Neuronal control of the vagina in vertebrates: A review.

BACKGROUND: At present, there is an increased interest in the vaginal microbiome. It is believed that microbes play equally important roles in the vagina, including the modulation of neuronal pathways, as in the gut. However, in man as well as in animals, the vagina is the least well-studied part of the female reproductive system. The vagina, a fibromuscular tract, having two main functions, i.e., childbirth and sexual intercourse, is mainly innervated by the pudendal nerve and the pelvic splanchnic nerves (the uterovaginal nerve plexus) containing sympathetic, parasympathetic and nociceptive nerve fibers. Innervation density in the vaginal wall undergoes significant remodeling due to hormonally mediated physiological activity. Knowledge about expression and function of neuropeptides and neurotransmitters in the vaginal fibers is incomplete or not established. Most research concerning the neuroregulation of the vagina and the function and expression of neuropeptides and neurotransmitters, is performed in several vertebrate species, including large farm animals, rodents, domestic fowl and lizards. METHODS: This review summarizes, on a bibliographic basis, the current knowledge on vaginal innervation and function of neuropeptides and neurotransmitters expressed in vaginal nerve fibers in several vertebrate species, including humans. The presence and role played by the local microbioma is also explored. CONCLUSION: A thorough knowledge of the vaginal innervation is necessary to unravel the putative communication of the vaginal microbiome and vaginal nerve fibers, but also to understand the effects of vaginal pathologies and of administered drugs on the neuroregulation of the vagina.

Sensibility, Sensation, and Nerve Regeneration after Reconstructive Genital Surgery: Evolving Concepts in Neurobiology.

BACKGROUND: Sensory recovery following phalloplasty and vaginoplasty for gender dysphoria is essential to the overall success of gender-confirming surgery. Anecdotal evidence suggests that superior reinnervation results are seen in genitoplasty compared to other peripheral nerve repair scenarios. Despite these observed differences, the quality of available literature is poor. METHODS: The authors reviewed the body of English language literature regarding sensory outcomes following genitoplasty for gender confirmation. RESULTS: The available body of literature discussing the basic science and clinical science aspects of sensory recovery following gender-confirming genitoplasty is small. Available data show that sensory recovery following vaginoplasty produces high rates of reported orgasmic ability, largely through the neoclitoris, and a neovagina with vibratory and pressure sensation similar to that of the native vagina. Phalloplasty sensory outcomes are variable, with the largest series reporting return of sensation in the neophallus that is slightly less than what is measured in control men. Erogenous sensation, including the ability to orgasm, is present in nearly all patients after several months. CONCLUSIONS: Existing series indicate that genitoplasty patients experience faster and more complete recovery than any other peripheral nerve regeneration scenarios. However, there are many potential confounding factors in assessment and reporting, and more consistent and reproducible measure endpoints measures are needed. Further research is needed to better understand both the basic science and clinical science of peripheral nerve regeneration in genitoplasty, which may change fundamental aspects of current paradigms of peripheral nerve regeneration.

The Anatomical Distribution of the Pudendal Nerve Block Injection: A Cadaveric Study.

OBJECTIVE: The objective of this study was to assess the accuracy of commonly used injection locations of the pudendal nerve block by examining the proximity of the injected dye to the pudendal nerve in a cadaveric model. METHODS: Pudendal block injections at 4 sites were placed transvaginally on 5 cadaveric pelvises. These sites were 1 cm proximal to the ischial spine (black dye), at the ischial spine (red dye), 1 cm distal to the ischial spine (blue dye), and 2 cm lateral and 2 cm distal to the ischial spine (green dye). The cadavers were dissected via a posterior approach. RESULTS: We measured the shortest distance from the center of the dye-stained tissue to the pudendal nerve. As expected, the injections at the ischial spine (red) resulted in a distribution of dye closest to the pudendal nerve, averaging 3.0 ± 0.95 mm. Dyes at other sites were close to the nerve: 3.1 ± 1.00 mm (black), 3.6 ± 1.14 mm (blue), and 4.05 ± 1.28 mm (green). CONCLUSIONS: Regardless of the injection site, all dyes were close the pudendal nerve, indicating accuracy. We observed wide variation in the dye distribution even though all injections were performed by the same provider, implicating lack of precision. Based on our findings, we propose that the most effective injection location is at the ischial spine because it is the closest to the pudendal nerve; however, all injections were within 4 mm of the pudendal nerve, suggesting that only 1 to 2 injections may be sufficient.

