Prenatal and Early Postnatal Effects of Lead Ions on Motor Activity According to Gender Differences in Rats
DOI:
https://doi.org/10.52340/GBMN.2026.01.01.176Keywords:
Female rat, Lead prenatal exposure, Locomotor activity, Male rat, Motor cortexAbstract
BACKGROUND. Lead exposure in the early stages of pregnancy and the prenatal period is extremely dangerous and could cause substantial health problems in the future. The majority of epidemiological studies have considered gender as a confounding factor when evaluating the neurodevelopmental toxicity of lead exposure. This paper examines the effects of prenatal lead exposure on locomotor activity in relation to motor cortex morphology. The results are discussed in female and male rats. OBJECTIVES. Offspring of Wistar rats that, during pregnancy, received lead acetate at a) 0%, b) 0.05%, c) 0.2% with water were used for experiments. METHODS. Blood lead levels were analyzed by atomic absorption spectrophotometry. The overall degree of locomotor activity was evaluated using Calvin S. Hall's Open Field Test. Histological analysis of motor cortex neuronal density was conducted using a light microscope. RESULTS. During the critical days of neurogenesis (PD7, PD14, PD21, PD28), a statistically significant decrease in the number of neurons in the motor cortex of experimental pups was observed compared with the control group. Additionally, there was a statistically significant difference even at low doses. The second series of experiments was conducted on PD61 offspring or young adult rats. Behavioral tests showed significant differences between female and male rats. Male rats exposed prenatally to lead ions showed reduced locomotor activity, as measured by the number of lines crossed in the open field test; in the high- dose group, this difference was statistically significant. Unlike male rats, female rats showed increased motor activity. There was a trend toward decreased motor cortex neurons in offspring of both sexes at both low and high doses, but the decrease was statistically significant in male rats at the high dose. CONCLUSIONS. Our results show that lead exposure during pregnancy significantly reduces the density of motor cortex neurons. However, this effect is gender-dependent: it was statistically significant in male offspring and later expressed in their motor activity. We can speculate that the motor area of the brain of developing male rats is more sensitive to lead ion exposure than that of female rats.References
Dsouza HS, Menezes G, Venkatesh T. Fetal lead exposure: encephalopathy in a child. Indian J Clin Biochem. 2002;17(1):9-11. doi:10.1007/BF02867934
Albores-Garcia D, McGlothan JL, Bursac Z, Guilarte TR. Chronic developmental lead exposure increases μ-opiate receptor levels in the adolescent rat brain. Neurotoxicology. 2021;82:119-129. doi:10.1016/j.neuro.2020.11.008.
Bjørklund G, Tippairote T, Hangan T, Chirumbolo S, Peana M. Early-life lead exposure: risks and neurotoxic consequences. Curr Med Chem. 2024;31(13):1620-1633. doi:10.2174/0929867330666230409135310
Parithathvi A, Choudhari N, Dsouza HS. Prenatal and early life lead exposure induced neurotoxicity. Hum Exp Toxicol. 2024;43. doi:10.1177/09603271241285523.
Dórea JG. Environmental exposure to low-level lead (Pb) co-occurring with other neurotoxicants in early life and its effects on children's neurodevelopment. Environ Res. 2019;177:108641. doi:10.1016/j.envres.2019.108641.
Chen WW, Zhang X, Huang WJ. Neural stem cells in lead toxicity. Eur Rev Med Pharmacol Sci. 2016;20(24):5174–5177.
Taylor CM, Kordas K, Golding J, Emond AM. Effects of low-level prenatal lead exposure on child IQ at 4 and 8 years in a UK birth cohort study. Neurotoxicology. 2017;62:162-169. doi:10.1016/j.neuro.2017.07.003.
Garry VF, Truran P. Teratogenicity. In: Gupta RC, ed. Reproductive and Developmental Toxicology. Academic Press; 2011:961-970.
Corbo D, Gasparotti R, Renzetti S. Exploring the neural correlates of metal exposure in motor areas. Brain Sci. 2025;15(7):679. doi:10.3390/brainsci15070679.
