{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:53:03Z","timestamp":1776232383469,"version":"3.50.1"},"reference-count":81,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,13]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Over 25% of active NASA astronauts are women who will be exposed to low daily doses and dose rates of galactic cosmic rays (GCR) in space. We hypothesized that exposing mice to a preliminary simulated GCR mixed heavy ion beam composed of iron, silicon, and titanium ions induces follicle depletion and dose-dependent ovarian tumors. Female mice were exposed to 10, or 20\u00a0cGy each of Fe, Si, and Ti ions or sham-irradiation in quick succession within 15\u00a0min for total doses of 0, 30, or 60\u00a0cGy of the three beams. 16\u00a0months later, their ovaries were removed. Hyperplasia of the ovarian surface epithelium (OSE) was noted in 13%, 59%, and 22% of the 0, 30, and 60\u00a0cGy irradiated mice, respectively. The prevalence of mixed ovarian tumors was 0, 6, and 89%, respectively, in the 0, 30, and 60\u00a0cGy groups. Low numbers of Ki67 positive OSE and tumor cells supported a benign tumor phenotype. In a separate study, Si ion irradiation alone at 32\u00a0cGy did not induce ovarian tumors in mice; however, the mixed heavy ions at all doses and Si ion irradiation alone reduced the total number of healthy ovarian follicles. Mixed heavy ion exposure reduced lipid peroxidation, fibrosis, inflammation, and lipofuscin accumulation at 60\u00a0cGy compared to 0\u00a0cGy, but elevated inflammation and lipofuscin accumulation at 30\u00a0cGy compared to 60\u00a0cGy. Preliminary simulated GCR exposure causes ovarian follicle death and tumorigenesis. This study provides insight into space-radiation induced ovarian damage and cancer risk in females.<\/jats:p>","DOI":"10.1093\/biolre\/ioag019","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T12:32:02Z","timestamp":1768912322000},"page":"1400-1415","source":"Crossref","is-referenced-by-count":0,"title":["Irradiation with a mixed heavy ion beam induces ovarian follicle loss and dose-dependent mixed ovarian tumor development"],"prefix":"10.1093","volume":"114","author":[{"given":"Kathleen N","family":"Leon Parada","sequence":"first","affiliation":[{"name":"Developmental & Cell Biology, University of California Irvine , Irvine, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gregory","family":"Lawson","sequence":"additional","affiliation":[{"name":"Office of Laboratory Animal Care, University of California Berkeley , Berkeley, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Polly","family":"Chang","sequence":"additional","affiliation":[{"name":"Biosciences Division, SRI International , Menlo Park, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eleanor A","family":"Blakely","sequence":"additional","affiliation":[{"name":"Biosciences Area, Lawrence Berkeley Laboratory , Berkeley, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lovleen","family":"Bajwa","sequence":"additional","affiliation":[{"name":"Developmental & Cell Biology, University of California Irvine , Irvine, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Gramajo-Aponte","sequence":"additional","affiliation":[{"name":"Environmental and Occupational Health, University of California Irvine , Irvine, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Samantha","family":"Getze","sequence":"additional","affiliation":[{"name":"Developmental & Cell Biology, University of California Irvine , Irvine, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8639-1326","authenticated-orcid":false,"given":"Ulrike","family":"Luderer","sequence":"additional","affiliation":[{"name":"Developmental & Cell Biology, University of California Irvine , Irvine, CA ,","place":["USA"]},{"name":"Environmental and Occupational Health, University of California Irvine , Irvine, CA ,","place":["USA"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"2026041501020685500_ref1","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1109\/TNS.2008.2001409","article-title":"The