Alpha 1 adrenergic receptor-mediated inflammatory responses in human testicular peritubular cells.

Stress activates the sympathetic nervous system and is linked to impaired fertility in man. We hypothesized that catecholamines by acting on testicular cells have a role in these events, possibly by fostering an inflammatory environment. The cells of the wall of seminiferous tubules, human testicular peritubular cells (HTPCs), express adrenergic receptors (ADRs) α1B, α1D, ß1 and ß2. A selective α1-ADR agonist, phenylephrine, increased intracellular Ca2+-levels in cultured HTPCs and induced COX-2, IL-6 and MCP-1 mRNA expression without affecting IL-1ß mRNA. These changes were paralleled by a significant increase in the secretion of IL-6 and MCP-1. Epinephrine was also effective, but salbutamol, a selective ß2-ADR agonist was not. Our results suggest that stress-associated elevation of catecholamines may be able to promote inflammatory events by targeting peritubular cells in the human testis. Blockage of α1-ADRs may therefore be a novel way to interfere with stress-related impairment of male reproductive functions.

ATP-mediated Events in Peritubular Cells Contribute to Sterile Testicular Inflammation.

Peritubular myoid cells, which form the walls of seminiferous tubules in the testis, are functionally unexplored. While they transport sperm and contribute to the spermatogonial stem cell niche, specifically their emerging role in the immune surveillance of the testis and in male infertility remains to be studied. Recently, cytokine production and activation of Toll-like receptors (TLRs) were uncovered in cultured peritubular cells. We now show that human peritubular cells express purinergic receptors P2RX4 and P2RX7, which are functionally linked to TLRs, with P2RX4 being the prevalent ATP-gated ion channel. Subsequent ATP treatment of cultured peritubular cells resulted in up-regulated (pro-)inflammatory cytokine expression and secretion, while characteristic peritubular proteins, that is smooth muscle cell markers and extracellular matrix molecules, decreased. These findings indicate that extracellular ATP may act as danger molecule on peritubular cells, able to promote inflammatory responses in the testicular environment.

No relationship between biopsy sites near the main testicular vessels or rete testis and successful sperm retrieval using conventional or microdissection biopsies in 220 non-obstructive azoospermic men.

In 220 consecutive patients with non-obstructive azoospermia, sperm retrieval was attempted by a combination of conventional and microdissection testicular sperm extraction (TESE). For sperm retrieval, 2-3 conventional biopsies were performed followed by a microdissection TESE in cases of negative conventional biopsies. During the surgery, the vasculature of the testis was assessed using the operative microscope, and the location of positive biopsies was registered in relation to the blood supply. The overall sperm retrieval rate was 58.2%. From the initial conventional biopsies, sperm could be retrieved in 46.8% of the patients. With microdissection TESE, sperm could be retrieved from an additional 11.4% of the patients. The further use of microdissection TESE improved the sperm retrieval rate significantly (P=0.017). No significant accumulation of positive biopsies was found towards the rete testis or the main testicular vessels.

Tunica albuginea underlap--a new modification of the Nesbit procedure: description of the technique and preliminary results.

INTRODUCTION: We describe a new surgical technique for the treatment of penile curvature that combines features of the Nesbit procedure with features of tunical plication. U-shaped flaps of tunica albuginea are freed from the corpus cavernosum. The flaps are brought under the remaining tunica albuginea and are fixated with single absorbable sutures. As the defects of the tunica are sealed tightly and with high tensile strength by double layers of tunica albuginea, correction of the abnormal curvature is achieved. AIM: To present our experience with a new surgical technique for the treatment of penile curvature. METHODS: Between 2008 and 2011, 50 patients underwent the underlap technique because of Peyronie's disease (37) or congenital penile deviation (13) in a single center. MAIN OUTCOME MEASURES: Preoperative and postoperative evaluation included the Erection Hardness Score (EHS) and the Symptom Score for Induratio penis plastica (IPP-SSC), a symptom score for penile deviation that was based on a consensus of regional andrologists. Clinical data concerning the early postoperative outcome were analyzed retrospectively using standardized items. RESULTS: Mean age ± standard deviation was 59.7 ± 8.4 years for patients with Peyronie's disease and 34.1 ± 7.8 years for patients with congenital penile deviation. The mean follow-up period was 27 months. The major complication rate was 4%, overall satisfaction 86%. Intraoperative correction of the curvature was achieved in 100%, significant relapse occurred in 6%. The mean difference of preoperative and postoperative IPP-SSC was 8.1 (95% confidence interval [CI] 7.24 to 8.96). The mean difference of preoperative and postoperative EHC was -0.03 (95% CI -0.16 to 0.09). CONCLUSIONS: Preliminary results obtained with the underlap technique showed promising outcome with minimal morbidity. The new technique might have three main advantages: more flexible intraoperative correctability of the curvature, tighter sealing of the tunical defects, and greater tensile strength of the plications.

Exploring human testicular peritubular cells: identification of secretory products and regulation by tumor necrosis factor-alpha.

