{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T05:03:10Z","timestamp":1789621390775,"version":"build-2803163510"},"reference-count":42,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100019259","name":"Sinop University","doi-asserted-by":"crossref","award":["SYO-1901-16-36"],"award-info":[{"award-number":["SYO-1901-16-36"]}],"id":[{"id":"10.13039\/100019259","id-type":"DOI","asserted-by":"crossref"}]},{"award":["SYO-1901-16-36"],"award-info":[{"award-number":["SYO-1901-16-36"]}],"id":[{"id":"https:\/\/ror.org\/004ah3r71","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Background: Chlorpyrifos (CPF) is a widely used organophosphate pesticide that can reach the developing organism during gestation. The finite ovarian follicle pool is established early, yet prenatal CPF effects on it remain poorly characterized by unbiased quantitative methods. This study evaluated the developmental ovarian toxicity of prenatal CPF exposure and the modulatory potential of curcumin in rat offspring. Methods: Pregnant Wistar rats were assigned to Control, Sham, CPF (5 mg\/kg\/day), CUR (100 mg\/kg\/day), and CPF + CUR groups (five dams per group). Anogenital distance was recorded at birth (PND1). Female offspring were examined at postnatal day 28 using ovarian weight, histopathology, unbiased stereological follicle quantification, cortical volume estimation, serum anti-M\u00fcllerian hormone (AMH), serum cholinesterase activity, and biochemical markers of ovarian oxidative status and inflammation. The litter was the unit of analysis (n = 5 litters per group). Results: Prenatal CPF exposure produced marked, quantifiable alterations in ovarian structure, including decreased cortical volume, structural disorganization, vascular alterations, and follicular degeneration. Primordial, preantral, and antral follicle counts were significantly reduced versus controls (p &lt; 0.0001), accompanied by significantly reduced ovarian weight and a shorter anogenital distance at birth. Serum AMH was lower in CPF-exposed offspring, and serum cholinesterase activity was reduced. In the curcumin co-treatment group, changes were partially less pronounced, with better-preserved follicular architecture and higher cortical volume than the CPF group. Ovarian oxidative and inflammatory activity increased with CPF exposure and was less marked with curcumin co-treatment. Reproductive-hormone measurements, including AMH, were not analytically validated in-house and are reported as exploratory. Conclusions: Prenatal CPF exposure induced structural and biochemical alterations consistent with developmental ovarian toxicity in rat offspring. Curcumin co-administration was associated with partially less pronounced changes, suggesting a modulatory rather than a fully protective role. Given the limited number of litters, findings should be interpreted with caution.<\/jats:p>","DOI":"10.3390\/toxics14090820","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T09:31:57Z","timestamp":1789464717000},"page":"820","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Prenatal Chlorpyrifos Exposure Induces Ovarian Toxicity in Rat Offspring: Modulatory Potential of Curcumin"],"prefix":"10.3390","volume":"14","author":[{"given":"Gonca","family":"G\u00fclsoy","sequence":"first","affiliation":[{"name":"Department of Environmental Health, Institute of Postgraduate Education, Sinop University, Sinop 57000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"}]},{"given":"Dilek","family":"Sa\u011f\u0131r","sequence":"additional","affiliation":[{"name":"Occupational Health and Safety, Faculty of Health Sciences, Sinop University, Sinop 57000, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ydbio.2006.06.023","article-title":"Fate of the Initial Follicle Pool: Empirical and Mathematical Evidence Supporting Its Sufficiency for Adult Fertility","volume":"298","author":"Kreeger","year":"2006","journal-title":"Dev. Biol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3329","DOI":"10.1210\/en.2002-0131","article-title":"Regulation of Ovarian Primordial Follicle Assembly and Development by Estrogen and Progesterone: Endocrine Model of Follicle Assembly","volume":"144","author":"Kezele","year":"2003","journal-title":"Endocrinology"},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Lahimer, M., Djekkoun, N., Tricotteaux-Zarqaoui, S., Corona, A., Lafosse, I., Ali, H.B., Ajina, M., Bach, V., Benkhalifa, M., and Khorsi-Cauet, H. (2023). Impact of Perinatal Coexposure to Chlorpyrifos and a High-Fat Diet on Kisspeptin and GnRHR Presence and Reproductive Organs. Toxics, 11.","DOI":"10.20944\/preprints202308.1783.v1"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"108735","DOI":"10.1016\/j.reprotox.2024.108735","article-title":"Chlorpyrifos and Dimethoate Exposure Impairs Female Fertility by Deregulating WNT Signaling Pathway & Uterine Receptivity","volume":"130","author":"Jan","year":"2024","journal-title":"Reprod. Toxicol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"11663","DOI":"10.1007\/s11356-020-07736-1","article-title":"Carnosic Acid Alleviates Chlorpyrifos-Induced Oxidative Stress and Inflammation in Mice Cerebral and Ocular Tissues","volume":"27","author":"AlKahtane","year":"2020","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jsbmb.2015.10.010","article-title":"Pesticide Chlorpyrifos Acts as an Endocrine Disruptor in Adult Rats Causing Changes in Mammary Gland and Hormonal Balance","volume":"156","author":"Ventura","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.cbi.2017.03.017","article-title":"Protective Properties of 6-Gingerol-Rich Fraction from Zingiber Officinale (Ginger) on Chlorpyrifos-Induced Oxidative Damage and Inflammation in the Brain, Ovary and Uterus of Rats","volume":"270","author":"Abolaji","year":"2017","journal-title":"Chem. Biol. Interact."