near-earth space radiation environment","volume":"55","author":"SaXM","year":"2008","journal-title":"IEEE Trans Nucl Sci"},{"key":"2026041501020685500_ref2","volume-title":"GCR Simulator Reference Field and a Spectral Approach for Laboratory Simulation","author":"Slaba","year":", ; 2015"},{"key":"2026041501020685500_ref3","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1016\/j.asr.2012.12.011","article-title":"Heavy ion contributions to organ dose equivalent for the 1977 galactic cosmic ray spectrum","volume":"51","author":"AWALWTAJWN","year":"2013","journal-title":"Adv Space Res"},{"key":"2026041501020685500_ref4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1177\/0146645315577539","article-title":"ICRP publication 130: occupational intakes of radionuclides: part 1","volume":"44","author":"Paquet","year":"2015","journal-title":"Ann ICRP"},{"key":"2026041501020685500_ref5","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1080\/095530096144680","article-title":"Non-random distribution of DNA double-strand breaks induced by particle irradiation","volume":"70","author":"L\u00f6brich","year":"1996","journal-title":"Int J Radiat Biol"},{"key":"2026041501020685500_ref6","doi-asserted-by":"crossref","first-page":"109370","DOI":"10.18632\/oncotarget.22679","article-title":"3D-structured illumination microscopy reveals clustered DNA double-strand break formation in widespread \u03b3H2AX foci after high LET heavy-ion particle radiation","volume":"8","author":"Hagiwara","year":"2017","journal-title":"Oncotarget"},{"key":"2026041501020685500_ref7","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21186602","article-title":"Comparison of high- and low-LET radiation-induced DNA double-Strand break processing in living cells","volume":"21","author":"Roobol","year":"2020","journal-title":"Int J Mol Sci"},{"key":"2026041501020685500_ref8","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1002\/ijc.26445","article-title":"Repair of DNA damage induced by accelerated heavy ions--a mini review","volume":"130","author":"Okayasu","year":"2012","journal-title":"Int J Cancer"},{"key":"2026041501020685500_ref9","doi-asserted-by":"publisher","first-page":"1816","DOI":"10.1093\/humrep\/dew126","article-title":"Charged iron particles, components of space radiation, destroy ovarian follicles","volume":"31","author":"Mishra","year":"2016","journal-title":"Hum Reprod"},{"key":"2026041501020685500_ref10","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1530\/REP-17-0101","article-title":"Very low doses of heavy oxygen ion radiation induce premature ovarian failure","volume":"154","author":"Mishra","year":"2017","journal-title":"Reproduction"},{"key":"2026041501020685500_ref11","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1667\/RR15028.1","article-title":"Charged-iron-particles found in galactic cosmic rays are potent inducers of epithelial ovarian Tumors","volume":"190","author":"Mishra","year":"2018","journal-title":"Radiat Res"},{"key":"2026041501020685500_ref12","doi-asserted-by":"publisher","first-page":"17","DOI":"10.3322\/caac.21763","article-title":"Cancer statistics, 2023","volume":"73","author":"Siegel","year":"2023","journal-title":"CA Cancer J Clin"},{"key":"2026041501020685500_ref13","doi-asserted-by":"crossref","first-page":"1093","DOI":"10.1038\/s41467-017-00962-1","article-title":"High grade serous ovarian carcinomas originate in the fallopian tube","volume":"8","author":"Labidi-Galy","year":"2017","journal-title":"Nat Commun"},{"key":"2026041501020685500_ref14","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1016\/S1470-2045(08)70281-X","article-title":"Ovarian ageing, follicle depletion, and cancer: a hypothesis for the aetiology of epithelial ovarian cancer involving follicle depletion","volume":"9","author":"Smith","year":"2008","journal-title":"Lancet Oncol"},{"key":"2026041501020685500_ref15","doi-asserted-by":"publisher","first-page":"e3000669","DOI":"10.1371\/journal.pbio.3000669","article-title":"NASA's