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

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 (AlCl) and Cd chloride (CdCl) co-exposures on neuroendocrine functions in mice offspring during postnatal life. The study comprised of four pregnant experimental groups. Group 1 received AlCl (10 mg/kg), group 2 were administered CdCl (1.5 mg/kg), while group 3 received both AlCl (10 mg/kg) and CdCl (1.5 mg/kg) (AlCl+CdCl), 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, AlCl and AlCl-CdCl significantly (p < 0.05) reduced triiodothyronine (T3) levels, with a profound increase in T3:T4 ratio by AlCl, and AlCl+CdCl compared to control. Furthermore, pups from pregnant mice treated with CdCl and AlCl+CdCl demonstrated increased testicular malondialdehyde concentration with increased catalase activity relative to controls, suggesting oxidative imbalance. In addition, AlCl, CdCl, and AlCl+CdCl exposures induced testicular and hypothalamic architectural disruption compared to controls, with marked architectural derangement in the AlCl+CdCl group. Our findings suggest that prenatal co-exposures to Alcl and CdCl induce testicular and hypothalamic alterations in offspring via a testicular oxidative stress and thyrotoxicosis-dependent mechanisms.