Preclinical Female Model of Urogenital Dysfunction and Pathophysiological Changes After Pelvic Radiation Therapy.

Introduction Radiation therapy (RT) is the gold standard for many pelvic cancers and improves overall patient survival. However, pelvic RT is associated with increased sexual dysfunction and urinary incontinence. Although the side effects of pelvic RT are well-documented, the pathological mechanisms leading to pelvic organ dysfunction are unknown, and a preclinical model has not been established.

Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity.

Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics. To elucidate the basis for these bacteria-independent bladder symptoms, we examined the bladders of patients with rUTI.

Characterizing the innervation of the vulvar vestibule and the immunohistochemical features of neuroproliferative vestibulodynia.

Background: Provoked vestibulodynia (PVD) is a chronic pain condition characterized by allodynia localized to the vulvar vestibule. The finding of increased densities of nerve fibers in the vestibular mucosa of patients with PVD has led to the identification of a neuroproliferative subtype. The etiology of PVD, including neuroproliferative vestibulodynia (NPV), is not fully understood.

In vitro high glucose increases apoptosis, decreases nerve outgrowth, and promotes survival of sympathetic pelvic neurons.

Background: Diabetes mellitus (DM) is a common cause of erectile dysfunction (ED), yet the molecular basis of DM neurogenic ED remains unknown.

Aim: In this study we examined the impact of high glucose on survival and growth of primary cultured pelvic neurons in a rat model and assessed whether coculturing with healthy Schwann cells (SCs) can rescue pelvic neuron growth in patients with DM.

Methods: Major pelvic ganglia (MPGs) from adult male Sprague Dawley rats ( = 8) were dissociated and plated on coverslips.

Patient and provider perspectives on LEEP/LLETZ treatment and outcomes: an interview study.

Background: The loop electrosurgical excision procedure (LEEP) and large loop excision of the transformation zone (LLETZ) effectively treat cervical dysplasia, though some women have reported negative outcomes postoperatively (e.g., sexual dysfunction, psychosexual sequalae).

The contribution of the cervix to sexual response: an online survey study.

Background: The role of the cervix in sexual response has been poorly studied, despite previous research indicating that some women experience pleasurable sexual sensations from cervical stimulation; given previous reports of sexual issues after cervix electrocautery, it is possible that cervical injury may compromise the role of the cervix in sexual functioning.

Aim: The aims of this study were to examine locations of pleasurable sexual sensations, to identify sexual communication barriers, and to investigate if cervical procedures are associated with negative impacts on sexual function.

Methods: Women with (n = 72) and without (n = 235) a history of a gynecological procedure completed an online survey assessing demographics, medical history, sexual function (including locations of sexual pleasure and pain on diagrams), and barriers.

The prostate in women: an updated histological and immunohistochemical profile of the female periurethral glands and their relationship to an implanted midurethral sling.

Background: There is evidence of glandular tissue in the region of the anterior vaginal wall-female periurethral tissue (AVW-FPT) that has similar morphology and immunohistochemistry to the prostate in men. Surgical injury to this tissue has been suggested as a potential cause of sexual dysfunction following midurethral sling (MUS) procedures. However, the anatomy and embryology of these glands have not been fully resolved.

Cocultured Schwann Cells Rescue Irradiated Pelvic Neuron Outgrowth and Increase Survival.

Background: Prostatic radiation therapy (RT) leads to erectile dysfunction by damaging peri-prostatic pro-erectile nerves of the pelvic ganglion. Schwann cells (SC) facilitate neuronal repair after mechanical injury, however, their role in repair of pelvic neurons post-radiation hasn't been explored.

Aim: To determine if SCs cocultured with primary pelvic neurons can rescue neuronal survival and growth after ex vivo RT.

An Innovative Use of Twitter to Disseminate and Promote Medical Student Scholarship During the COVID-19 Pandemic: Usability Study.

Background: Due to the emergence of the COVID-19 pandemic in March 2020, the cancellation of in-person learning activities forced every aspect of medical education and student engagement to pivot to a web-based format, including activities supporting the performance and dissemination of scholarly work. At that time, social media had been used to augment in-person conference learning, but it had not been used as the sole platform for scholarly abstract presentations.