Psychological Pathologies and Sexual Orientation in Transgender Women Undergoing Gender Confirming Treatment.

BACKGROUND: There are few studies evaluating depression, self-esteem, and mental health after gender confirming treatment of transgender women. Most of these studies include different surgical techniques and nonvalidated questionnaires. With our survey, we are aiming to assess psychopathologies and mental health as well as sexuality among a group of patients treated by the same surgeon performing our self-developed combined surgical technique. This vaginoplasty approach is characterized by constructing the vaginal cavity with parts of the penile and scrotal skin as well as the longitudinally incised urethra. MATERIALS AND METHODS: Forty-seven transgender women who underwent gender confirming treatment between 2007 and 2013 were included in a retrospective study. The assessment of our study group was performed by means of self-developed indication-specific questionnaires and 3 standardized questionnaires that can be compared with norm data. RESULTS: Preoperative psychotherapy was mostly considered as helpful by the patients, yet postoperatively, only a third of our study participants were still under therapeutic treatment. Furthermore, we could show a change in sexual preference toward a more bisexual orientation. Gender confirming treatment satisfied the expectations for most of the patients and, in their opinion, should have been performed earlier. Results of the standardized Patient Health Questionnaire 4, a short depression screening questionnaire, did not significantly differ from healthy norm data. The Freiburg Personality Inventory, Revised, revealed normal emotionality and sane self-assessment within our study group. High self-esteem and significantly higher scores than norm data were found for the Rosenberg Self-esteem Scale. CONCLUSIONS: Gender confirming treatment with the combined technique is an important part of a multi-structured treatment of transgenders and does have effects on psychological well-being. It seems to decrease psychopathologies and implicates several ameliorations for transgender women. Findings need to be verified in prospective studies including preoperative evaluations.

Neurovascular alterations of muscularis propria in the human anterior vaginal wall in pelvic organ prolapse.

In the pathophysiology and progression of pelvic organ prolapse (POP), it has been demonstrated that there is a reorganisation of the muscularis propria of the anterior vaginal wall due to a phenotypic smooth muscle cell to myofibroblast switch. An abnormal deposition of collagen type III seems to be influenced by the involvement of advanced glycation end-products. The aim of the present study was to evaluate the hypothesis that this connective tissue remodelling could also be associated with neurovascular alterations of the muscularis in women with POP compared with control patients. We examined 30 women with POP and 10 control patients treated for uterine fibromatosis. Immunohistochemical analysis, using glial fibrillary acidic protein, S-100 protein, receptor tyrosine kinase, neurofilament and α-smooth muscle actin antibodies, was performed. S-100, receptor tyrosine kinase and neurofilament were also evaluated using Western blot analysis. We observed a decrease in all neurovascular-tested markers in nerve bundles, ganglia and interstitial cells of Cajal from POP samples as compared with controls. Even if the processes responsible for these morphological alterations are still not known, it is conceivable that collagen III deposition in the anterior vaginal wall affects not only the architecture of the muscle layer but could also modify the intramuscular neurovascularisation and account for an alteration of the neuromuscular plasticity of the layer.

Impact of polypropylene prolapse mesh on vaginal smooth muscle in rhesus macaque.

