Male sexual dysfunction and infertility associated with neurological disorders

Normal sexual and reproductive functions depend largely on neurological mechanisms. Neurological defects in men can cause infertility through erectile dysfunction, ejaculatory dysfunction and semen abnormalities. Among the major conditions contributing to these symptoms are pelvic and retroperitoneal surgery, diabetes, congenital spinal abnormalities, multiple sclerosis and spinal cord injury. Erectile dysfunction can be managed by an increasingly invasive range of treatments including medications, injection therapy and the surgical insertion of a penile implant. Retrograde ejaculation is managed by medications to reverse the condition in mild cases and in bladder harvest of semen after ejaculation in more severe cases. Anejaculation might also be managed by medication in mild cases while assisted ejaculatory techniques including penile vibratory stimulation and electroejaculation are used in more severe cases. If these measures fail, surgical sperm retrieval can be attempted. Ejaculation with penile vibratory stimulation can be done by some spinal cord injured men and their partners at home, followed by in-home insemination if circumstances and sperm quality are adequate. The other options always require assisted reproductive techniques including intrauterine insemination or in vitro fertilization with or without intracytoplasmic sperm injection. The method of choice depends largely on the number of motile sperm in the ejaculate

Sexually Transmitted Disease and Male Infertility: A Systematic Review

Context Theoretically, sexually transmitted diseases (STDs) have the potential to disrupt male fertility; however, the topic remains controversial. Objective To describe the possible association between STDs and male infertility and to explore possible pathophysiologic mechanisms. Evidence acquisition We performed a systematic literature review in accordance with the PRISMA guidelines. PubMed, Embase, and the Cochrane Library were searched for articles published before January 1, 2016, using the MeSH terms for a variety of STDs and infertility. The search was restricted to human studies performed in men and published in English. Studies were included if they contained original data on a possible association or a cause-and-effect relationship between STD and male infertility. Studies were considered only if they included an appropriate control group and/or comprehensive laboratory data. Due to heterogeneity in the literature, a qualitative analysis was performed. Evidence synthesis Relevant studies on Chlamydia trachomatis, genital mycoplasmas, Neisseria gonorrhoeae, Trichomonas vaginalis, and viral infections were identified. For all pathogens, the studies were contradictory and generally of limited quality. In studies confirming an association, there was a tendency for authors to perform multiple analyses without appropriate corrections and to subsequently focus solely on outcomes that seemed to suggest a positive association; however, the body of literature that does not confirm an association between STDs and male infertility is also of inadequate quality. The data regarding possible pathophysiologic mechanisms are inconclusive. Conclusions There may be an association between STDs and male infertility of unknown genesis and possibly with different pathogenic mechanisms for different pathogens. Alternatively, some STDs may cause male infertility, whereas others may not; however, there is hardly a strong correlation. High-quality studies of the subject are needed. Patient summary Sexually transmitted diseases may cause male infertility through unknown mechanisms; however, from the available research, we cannot be sure that there is an association, and more studies are needed

Lpd depletion reveals that SRF specifies radial versus tangential migration of pyramidal neurons

During corticogenesis, pyramidal neurons (~80% of cortical neurons) arise from the ventricular zone, pass through a multipolar stage to become bipolar and attach to radial glia[superscript 1, 2], and then migrate to their proper position within the cortex[superscript 1, 3]. As pyramidal neurons migrate radially, they remain attached to their glial substrate as they pass through the subventricular and intermediate zones, regions rich in tangentially migrating interneurons and axon fibre tracts. We examined the role of lamellipodin (Lpd), a homologue of a key regulator of neuronal migration and polarization in Caenorhabditis elegans, in corticogenesis. Lpd depletion caused bipolar pyramidal neurons to adopt a tangential, rather than radial-glial, migration mode without affecting cell fate. Mechanistically, Lpd depletion reduced the activity of SRF, a transcription factor regulated by changes in the ratio of polymerized to unpolymerized actin. Therefore, Lpd depletion exposes a role for SRF in directing pyramidal neurons to select a radial migration pathway along glia rather than a tangential migration mode.Ruth L. Kirschstein National Research Service Award (grant F32- GM074507)National Institutes of Health (U.S.) (grant # GM068678