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1515\/REVEH.2001.16.1.1","article-title":"Pesticide-Induced Oxidative Stress: Perspective and Trends","volume":"16","author":"Banerjee","year":"2001","journal-title":"Rev. Environ. Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"490","DOI":"10.2174\/0113892010297408240319073735","article-title":"Protective Effects of Curcumin and Nanomicelle Curcumin on Chlorpyrifos-Induced Oxidative Damage and Inflammation in the Uterus, Ovary and Brain of Rats","volume":"26","author":"Nazarian","year":"2025","journal-title":"Curr. Pharm. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/S0890-6238(02)00121-1","article-title":"Developmental Toxicity Study of Chlorpyrifos in Rats","volume":"17","author":"Farag","year":"2003","journal-title":"Reprod. Toxicol."},{"key":"ref_11","first-page":"17","article-title":"Ameliorative Effects of Green Tea Polyphenol Epigallocatechin-3-Gallate on Chlorpyrifos Ovarian Toxicity in Adult Albino Rats","volume":"19","author":"Farag","year":"2020","journal-title":"Mansoura J. Forensic Med. Clin. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.fct.2013.10.006","article-title":"Chlorpyrifos Induced Toxicity in Reproductive Organs of Female Wistar Rats","volume":"62","author":"Nishi","year":"2013","journal-title":"Food Chem. Toxicol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1002\/em.22355","article-title":"Insecticides and Ovarian Functions","volume":"61","author":"Sharma","year":"2020","journal-title":"Environ. Mol. Mutagen."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Kaur, K., Al-Khazaleh, A.K., Bhuyan, D.J., Li, F., and Li, C.G. (2024). A Review of Recent Curcumin Analogues and Their Antioxidant, Anti-Inflammatory, and Anticancer Activities. Antioxidants, 13.","DOI":"10.20944\/preprints202403.1292.v1"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4503","DOI":"10.2147\/DDDT.S327378","article-title":"Anti-Inflammatory Effects of Curcumin in the Inflammatory Diseases: Status, Limitations and Countermeasures","volume":"15","author":"Peng","year":"2021","journal-title":"Drug Des. Dev. Ther."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1016\/j.ijsu.2013.06.007","article-title":"The Protective Effect of Curcumin on Ischemia-Reperfusion Injury in Rat Ovary","volume":"11","author":"Sak","year":"2013","journal-title":"Int. J. Surg."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1530\/JME-17-0214","article-title":"Curcumin Exerts a Protective Effect against Premature Ovarian Failure in Mice","volume":"60","author":"Yan","year":"2018","journal-title":"J. Mol. Endocrinol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1186\/s13048-018-0409-9","article-title":"Beneficial Effects of Curcumin and Capsaicin on Cyclophosphamide-Induced Premature Ovarian Failure in a Rat Model","volume":"11","author":"Melekoglu","year":"2018","journal-title":"J. Ovarian Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"pgac108","DOI":"10.1093\/pnasnexus\/pgac108","article-title":"Identification of Curcumin as a Novel Potential Drug for Promoting the Development of Small Ovarian Follicles for Infertility Treatment","volume":"1","author":"Zhao","year":"2022","journal-title":"PNAS Nexus"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1093\/toxsci\/57.2.250","article-title":"Lack of Selective Developmental Neurotoxicity in Rat Pups from Dams Treated by Gavage with Chlorpyrifos","volume":"57","author":"Maurissen","year":"2000","journal-title":"Toxicol. Sci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1093\/toxsci\/53.2.438","article-title":"Lack of Differential Sensitivity to Cholinesterase Inhibition in Fetuses and Neonates Compared to Dams Treated Perinatally with Chlorpyrifos","volume":"53","author":"Mattsson","year":"2000","journal-title":"Toxicol. Sci."},{"key":"ref_22","first-page":"109","article-title":"Comparative Effects of Ripe and Unripe Lime (Citrus aurantifolia) on Spermatozoa and Gonadosomatic Index in Matured Male Wistar Rats","volume":"13","author":"Ogbonnaya","year":"2024","journal-title":"Biol. Med. Nat. Prod. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"569","DOI":"10.1530\/rep.1.00095","article-title":"Methods for Quantifying Follicular Numbers within the Mouse Ovary","volume":"127","author":"Myers","year":"2004","journal-title":"Reproduction"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2818.1986.tb02764.x","article-title":"Stereology of arbitrary particles","volume":"143","author":"Gundersen","year":"1986","journal-title":"J. Microsc."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"229","DOI":"10.1111\/j.1365-2818.1987.tb02837.x","article-title":"The Efficiency of Systematic Sampling in Stereology and Its Prediction","volume":"147","author":"Gundersen","year":"1987","journal-title":"J. Microsc."