Llop S, Lopez-Espinosa M, Rebagliato M, Ballester F. Gender differences in the neurotoxicity of metals in children. Toxicology. 2013;311(1-2):3-12. doi:10.1016/j.tox.2013.04.015.
Joo H, Choi JH, Burm E, et al. Gender difference in the effects of lead exposure at different time windows on neurobehavioral development in 5-year-old children. Sci Total Environ.
Singh G, Singh V, Sobolewski M, Cory-Slechta DA, Schneider JS. Sex-dependent effects of developmental lead exposure on the brain. Front Genet. 2018;9:89. doi:10.3389/fgene.2018.00089.
Shvachiy L, Amaro-Leal A, Machado F, Rocha I, Outeiro TF, Geraldes V. Gender-specific effects on the cardiorespiratory system and neurotoxicity of intermittent and permanent low-level lead exposures. Biomedicines. 2024;12(4):711. doi:10.3390/biomedicines12040711.
Joo H, Choi JH, Burm E, et al. Corrigendum to "Gender difference in the effects of lead exposure at different time windows on neurobehavioral development in 5-year-old children." Sci Total Environ. 2018;644:1648. doi:10.1016/j.scitotenv.2018.08.290.
Bishnoi IR, Ossenkopp KP, Kavaliers M. Sex and age differences in locomotor and anxiety-like behaviors in rats: from adolescence to adulthood. Dev Psychobiol. 2021;63(3):496-511. doi:10.1002/dev.22037.
Kasten-Jolly J, Pabello N, Bolivar VJ, Lawrence DA. Developmental lead effects on behavior and brain gene expression in male and female BALB/cAnNTac mice. Neurotoxicology. 2012;33(5):1005-1020. doi:10.1016/j.neuro.2012.04.017.
Lisboa SFD, Gonzalves G, Komatsu F, Queiroz CAS, Almeida AA, Moreira EG. Developmental lead exposure induces depressive-like behavior in female rats. Drug Chem Toxicol. 2005;28(1):67-77. doi:10.1081/DCT-39696.
Molendijk ML, de Kloet ER. Immobility in the forced swim test is adaptive and does not reflect depression. Psychoneuroendocrinology. 2015;62:389-391. doi:10.1016/j.psyneuen.2015.08.028.
Anderson DW, Mettil W, Schneider JS. Effects of low-level lead exposure on associative learning and memory in the rat: influences of sex and developmental timing of exposure. Toxicol Lett. 2016;246:57-64. doi:10.1016/j.toxlet.2016.01.011.
Jett DA, Kuhlmann AC, Farmer SJ, Guilarte TR. Age-dependent effects of developmental lead exposure on performance in the Morris water maze. Pharmacol Biochem Behav. 1997;57(1-2):271-279. doi:10.1016/S0091-3057(96)00350-4.
Gundacker C, Hengstschläger M. The role of the placenta in fetal exposure to heavy metals. Wien Med Wochenschr. 2012;162(9-10):201-206. doi:10.1007/s10354-012-0074-3.
Neda AN, Fahimeh S, Tahereh ZK, et al. Lead level in umbilical cord blood and its effects on newborns' anthropometry. J Clin Diagn Res. 2017;11(6):SC01-SC04. doi:10.7860/JCDR/2017/24865.10016.
Scallet AC, Meredith JM. Quantitative three-dimensional reconstruction: feasibility for studies of sexually dimorphic hypothalamic development in rats. Neurotoxicol Teratol. 2002;24(1):81-85. doi:10.1016/S0892-0362(01)00189-1.
Miller AA, De Silva TM, Jackman KA, Sobey CG. Effect of gender and sex hormones on vascular oxidative stress. Clin Exp Pharmacol Physiol. 2007;34(10):1037-1043. doi:10.1111/j.1440-1681.2007.04732.x.
Abdelouahab N, Mergler D, Takser L, et al. Gender differences in the effects of organochlorines, mercury, and lead on thyroid hormone levels in lakeside communities of Quebec (Canada). Environ Res. 2008;107(3):380-392. doi:10.1016/j.envres.2008.01.006.
