Abstract
Malathion is an organophosphate pesticide (OP) commonly used in agriculture, industry, and veterinary medicine. Sex is a crucial factor in responding to neurotoxicants, yet the sex-specific effects of OP exposure, particularly neurological impairments following chronic low-level exposure remains limited. Our study aims to evaluate the neurobehavioral and biochemical effects of developmental exposure to Malathion across sexes. Pregnant mice were exposed to a low oral dose of Malathion from gestation up to the weaning of the pups, which were individually gavaged with a similar dose regimen until postnatal day 70. Our results show that Malathion decreased body weight and food intake, reduced locomotor activity and recognition memory. Motor coordination and special memory were only altered in females, whereas we found a male-specific effect of Malathion on social behavior and marble burying. These alterations were accompanied by increased malondialdehyde (MDA), decreased brain acetylcholinesterase activity (AChE), and disrupted brain redox homeostasis. Our findings about the effects of Malathion exposure across sexes may, in part, contribute to understanding the dimorphic susceptibilities observed in neurological disorders.
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Aebi H (1974) Catalase. In: Bergmeyer HU (ed) Methods of enzymatic analysis. Verlag Chemie/Academic Press Inc., Weinheim/NewYork, p 673–680. https://doi.org/10.1016/b978-0-12-091302-2.50032-3
Alonso-Caraballo Y, Ferrario CR (2019) Effects of the estrous cycle and ovarian hormones on cue-triggered motivation and intrinsic excitability of medium spiny neurons in the Nucleus Accumbens core of female rats. Horm Behav 116:104583. https://doi.org/10.1016/j.yhbeh.2019.104583
Angoa-Pérez M, Kane MJ, Briggs DI, Francescutti DM, Kuhn DM (2013) Marble burying and nestlet shredding as tests of repetitive, compulsive-like behaviors in mice. J Vis Exp 82:50978. https://doi.org/10.3791/50978
Ardebili Dorri S, Hosseinzadeh H, Abnous K, Vahdati Hasani F, Yazdian Robati R, Razavi BM (2015) Involvement of brain‐derived neurotrophic factor (BDNF) on malathion induced depressive‐like behavior in subacute exposure and protective effects of crocin. Iran J Basic Med Sci 18(10):958–966
Asada K, Takahashi MA, Nagate M (1974) Assay and inhibitors of spinach superoxide dismutase. Agric Biol Chem 38(2):471–473. https://doi.org/10.1080/00021369.1974.10861178
Asarian L, Geary N (2002) Cyclic estradiol treatment normalizes body weight and restores physiological patterns of spontaneous feeding and sexual receptivity in ovariectomized rats. Horm Behav 42(4):461–471. https://doi.org/10.1006/hbeh.2002.1835
Avena NM, Rada PV (2012) Cholinergic modulation of food and drug satiety and withdrawal. Physiol Behav 106(3):332–336. https://doi.org/10.1016/j.physbeh.2012.03.020
Badr AM (2020) Organophosphate toxicity: updates of malathion potential toxic effects in mammals and potential treatments. Environ Sci Pollut Res 27(21):26036–26057. https://doi.org/10.1007/s11356-020-08937-4
Beard JD et al (2014) Pesticide exposure and depression among male private pesticide applicators in the agricultural health study. Environ Health Perspect 122(9):984–991. https://doi.org/10.1289/ehp.1307450
Bliss TVP, Collingridge GL (1993) A synaptic model of memory: Long-term potentiation in the hippocampus. Nature 361(6407):31–39. https://doi.org/10.1038/361031a0
