In order to verify the effects of exposure to Cd and Zn on testicular DAAM1 gene and protein expression and also to ascertain their involvement in the protective role of Zn in prevent the testicular toxicity Cd-induced in male offspring rats at adult age after gestational and lactational exposure, male offspring rats, from mothers receiving either tap water, Cd, Zn, or Cd + Zn during gestation and lactation periods, were scarified on postnatal days (PND) 70. The reproductive organ (testis, epididymis, and vesicle seminal) were collected, weighed, and analyzed. The results showed that exposure to Cd in utero and through lactation decreased the relative reproductive organ weight, altered the testicular histology at the interstitial and tubular levels, and causing a significant reduction in the daily sperm production (DSP) per testis and per gram of testis, and other then altering the epididymal sperm quality. Furthermore, both mRNA and protein expression of rat testicular DAAM1 were also inhibited in Cd-treated group. Zn supply has completely corrected the most of these toxic effects. Our results imply that Zn could prevent Cd-induced testicular toxicity and sperm quality alteration in adult male rat after gestational and lactational exposure, probably via the restoration of the testicular DAAM1 expression inhibited by Cd.

Oxidative stress is a major factor involved in the pathogenesis of renal ischemia/reperfusion (I/R). Exogenous zinc (Zn) was suggested as a potent antioxidant; however, the mechanism by which it strengthens the organ resistance against the effects of reactive oxygen species (ROS) is not yet investigated. The present study aims to determine whether acute zinc chloride (ZnCl ) administration could attenuate endoplasmic reticulum (ER) stress, autophagy, and inflammation after renal I/R. Rats were subjected to either sham operation (Sham group, n = 6), or 1 hr of bilateral ischemia followed by 2 hr of reperfusion (I/R groups, n = 6), or they received ZnCl orally 24 hr and 30 min before ischemia (ZnCl group, n = 6). Rats were subjected to 1 hr of bilateral renal ischemia followed by 2 hr of reperfusion (I/R group, n = 6). Our results showed that ZnCl enhances renal function and reduces cytolysis (p < 0,05). In addition, it increased significantly the activities of antioxidant enzymes (SOD, CAT, and GPX) and the level of GSH in comparison to I/R (p < 0,05). Interestingly, ZnCl treatment resulted in significant decreased ER stress, as reflected by GRP78, ATF-6,p-eIF-2α, XPB-1, and CHOP downregulaion. Rats undergoing ZnCl treatment demonstrated a low expression of autophagy parameters (Beclin-1 and LAMP-2), which was correlated with low induction of apoptosis (caspase-9, caspase-3, and p-JNK), and reduction of inflammation (IL-1ß, IL-6, and MCP-1) (p < 0,05). In conclusion, we demonstrated the potential effect of Zn supplementation to modulate ER pathway and autophagic process after I/R.

Highlights Effects of Cd and Zn on testicular development were assessed. Cd accumulation and Zn depletion in testis during lactation were noted. Cd-induced abnormal seminiferous tubules and a plasmatic testosterone decrease. Zn supply induced a significant protection against Cd toxicity. Cd toxicity observed in pups is mediated by disruption of maternal Zn metabolism. *Research Highlights AbstractTo assess the effects of exposure to Cd and Zn on rat testicular development, offspring, from mothers receiving either tap water, Cd, Zn or Cd+Zn during gestation and lactation periods, were observed on gestational day (GD) 20 and on postnatal days (PND) 12, 21 and 35. During gestation, Cd induced maternal hypozincemia and less transfer of Zn to the fetus. During lactation, progressive Cd accumulation and Zn depletion in testis at PND12 and PND21 werenoted. An increase of abnormal seminiferous tubules and a decrease in testis weight and plasmatic testosterone concentration were also observed at PND21 and PND35 respectively. Interestingly, Zn supply induced a significant protection against Cd toxicity. These results suggest that the toxic effects of Cd observed during development are mediated by the disruption of Zn metabolism, which is established in mothers during pregnancy causing Zn deficiency in fetuses and continues to become more pronounced during lactation.

The objective of this study was to determine if the brain development impairment induced by early-life exposure to cadmium (Cd) could result from changes in the expression pattern of distinct zinc (Zn)-dependent proteins. For this purpose, adult female rats receiving either tap water, Cd, Zn, or Cd + Zn in their drinking water during gestation and lactation periods were used. After birth, the male offspring were screened for locomotors and sensorial defects. At postnatal day 21 (PND 21), the male pups were sacrificed and their brains, liver, and plasma were taken for chemical, biochemical, and molecular analyses. Our results show that exposure to Cd significantly increased the metal accumulation and decreased Zn concentrations in the brain of male pups from Cd-treated mothers. Besides, Cd exposure reduced significantly the locomotor activity of the offspring in open-field test, the body weight, and the cranio-caudal length at PND21. Insulin-like growth factor-I (IGF-1) levels in the plasma and liver were also decreased in male pups from Cd-treated mothers. Cd-induced brain development disruption was accompanied by a significant increase of the superoxide dismutase (SOD) activity, induction of the metallothionein (MT) synthesis, and, at the molecular level, by an upregulation of Zrt-,Irt-related protein 6 (ZIP6) gene and a significant downregulation of the expression of the Zn transporter 3 (ZnT3) and brain-derived neurotrophic factor (BDNF) genes in the brain. No significant changes on the expression of genes encoding other Zn-dependent proteins and factors such as ZnT1, ZIP12, NF-κB, and Zif268. Interestingly, Zn supplementation provided a total or partial correction of the changes induced by the Cd exposure. These data indicated that changes in expression of ZnT3 and ZIP6 as well as alteration of other transcription factors, such as BDNF, or Zn-dependent proteins, such as SOD and MTs, in response to Cd exposure might be an underlying mechanism of Cd-induced brain development impairment.