal-title":"J Adv Res"},{"key":"2024121609352628500_ref21","doi-asserted-by":"crossref","first-page":"6858","DOI":"10.1038\/s41467-023-42634-3","article-title":"Mitochondrial dysfunction promotes the transition of precursor to terminally exhausted T cells through HIF-1\u03b1-mediated glycolytic reprogramming","volume":"14","author":"Wu","year":"2023","journal-title":"Nat Commun"},{"key":"2024121609352628500_ref22","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/S0955-0674(00)00194-0","article-title":"HIF-1 and mechanisms of hypoxia sensing","volume":"13","author":"Semenza","year":"2001","journal-title":"Curr Opin Cell Biol"},{"key":"2024121609352628500_ref23","doi-asserted-by":"crossref","first-page":"1364","DOI":"10.1080\/15548627.2017.1327941","article-title":"Protective mechanism of FSH against oxidative damage in mouse ovarian granulosa cells by repressing autophagy","volume":"13","author":"Shen","year":"2017","journal-title":"Autophagy"},{"key":"2024121609352628500_ref24","doi-asserted-by":"crossref","first-page":"1864","DOI":"10.1080\/15548627.2021.2005415","article-title":"Autophagy regulates differentiation of ovarian granulosa cells through degradation of WT1","volume":"18","author":"Shao","year":"2022","journal-title":"Autophagy"},{"key":"2024121609352628500_ref25","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1007\/s10815-015-0615-y","article-title":"The anti-M\u00fcllerian hormone (AMH) acts as a gatekeeper of ovarian steroidogenesis inhibiting the granulosa cell response to both FSH and LH","volume":"33","author":"Sacchi","year":"2016","journal-title":"J Assist Reprod Genet"},{"key":"2024121609352628500_ref26","doi-asserted-by":"crossref","first-page":"101830","DOI":"10.1016\/j.jbc.2022.101830","article-title":"FSH mediates estradiol synthesis in hypoxic granulosa cells by activating glycolytic metabolism through the HIF-1\u03b1-AMPK-GLUT1 signaling pathway","volume":"298","author":"Wu","year":"2022","journal-title":"J Biol Chem"},{"key":"2024121609352628500_ref27","doi-asserted-by":"crossref","first-page":"643","DOI":"10.1093\/humrep\/dex010","article-title":"FSH stimulation promotes progesterone synthesis and output from human granulosa cells without luteinization","volume":"32","author":"Oktem","year":"2017","journal-title":"Hum Reprod"},{"key":"2024121609352628500_ref28","doi-asserted-by":"crossref","first-page":"452","DOI":"10.1038\/s41419-018-0492-2","article-title":"Starvation during pregnancy impairs fetal oogenesis and folliculogenesis in offspring in the mouse","volume":"9","author":"Wang","year":"2018","journal-title":"Cell Death Dis"},{"key":"2024121609352628500_ref29","doi-asserted-by":"crossref","first-page":"4787","DOI":"10.1210\/en.2010-0208","article-title":"LIM homeodomain transcription factor Isl-1 enhances follicle stimulating hormone-beta and luteinizing hormone-beta gene expression and mediates the activation of leptin on gonadotropin synthesis","volume":"151","author":"Wu","year":"2010","journal-title":"Endocrinology"},{"key":"2024121609352628500_ref30","doi-asserted-by":"crossref","DOI":"10.3390\/ijms21103592","article-title":"Mitochondrial function in modulating human granulosa cell steroidogenesis and female fertility","volume":"21","author":"Sreerangaraja, Urs","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2024121609352628500_ref31","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.stem.2021.10.009","article-title":"Hif-1a suppresses ROS-induced proliferation of cardiac fibroblasts following myocardial infarction","volume":"29","author":"Janbandhu","year":"2022","journal-title":"Cell Stem Cell"},{"key":"2024121609352628500_ref32","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1002\/hed.26530","article-title":"HIF-1a expression and differential effects on survival in patients with oral cavity, larynx, and oropharynx squamous cell carcinomas","volume":"43","author":"Swartz","year":"2021","journal-title":"Head Neck"},{"key":"2024121609352628500_ref33","first-page":"1198","article-title":"Inhibition of HIF-1\u03b1 by PX-478 suppresses tumor growth of esophageal squamous cell cancer in vitro and in vivo","volume":"7","author":"Zhu","year":"2017","journal-title":"Am J Cancer Res"},{"key":"2024121609352628500_ref34","doi-asserted-by":"crossref","first-page":"98482","DOI":"10.18632\/oncotarget.21445","article-title":"Role of HIF-1a in regulating autophagic cell survival during cerebral ischemia reperfusion in rats","volume":"8","author":"Guo","year":"2017","journal-title":"Oncotarget"},{"key":"2024121609352628500_ref35","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1126\/science.1189406","article-title":"Genetic evidence for high-altitude adaptation in Tibet","volume":"329","author":"Simonson","year":"2010","journal-title":"Science (New York, NY)"},{"key":"2024121609352628500_ref36","doi-asserted-by":"crossref","DOI":"10.3390\/genes10020150","article-title":"Human genetic adaptation to high altitude: evidence from the Andes","volume":"10","author":"Julian","year":"2019","journal-title":"Genes"},{"key":"2024121609352628500_ref37","doi-asserted-by":"crossref","first-page":"S19","DOI":"10.1016\/j.ejogrb.2004.01.010","article-title":"Granulosa cell-oocyte interactions","volume":"115","author":"Cecconi","year":"2004","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2024121609352628500_ref38","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1006\/dbio.2000.9863","article-title":"Oocyte-granulosa cell heterologous gap junctions are required for the coordination of nuclear and cytoplasmic meiotic competence","volume":"226","author":"Carabatsos","year":"2000","journal-title":"Dev Biol"},{"key":"2024121609352628500_ref39","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1016\/j.fertnstert.2011.03.030","article-title":"Patients