Bradman A, Whyatt RM (2005) Characterizing exposures to nonpersistent pesticides during pregnancy and early childhood in the National Children’s Study: a review of monitoring and measurement methodologies. Environ Health Perspect 113(8):1092–1099. https://doi.org/10.1289/ehp.7769
Buege JA, Aust SD (1978) Biomembranes - Part C: Biological Oxidations. Methods Enzymol 52:302–310
Chari T, Griswold S, Andrews NA, Fagiolini M (2020) The stage of the Estrus cycle is critical for interpretation of female mouse social interaction behavior. Front Behav Neurosci 14:113. https://doi.org/10.3389/fnbeh.2020.00113
Chen X, McClusky R, Chen J, Beaven S. W, Tontonoz P, Arnold A. P, & Reue K (2012) The number of X chromosomes causes sex differences in adiposity in mice. PLoS genetics 8(5). https://doi.org/10.1371/journal.pgen.1002709
Coban FK, Ince S, Kucukkurt I, Demirel HH, Hazman O (2014) “Boron attenuates malathion-induced oxidative stress and acetylcholinesterase inhibition in rats. Drug and chemical toxicology 38(4):391–399. https://doi.org/10.3109/01480545.2014.974109
Comfort N, Re DB (2017) Sex-specific neurotoxic effects of organophosphate pesticides across the life course. Curr Env Heal Rep 4(4):392–404. https://doi.org/10.1007/s40572-017-0171-y
Crawley JN (2004) Designing mouse behavioral tasks relevant to autistic-like behaviors. Ment Retard Dev Disabil Res Rev 10(4):248–258. https://doi.org/10.1002/mrdd.20039
Delgado EHB, Streck EL, Quevedo JL, Dal-Pizzol F (2006) Mitochondrial respiratory dysfunction and oxidative stress after chronic malathion exposure. Neurochem Res 31(8):1021–1025. https://doi.org/10.1007/s11064-006-9111-1
Denninger JK, Smith BM, Kirby ED (2018) Novel object recognition and object location behavioral testing in mice on a budget. J vis Exp 2018(141):1–10. https://doi.org/10.3791/58593
Djekkoun N, Depeint F, Guibourdenche M, El Khayat El Sabbouri H, Corona A, Rhazi L, Gay-Queheillard J, Rouabah L, Hamdad F, Bach V, Benkhalifa M, & Khorsi-Cauet H (2022) Chronic perigestational exposure to chlorpyrifos induces perturbations in gut bacteria and glucose and lipid markers in female rats and their offspring. Toxics 10(3):138. https://doi.org/10.3390/toxics10030138
dos Santos AA et al (2016) Long-term and low-dose malathion exposure causes cognitive impairment in adult mice: evidence of hippocampal mitochondrial dysfunction, astrogliosis and apoptotic events. Arch Toxicol 90(3):647–660. https://doi.org/10.1007/s00204-015-1466-0
Dunham NW, Miya TS (1957) A note on a simple apparatus for detecting neurological deficit in rats and mice. J Am Pharm Assoc Am Pharm Assoc (Baltim) 46(3):208–209
Dworzynski K, Ronald A, Bolton P, Happé F (2012) How different are girls and boys above and below the diagnostic threshold for autism spectrum disorders? J Am Acad Child Adolesc Psychiatry 51(8):788–797. https://doi.org/10.1016/j.jaac.2012.05.018
Ellman GL, Courtney KD, Andres V, Featherstone RM (1961) A new and rapid colorimetric determination of acetylcholinesterase activity. Biochem Pharmacol 7(2):88–95. https://doi.org/10.1016/0006-2952(61)90145-9
Ennaceur A, Delacour J (1988) A new one-trial test for neurobiological studies of memory in rats. 1: behavioral data. Behav Brain Res 31(1):47–59. https://doi.org/10.1016/0166-4328(88)90157-X
Fereidounni S, Dhawan DK (2018) Understanding the role of quercetin during neurotoxicity induced by Chlorpyrifos. J Phytopharm 7(1):33–39.
