The wall of the seminiferous tubules contains contractile smooth-muscle-like peritubular cells, thought to be important for sperm transport. Impaired spermatogenesis in men typically involves remodeling of this wall, and we now found that smooth muscle cell (SMC) markers, namely myosin heavy chain (MYH11) and smooth muscle actin (SMA) are often lost or diminished in peritubular cells of testes of men with impaired spermatogenesis. This suggests reduced contractility of the peritubular wall, which may contribute to sub- or infertility. In these cases, testicular expression of cyclooxygenase-2 (COX-2) implies formation of prostaglandins (PGs). When screening different PGs for their ability to target human testicular peritubular cells (HTPCs), only a PG metabolite, 15-deoxy-Delta(12-14)-prostaglandin-J2 (15dPGJ2), was effective. In primary cultures of HTPCs, 15dPGJ2 increased cell size in a reversible manner. Importantly, 15dPGJ2 treatment resulted in a loss of typical differentiation markers for SMCs, namely MYH11, calponin, and SMA, whereas fibroblast markers were unchanged. Collagen gel contraction assays revealed that this loss correlates with a reduced ability to contract. Experiments with an antagonist (bisphenol A diglycidyl ether) and agonist (troglitazone) for a cognate 15dPGJ2 receptor (i.e. peroxisome proliferator-activated receptor-gamma) indicated that peroxisome proliferator-activated receptor-gamma is not directly involved. Rather, the mode of action of 15dPGJ2 involves reactive oxygen species. The antioxidant N-acetylcysteine not only blocked ROS formation but also prevented the increase in cell size and the loss of contractility in HTPCs challenged with 15dPGJ2. We conclude that 15dPGJ2, via reactive oxygen species, influences SMC phenotype and contractility of human peritubular cells and possibly is involved in the development of human male sub-/infertility.

Aim The aim of this official guideline published by the German Society of Gynecology and Obstetrics (DGGG) and coordinated with the German Society of Urology (DGU) and the German Society of Reproductive Medicine (DGRM) is to provide consensus-based recommendations, obtained by evaluating the relevant literature, on counseling and fertility preservation for prepubertal girls and boys as well as patients of reproductive age. Statements and recommendations for girls and women are presented below. Statements or recommendations for boys and men are not the focus of this guideline. Methods This S2k guideline was developed at the suggestion of the guideline commission of the DGGG, DGU and DGRM and represents the structured consensus of representative members from various professional associations (n = 40). Recommendations The guideline provides recommendations on counseling and fertility preservation for women and girls which take account of the patientʼs personal circumstances, the planned oncologic therapy and the individual risk profile as well as the preferred approach for selected tumor entities.

Increased numbers of mast cells (MCs) were described in the testes of males exhibiting infertility many years ago. Since beneficial effects of treatment with MC blockers on impaired male fertility were reported, more attention has been drawn on the role of MCs in the male reproductive tract. The main interest is focused on testicular MCs, however MCs also occur in the epididymis and seminal fluid, which may be relevant for fertility as well. The increase in testicular MCs in close contact to the seminiferous tubules indicates a relationship between MC proliferation and a dysfunction of the blood-testis barrier. Activated MCs not only coincide with fibrotic events, but also with elevated numbers of several types of immune cells in the testes of infertile men and may, therefore, be involved in the pathogenesis of testicular inflammatory processes as well. Outside the testis, MCs have really been assigned a key role in chronic protatitis/chronic pelvic pain syndrome. The occurrence of MCs in the seminal plasma of fertile/infertile men and negative effects on sperm functions has not been clarified so far and require further investigation. Optimistic reports on the beneficial effects of the treatment with MC blockers on disturbed male fertility also warrant further confirmation.

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.

Although sexual-related problems are very prevalent, inadequate training for physicians has been reported. The aim was to investigate the educational situation in sexual medicine, including sexual dysfunctions, gender dysphoria and paraphilia, among German physicians in urology and andrology. Additional, barriers when addressing sexual health issues and confidence in taking care of patients with sexual-related problems were evaluated. A questionnaire was sent to 5955 urologists, urology residents and andrologists throughout Germany. The results of this study emphasise the need for continuing education and training in sexual medicine including sexual dysfunctions (83.9%), gender dysphoria (58.2%) and paraphilia (56.6%). Physicians, especially when working in urology, need basic skills in order to feel confident (89.0% in taking care of patients with sexual dysfunctions, 25.8% with gender dysphoria and 22.9% with paraphilia) and be able to reduce several barriers when addressing sexual health issues. The main reported barriers were lack of time (61.0%), inadequate financial compensation (42.5%), lack of necessity (29.9%) and the assumption of patients feeling uncomfortable (20.9%). It is within the competence of urologists and andrologists to correctly assess the situation and to refer patients to multidisciplinary support, such as psychologists, psychosomatics or couple therapists.