Objective: Our aim was to assess the feasibility of using Twitter to provide a completely web-based forum for real-time dissemination of and engagement with student scholarly work as an alternative to a traditional in-person poster presentation session.

Should We Call It a Prostate? A Review of the Female Periurethral Glandular Tissue Morphology, Histochemistry, Nomenclature, and Role in Iatrogenic Sexual Dysfunction.

Introduction: There is evidence of glandular tissue within the region of the anterior vaginal wall-female periurethral tissue (AVW-FPT) having similar morphology and immunohistochemistry to the prostate in men and having physiological roles in the female sexual response (FSR). Whether this tissue should be called a prostate in women has been debated. Iatrogenic injury to structures of the AVW-FPT, including these glands and the associated neurovasculature, could be a cause of female sexual dysfunction (FSD).

Cardiometabolic Diseases and Female Sexual Dysfunction: Animal Studies.

Background: The association between erectile dysfunction and cardiometabolic disease is well characterized; men are often diagnosed with cardiovascular disease 2-5 years following the incidence of erectile dysfunction. There is evidence that this relationship may also exist for cardiometabolic diseases and female sexual dysfunction (FSD) - particularly sexual arousal disorders.

Aim: To provide a summary of the preclinical literature related to the evidence of FSD in animal models of cardiometabolic diseases and indicate where further research is needed.

Ex vivo Akt inhibition reverses castration induced internal pudendal artery and penile endothelial dysfunction.

Aims: Androgen deprivation therapy is a common prostate cancer treatment which causes men to have castrate levels of testosterone. Unfortunately, most testosterone deficient patients will suffer severe erectile dysfunction (ED) and have no effective ED treatment options. Testosterone deficiency causes endothelial dysfunction and impairs penile vasodilation necessary to maintain an erection.

Dysfunctional voiding behavior and impaired muscle contractility in a rat model of detrusor underactivity.

Aims: Detrusor underactivity (DU) is an understudied health concern with inadequate clinical management. The pathophysiology of DU is unclear, and current therapies fail to improve symptoms. The current studies characterized voiding function and contractility of bladder and urethral tissues in a novel rat model of DU.

Increased Level of Tumor Necrosis Factor-Alpha (TNF-α) Leads to Downregulation of Nitrergic Neurons Following Bilateral Cavernous Nerve Injury and Modulates Penile Smooth Tone.

Background: Erectile dysfunction (ED) after injury to peripheral cavernous nerve (CN) is partly a result of inflammation in pelvic ganglia, suggesting that ED may be prevented by inhibiting neuroinflammation.

Aim: The aim of this study is to examine temporal changes of TNF-α, after bilateral CN injury (BCNI), to evaluate effect of exogenous TNF-α on neurite outgrowth from major pelvic ganglion (MPG), and to investigate effect of TNF-α signal inhibition to evaluate effects of TNF-α on penile tone with TNF-α receptor knockout mice (TNFRKO).

Methods: Seventy Sprague-Dawley rats were randomized to undergo BCNI or sham surgery.

Sex Differences in Pulmonary Eicosanoids and Specialized Pro-Resolving Mediators in Response to Ozone Exposure.

Ozone (O3) is a criteria air pollutant known to increase the morbidity and mortality of cardiopulmonary diseases. This occurs through a pulmonary inflammatory response characterized by increased recruitment of immune cells into the airspace, pro-inflammatory cytokines, and pro-inflammatory lipid mediators. Recent evidence has demonstrated sex-dependent differences in the O3-induced pulmonary inflammatory response.

Impact of prostatic radiation therapy on bladder contractility and innervation.

Aims: To determine the effect of prostatic radiation therapy (RT) on bladder contractility and morphology, and axon, or neuron profiles within the detrusor and major pelvic ganglia (MPG) in male rats.

Methods: Male Sprague-Dawley rats (8 weeks) received a single dose of prostatic RT (0 or 22 Gy). Bladders and MPG were collected 2- and 10-weeks post-RT.

High-fat diet induces obesity in adult mice but fails to develop pre-penile and penile vascular dysfunction.