Ferreira-Paes T, Seixas-Costa P, Almeida-Amaral EE (2021) Validation of a feed protocol in a mouse model that mimics marasmic malnutrition. Front Vet Sci 8(November):1–10. https://doi.org/10.3389/fvets.2021.757136
Ferri SL, Abdel T, Brodkin ES (2018) Sex differences in autism spectrum disorder: a review. Curr Psychiatry Rep 20(2):69–86. https://doi.org/10.4324/9780429454646
Flohé L, Günzler WA (1984) Assays of gluthathione peroxidase. Methods Enzymol 105:114–120
Fortunato JJ, Feier G, Vitali AM, Petronilho FC, Dal-Pizzol F, Quevedo J (2006) Malathion-induced oxidative stress in rat brain regions. Neurochem Res 31(5):671–678. https://doi.org/10.1007/s11064-006-9065-3
Furlong MA, Engel SM, Barr DB, Mary SW (2014) Prenatal exposure to organophosphate pesticides and reciprocal social behavior in childhood. Env Int 70:125–131. https://doi.org/10.1016/j.envint.2014.05.011
Gobinath AR, Mahmoud R, Galea LA (2015) Influence of sex and stress exposure across the lifespan on endophenotypes of depression: Focus on behavior, glucocorticoids, and hippocampus. Front Neurosci 8:420. https://doi.org/10.3389/fnins.2014.00420
Gómez-Giménez B, Felipo V, Cabrera-Pastor A, Agustí A, Hernández-Rabaza V, Llansola M (2018) Developmental exposure to pesticides alters motor activity and coordination in rats: sex differences and underlying mechanisms. Neurotox Res 33(2):247–258. https://doi.org/10.1007/s12640-017-9823-9
Gupta VK, Kumar A, de L. Pereira M, Siddiqi NJ, Sharma B (2020) Anti-inflammatory and antioxidative potential of aloe vera on the cartap and malathion mediated toxicity in wistar rats. Int J Environ Res Public Health 17(14):1–19. https://doi.org/10.3390/ijerph17145177
Happé F, Ronald A (2008) The ‘ Fractionable Autism Triad’:a review of evidence from behavioural, genetic, cognitive and neural research. Neuropsychology review, 18(4):287–304. https://doi.org/10.1007/s11065-008-9076-8
Harrison V, Mackenzie S (2016) Anxiety and depression following cumulative low-level exposure to organophosphate pesticides. Environ Res 151:528–536. https://doi.org/10.1016/j.envres.2016.08.020
Hawley WR, Grissom EM, Barratt HE, Conrad TS, Dohanich GP (2012) The effects of biological sex and gonadal hormones on learning strategy in adult rats. Physiol Behav 105(4):1014–1020. https://doi.org/10.1016/j.physbeh.2011.11.021
Hazarika A, Sarkar SN, Hajare S, Kataria M (2003) Influence of malathion pretreatment on the toxicity of anilofos in male rats: a biochemical interaction study. Toxicology 185(1–2):1–8. https://doi.org/10.1016/s0300-483x(02)00574-7
Heyer DB, Meredith RM (2017) Environmental toxicology: sensitive periods of development and neurodevelopmental disorders. Neurotoxicology 58:23–41. https://doi.org/10.1016/j.neuro.2016.10.017
Hodes GE, Walker DM, Labonté B, Nestler EJ, Russo SJ (2017) Understanding the epigenetic basis of sex differences in depression. J Neurosci Res 95(1–2):692–702. https://doi.org/10.1002/jnr.23876
Hohmann CF (2003) A morphogenetic role for acetylcholine in mouse cerebral neocortex. Neurosci Biobehav Rev 27(4):351–363. https://doi.org/10.1016/S0149-7634(03)00066-6
Hu Y et al (2012) Hippocampal nitric oxide contributes to sex difference in affective behaviors. Proc Natl Acad Sci U S A 109(35):14224–14229. https://doi.org/10.1073/pnas.1207461109
Institute of Medicine (US) Committee on Understanding the Biology of Sex and Gender Differences (2001) Exploring the Biological Contributions to Human Health: Does Sex Matter? National Academies Press (US), Washington (DC)
Jeon SJ et al (2018) Sex-specific behavioral features of rodent models of autism spectrum disorder. Exp Neurobiol 27(5):321–343. https://doi.org/10.5607/en.2018.27.5.321
Khan AM, Raina R, Dubey N, Verma PK (2017) Effect of deltamethrin and fluoride co-exposure on the brain antioxidant status and cholinesterase activity in Wistar rats. Drug Chem Toxicol 41(2):123–127. https://doi.org/10.1080/01480545.2017.1321009
