الفهرس 
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Abstract
The inability of a sexually active, non-contraceptive couple to conceive after a year of regular sexual activity is known as infertility. Idiopathic infertility, which affects 30% of cases but is characterised by abnormal semen analysis of unknown otology and normal physical and endocrine laboratory examinations, is one of the major clinical problems that can affect a person in their lifetime.
One of the most well-known reproductive toxins to which people who are exposed at work or in the environment are subject to have detrimental effects on testicular function is cadmium.
The objective of this study is to assess the parameters affecting epigenetics during spermatogenesis.
In this way and following the institutional ethics committee’s approval at the Medical Research Institute of Alexandria University. Before being enrolled in the study, the volunteer participant’s agreement was obtained. 45 males between the ages of 25 and 45 was classified into:
group I: 12 healthy subjects are fertile, with proven fertility, and have at least one child.
group II: 33 patients with idiopathic male infertility were recruited from the Andrology unit of the Dermatology and Andrology department, Alexandria university hospital.
In humans, cd has a potent cumulative effect, and nutrition, age, and smoking all raise an organism’s cd content. Once absorption occurs within the body, Cd uses the process of metallothionine production, a tiny metal-binding protein with a high cysteine content. The thiol group (-SH) of cysteine is the critical target of cadmium.
Recent research suggests that Cd can alter epigenetic processes. The study of heritable changes in gene expression that occur without a change in the DNA sequence is known as epigenetics. The most well-studied epigenetic alteration is DNA methylation, which can sometimes silence MT1A and prevent the MT1A protein from sufficiently cleaving Cd.
Due to biomagnification over time, metals that are deposited in aquatic environments may accumulate in the food chain and harm the ecosystem as well as pose a concern to human health. Heavy metals have been found to accumulate in aquatic creatures’ tissues several times above background levels.
In our study, the concentration of Cd in mussels collected from El-Max Bay was less than the concentration in mussels collected from Abu Qir.
We measured cadmium levels in seminal plasma and blood as part of this investigation to look into a potential common environmental exposure that could partially account for the observed decline in the quality of human semen.
The results of our study revealed a significant increase in the concentration of Cd in the seminal plasma of cases with idiopathic male infertility when compared with the control group.
Blood cadmium levels appear to be predominantly a reflection of exposure. Because Cd has an extremely long biological half-life in humans (between 20 and 40 years) and a very poor rate of elimination, buildup over an extended period of time causes many organs to operate improperly.
The study’s participants might have come into contact with harmful metals in the air, water, food, & smoke. Until the blood-testis barrier is breached by high amounts of toxicant exposure, developing sperm are protected.
Cd causes BTB disruption. Cd targets BTB by causing Sertoli Cell actin filaments to fracture.
Exposure to Cd may lower gamete quality and aneuploidy, and cadmium may impede the ability to reproduce.
In the present study, semen analysis of the studied cases showed that 14% has isolated oligozoospermia, 10% has isolated asthenozoospermia, 3% isolated teratozoospermia, 11% oligoasthenozoospermia, 13% oligoteratozoospermia, 10% asthenoteratozoospermia,13% isolated Oligoasthenoteratozoospermia, and 26% had a normal seminal profile.
Oligoasthenoteratozoospermia (OAT) regarding semen parameters in cases and control group, sperm concentration was significantly decreased in cases compared with the control group. There was a positive significant correlation between sperm count and blood Cd level.
Reduced lipid peroxidation brought on by ROS and the ensuing antioxidant depression (lower TAC) seen in infertile patients may lead to reduced sperm concentration and percentage motility. Sperm function has been proven to be toxically affected by excessive ROS and OS, which impairs sperm motility, concentration, and morphology.
Lower sperm concentration and percentage motility. may result from increased lipid peroxidation induced by ROS and the consequent antioxidant depression (lower TAC)
Impaired motility may result from inhibition of mitochondrial function, decreased axonemal protein phosphorylation, decreased sperm viability, increased mid-piece sperm defects, and sperm immobilization arising from lipid peroxidation.
Cadmium ions show a high affinity for biological structures containing –SH groups (cysteine and glutathione GSH), as well as disulfide –S–S– groups (cystine and reduced glutathione GS-SG), causing disturbance of their functions. The bivalent cadmium cation is unable to generate free radicals directly; however, after cadmium exposure, there is increased production of ROS, namely superoxide radicals, hydrogen peroxide, and hydroxyl radicals. Cadmium induces oxidative stress and the production of ROS that nc normally balanced by the enzymatic (SOD, CAT, GPx) and non-enzymatic (GSH, vitamin C, vitamin E) antioxidative barriers. The xenobiotic-induced oxidative stress results in the oxidation and damage of biologically important macromolecules, such as proteins, DNA, lipids, and cellular membrane phospholipids.
There was a significant positive correlation between TAC and progressive motility, a positive significant correlation between serum MDA and blood Cd level, a negative significant correlation between GSH and Cd level in Both blood and seminal, a positive significant correlation between serum MDA and blood Cd level, and a negative significant correlation between serum TAC and seminal MDA.
Metallothionein expression indicates exposure to certain metals. The existence of metallothionein has at least two main functions cleaning free radical materials in the body and detoxifying metals to reach a state of homeostasis. The induction of metallothionein (MT) expression is involved in metal homeostasis and detoxification.
Our result demonstrated a highly significant increase in MT1 in serum of the infertile group when compared with their control group.
Measurement of MT levels in body fluids can be used as a biological indicator of metal exposure in humans. MT gene identification can be used for early detection of heavy metal exposure in humans. Recent studies indicate that Cd is capable of inducing epigenetic changes. Epigenetics is the study of heritable changes in gene expression without any modification in DNA sequence. The best well-studied epigenetic modification is DNA methylation, 5’MT1A CGI is sometimes methylated, resulting in silencing of MT1A, leading to insufficient cleating of Cd by MT1 protein.
Our result shows that there was a significant increase in the methylated percent of the MT1A gene of the cases group when compared with the control group.
There was a significant negative correlation between MT1A gene methylation and sperm count concentration.