## 3 Results and Discussion
### Cd Exposure Schemes
#### 3.2.3 Cd Exposure of Dams during Pregnancy-Lactation Period
Cd administered in drinking water at 50 mg/L from GD 0 to PND 21 altered acetylcholinesterase, Na+-, K+- [14; 40], and Mg2+-ATPase activities [40], while 10 mg Cd/L (estimated as 1 mg/kg bw) by identical administration via decreased serotonin, dopamine, 3,4-dihydroxybenzoic acid [31], glutamate, and \(\gamma\)-aminobutyric acid [30] in different brain zones. This suggest that a Cd concentration five times lower than 50 mg/L also generates also alterations in neurotransmitters content. Both concentrations were administered by other authors using drinking water, they observed structural alterations in brain, such as synapses and neurites in the hippocampus being destroyed [29], sparse arrangement of cells in the hippocampal area, as well as changes in the expression of \(\gamma\)-aminobutyric acid receptor subunits, cognitive deficit [29; 43], impairment of memory, altered exploratory activities, and increased escape latency [43]. Altered exploratory activities was also reported at lower Cd doses (14, 7 and 3.5 mg/kg bw intragastrically) [50] accompanied by changes in spontaneous/evoked physiological functions [15; 50]. Cd modified cocaine [51; 52] and morphine [53] sensitization, and studies of oxidative stress in the brain showed an increase in lipid peroxidation [42], and an increment of thiobarbituric acid reactive substances and elevated activity of superoxide dismutase, glutathione peroxidase, catalase, and glutathione reductase [37]. Overall, the results suggested that maternal Cd exposure could lead to nervous system dysfunction. On the other hand, Cd caused sexual alterations. In male offspring were observed testicular development disorder, decrease in serum testosterone [54], steroid hormones and steroid enzyme, low relative testis weight, disrupted Leydig cells development [55], sperm quality impairment, and increased apoptosis in testis [46; 56]. Histologic studies revealed stromal inflammatory foci and multifocal inflammation increased in ventral prostates [45], and in testis alteration of spermatogenic epithelial [34], and changes in genetic regulation of cytoskeleton related proteins (CORO1A, cofilin 1 and profilin) [57]. Male pups presented increased body weight, reduced anogenital index, and delayed physical and reflex development [58]. In female offspring, authors reported alterations in ovarian granulosa cells, such as lipid droplets smaller than normal and down-regulation of adipose differentiation-related protein, that resulted in a high level of progesterone in serum [59]. Additionally, Cd increased the biosynthesis of steroid hormones by activation of cAMP/PKA pathway and up-regulated steroidogenesis related proteins increasing the levels of steroid hormones and contributingto early puberty onset and promotion of differentiation and maturation of follicles [60]. In contrast, other authors observed impairment in sexual development [33], vaginal opening delay [1,47], irregular estrous cycle [47], inhibition of follicular development, reduction of serum estradiol, and down-regulation of mRNA of genes related to steroidogenesis [1]. The lowest dose of 100 \(\mu\)g/kg b.w. administered in drinking water and estimated from Cd concentration (0.1 mg/L) and water consumption induced alterations in spermatogenic epithelial of testis [34], that compared to the highest dose of 20 mg Cd/kg b.w. administered intragractically demonstrates that Cd-effects on sexual organs can be provoked even at minimal doses. Biochemical effects determined after pregnancy-lactation exposure included hematotoxic effects, diminished Zn and Fe [41], liver injury related to nonalcoholic fatty liver disease development [38], changes in insulin secretion [61], and altered heart morphology accompanied by reduced endothelium-dependent reactivity and increased hem-oxygenase 1 in aortic rings [36].