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Prenatal double-hit with aluminium and cadmium mediate testicular atrophy and hypothalamic hypoplasia: the role of oxido-nitrergic stress and endocrine perturbations

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Abstract

There is limited experimental evidence on the biochemical consequences of aluminium (Al) and cadmium (Cd) co-exposures during pregnancy and postnatal life.This study investigated the impacts of perinatal Al chloride (AlCl3) and Cd chloride (CdCl2) co-exposures on neuroendocrine functions in mice offspring during postnatal life. The study comprised of four pregnant experimental groups. Group 1 received AlCl3 (10 mg/kg), group 2 were administered CdCl2 (1.5 mg/kg), while group 3 received both AlCl3 (10 mg/kg) and CdCl2 (1.5 mg/kg) (AlCl3+CdCl2), and group 4 received saline (10 mL/kg) only and served as control group. All experimental animals were chemically exposed once daily from gestation days 7–20. Upon delivery, male pups were regrouped based on maternal chemical exposure on postnatal day 21 (PND 21) and allowed to grow to adulthood until PND 78, after which they were sacrificed for assessment of neuroendocrine markers and histological investigations. There was no statistical significance (p > 0.05) on follicle stimulating hormone, testosterone, estrogen and progesterone, thyroid stimulating hormone, thyroxine (T4) in all treatment groups relative to controls|. However, AlCl3 and AlCl3-CdCl2 significantly (p < 0.05) reduced triiodothyronine (T3) levels, with a profound increase in T3:T4 ratio by AlCl3, and AlCl3+CdCl2 compared to control. Furthermore, pups from pregnant mice treated with CdCl2 and AlCl3+CdCl2 demonstrated increased testicular malondialdehyde concentration with increased catalase activity relative to controls, suggesting oxidative imbalance. In addition, AlCl3, CdCl2, and AlCl3+CdCl2 exposures induced testicular and hypothalamic architectural disruption compared to controls, with marked architectural derangement in the AlCl3+CdCl2 group. Our findings suggest that prenatal co-exposures to Alcl3 and CdCl2 induce testicular and hypothalamic alterations in offspring via a testicular oxidative stress and thyrotoxicosis-dependent mechanisms.

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Funding

This study did not receive any form of sponsorship or external funding.

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Authors and Affiliations

  1. Department of Biochemistry, Faculty of Science, Delta State University, Abraka, Nigeria

    Emmanuel Okhue, Helen Ejiro Kadiri, Patrick Chukwuyenum Ichipi-Ifukor, Samuel Ogheneovo Asagba & Fidelis Ifeakachuku Achuba

  2. DELSU Joint Canada-Israel Neuroscience and Biopsychiatry Laboratory, Department of Pharmacology, Faculty of Basic Medical Sciences, Delta State University, Abraka, Nigeria

    Benneth Ben-Azu

  3. Department of Anatomy, Faculty of Basic Medical Sciences, Novena University, Ogume, Nigeria

    John Chukwuma Oyem

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  1. Emmanuel Okhue
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  2. Helen Ejiro Kadiri
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  5. Samuel Ogheneovo Asagba
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Contributions

PCI and EO conceptualized and carried out the experiment, JCO carried out histological and data analysis, PCI and EO wrote the initial draft, BB carried out literature search and improved conceptual framework, BB and PCI drafted the final manuscript, HEK, SOA and FIA supervised the study and improved initial experimental concepts. Final manuscript was read by all contributing authors and conclusions made were agreed upon.

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Correspondence to Patrick Chukwuyenum Ichipi-Ifukor.

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Okhue, E., Kadiri, H.E., Ichipi-Ifukor, P.C. et al. Prenatal double-hit with aluminium and cadmium mediate testicular atrophy and hypothalamic hypoplasia: the role of oxido-nitrergic stress and endocrine perturbations. Biometals 37, 477–494 (2024). https://doi.org/10.1007/s10534-023-00563-0

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