TGA2 signaling in response to reactive electrophile species is not dependent on cysteine modification of TGA2

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Reactive electrophile species (RES), including prostaglandins, phytoprostanes and 12-oxo phytodienoic acid (OPDA), activate detoxification responses in plants and animals. However, the pathways leading to the activation of defense reactions related to abiotic or biotic stress as a function of RES formation, accumulation or treatment are poorly understood in plants. Here, the thiol-modification of proteins, including the RES-activated basic region/leucine zipper transcription factor TGA2, was studied. TGA2 contains a single cysteine residue (Cys186) that was covalently modified by reactive cyclopentenones but not required for induction of detoxification genes in response to OPDA or prostaglandin A1. Activation of the glutathione-S-transferase 6 (GST6) promoter was responsive to cyclopentenones but not to unreactive cyclopentanones, including jasmonic acid suggesting that thiol reactivity of RES is important to activate the TGA2-dependent signaling pathway resulting in GST6 activation We show that RES modify thiols in numerous proteins in vivo, however, thiol reactivity alone appears not to be sufficient for biological activity as demonstrated by the failure of several membrane permeable thiol reactive reagents to activate the GST6 promoter.Peer reviewedFinal Published versio

Multiple needle‐pass percutaneous testicular sperm aspiration as first‐line treatment in azoospermic men

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/144689/1/andr12143_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/144689/2/andr12143.pd

Patient‐reported outcomes from a single‐centre prospective post‐marketing study on Collagenase Clostridium Histolyticum injections for Peyronie’s disease

The aim of this study was to evaluate patient‐reported outcomes of Collagenase Clostridium Histolyticum (CCHi) for Peyronie’s Disease. Patients treated with 2–4 cycles of CCHi between 01/2016 and 08/2018 were asked to fill out the “bother domain” of the Peyronie’s Disease Questionnaire (PDQ) at scheduled appointments for injections. CCHi cycles involved two injections (0.58 mg) separated by 48–72 hr. During the study, 34 patients were treated, seven patients were excluded due to incomplete baseline values. Mean (standard deviation) PDQ bother domain baseline score was 11.1 (2.6). ANOVA demonstrated statistically significant effects of injections (p < .001) with a decrease in PDQ bother domain scores 6 weeks after the 1st cycle (9.9 [3.3], p = .013), 6 weeks after the 2nd cycle (8.2 [4.0], p = .009) and 6 weeks after the 3rd cycle (6.5 [3.6], p < .001). After 2–4 cycles of CCHi treatment, patients reported changes in penile curvature as “Worse” (0), “No Change” (2), “Little decrease” (10), Decrease (10) and “Significant decrease” (4). After completion of CCHi treatment, 82% of patients still reported that vaginal intercourse was difficult or impossible. Patients with Peyronie’s Disease undergoing CCHi treatment reported statistically significant decreases in PDQ bother domain scores. However, most patients still report difficulty with intercourse after treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163382/2/and13733_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163382/1/and13733.pd

Sonic hedgehog expression in zebrafish forebrain identifies the teleostean pallidal signaling center and shows preglomerular complex and posterior tubercular dopamine cells to arise from shh cells