BACKGROUND: The use of polypropylene prolapse mesh to treat pelvic organ prolapse has been limited by mesh-related complications. Gynemesh PS mesh, implanted via sacrocolpopexy in rhesus macaques, had a negative impact on the vagina with thinning of vaginal muscularis and decreased vaginal smooth muscle contractility. The negative effect was attenuated when a bioscaffold derived from urinary bladder extracellular matrix was used as a composite with Gynemesh PS. OBJECTIVE: The objective of the study was to further elucidate the impact of Gynemesh PS polypropylene mesh and MatriStem extracellular matrix bioscaffolds on the vaginal smooth muscle in terms of micromorphology of vaginal smooth muscle (muscle bundles and individual myocytes), innervation, and nerve-mediated contractile function following their implantations in a rhesus macaque model via sacrocolpopexy. STUDY DESIGN: Thirty-two middle-aged rhesus macaques were randomized to undergo either a sham surgery (sham, n = 8), or the implantation of Gynemesh PS alone (n = 8) vs composite mesh comprised of Gynemesh PS plus 2-ply MatriStem (n = 8) vs 6-ply MatriStem alone (n = 8) via sacrocolpopexy. The graft-vagina complexes were harvested 3 months later. Histomorphometrics of smooth muscle bundles and myocytes were performed by immunofluorescent labeling of alpha smooth muscle actin, caveolin-3 (membrane protein), and cell nuclei followed by confocal imaging. The cross-sectional diameters of smooth muscle bundles and individual myocytes were quantified using images randomly taken in at least 5 areas of each section of sample. Contractile proteins alpha smooth muscle actin and smoothelin were quantified by Western immunoblotting. Nerve density was measured by immunohistochemical labeling of a pan-neuron marker, PGP9.5. Nerve-mediated smooth muscle contractility was quantified using electrical field stimulation. One-way analysis of variance and appropriate post hoc tests were used for statistical comparisons. RESULTS: Compared with sham, the implantation of Gynemesh PS alone resulted in a disorganized smooth muscle morphology with the number of small muscle bundles (cross-sectional diameter less than 20 µm) increased 67% (P = .004) and the myocyte diameter decreased 22% (P < .001). Levels of contractile proteins were all decreased vs sham with alpha smooth muscle actin decreased by 68% (P = .009), low-molecular-weight smoothelin by 51% (P = .014), and high-molecular-weight smoothelin by 40% (P = .015). Nerve density was decreased by 48% (P = .03 vs sham) paralleled by a 63% decrease of nerve-mediated contractility (P = .02). Following the implantation of composite mesh, the results of measurements were similar to sham (all P > .05), with a 39% increase in the myocyte diameter (P < .001) and a 2-fold increase in the level of alpha smooth muscle actin relative to Gynemesh (P = .045). Following the implantation of MatriStem alone, the number of small muscle bundles were increased 54% vs sham (P = .002), while the other parameters were not significantly different from sham (all P > .05). CONCLUSION: The implantation of Gynemesh PS had a negative impact on the structural and functional integrity of vaginal smooth muscle evidenced by atrophic macro- and microscopic muscle morphology, decreased innervation, and impaired contractile property, consistent with a maladaptive remodeling response. The extracellular matrix bioscaffold (MatriStem), when used with Gynemesh PS as a composite (2 ply), attenuated the negative impact of Gynemesh PS; when used alone (6 ply), it induced adaptive remodeling as evidenced by an increased fraction of small smooth muscle bundles with normal contractility.

Cadaver Study of Combined Neurovascular Sensate Flaps to Create Vaginal Erogenous Sensation During Male-to-Female Genital Confirmation Surgery: The Pedicle "O" Flap.

PURPOSE: The lack of erogenous sensitivity in the neovagina is one of the major shortcomings for patients undergoing male-to-female genital confirmation surgery. Remnant fibers of the dorsal nerve of the penis (DNP) after clitroplasty can potentially be used for a second neurovascular pedicle flap for intravaginal erogenous sensation. METHODS: An anatomic dissection of the DNP was performed in 10 male frozen pelvises to identify major trunks and their branches. Lateral branches of DNP were preserved for a sensate "O" pedicle flap for the vagina. The number of main branches in the lateral dorsal aspect of the penis was calculated to ensure sufficient erogenous innervation to the vagina. Cross sections of the penis were used for histological analysis. Optimal width and length of the new sensate flap were described. RESULTS: There were 1, 2, and 3 main branches in the lateral compartment in 2 (20%), 6 (30.7%), and 2 (42.8%) cadavers, respectively. A sensate pedicle flap from the lateral aspect of the glans penis with a mean width of 1.14 cm (range, 0.9-1.28 cm) ensured at least one main branch of the DNP for erogenous sensitivity of the vagina. This sensate vaginal flap and its neurovascular pedicle had a mean length of 9.8 cm (range, 8.7-10.3 cm) allowing its inset into the anterior vaginal canal. CONCLUSION: Lateral branches of the DNP can be preserved for a pedicle sensate flap to the vagina, which can provide patients with an erogenous vaginal "spot" during male-to-female confirmation surgery.