Kwong TC (2002) Organophosphate pesticides: biochemistry and clinical toxicology. Ther Drug Monit 24(1):144–149. https://doi.org/10.1097/00007691-200202000-00022
Lan A, Stein D, Portillo M, Toiber D, Kofman O (2019) Impaired innate and conditioned social behavior in adult C57Bl6/J mice prenatally exposed to chlorpyrifos. Behav Brain Funct 15(1):1–9. https://doi.org/10.1186/s12993-019-0153-3
Lasram MM, El-Golli N, Lamine A. J, Douib I. B, Bouzid K, Annabi A, El Fazaa S, Abdelmoula J, & Gharbi N (2014) Changes in glucose metabolism and reversion of genes expression in the liver of insulin-resistant rats exposed to malathion. The protective effects of N-acetylcysteine. Gen Comp Endocrinol 215:88–97. https://doi.org/10.1016/j.ygcen.2014.10.002
Leary TPO, Askari B, Lee BH, Darby K, Knudson C, Ash AM, Seib DR, Espinueva DF, Snyder JS (2022) Sex differences in the spatial behavior functions of adult-born neurons in rats. eNeuro. 9(3). https://doi.org/10.1523/ENEURO.0054-22.2022
Lo SC, Scearce-Levie K, Sheng M (2016) Characterization of social behaviors in caspase-3 deficient mice. Sci Rep 6(January):1–9. https://doi.org/10.1038/srep18335
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193(1):265–275. https://doi.org/10.1016/s0021-9258(19)52451-6
MacQueen G, Frodl T (2011) The hippocampus in major depression: evidence for the convergence of the bench and bedside in psychiatric research. Mol Psychiatry 16(3):252–264. https://doi.org/10.1038/mp.2010.80
Malekirad AA, Faghih M, Mirabdollahi M, Kiani M, Fathi A, Abdollahi M (2013) Neurocognitive, mental health, and glucose disorders in farmers exposed to organophosphorus pesticides. Arh Hig Rada Toksikol 64(1):1–8. https://doi.org/10.2478/10004-1254-64-2013-2296
Malqui H, Anarghou H, Ouardi FZ, Ouasmi N, Najimi M, Chigr F (2018) Continuous exposure to inorganic mercury affects neurobehavioral and physiological parameters in mice. J Mol Neurosci 66(2):291–305. https://doi.org/10.1007/s12031-018-1176-1
Manto M et al (2012) Consensus paper : roles of the cerebellum in motor control — the diversity of ideas on cerebellar involvement in movement. Cerebellum 11(2):457–487. https://doi.org/10.1007/s12311-011-0331-9
Maris AF et al (2010) Gender effects of acute malathion or zinc exposure on the antioxidant response of rat hippocampus and cerebral cortex. Basic Clin Pharmacol Toxicol 107:965–970. https://doi.org/10.1111/j.1742-7843.2010.00614.x
McCarthy MM, Woolley CS, Arnold AP (2017) Incorporating sex as a biological variable in neuroscience: what do we gain? Nat Rev Neurosci 18(12):707–708. https://doi.org/10.1038/nrn.2017.137
McLean AC, Valenzuela N, Fai S, Bennett SAL (2012) Performing vaginal lavage, crystal violet staining, and vaginal cytological evaluation for mouse estrous cycle staging identification. J vis Exp 67:4–9. https://doi.org/10.3791/4389
Monfort P, Gomez-Gimenez B, Llansola M, Felipo V (2015) Gender differences in spatial learning, synaptic activity, and long-term potentiation in the hippocampus in rats: molecular mechanisms. ACS Chem Neurosci 6(8):1420–1427. https://doi.org/10.1021/acschemneuro.5b00096
Morris RGM, Frey U (1997) Hippocampal synaptic plasticity: Role in spatial learning or the automatic recording of attended experience? Philos Trans r Soc B Biol Sci 352(1360):1489–1503. https://doi.org/10.1098/rstb.1997.0136
Mostafalou S, Abdollahi M (2017) Pesticides: an update of human exposure and toxicity. Arch Toxicol 91(2):549–599. https://doi.org/10.1007/s00204-016-1849-x
Moura CA, Oliveira MC, Costa LF, Tiago PRF, Holanda VAD, Lima RH, Cagni FC, Lobão-Soares B, Bolaños-Jiménezet F, Gaviolial EC (2020) Prenatal restraint stress impairs recognition memory in adult male and female offspring. Acta Neuropsychiatr 29:1–6. https://doi.org/10.1017/neu.2020.3