Testicular peritubular cells are myofibroblastic cells, which represent the major cellular components of the wall of the seminiferous tubules. In men their phenotypic characteristics, including possible secretory activity and regulation, are not well known, in neither normal nor pathologically altered testes. Especially in testes of men with impaired spermatogenesis, the cytoarchitecture of the tubular wall is frequently remodeled and presents fibrotic thickening, increased innervation, and infiltration by macrophages and mast cells. The latter are two sources of TNF-alpha. The purpose of our study was to explore human testicular peritubular cells and mechanisms of their regulation. To this end we primarily studied cultured human testicular peritubular cells (HTPCs), isolated from adult human testes. Having established that HTPCs express TNF-alpha receptors 1 and 2 and respond to recombinant human TNF-alpha by a rapid phosphorylation of ERK1/2, we used complementary approaches, including gene array/RT-PCR studies, Western blotting/immunocytochemistry, and ELISA techniques to study phenotypic characteristics of HTPCs and actions of TNFalpha. We found that HTPCs express the nerve growth factor gene and TNF-alpha-stimulated mRNA levels and secretion of nerve growth factor in a dose- and time-dependent manner. Similarly, monocyte chemoattractant protein-1 was identified as a product of HTPCs, which was regulated by TNF-alpha in a concentration- and time-dependent manner. TNF-alpha furthermore strongly enhanced expression and/or synthesis of other inflammatory molecules, namely IL-6 and cyclooxygenase-2. Active cyclooxygenase-2 is indicated by increased prostaglandin D2 levels. In addition, intercellular adhesion molecule-1, which was not detected at protein level in the absence of TNF-alpha, was induced upon TNF-alpha stimulation. In conclusion, these results provide novel insights into the nature of human peritubular cells, which are able to secrete potent signaling molecules and are regulated by TNF-alpha. These results also hint to an as-yet-unknown role of peritubular cells in normal human testis and involvement in the pathomechanisms associated with impaired spermatogenesis in men.

Penile corporoplasty using tunica albuginea free graft from proximal corpus cavernosum: a new technique for treatment of penile curvature in Peyronie's disease.

OBJECTIVES: In Peyronie's disease, any kind of plication technique for correcting penile deformities is associated with penile shortening in addition to the disease-related shrinkage. To minimize penile shortening we describe a new technique of penile corporoplasty using a free graft from the tunica albuginea. PATIENTS AND METHODS: From October 2001 to February 2003 we treated 18 patients with the new technique. All patients had stable Peyronie's disease with relevant curvature and sufficient erectile rigidity without any signs of inflammatory disease. Penile corporoplasty was performed by incision of the plaques to produce straightening. The resulting gap was covered with a free graft of tunica albuginea removed from the crural segment of the corpora cavernosa. RESULTS: In a preliminary follow-up of 16 patients, 12 penises were straight and 4 had a residual curvature less than 20 degrees. Two patients needed sildenafil for sufficient penile rigidity. Fourteen of 16 patients were satisfactory with the result of penile straightening. No severe perioperative complication was noted. CONCLUSION: The technique of penile straightening using a free tunica albuginea graft is effective and avoids additional shortening of the penis. As the results are preliminary, the study is continued to gain experience with a larger number of patients.

Sperm retrieval procedures and intracytoplasmatic spermatozoa injection with epididymal and testicular sperms.

INTRODUCTION: Male infertility caused by azoospermia due to non-reconstructable obstruction or non-obstructive azoospermia can be treated by microsurgical epididymal aspiration (MESA) or testicular sperm extraction (TESE) followed by an intracytoplasmatic spermatozoa injection (ICSI). MATERIAL AND METHODS: From 9/93 to 6/01, we carried out 1,025 ICSI procedures with aspirated epididymal or testicular sperms in 684 cases. 163 ICSI cycles were performed with epididymal sperms and 862 ICSI cycles with testicular sperms or spermatids. The TESE was carried out by open biopsy, frequently in a multilocular technique. The aspirated spermatozoas were used after cryopreservation (frozen) or immediately after aspiration (fresh). RESULTS: 538 patients had obstructive azoospermia or ejaculation failure. In 487 cases the underlying cause of azoospermia was an impaired spermatogenesis, following maldescensus testis, chemotherapy, radiotherapy, or caused by Sertoli-cell-only syndrome, a genetic disorder or an unknown etiology. The transfer rates, pregnancy rates and birth rates per ICSI cycle showed no statistically significant differences between testicular and epididymal sperms in the cases of seminal obstruction (28% average birth rates in both cases). However, highly significant was the difference in birth rates with regard to the underlying cause of infertility. In contrast, in treating non-obstructive azoospermia we observed a birth rate of 19% per cycle. In all patient groups the birth rate with fresh spermatozoas did not differ from those with cryopreserved spermatozoa. 40% of patients after multilocular TESE showed clinical signs of testicular lesion. CONCLUSION: The underlying cause of azoospermia is the most important factor for the outcome of ICSI using epididymal and testicular sperms. In cases of non-obstructive azoospermia, the pregnancy rate is low compared with the results in cases of obstructive azoospermia. There is no difference between fresh and cryopreserved sperms. TESE with ICSI is the most efficient treatment of azoospermia caused by hypergonadotropic hypogonadism. The morbidity of the TESE procedure is highly relevant and must be considered if this technique is indicated.