Summary
Varicocele has an incidence of 4.4%–22.6% in the general population. It is likely multi-factorial and the exact mechanism of its occurrence is unclear.
Varicocele has detrimental effects on spermatogenesis and testicular function and induces a number of changes in the testicular microenvironment. Hyperthermia and alterations in the hemodynamics, venous pressure, testicular blood flow, hormonal imbalance, toxic substances, reactive oxygen species, antioxidant concentrations, which are present in varicocele, have been implicated to produce deleterious effects on spermatogenesis with a progressive decrease in testicular activity.
Varicocele due to its adverse effects is considered to be a sort of inflammation which increases the number of activated leukocytes with increased cytokines secretion. The elevated levels of pro-inflammatory cytokine and oxidative stress may contribute to the pathophysiology of the infertility in men with varicocele.
Adiposity, obesity with an excessive growth of adipose tissue, is associated with increased macrophage infiltration in white adipose tissue and contributes to the chronic low-grade subclinical inflammation and the dysregulated elevated secretion of adipokines, most of them are of the proinflammatory type as TNF-α, IL-6, resistin, leptin, visfatin, and others. Adipokines can modify many obesity related diseases, including reproductive functions.
The reproductive system is tightly coupled with energy balance. Thus, adipokines are considered to be a link between reproduction and energy metabolism and partly explain some infertility problems related to obesity. Adipokines such as resistin, adiponectin, ghrelin and leptin are involved in the close relationship between reproductive function and energy status and are able to regulate the functions of male gonads and of the hypothalamic-pituitary axis. They modulate steroidogenesis of gonadic somatic cells, germ cell maturation and secretion of gonadotrope hormones in various species.
Resistin is an adipose-tissue-specific secretory factor. In humans, macrophages, monocytes and peripheral blood mononuclear cells are the key producers of resistin and its production is dramatically induced by inflammatory stimuli. It has pro-inflammatory effects on different body cells. It has a hormonal impact upon the testes and its association with inflammation draw the attention of andrologists to this adipocytokine as the variety of signaling mechanisms by which resistin exerts its biological effects are incompletely understood.
TNF-α is a powerful proinflammatory cytokine that is made primarily by activated monocyte, macrophages, also it can be produced by a broad variety of cell types. In male reproductive system, together with its proinflammatory effects, it acts on the androgenic receptor regulating testosterone activity, influences spermatogenesis and sperm function by multiple mechanisms.
The aim of this study was to evaluate the serum and seminal plasma resistin and TNF-α levels and their correlations with semen quality in obese and non-obese patients with varicocele.
This study is a cross sectional study carried out on eighty clinically and ultrasonography diagnosed varicocele patients. They were selected from those attending the Outpatient Clinic of the Dermatology & Andrology Department, Benha University Hospital during the period from January 2016 to December 2016. All patients were above 18 years old.
Any patient presented with any of the following conditions was excluded from this study including diabetes mellitus or hypertension, hepatic and/or renal impairment, any endocrinal diseases, history of surgical repair of varicocele or intake of anti-hyperlipidemic drugs within one year prior to the study.
Patients were divided into 2 groups according to their BMI:
Group 1: Forty non-obese patients with varicocele of any grade and their BMI were 30 kg/m2.
All of them were subjected to written informed consent, complete history taking, local examination, scrotal Doppler, determination of obesity-associated markers, semen analysis, blood samples and determination of resistin and TNF-α concentrations in their serum and seminal plasma by commercially available human resistin ELISA kits and human TNF-α ELISA kits.
The results of this study showed that the age and BMI were significantly higher in obese than non-obese patients. Left varicocele was found in all the eighty patients while right varicocele was reported in twenty five out of forty non-obese patients and fifteen out of forty obese patients.
Obesity has no effect on sperm parameters as the differences between non-obese and obese varicocele patients as regards the seminal volume, total sperm count, sperm concentration, percentage of sperms with abnormal forms, pus cells percentage and motility were found to be of no significance.
Both resistin and TNF-α were detected in the serum and seminal plasma of all patients.
Serum resistin levels were found to be four folds higher in obese than in non-obese patients. In seminal plasma resistin levels showed significant difference between obese and non-obese patients being higher in obese than in non-obese patients.
There is a significant difference found between resistin levels in both serum and seminal plasma, being higher in seminal plasma than in serum whether the patients are obese or non-obese.
TNF-α has higher levels in serum and seminal plasma of obese than non-obese patients but with no statistical significance.
There was a positive significant correlation between resistin and TNF-α levels in the seminal plasma of all patients either non-obese or obese.
In patients having pus cells in their semen samples, it was found that both seminal plasma resistin and TNF-α levels were significantly higher in pus positive patients, both obese and non-obese, than those having no pus cells in their semen analysis.
The seminal plasma resistin levels were significantly higher in patients with poor progressive motility than those having good progressive motility.
It was found that obese patients having poor sperm progressive motility had significantly higher levels of seminal plasma resistin compared to those with good sperm progressive motility while there were no differences between seminal plasma resistin levels and sperm progressive motility either good or poor in non-obese patients.
In obese pateints, the seminal plasma resistin and TNF- α levels were significantly higher in smokers than non-smokers. In non-obese patients, the seminal plasma resistin and TNF-α levels were higher in smokers than non-smokers but with no significant differences
conclusion
The existence of higher levels of both resistin and TNF-α in the seminal plasma of patients having leukocytospermia either obese or non-obese support the link between resistin, TNF-α and inflammation and suggest that resistin and TNF-α are potential regulators of inflammation in the male reproductive system and could be considered as local markers of inflammation.
The association which was found between the increased levels of seminal plasma resistin and factors known to be associated with inflammation as varicocele, obesity, smoking and the presence of pus cells in patient’s semen add more support to the link between resistin and inflammation and suggest that resistin is a potential regulator of inflammation rather than having just a metabolic role in humans.
Although both serum and seminal plasma resistin levels are higher in obese than in non-obese varicocele patients, the relation between resistin and obesity may be related to inflammation induced by obesity as macrophages rather than adipocytes are the major source of resistin production in humans.
The presence of resistin in higher levels in seminal plasma than in serum whether the patients were obese or non-obese points to the suggestion that obesity is not the only determinant of resistin production but other factor as varicocele could be incriminated in that issue.
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