first ground-based galactic cosmic ray simulator: enabling a new era in space radiobiology research","volume":"18","author":"Simonsen","year":"2020","journal-title":"PLoS Biol"},{"key":"2026041501020685500_ref16","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1007\/978-1-4615-2916-3_12","volume-title":"Biological Effects and Physics of Solar and Galactic Cosmic Radiation: Part B","author":"Wilson","year":"1993"},{"key":"2026041501020685500_ref17","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1016\/S1470-2045(06)70695-7","article-title":"Cancer risk from exposure to galactic cosmic rays: implications for space exploration by human beings","volume":"7","author":"Cucinotta","year":"2006","journal-title":"Lancet Oncol"},{"key":"2026041501020685500_ref18","first-page":"1","volume-title":"ICRP Publication 103","author":"The 2007 Recommendations of the International Commission on Radiological Protection","year":"2007"},{"key":"2026041501020685500_ref19","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1534\/genetics.116.191759","article-title":"The Hiroshima\/Nagasaki survivor studies: discrepancies between results and general perception","volume":"203","author":"Jordan","year":"2016","journal-title":"Genetics"},{"key":"2026041501020685500_ref20","doi-asserted-by":"publisher","first-page":"908","DOI":"10.1158\/0008-5472.CAN-12-3636","article-title":"Glutathione-deficient mice have increased sensitivity to transplacental benzo[a]pyrene-induced premature ovarian failure and ovarian tumorigenesis","volume":"73","author":"Lim","year":"2013","journal-title":"Cancer Res"},{"key":"2026041501020685500_ref21","doi-asserted-by":"crossref","first-page":"555","DOI":"10.1530\/jrf.0.0170555","article-title":"Proposal for a classification of oocytes and follicles in the mouse ovary","volume":"17","author":"Pedersen","year":"1968","journal-title":"J Reprod Fertil"},{"key":"2026041501020685500_ref22","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.2353\/ajpath.2007.060769","article-title":"A reduction of cyclooxygenase 2 gene dosage counters the ovarian morphological aging and tumor phenotype in Wv mice","volume":"170","author":"Yang","year":"2007","journal-title":"Am J Pathol"},{"key":"2026041501020685500_ref23","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1002\/(SICI)1097-4652(200003)182:3<311::AID-JCP1>3.0.CO;2-9","article-title":"The Ki-67 protein: from the known to the unknown","volume":"182","author":"Scholzen","year":"2000","journal-title":"J Cell Physiol"},{"key":"2026041501020685500_ref24","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1042\/bj2080129","article-title":"Separation and characterization of the aldehydic products of lipid peroxidation stimulated by ADP-Fe2+ in rat liver microsomes","volume":"208","author":"Esterbauer","year":"1982","journal-title":"Biochem J"},{"key":"2026041501020685500_ref25","doi-asserted-by":"publisher","first-page":"484","DOI":"10.1097\/PAS.0b013e31820a406c","article-title":"FOXL2 is a sensitive and specific marker for sex cord-stromal Tumors of the ovary","volume":"35","author":"Al-Agha","year":"2011","journal-title":"Am J Surg Pathol"},{"key":"2026041501020685500_ref26","doi-asserted-by":"crossref","first-page":"5351","DOI":"10.1210\/endo.142.12.8537","article-title":"Zonal expression of endothelial nitric oxide synthase in sheep and rhesus adrenal cortex","volume":"142","author":"Peterson","year":"2001","journal-title":"Endocrinology"},{"key":"2026041501020685500_ref27","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1093\/toxsci\/kfac086","article-title":"Gestational benzo[a]pyrene exposure destroys F1 ovarian germ cells through mitochondrial apoptosis pathway and diminishes surviving oocyte quality","volume":"190","author":"Malott","year":"2022","journal-title":"Toxicol Sci"},{"key":"2026041501020685500_ref28","doi-asserted-by":"publisher","first-page":"dvab010","DOI":"10.1093\/eep\/dvab010","article-title":"Prenatal exposure to a mixture of phthalates accelerates the age-related decline in reproductive