N’Go PK et al (2013b) Developmental effects of malathion exposure on recognition memory and spatial learning in males wistar rats. J Behav Brain Sci 03(03):331–340. https://doi.org/10.4236/jbbs.2013.33033
N’Go PK, Azzaoui F-Z, Ahami AOT, Soro PR, Najimi M, Chigr F (2013) Developmental effects of Malathion exposure on locomotor activity and anxiety-like behavior in Wistar rat. Health (Irvine. Calif) 05(03): 603–611. https://doi.org/10.4236/health.2013.53a080
Olofsson LE, Pierce AA, Xu AW (2009) Functional requirement of AgRP and NPY neurons in ovarian cycle-dependent regulation of food intake. Proc Natl Acad Sci U S A 106(37):15932–15937. https://doi.org/10.1073/pnas.0904747106
Ouardi FZ et al (2019) Gestational and lactational exposure to malathion affects antioxidant status and neurobehavior in mice pups and offspring. J Mol Neurosci 69(1):17–27. https://doi.org/10.1007/s12031-018-1252-6
N’go PK et al (2021) Comparison of the effects of argan and nigella oils on malathion-induced cognitive-behavioral alterations and brain histopathology in male Wistar rats. Curr Top Toxicol 17:131–142. https://doi.org/10.31300/cttx.17.2021.131-142
Palmer BF, Clegg DJ (2015) The sexual dimorphism of obesity. Mol Cell Endocrinol 402:113–119. https://doi.org/10.1016/j.mce.2014.11.029
Pinto Savall AS, Fidelis EM, Quines CB, Bresolin L, Gervini V, Pinton S (2021) Potential role of a newly AChE reactivator in the depressive-like behavior induced by malathion. Neuroscience letters 749:135697. https://doi.org/10.1016/j.neulet.2021.135697
Prendergast BJ, Onishi KG, Zucker I (2014) Female mice liberated for inclusion in neuroscience and biomedical research. Neurosci Biobehav Rev 40:1–5. https://doi.org/10.1016/j.neubiorev.2014.01.001
Ramos ZR, Fortunato JJ, Agostinho FR, Martins MR, Correa M, Schetinger M. R, Dal-Pizzol F, & Quevedo J (2006) Influence of malathion on acetylcholinesterase activity in rats submitted to a forced swimming test. Neurotox Res 9(4):285–290. https://doi.org/10.1007/BF03033318
Raney T, Croppenstedt A, Anriquez G, Lowder S (2011) The state of food and agriculture 2010-11: Women in Agriculture: Closing the Gender Gap for Development. 2.
Rauh VA et al (2012) Brain anomalies in children exposed prenatally to a common organophosphate pesticide. Proc Natl Acad Sci U S A 109(20):7871–7876. https://doi.org/10.1073/pnas.1203396109
Reygner J et al (2016) Inulin supplementation lowered the metabolic defects of prolonged exposure to chlorpyrifos from gestation to young adult stage in offspring rats. PLoS ONE 11(10):1–17. https://doi.org/10.1371/journal.pone.0164614
Ruszkiewicz JA et al (2019) Sex-specific differences in redox homeostasis in brain norm and disease. J Mol Neurosci 67(2):312–342. https://doi.org/10.1007/s12031-018-1241-9
Saeedi Saravi SS et al (2016) On the effect of minocycline on the depressive-like behavior of mice repeatedly exposed to malathion: interaction between nitric oxide and cholinergic system. Metab Brain Dis 31(3):549–561. https://doi.org/10.1007/s11011-015-9764-z
Safari S et al (2021) Sex differences in spatial learning and memory and hippocampal long-term potentiation at perforant pathway-dentate gyrus (PP-DG) synapses in Wistar rats. Behav Brain Funct 17(1):1–11. https://doi.org/10.1186/s12993-021-00184-y
Sanghi R, Pillai MKK, Jayalekshmi TR, Nair A (2003) Organochlorine and organophosphorus pesticide residues in breast milk from Bhopal, Madhya Pradesh, India. Hum Exp Toxicol 22(2):73–76. https://doi.org/10.1191/0960327103ht321oa
Savall ASP et al (2020) Antidepressant-like effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one in rats exposed to malathion: involvement of BDNF-Trkβ pathway and AChE. Life Sci 256:117892. https://doi.org/10.1016/j.lfs.2020.117892
Schwartz MW, Woods SC, Porte D, Seeley RJ, Baskin DG (2000) Central nervous system control of food intake. Nature 404(6778):661–671. https://doi.org/10.1038/35007534
