ESSM Newsletter # 40

23 ESSM Today Have you read? Best of the best: Basic research by Nuno Louro Female sexual dysfunction Zhang H, Liu T, Zhou Z et al. mi-R137 Affects vaginal lubrication in female sexual dysfunc- tion by targeting Aquaporin-2. Sex Med. 2018; 6(4): 339-347 Female sexual arousal disorders are very com- mon worldwide but are rarely the subject of basic investigation. The pathophysiology of vaginal lubrication is poorly understood. As the last barrier of vaginal lubrication, epithe- lial tissue is responsible for the transport and rematching of ions, water, and other molecules that play an important role in the formation of vaginal lubricants. Therefore, the role of fluid transport in vaginal lubrication has attracted increasing attention. It has been suggested that microRNAs (miRNAs) play an important role in the regulation of fluid transport. By comparing vaginal samples obtained from 15 women with lubrication disorder and 15 women with normal function, the authors screened differentially expressed miRNAs in women with and without vaginal lubrica- tion disorder by microarray analysis and they found that miR-137 was highly expressed in the vaginal epithelial tissues of women with lubrication problems. Additionally, functional studies in vitro validated the important role of miR-137 in the modulation of vaginal epithe- lial cell water permeability. They suggested that the overexpression of miR-137 might downregulate the expression of aquaporin-2 (AQP2), a key protein in fluid transport in vagi- nal epithelial cells. Decreased expression of AQP2 in vaginal epithelial cells may lead to impaired vaginal epithelial fluid transport ca- pacity, thus inhibiting the secretion of vaginal lubricant, resulting in vaginal lubrication dis- orders. If confirmed in larger samples and in vivo, AQP2 could be manipulated as a thera- peutic target against lubrication disorder and its sexual consequences. Erectile dysfunction Assaly R, Gorny D, Compangnie S, et al. The favorable effect of empagliflozin on erec- tile function in an experimental model of type 2 diabetes. J Sex Med. 2018; 15(9): 1224-1234 Erectile dysfunction is very common in men with Type 2 Diabetes (T2DM), and this is a well-known difficult-to-treat group of patients. Specific sodium/glucose cotransporteur 2 in- hibitors (SGLT-2Is), which are approved for the treatment of T2DM, regulate blood glucose levels by blocking the re-uptake of filtered glucose in the proximal tubule of the kidney, leading to excretion of glucose via the urine. The EMPA-REG Outcome trial results showed that empagliflozin (a SGLT-2I) reduces the car- diovascular and renovascular complications in patients with T2DM. In this study the authors investigated the effects of empagliflozin on ED in a T2DM rat model (male Goto-Kakizaki). 48 GK rats were randomly assigned to 2 ex- perimental groups where they were fed ad libitum over 4 weeks with regular diet or medicated diet (regular diet pre-mixed with empagliflozin) and also compared to age- matched Wistar rats, fed with regular diet. The in vivo effect of empagliflozin on erectile function was assessed by electrical stimulation of the cavernous nerve at different frequencies under anesthesia in the presence or absence of acute intravenous injection of sildenafil. Endothelium-dependent, independent, and nitrergic relaxations of cavernosal strips from the rats were studied. The results showed a beneficial effect of chronic empagliflozin in erectile function, and although the potential mechanism could not be elucidated, it could be associated with an improvement in the im- paired diabetes-induced nitrergic relaxations of the corpus cavernosum in GK rats and partly attributable to an attenuation of the diabetes- related inflammation state. It would be very interesting to investigate if this positive effect is also seen in humans. Nunes KP, de Oliveira AA, Szasz T, et al. Block- ade of toll-like receptor 4 attenuates erec- tile dysfunction in diabetic rats. J Sex Med. 2018; 15(9): 1235-1245 An emerging body of evidence suggests that toll-like receptor (TLR4), an important component of the innate immunity, mediates vascular dysfunction. The hypothesis that the TLR4 pathway participates in the development and maintenance of vascular pathologies has gathered wide support but, despite advance- ment in the understanding of TLR4 signaling transduction, the precise model of interaction between this receptor with its ligands is still a debatable issue. This group has previously demonstrated that TLR4 activation contributes to diabetic bladder dysfunction and hyper- tension-associated ED. In the current study, the authors aimed at determining not only if TLR4 regulates penile vascular tone but also whether this receptor mediates ED in vivo in a rodent model of diabetes. Streptozotocin- induced diabetic rats received a daily intra- peritoneal injection of an anti-TLR4 antibody. Control animals (CTL) were injected with vehicle alone. Additionally, cavernosal strips were acutely incubated for 30 minutes with CLI-095, a TLR4 inhibitor. Functional studies, Western blotting, erectile function, immunohis- tochemistry, and biochemical analyses were performed. The results suggest that penile tissue from diabetic rats have higher TLR4 density compared to CTL animals. Functional experiments revealed that the sensitivity to phenylephrine (PE) in diabetic penile tissue decreases not only with the chronic treat- Nuno Louro, MD Department of Urology Hospital of Porto University of Porto Porto, Portugal nunorlouro@gmail.com