capacity but may not affect direct biomarkers of ovarian aging in the F1 generation of female mice","volume":"7","author":"Brehm","year":"2021","journal-title":"Environ Epigenet"},{"key":"2026041501020685500_ref29","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1530\/REP-16-0129","article-title":"Reproductive age-associated fibrosis in the stroma of the mammalian ovary","volume":"152","author":"Briley","year":"2016","journal-title":"Reproduction"},{"key":"2026041501020685500_ref30","volume-title":"Quantifying Stained Liver Tissue","author":"ImageJ"},{"key":"2026041501020685500_ref31","doi-asserted-by":"publisher","first-page":"1381","DOI":"10.1111\/acel.12676","article-title":"Age-associated dysregulation of protein metabolism in the mammalian oocyte","volume":"16","author":"Duncan","year":"2017","journal-title":"Aging Cell"},{"key":"2026041501020685500_ref32","first-page":"390","volume-title":"Pathology of Tumors in Laboratory Animals, vol. II-Tumors of the Mouse","author":"Lemon","year":"1979"},{"key":"2026041501020685500_ref33","first-page":"66","article-title":"Neoplastic diseases occurring among mice subjected to general irradiation with X-rays: II. Ovarian Tumors and associated Lesions1. The","volume":"28","author":"Furth","year":"1936","journal-title":"Am J Cancer"},{"key":"2026041501020685500_ref34","doi-asserted-by":"crossref","first-page":"1559325818820981","DOI":"10.1177\/1559325818820981","article-title":"Effects of (60)Co \u03b3 irradiation on the reproductive function of Caenorhabditis elegans","volume":"17","author":"Cui","year":"2019","journal-title":"Dose-Response"},{"key":"2026041501020685500_ref35","doi-asserted-by":"crossref","first-page":"125707","DOI":"10.1088\/1361-6528\/aaa80e","article-title":"Antioxidant activity of hydrated carboxylated nanodiamonds and its influence on water \u03b3-radiolysis","volume":"29","author":"Santacruz-Gomez","year":"2018","journal-title":"Nanotechnology"},{"key":"2026041501020685500_ref36","first-page":"1289103","article-title":"Parity-dependent hemosiderin and lipofuscin accumulation in the reproductively aged mouse ovary","volume":"2018","author":"Urzua","year":"2018","journal-title":"Anal Cell Pathol (Amst)"},{"key":"2026041501020685500_ref37","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1007\/BF02382770","article-title":"Lipofuscin in the corpus luteum of macaque ovaries","volume":"33","author":"Hayama","year":"1992","journal-title":"Primates"},{"key":"2026041501020685500_ref38","doi-asserted-by":"crossref","first-page":"433","DOI":"10.1016\/S0002-9378(15)33200-2","article-title":"Ceroid pigment in the human ovary","volume":"59","author":"Reagan","year":"1950","journal-title":"Am J Obstet Gynecol"},{"key":"2026041501020685500_ref39","doi-asserted-by":"crossref","first-page":"263","DOI":"10.1007\/s10815-007-9130-0","article-title":"Lipofuscin bodies in human oocytes as an indicator of oocyte quality","volume":"24","author":"Otsuki","year":"2007","journal-title":"J Assist Reprod Genet"},{"key":"2026041501020685500_ref40","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/biomedicines10123068","article-title":"A high-fat and high-carbohydrate diet promotes reminiscent hallmarks of an aging ovary in the rabbit model","volume":"10","author":"D\u00edaz-Hern\u00e1ndez","year":"2022","journal-title":"Biomedicine"},{"key":"2026041501020685500_ref41","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1095\/biolreprod.110.088583","article-title":"Oxidative damage increases and antioxidant gene expression decreases with aging in the mouse ovary","volume":"84","author":"Lim","year":"2011","journal-title":"Biol Reprod"},{"key":"2026041501020685500_ref42","doi-asserted-by":"publisher","first-page":"10","DOI":"10.3390\/cancers10080251","article-title":"The role of inflammation and inflammatory mediators in the development, progression, metastasis, and Chemoresistance of epithelial ovarian cancer","volume":"10","author":"Savant","year":"2018","journal-title":"Cancers (Basel)"},{"key":"2026041501020685500_ref43","doi-asserted-by":"publisher","first-page":"133","DOI":"10.1016\/j.cyto.2012.01.015","article-title":"Inflammation and ovarian cancer","volume":"58","author":"Macci\u00f2","year":"2012","journal-title":"Cytokine"},{"key":"2026041501020685500_ref44","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1093\/biolre\/ioaa219","article-title":"Macrophages: an indispensable piece of ovarian health","volume":"104","author":"Zhang","year":"2021","journal-title":"Biol Reprod"},{"key":"2026041501020685500_ref45","doi-asserted-by":"crossref","first-page":"2119","DOI":"10.1093\/humrep\/15.10.2119","article-title":"Different patterns of structural luteolysis in the human corpus luteum of menstruation","volume":"15","author":"Morales","year":"2000","journal-title":"Hum Reprod"},{"key":"2026041501020685500_ref46","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/j.neurobiolaging.2005.12.006","article-title":"You say lipofuscin, we say ceroid: defining autofluorescent storage material","volume":"27","author":"Seehafer","year":"2006","journal-title":"Neurobiol Aging"},{"key":"2026041501020685500_ref47","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1269\/jrr.47.49","article-title":"A pathology study of malignant and benign ovarian Tumors among atomic bomb survivors","volume":"47","author":"Inai","year":"2006","journal-title":"J Radiat Res"},{"key":"2026041501020685500_ref48","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1667\/RADE-20-00170.1","article-title":"Radiation risk of ovarian cancer in atomic bomb survivors: 1958-2009","volume":"195","author":"Utada","year":"2021","journal-title":"Radiat Res"},{"key":"2026041501020685500_ref49","doi-asserted-by":"publisher","first-page":"172ra121","DOI":"10.1126\/scitranslmed.3004925","article-title":"Impairment of BRCA1-related DNA double-strand break repair leads to ovarian aging in mice and humans","volume":"5","author":"Titus","year":"2013","journal-title":"Sci Transl Med"},{"key":"2026041501020685500_ref50","first-page":"109","article-title":"Cardiovascular health in patients with premature ovarian insufficiency","volume":"17","author":"Podfigurna","year":"2018","journal-title":"Management of long-term consequences Prz Menopauzalny"},{"key":"2026041501020685500_ref51","doi-asserted-by":"publisher","first-page":"983","DOI":"10.1007\/s40618-016-0467-z","article-title":"Premature ovarian insufficiency: the context of long-term effects","volume":"39","author":"Podfigurna-Stopa","year":"2016","journal-title":"J Endocrinol Investig"},{"key":"2026041501020685500_ref52","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040952","article-title":"High-grade serous ovarian cancer: basic sciences, clinical and therapeutic standpoints","volume":"20","author":"Lisio","year":"2019","journal-title":"Int J Mol Sci"},{"key":"2026041501020685500_ref53","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1158\/0008-5472.CAN-19-2558","article-title":"Murine Oviductal high-grade serous carcinomas Mirror the genomic alterations, gene expression profiles, and immune microenvironment of their human counterparts","volume":"80","author":"McCool","year":"2020","journal-title":"Cancer Res"},{"key":"2026041501020685500_ref54","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/s41598-020-79488-4","article-title":"Evaluation of inflammation and follicle depletion during ovarian ageing in mice","volume":"11","author":"Lliberos","year":"2021","journal-title":"Sci Rep"},{"key":"2026041501020685500_ref55","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1095\/biolreprod49.2.221","article-title":"Germ cell deficient (gcd) mouse as a model of premature ovarian failure","volume":"49","author":"Duncan","year":"1993","journal-title":"Biol Reprod"},{"key":"2026041501020685500_ref56","first-page":"1283","article-title":"Hyperplastic and early neoplastic changes in the ovaries of mice after genic deletion of germ cells","volume":"48","author":"Murphy","year":"1972","journal-title":"J Natl Cancer