الفهرس 
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Abstract
A sexually active couple experiences infertility if they fail to reproduce within one year after having frequent, unprotected sex. There are about 15% of couples suffering from infertility globally with male aspect infertility accounting for 50% of instances. Male infertility can have a recognized or unknown origin, with 30 to 50 percent of instances being idiopathic. iOAT is characterized by an inexplicable decline in a male’s sperm quality, like count and motility, and an increase in aberrant sperm morphology, and without any clear actual disease or endocrine conditions. Environmental occurrence to harmful compounds, notably toxic metals, is frequently linked to impaired reproductive function. The HPG pathway, testicular function, sperm production, and sperm trafficking are all affected by heavy metal toxicity.
Cadmium is found in tobacco smoke and is emitted into the environment during different industrial processes such as metal smelting and battery manufacturing. An elevated level of cadmium intake, above the standard level causes toxic effects on the tissues especially the testes. Studies of cadmium toxicity have introduced it as one of the well-known reproductive toxicants. In humans, elevated cadmium levels were detected in infertile men subjected to chronic environmental-relevant cadmium. It is known that Cd which is reproductive toxin can damage the HPG pathway. According to some theories, cadmium produces more sperm DNA damage and lowers the numbers and concentration of sperm.
The aim of the present study was directed to investigate the possible mechanisms by which Cd may induce toxicity in male reproductive organs and sperm through its effect on lncRNAs ENST00000414355 and MT1DP, the DNA damage and repair- related genes expression levels and oxidative stress status.
The present study included 45 males divided into two main groups: group I: 13 healthy control fertile males, group II: 32 heavy smokers with idiopathic male infertility. Ten milliliters of venous blood sample was withdrawn from all subjects. This blood sample was divided into two parts:
- The first part was pipetted into a tube containing EDTA for the evaluation of Cd and GSH concentrations.
- The second part was allowed to clot for 30 minutes and then centrifuged at 3000 rpm for separating serum. Serum was stored at -80°C until used for assaying MT1, MDA, FSH, LH, testosterone and prolactin concentrations.
- The semen samples were collected from all participants involved in the study, after the seminal parameters analysis. The seminal plasma were separated from the semen by centrifugation and stored at -80°C until used for evaluation of Cd, metallothionein, GSH and MDA concentrations.
- The sperm pellets were used to for assaying the gene expression of sperm lncRNAs MT1DP and ENST00000414355, and mRNAs ATM, ATR, OGG1, RAD 50, XRCC1 and SOD 1.
Our results showed that:
1- The findings of the current research revealed that idiopathic infertile males had Cd concentrations in their blood and seminal plasma significantly higher than did the healthy fertile men. The current investigation showed that the MT1 concentrations in the seminal plasma and serum of the fertile and infertile males were identical.
2- The present study revealed a marked depletion of GSH in the seminal plasma and blood of infertile male compared to healthy fertile male. On the other hand, our study showed a marked elevation in MDA concentrations in the serum and seminal plasma in infertile male paralleled to healthy fertile male. Furthermore, our results revealed that Cd correlated positively with MDA and negatively with GSH
3- The present study showed a decrease in the total and progressive motility in infertile men than in healthy fertile men and a decrease in sperm total count and concentration in infertile men compared to healthy fertile men. Also, the present study showed that there was no correlation between Cd concentration and seminal parameters.
4- The results of the present study illustrated a significant elevation of FSH levels, an increase in Testosterone levels, a slight elevated in LH concentrations, and a slight reduced in prolactin concentrations in infertile men than fertile men.
5- Our results revealed that the abnormal sperm morphology of idiopathic infertile men was significantly upper than healthy fertile men.
6- Our results demonstrated that the relative gene expression of lncRNA ENST00000414355 in sperm of the idiopathic infertile male was elevated than that in the healthy fertile male. The results of the current study showed no association between Cd concentration and the expression of ENST00000414355. The present study revealed that the lncRNA MT1DP expression in sperm of idiopathic infertile men was higher than that of healthy fertile men. The present study exposed that there was no correlation between the expression of MT1DP in sperm and Cd concentration in blood and seminal plasma and this may be due to the same reason previously mentioned.
7- Our study, the expression levels of ATM, ATR are higher in sperm of idiopathic infertile patients than that in healthy fertile men. The present study revealed there was a significant positive association in ENST00000414355 expression and ATM expression. On the other hand, our results revealed no correlation between the expression of ENST00000414355 and ATR expression.
8- The present study indicated that there was a decrease in the expression level of DNA repair genes OGG1and RAD 50 and an increase in the expression level of XRCC1 repair gene in sperm of idiopathic infertile patients than that in healthy fertile men. The present study revealed that there was a significant positive correlation between ENST00000414355 expression and RAD 50 and XRCC1. On the other hand, no correlation found between the expression of ENST00000414355 and OGG1 expression in our study.
9- Our results revealed that the expression level of mRNA of SOD1 in sperm of idiopathic infertile men was elevated than that of healthy fertile men.