Ventralization, a major patterning process in the developing vertebrate neural tube (central nervous system, CNS), depends on Sonic hedgehog (SHH) as a main signaling morphogen. We studied the CNS of late larval and young adult zebrafish in a transgenic shh‐GFP line revealing increased neuroanatomical detail due to the progressed differentiation state compared to earlier stages. Some major findings emerge from the present study. (a) shh –GFP is still expressed along the adult zebrafish CNS neuraxis in most locations seen in larvae. (b) We newly identify a ventroposterior shh pallidal domain representing the basal telencephalic signaling center important for basal ganglia development known in other vertebrates (i.e., the anterior entopeduncular area—basal medial ganglionic eminence of mammals). (c) We further show late‐emerging shh‐GFP positive radial glia cells in the medial zone of the dorsal telencephalon (i.e., the teleostan pallial amygdala). (d) Immunostains for tyrosine hydroxylase demonstrate that there is selective colocalization in adult dopamine cells with shh‐GFP in the posterior tuberculum, including in projection cells to striatum, which represents a striking parallel to amniote mesodiencephalic dopamine cell origin from shh expressing floor plate cells. (e) There is no colocalization of shh and islet1 as shown by respective shh‐GFP and islet1‐GFP lines. (f) The only radially far migrated shh‐GFP cells are located in the preglomerular area. (g) There are no adult cerebellar and tectal shh‐GFP cells confirming their exclusive role during early development as previously reported by our laboratory

Current opinions on the management of prolonged ischemic priapism: does penoscrotal decompression outperform corporoglanular tunneling?

Prolonged ischemic priapism presents a treatment challenge given the difficulty in achieving detumescence and effects on sexual function. To evaluate current practice patterns, an open, web-based multi-institutional survey querying surgeons' experience with and perceived efficacy of tunneling maneuvers (corporoglanular tunneling and penoscrotal decompression), as well as impressions of erectile recovery, was administered to members of societies specializing in male genital surgery. Following distribution, 141 responses were received. Tunneling procedures were the favored first-line surgical intervention in the prolonged setting (99/139, 71.2% tunneling vs. 14/139, 10.1% implant, p &lt; .001). Although respondents were more likely to have performed corporoglanular tunneling than penoscrotal decompression (124/138, 89.9% vs. 86/137, 62.8%, p &lt; .001), penoscrotal decompression was perceived as more effective among those who had performed both (47.3% Very or Extremely Effective for penoscrotal decompression vs. 18.7% for corporoglanular tunneling; p &lt; .001). Many respondents who had performed both tunneling procedures felt that most regained meaningful sexual function after either corporoglanular tunneling or penoscrotal decompression (33/75, 44.0% vs. 33/74, 44.6%, p = .942). While further patient-centered investigation is warranted, this study suggests that penoscrotal decompression may outperform corporoglanular tunneling for prolonged priapism, and that recovery of sexual function may be higher than previously thought after tunneling procedures

Two randomised phase II trials of subcutaneous interleukin-2 and histamine dihydrochloride in patients with metastatic renal cell carcinoma

Histamine inhibits formation and release of phagocyte-derived reactive oxygen species, and thereby protects natural killer and T cells against oxidative damage. Thus, the addition of histamine may potentially improve the efficacy of interleukin-2 (IL-2). Two randomised phase II trials of IL-2 with or without histamine dihydrochloride (HDC) in patients with metastatic renal cell carcinoma (mRCC) were run in parallel. A total of 41 patients were included in Manchester, UK and 63 in Aarhus, Denmark. The self-administered, outpatient regimen included IL-2 as a fixed dose, 18 MIU s.c. once daily, 5 days per week for 3 weeks followed by 2 weeks rest. Histamine dihydrochloride was added twice daily, 1.0 mg s.c., concomitantly with IL-2. A maximum of four cycles were given. The Danish study showed a statistically significant 1-year survival benefit (76 vs 47%, P=0.03), a trend towards benefit in both median survival (18.3 vs 11.4 months, P=0.07), time to PD (4.5 vs 2.2 months, P=0.13) and clinical benefit (CR+PR+SD) (58 vs 37%, P=0.10) in favour of IL-2/HDC, whereas the UK study was negative for all end points. Only three patients had grade 4 toxicity; however, two were fatal. A randomised phase III trial is warranted to clarify the potential role of adding histamine to IL-2 in mRCC