Inst"},{"key":"2026041501020685500_ref57","first-page":"721","article-title":"Plasma gonadotropin levels during early stages of ovarian tumorigenesis in mice of the W x -W u genotype","volume":"33","author":"Murphy","year":"1973","journal-title":"Cancer Res"},{"key":"2026041501020685500_ref58","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1679\/aohc.49.379","article-title":"Ultrastructural changes in the ovaries of Sl\/Slt mutant mice, showing developmental deficiency of follicles and tubular adenomas","volume":"49","author":"Ishimura","year":"1986","journal-title":"Arch Histol Jpn"},{"key":"2026041501020685500_ref59","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1186\/1477-7827-1-67","article-title":"Animal models of ovarian cancer","volume":"1","author":"Vanderhyden","year":"2003","journal-title":"Reprod Biol Endocrinol"},{"key":"2026041501020685500_ref60","first-page":"1449","article-title":"Chronic hypersecretion of luteinizing hormone in transgenic mice selectively alters responsiveness of the alpha-subunit gene to gonadotropin-releasing hormone and estrogens","volume":"13","author":"Abbud","year":"1999","journal-title":"Mol Endocrinol"},{"key":"2026041501020685500_ref61","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1073\/pnas.97.1.383","article-title":"Luteinizing hormone induction of ovarian tumors: Oligogenic differences between mouse strains dictates tumor disposition","volume":"97","author":"Keri","year":"2000","journal-title":"Proc Natl Acad Sci"},{"key":"2026041501020685500_ref62","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1095\/biolreprod34.4.751","article-title":"Ovarian tumors not induced by irradiation and gonadotropins in hypogonadal (hpg) mice","volume":"34","author":"Tennent","year":"1986","journal-title":"Biol Reprod"},{"key":"2026041501020685500_ref63","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1038\/s41526-025-00459-y","article-title":"Validated space radiation exposure predictions from earth to mars during Artemis-I","volume":"11","author":"Slaba","year":"2025","journal-title":"NPJ Microgravity"},{"key":"2026041501020685500_ref64","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2025.1558711","article-title":"Microgravity impairs endocrine signaling and reproductive health of women. A narrative review","volume":"16","author":"Cutigni","journal-title":"Frontiers in Physiology 2025"},{"key":"2026041501020685500_ref65","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/B978-0-443-22259-7.00018-7","volume-title":"Precision Medicine for Long and Safe Permanence of Humans in Space","author":"","year":"2025"},{"key":"2026041501020685500_ref66","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1093\/jnci\/91.17.1459","article-title":"Possible role of ovarian epithelial inflammation in ovarian cancer","volume":"91","author":"Ness","year":"1999","journal-title":"JNCI J Natl Cancer Inst"},{"key":"2026041501020685500_ref67","doi-asserted-by":"crossref","first-page":"100","DOI":"10.1186\/s13048-022-01032-x","article-title":"The role of oxidative stress in ovarian aging: a review","volume":"15","author":"Yan","year":"2022","journal-title":"J Ovarian Res"},{"key":"2026041501020685500_ref68","doi-asserted-by":"publisher","first-page":"eabq1475","DOI":"10.1126\/sciadv.abq1475","article-title":"Metformin prevents age-associated ovarian fibrosis by modulating the immune landscape in female mice","volume":"8","author":"Landry","year":"2022","journal-title":"Sci Adv"},{"key":"2026041501020685500_ref69","doi-asserted-by":"publisher","first-page":"eabn4564","DOI":"10.1126\/sciadv.abn4564","article-title":"Female reproductive life span is extended by targeted removal of fibrotic collagen from the mouse ovary","volume":"8","author":"Umehara","year":"2022","journal-title":"Sci Adv"},{"key":"2026041501020685500_ref70","doi-asserted-by":"crossref","first-page":"360438","DOI":"10.1155\/2014\/360438","article-title":"Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal","volume":"2014","author":"Ayala","year":"2014","journal-title":"Oxidative Med Cell