Innervation Changes Induced by Inflammation in the Murine Vagina.

Vulvodynia is a prevalent chronic pain disorder associated with high medical costs and often ineffective treatments. The major pathological feature is proliferation of vaginal nerve fibers. This study aimed to develop a highly reproducible animal model to study neuroproliferation in the vagina and aid the identification of appropriately targeted treatments for conditions such as vulvodynia. Mild chronic inflammation was induced using microinjection of complete Freund's adjuvant in the distal vagina of C57Bl/6 mice. Control mice received saline. Inflammation and innervation density were assessed at 7 and 28 days after a single administration or 14 days following repeated administration of complete Freund's adjuvant or saline. Histochemistry and blinded-analysis of images were used to assess vaginal morphology (H & E) and abundance of macrophages (CD68-labeling), mast cells (toluidine blue staining, mast cell tryptase-immunoreactivity), blood vessels (αSMA-immunoreactivity) and nerve fibers immunoreactive for the pan-neuronal marker PGP9.5. Subpopulations of nerve fibers were identified using immunoreactivity for calcitonin gene-related peptide (CGRP), substance P (SP), vasoactive intestinal peptide (VIP) and neuropeptide Y (NPY). Single administration of complete Freund's adjuvant resulted in vaginal swelling, macrophage infiltration, vascular proliferation and increased abundance of nerve fibers immunoreactive for CGRP, SP, VIP and/or PGP9.5 but not NPY, evident at seven days. Inflammation further increased following repeated administration of complete Freund's adjuvant but nerve fiber proliferation did not. Nerve fiber proliferation continued to be evident at 28 days. The inter-individual differences within each treatment group were small, indicating that this model may be useful to study mechanisms underlying vaginal nerve fiber proliferation associated with inflammation.

Does vaginal estriol make urodynamic changes in women with overactive bladder syndrome and genitourinary syndrome of menopause?

OBJECTIVES: OAB is a common finding in postmenopausal women. Hypoestrogenism is the root cause of many signs and symptoms of Genitourinary Syndrome of Menopause (vaginal dryness, atrophy, dyspareunia, urinary disorders, etc.). As such the aim of this study was to evaluate the urodynamic effects of ultralowdose estriol vaginal gel formulation to treat women with Genitourinary Syndrome of Menopause and Overactive Bladder Syndrome. STUDY DESIGN: This open-labeled, single center, prospective study involved 37 women with OAB recruited in our Urogynecological Unit between January and July 2016. They received estriol 50 mcg/g vaginal gel, one applicator-dose per day for 3 weeks followed by one dose twice a week for 12 weeks. Objective and subjective parameters were evaluated before and after treatment through the urodynamic examination, Overactive Bladder symptom score and Short Form Health Survey-36 questionnaires. RESULTS: Vaginal atrophy symptoms and signs as well as the overactive bladder subjective symptom parameter improved significantly. Urodynamic evaluation showed significant improvement in first desire to void and maximum cystometric capacity after estriol usage. Patients who had detrusor overactivity did not show any improvement for this parameter after treatment. The voiding function parameters did not significantly change. Short form-36 showed a better quality of life after treatment especially for the emotional role, as well as mental and general health. CONCLUSIONS: A local ultra-low dose concentration of estriol could be effective in women with vaginal atrophy and Overactive Bladder Syndrome for improving both subjective symptoms and urodynamic parameters of storage function not affecting voiding function.