Seif MM, Khalil FA, Abou Arab AA, Donia AMA, El-Sherbiny AM, Mohamed SR (2015) Ameliorative role of Melissa officinal is against hepatorenal toxicities of organophosphorus malathion in male rats. MOJ Toxicolology 1(3). https://doi.org/10.15406/mojt.2015.01.00014
Silver MK, Shao J, Zhu B, Chen M, Xia Y, Kaciroti N, Lozoff B, Meeker JD (2017) Prenatal naled and chlorpyrifos exposure is associated with deficits in infant motor function in a cohort of Chinese infants. Environ Int 106:148-256. https://doi.org/10.1016/j.envint.2017.05.015
Silverman JL, Yang M, Lord C, Crawley JN (2010) Behavioural phenotyping assays for mouse models of autism. Nat Rev Neurosci 11 (7):490–502. https://doi.org/10.1038/nrn2851
Squire LR (1992) Memory and the hippocampuss: a synthesis from findings with rats, monkeys, and humans. Psychol Rev 99(2):195–231. https://doi.org/10.1037/0033-295X.99.2.195
Thomas A, Burant A, Bui N, Graham D, Yuva-Paylor LA, Paylor R (2009) Marble burying reflects a repetitive and perseverative behavior more than novelty-induced anxiety. Psychopharmacology (Berl) 204(2):361–73. https://doi.org/10.1007/s00213-009-1466-y.Marble
Todd SW, Lumsden EW, Aracava Y, Mamczarz J, Albuquerque EX, Pereira EFR (2020) Gestational exposures to organophosphorus insecticides: from acute poisoning to developmental neurotoxicity. Neuropharmacology 180:108271. https://doi.org/10.1016/j.neuropharm.2020.108271
Venkatesan R, Park YU, Ji E, Yeo EJ, Kim SY (2017) Malathion increases apoptotic cell death by inducing lysosomal membrane permeabilization in N2a neuroblastoma cells: a model for neurodegeneration in Alzheimer’s disease. Cell Death Discov 3: 17007. https://doi.org/10.1038/cddiscovery.2017.7
Von Ehrenstein OS et al (2019) Prenatal and infant exposure to ambient pesticides and autism spectrum disorder in children: population based case-control study. BMJ 364:1–10. https://doi.org/10.1136/bmj.l962
Wang C et al (2018) TAp63 contributes to sexual dimorphism in POMC neuron functions and energy homeostasis. Nat Commun 9(1):1–11. https://doi.org/10.1038/s41467-018-03796-7
Williams KW, Elmquist JK (2012) From neuroanatomy to behavior: central integration of peripheral signals regulating feeding behavior. Nat Neurosci 15(10):1350–1355. https://doi.org/10.1038/nn.3217
Woolley CS, McEwen BS (1992) Estradiol mediates fluctuation in hippocampal synapse density during the estrous cycle in the adult rat. J Neurosci 12(7):2549–2554. https://doi.org/10.1523/JNEUROSCI.12-07-02549.1992
Yagi S, Galea LAM (2019) Sex differences in hippocampal cognition and neurogenesis. Neuropsychopharmacology 44(1):200–213. https://doi.org/10.1038/s41386-018-0208-4
Yin C et al (2011) Antidepressant-like effects of L-theanine in the forced swim and tail suspension tests in mice. Phyther Res 25(11):1636–1639. https://doi.org/10.1002/ptr.3456
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L.B. performed the experiments and wrote the manuscript with support from all authors. M.L. performed the statistical analysis. L.B., M.L. and O.E. processed the experimental data and designed the figures. H.M. and H.A. along with L.B., M.L. and O.E. contributed to sample preparation and biochemical analysis. F.C., M.N. and A.C. supervised the project. All authors have read and agreed to the published version of the manuscript. The authors declare that all data were generated in-house and that no paper mill was used.
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Berroug, L., Laaroussi, M., Essaidi, O. et al. Sex-specific neurobehavioral and biochemical effects of developmental exposure to Malathion in offspring mice. Naunyn-Schmiedeberg's Arch Pharmacol 397, 2215–2231 (2024). https://doi.org/10.1007/s00210-023-02749-2
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DOI: https://doi.org/10.1007/s00210-023-02749-2