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/0006-2952(61)90145-9","article-title":"A New and Rapid Colorimetric Determination of Acetylcholinesterase Activity","volume":"7","author":"Ellman","year":"1961","journal-title":"Biochem. Pharmacol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1093\/clinchem\/34.3.497","article-title":"A Simple Method for Clinical Assay of Superoxide Dismutase","volume":"34","author":"Sun","year":"1988","journal-title":"Clin. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Aebi, H. (1984). Catalase in Vitro. Methods in Enzymology, Academic Press.","DOI":"10.1016\/S0076-6879(84)05016-3"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1016\/0006-291X(76)90747-6","article-title":"Glutathione Peroxidase Activity in Selenium-Deficient Rat Liver","volume":"71","author":"Lawrence","year":"1976","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/0003-2697(66)90167-9","article-title":"Estimation of Product of Lipid Peroxidation (Malonyl Dialdehyde) in Biochemical Systems","volume":"16","author":"Placer","year":"1966","journal-title":"Anal. Biochem."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/0003-2697(68)90092-4","article-title":"Estimation of Total, Protein-Bound, and Nonprotein Sulfhydryl Groups in Tissue with Ellman\u2019s Reagent","volume":"25","author":"Sedlak","year":"1968","journal-title":"Anal. Biochem."},{"key":"ref_32","first-page":"3","article-title":"Prenatal Pesticide Exposure: Meconium as a Biomarker and Impact on Fetal Weight","volume":"5","author":"Nsar","year":"2015","journal-title":"J. Environ. Anal. Toxicol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"151621","DOI":"10.1016\/j.acthis.2020.151621","article-title":"Protective Effects of Curcumin and Ganoderma Lucidum on Hippocampal Damage Caused by the Organophosphate Insecticide Chlorpyrifos in the Developing Rat Brain: Stereological, Histopathological and Immunohistochemical Study","volume":"122","author":"Eronat","year":"2020","journal-title":"Acta Histochem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1055\/a-1542-8992","article-title":"The Influence of Turmeric and Curcumin on Female Reproductive Processes","volume":"88","author":"Sirotkin","year":"2022","journal-title":"Planta Med."},{"key":"ref_35","first-page":"586","article-title":"Protective Effects of Curcumin on Liver Damage in Rats Treated with Chlorpyrifos during Pregnancy","volume":"8","author":"Sagir","year":"2019","journal-title":"Med. Sci. Int. Med. J."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.taap.2008.09.010","article-title":"Developmental Methoxychlor Exposure Affects Multiple Reproductive Parameters and Ovarian Folliculogenesis and Gene Expression in Adult Rats","volume":"233","author":"Armenti","year":"2008","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1016\/j.taap.2003.06.001","article-title":"Cholinergic Systems in Brain Development and Disruption by Neurotoxicants: Nicotine, Environmental Tobacco Smoke, Organophosphates","volume":"198","author":"Slotkin","year":"2004","journal-title":"Toxicol. Appl. Pharmacol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1289\/ehp.5828","article-title":"Fetal Chlorpyrifos Exposure: Adverse Effects on Brain Cell Development and Cholinergic Biomarkers Emerge Postnatally and Continue into Adolescence and Adulthood","volume":"111","author":"Qiao","year":"2003","journal-title":"Environ. Health Perspect."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3228","DOI":"10.1210\/en.2005-1588","article-title":"Serum Anti-M\u00fcllerian Hormone Levels Reflect the Size of the Primordial Follicle Pool in Mice","volume":"147","author":"Kevenaar","year":"2006","journal-title":"Endocrinology"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.tox.2006.01.005","article-title":"Effect of Chlorpyrifos-Methyl on Steroid and Thyroid Hormones in Rat F0- and F1-Generations","volume":"220","author":"Jeong","year":"2006","journal-title":"Toxicology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"118325","DOI":"10.1016\/j.envres.2024.118325","article-title":"Association of Prenatal Chlorpyrifos Exposure with Sexually Dimorphic Differences in Anogenital Distance among Thai Farmworker Children","volume":"248","author":"Dang","year":"2024","journal-title":"Environ. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"10553","DOI":"10.1021\/acs.jafc.9b03602","article-title":"Chlorpyrifos Induces Metabolic Disruption by Altering Levels of Reproductive Hormones","volume":"67","author":"Li","year":"2019","journal-title":"J. Agric. Food Chem."}],"container-title":["Toxics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/9\/820\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T04:21:11Z","timestamp":1789618871000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2305-6304\/14\/9\/820"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,15]]},"references-count":42,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["toxics14090820"],"URL":"https:\/\/doi.org\/10.3390\/toxics14090820","relation":{},"ISSN":["2305-6304"],"issn-type":[{"value":"2305-6304","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,15]]}}}