Longev"},{"key":"2026041501020685500_ref71","doi-asserted-by":"crossref","first-page":"235","DOI":"10.3390\/w3010235","article-title":"Water radiolysis: influence of oxide surfaces on H2 production under ionizing radiation","volume":"3","author":"Le Ca\u00ebr","year":"2011","journal-title":"Water"},{"key":"2026041501020685500_ref72","doi-asserted-by":"crossref","first-page":"651","DOI":"10.3390\/futurepharmacol4030035","article-title":"Understanding the impact of oxidative stress on ovarian cancer: advances in diagnosis and treatment","volume":"4","author":"Meshkovska","year":"2024","journal-title":"Future Pharmacology"},{"key":"2026041501020685500_ref73","doi-asserted-by":"publisher","first-page":"1431","DOI":"10.1016\/j.yexcr.2013.02.017","article-title":"Metabolic changes during ovarian cancer progression as targets for sphingosine treatment","volume":"319","author":"Anderson","year":"2013","journal-title":"Exp Cell Res"},{"key":"2026041501020685500_ref74","doi-asserted-by":"publisher","first-page":"44","DOI":"10.1016\/j.yexcr.2014.08.028","article-title":"Ovarian tumor-initiating cells display a flexible metabolism","volume":"328","author":"Anderson","year":"2014","journal-title":"Exp Cell Res"},{"key":"2026041501020685500_ref75","doi-asserted-by":"crossref","first-page":"80","DOI":"10.3892\/ol.2022.13200","article-title":"Revisiting therapeutic strategies for ovarian cancer by focusing on redox homeostasis","volume":"23","author":"Kobayashi","year":"2022","journal-title":"Oncol Lett"},{"key":"2026041501020685500_ref76","doi-asserted-by":"publisher","first-page":"e13259","DOI":"10.1111\/acel.13259","article-title":"Ovarian stiffness increases with age in the mammalian ovary and depends on collagen and hyaluronan matrices","volume":"19","author":"Amargant","year":"2020","journal-title":"Aging Cell"},{"key":"2026041501020685500_ref77","doi-asserted-by":"publisher","first-page":"42","DOI":"10.4161\/cbt.26605","article-title":"In vivo time-serial multi-modality optical imaging in a mouse model of ovarian tumorigenesis","volume":"15","author":"Watson","year":"2014","journal-title":"Cancer Biol Ther"},{"key":"2026041501020685500_ref78","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1117\/1.JBO.23.6.066501","article-title":"Polarization-resolved second harmonic generation imaging of human ovarian cancer","volume":"23","author":"Campbell","year":"2018","journal-title":"J Biomed Opt"},{"key":"2026041501020685500_ref79","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1530\/REP-18-0089","article-title":"Radiation-induced ovarian follicle loss occurs without overt stromal changes","volume":"155","author":"Kimler","year":"2018","journal-title":"Reproduction"},{"key":"2026041501020685500_ref80","doi-asserted-by":"publisher","first-page":"14","DOI":"10.3390\/cancers14092220","article-title":"Tumor-associated macrophages and ovarian cancer: implications for therapy","volume":"14","author":"Schweer","year":"2022","journal-title":"Cancers (Basel)"},{"key":"2026041501020685500_ref81","doi-asserted-by":"publisher","first-page":"V5","DOI":"10.1530\/REP-20-0489","article-title":"Macrophage-derived multinucleated giant cells: hallmarks of the aging ovary","volume":"161","author":"Foley","year":"2021","journal-title":"Reproduction"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioag019\/66510947\/ioag019.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/114\/4\/1400\/66510947\/ioag019.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/114\/4\/1400\/66510947\/ioag019.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,15]],"date-time":"2026-04-15T05:02:19Z","timestamp":1776229339000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/114\/4\/1400\/8435256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,21]]},"references-count":81,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,1,21]]},"published-print":{"date-parts":[[2026,4,13]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioag019","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2026,1,21]]}}}