Obesity can lead to cardiovascular disease, diabetes, and erectile dysfunction (ED), which decreases overall quality of life. Mechanisms responsible for obesity-induced ED are unknown. Current mouse models of high-fat diet (HFD)-induced obesity yield conflicting results.

Ex Vivo Radiation Leads to Opposing Neurite Growth in Whole Ganglia vs Dissociated Cultured Pelvic Neurons.

Background: Prostatic radiation therapy (RT) often causes erectile dysfunction (ED) and the mechanisms governing RT-induced ED are unclear with a lack of therapeutic strategies.

Aim: To determine the effects of ex vivo RT on major pelvic ganglion (MPG) neuron survival, and neurite growth in whole vs dissociated culture.

Methods: MPGs were removed and irradiated (0 or 8 Gy) from male Sprague Dawley rats.

Managing female pelvic floor disorders: a medical device review and appraisal.

Pelvic floor disorders (PFDs) will affect most women during their lifetime. Sequelae such as pelvic organ prolapse, stress urinary incontinence, chronic pain and dyspareunia significantly impact overall quality of life. Interventions to manage or eliminate symptoms from PFDs aim to restore support of the pelvic floor.

Chronic high-fat diet decreased detrusor mitochondrial respiration and increased nerve-mediated contractions.

Aims: To assess the impact of chronic high-fat diet (HFD) on behavioral voiding patterns, detrusor contractility, and smooth muscle mitochondrial function in male mice.

Materials And Methods: Male C57BL/6J mice (6 weeks) were fed a control or HFD for 20 weeks. Bladder function was assessed by void spot assays.

A free-choice high-fat, high-sucrose diet induces hyperphagia, obesity, and cardiovascular dysfunction in female cycling and pregnant rats.

The main objective of these studies was to characterize metabolic, body composition, and cardiovascular responses to a free-choice high-fat, high-sucrose diet in female cycling and pregnant rats. In the nonpregnant state, female Sprague-Dawley rats offered a 3-wk free-choice high-fat, high-sucrose diet had greater energy intake, adiposity, serum leptin, and triglyceride concentrations compared with rats fed with standard chow and developed glucose intolerance. In addition, choice-diet-fed rats had larger cardiac ventricular weights, smaller kidney and pancreas weights, and higher blood pressure than chow-fed rats, but they did not exhibit resistance artery endothelial dysfunction.

Prostate-Confined Radiation Decreased Pelvic Ganglia Neuronal Survival and Outgrowth.

Background: Erectile dysfunction (ED) is common following radiation therapy (RT) for prostate cancer. Although the cause of RT-induced ED is unknown, damage to both the neuronal and vascular components supporting erections are often implicated.

Aim: To determine the effects of prostatic RT on erections, penile vascular physiology, and major pelvic ganglia (MPG) neuron growth and survival in a rat model.

Clarifying the Relative Impacts of Vascular and Nerve Injury That Culminate in Erectile Dysfunction in a Pilot Study Using a Rat Model of Prostate Irradiation and a Thrombopoietin Mimetic.

Purpose: Radiation therapy (RT) offers an important and curative approach to treating prostate cancer, but it is associated with a high incidence of erectile dysfunction (ED). It is not clear whether the etiology of radiation-induced ED (RI-ED) is driven by RT-mediated injury to the vasculature, the nerves, or both. This pilot study sought to distinguish the effects of vascular and nerve injury in RI-ED by applying a vascular radioprotectant in a rat model of prostate RT.

Galanin Administration Partially Restores Erectile Function After Cavernous Nerve Injury and Mediates Endogenous Nitrergic Nerve Outgrowth In Vitro.

Background: Previously, we found that the neuropeptide galanin was strongly upregulated soon after bilateral cavernous nerve injury (BCNI) and that galanin and its receptors were expressed in nitrergic erectile innervation. Galanin has been observed to exert neuroregenerative effects in dorsal root ganglion neurons, but evidence for these effects in the major pelvic ganglion (MPG) after BCNI is lacking.

Aim: To evaluate the neurotropic effects of galanin receptor agonists and antagonists in vitro in nitrergic neurons and MPG and in vivo in rats after BCNI.