الفهرس 
ACKNOWLEDGEMENT
DEVELOPMENT AND MATURATION OF THETESTISOnly 14 pages are availabe for public view
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Abstract
Human testis comprises two interacting compartments: seminiferous tubules and interstitial tissue. There is still unexplained complex interrelationship between the spermatogenic cells and interstitial cells .Aim of the work
Male infertility continues to be a highly prevalent condition. Although assisted reproduction technology (ART) is effective, it is costy. The present work was done to study the histological, ultrastructural, and immunohistochemical profiles of testicular interstitial tissue in obstructive azoospermia patients (OA) compared to non-obstructive azoospermia patients (NOA) and to understand more about microenvironment of testis trying to find a clue for therapy.
Patients and methods
This study was carried out on 39 infertile azoospermic men aged 25 to 35 years, attending the Andrology outpatient clinic in Assuit University Hospital. Patients were divided into two groups.GroupI (GI): Obstructive azoospermia (n:9).GroupII (GII): Non obstructive azoospermia (NOA) were subdivided into: GIIA: Sertoli cell-only syndrome (n:9),GIIB: Germ cell arrest (n:10), GIIC: Hypospermatogenisis (n:11). Hormonal evaluation was done.Testicular biopsies were obtained and processed for light, immunohistochemical, morphometric analysis and electron microscopic examinations.
Results
It was observed that light microscopic examination of (GI)OA showed normal spermatogenesis and interstitial tissueregarding cellular and fibrous componentswithfew collagen and reticular fibers deposition in the interstitium. In GIIA; (SCO), the tubules have thickened basement membrane surrounded by laminae of peritubular myoid cells, densely stained rounded and slender shaped nuclei.In GIIB, Leydig cells showed degenerative changes in the form of irregullary shaped nuclei with peripheral chromatin margination. In GIIC,the peritubular tissue showed increase collagen fibers which appeared in the form of multilayers .Leydig cells aggregated in close contact to peritubular myoid cells. They had pale nuclei and vacuolated cytoplasm.
Morphometric results showed thatPeritubular mast cells showed significant increasein GIIA compared to GI .The mean count of total positive CD68 macrophages showed non-significant increase in cases of OA (GI) compared to other groups of NOA.The mean count of TNFα positive cell showed significant increase in GIIA comparedto GI.The mean area% of collagen fibers increased significantly in GIIA,GIIBGIIC compared to GI.
Testosterone, LH serum levels were within the normal range in the OA and NOA groups of patients.Concerning FSH level, significant increase was detected in GIIA compared to GI andsignificant decrease in GIIC compared to GIIA.
Electron microscopic examination showed that in GIIA undulated tubular basement membrane surrounded by altered morphological characters of peritubular myoid cells andhyperactive Leydig cells.A predominance of peritubular mast cells establishing cytoplasmic projections towards peritubular cells was observed.Thetubular basement membrane in GIIB showed multilayer appearance with bundles of microfibrilspresent next to the first layer of peritubular myoid cells. Apoptotic changes in Leydig cells were observed. GIIC was characterized byincreased deposition of extracellular matrix components,euchromatic Leydig cells and apoptotic bodieswhich were encountered in messy manner surrounded by macrophages and mast cells.
Conclusion:
• Complex cell interactions betweeninterstitium and the germinal epithelium communicated through healthy ECM.
• Tumor necrosis factor-alpha (TNF-α) secreted by macrophages and mast cells is one of the most important pro-inflammatory cytokines which plays a central role in the inflammatory response related to interstitial tissue injury.
• Apoptosis found in theinterstitium in cases of NOA might result from fibrotic ischemic changeswhich in turn was a mirror for the disturbed relationshipbetween germ and interstitial cells.
Recommendations:
• More studies are necessary to investigate the role ofhypothalamic pituitary testicular axis as a central structure controlling gonadal function and its relation to the morphological changes of testicular interstitium in cases of azoospermia.
• The mast cells could be involved in the etiology of fibrotic changes occurring in infertile patients. Therefore, mast cell blockers may have a role in the treatment of infertility.Further population-based studies are required to examine this possibility.
Applying new therapeutic trends as the use ofTNF-αsuppressor to reduce inflammation and subsequent fibrosis.