with endometriosis and patients with poor ovarian reserve have abnormal follicle-stimulating hormone receptor signaling pathways","volume":"95","author":"Gonz\u00e1lez-Fern\u00e1ndez","year":"2011","journal-title":"Fertil Steril"},{"key":"2024121609352628500_ref40","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1093\/humupd\/dmw027","article-title":"Interactions between androgens, FSH, anti-M\u00fcllerian hormone and estradiol during folliculogenesis in the human normal and polycystic ovary","volume":"22","author":"Dewailly","year":"2016","journal-title":"Hum Reprod Update"},{"key":"2024121609352628500_ref41","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.ejogrb.2014.02.020","article-title":"The dynamics of serum anti-Mullerian-hormone levels during controlled ovarian hyperstimulation with GnRH-antagonist short protocol in polycystic ovary syndrome and low responders","volume":"176","author":"Weintraub","year":"2014","journal-title":"Eur J Obstet Gynecol Reprod Biol"},{"key":"2024121609352628500_ref42","doi-asserted-by":"crossref","first-page":"349623","DOI":"10.1155\/2014\/349623","article-title":"Autophagy in development, cell differentiation, and homeodynamics: from molecular mechanisms to diseases and pathophysiology","volume":"2014","author":"Nezis","year":"2014","journal-title":"Biomed Res Int"},{"key":"2024121609352628500_ref43","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1007\/s00018-012-1032-3","article-title":"Tightrope act: autophagy in stem cell renewal, differentiation, proliferation, and aging","volume":"70","author":"Phadwal","year":"2013","journal-title":"Cell Mol Life Sci"},{"key":"2024121609352628500_ref44","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1186\/s13048-023-01228-9","article-title":"Lysophosphatidic acid is associated with oocyte maturation by enhancing autophagy via PI3K-AKT-mTOR signaling pathway in granulosa cells","volume":"16","author":"Liu","year":"2023","journal-title":"J Ovarian Res"},{"key":"2024121609352628500_ref45","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1530\/REP-19-0285","article-title":"miR-21-3p inhibits autophagy of bovine granulosa cells by targeting VEGFA via PI3K\/AKT signaling","volume":"158","author":"Ma","year":"2019","journal-title":"Reproduction (Cambridge, England)"},{"key":"2024121609352628500_ref46","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.apsb.2021.07.023","article-title":"Targeting PI3K\/AKT signaling for treatment of idiopathic pulmonary fibrosis","volume":"12","author":"Wang","year":"2022","journal-title":"Acta Pharm Sin B"},{"key":"2024121609352628500_ref47","first-page":"783","article-title":"PI3K\/Akt signaling transduction pathway, erythropoiesis and glycolysis in hypoxia (review)","volume":"19","author":"Xie","year":"2019","journal-title":"Mol Med Rep"},{"key":"2024121609352628500_ref48","doi-asserted-by":"crossref","first-page":"101954","DOI":"10.1016\/j.redox.2021.101954","article-title":"Dexmedetomidine ameliorates endotoxin-induced acute lung injury in vivo and in vitro by preserving mitochondrial dynamic equilibrium through the HIF-1a\/HO-1 signaling pathway","volume":"41","author":"Shi","year":"2021","journal-title":"Redox Biol"},{"key":"2024121609352628500_ref49","doi-asserted-by":"crossref","first-page":"1095427","DOI":"10.3389\/fimmu.2022.1095427","article-title":"HIF-1\u03b1\/BNIP3L induced cognitive deficits in a mouse model of sepsis-associated encephalopathy","volume":"13","author":"Zhao","year":"2022","journal-title":"Front Immunol"},{"key":"2024121609352628500_ref50","doi-asserted-by":"crossref","first-page":"3009","DOI":"10.1016\/j.celrep.2019.11.007","article-title":"Metabolic rewiring in response to Biguanides is mediated by mROS\/HIF-1a in malignant lymphocytes","volume":"29","author":"Khan","year":"2019","journal-title":"Cell Rep"},{"key":"2024121609352628500_ref51","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1262\/jrd.2012-089","article-title":"Regulatory effect of hypoxia-inducible factor-1\u03b1 on hCG-stimulated endothelin-2 expression in granulosa cells from the PMSG-treated rat ovary","volume":"58","author":"Zhang","year":"2012","journal-title":"J Reprod Dev"},{"key":"2024121609352628500_ref52","doi-asserted-by":"crossref","first-page":"eaba9112","DOI":"10.1126\/scitranslmed.aba9112","article-title":"HIF-1\u03b1 inhibitor PX-478 preserves pancreatic \u03b2 cell function in diabetes","volume":"14","author":"Ilegems","year":"2022","journal-title":"Sci Transl Med"},{"key":"2024121609352628500_ref53","doi-asserted-by":"crossref","first-page":"114333","DOI":"10.1016\/j.biopha.2023.114333","article-title":"Autophagy inhibition and ferroptosis activation during atherosclerosis: hypoxia-inducible factor 1\u03b1 inhibitor PX-478 alleviates atherosclerosis by inducing autophagy and suppressing ferroptosis in macrophages","volume":"161","author":"Hu","year":"2023","journal-title":"Biomed Pharmacother"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioae141\/59809548\/ioae141.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/111\/6\/1220\/61134212\/ioae141.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/111\/6\/1220\/61134212\/ioae141.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,16]],"date-time":"2024-12-16T09:35:54Z","timestamp":1734341754000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/111\/6\/1220\/7810219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,3]]},"references-count":53,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2024,10,3]]},"published-print":{"date-parts":[[2024,12,12]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioae141","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,12]]},"published":{"date-parts":[[2024,10,3]]}}}