Restoring normal anatomy in female patients with atypical genitalia.

Female patients with congenital adrenal hyperplasia (CAH) have varying degrees of atypical genitalia secondary to prenatal and postnatal androgen exposure. Surgical treatment is focused on restoring normal genitalia anatomy by bringing the vagina to the normal position on the perineum, separating the distal vagina from the urethra, forming a normal introitus and preserving sexual function of the clitoris by accepting moderate degrees of hypertrophy as normal and strategically reducing clitoral size only in the most severely virilized patients. There remains a need for continued monitoring of patients as they go through puberty with the possibility of additional surgery for vaginal stenosis. Anatomically based surgery and refinement in surgical techniques with acceptance of moderate degrees of clitoral hypertrophy as normal should improve long-term outcomes.

Estrogen Replacement Regulates Vaginal Innervations in Ovariectomized Adult Virgin Rats: A Histological Study.

Background. Our previous Gräfenberg spot findings confirmed that the distal-third areas of the anterior vaginal wall bore a significantly greater number of nerves and sexual hormone may have certain degree of influence on these significant differences. However, the role of estrogen in vaginal innervations remains controversial. Methods. To investigate whether hormonal-neural interactions occur in the vagina, sixty rats were randomly divided into six groups: Sham-operated, ovariectomy, and 4 treatment groups. After 2 weeks of treatment, vaginal biopsies were prepared with hematoxylin and eosin and PGP9.5 using immunohistochemistry. Results. The density of small nerve fibers was significantly higher in the distal-half areas of intact vaginal walls than the proximal-half areas (P = 0.001). In contrast, the overall PGP 9.5-ir fiber innervation density was significantly decreased in the OVX rats subjected to surgical menopause. Sustained estrogen administration for 2 weeks resulted in nerve fiber proliferation, with values reaching normal levels in the low-dose estradiol valerate group. Conclusion. Our findings indicate that systemic hormonal therapy with low-dose estradiol valerate is effective and safe for treating deficient vaginal innervation caused by low level of estrogen activity in menopausal women and may aid studies to identify an optimal estradiol dose to provide relief from vaginal discomfort.

Role of Estrogens in the Size of Neuronal Somata of Paravaginal Ganglia in Ovariectomized Rabbits.

We aimed to determine the role of estrogens in modulating the size of neuronal somata of paravaginal ganglia. Rabbits were allocated into control (C), ovariectomized (OVX), and OVX treated with estradiol benzoate (OVX + EB) groups to evaluate the neuronal soma area; total serum estradiol (E2) and testosterone (T) levels; the percentage of immunoreactive (ir) neurons anti-aromatase, anti-estrogen receptor (ERα, ERß) and anti-androgen receptor (AR); the intensity of the immunostaining anti-glial cell line-derived neurotrophic factor (GDNF) and the GDNF family receptor alpha type 1 (GFRα1); and the number of satellite glial cells (SGCs) per neuron. There was a decrease in the neuronal soma size for the OVX group, which was associated with low T, high percentages of aromatase-ir and neuritic AR-ir neurons, and a strong immunostaining anti-GDNF and anti-GFRα1. The decrease in the neuronal soma size was prevented by the EB treatment that increased the E2 without affecting the T levels. Moreover, there was a high percentage of neuritic AR-ir neurons, a strong GDNF immunostaining in the SGC, and an increase in the SGCs per neuron. Present findings show that estrogens modulate the soma size of neurons of the paravaginal ganglia, likely involving the participation of the SGC.

Histologic Anatomy of the Anterior Vagina and Urethra.

BACKGROUND: Vaginal and urethral histology is important to understanding the pathophysiology of the pelvic floor. METHODS: En bloc removal of 4 female cadaveric pelvises was performed, with 18 to 25 serial sections obtained from each. The vaginal and urethral lengths were divided into distal and proximal sections; urethra was divided into anterior and posterior segments as well. Innervation and vasculature were qualified as small and large and quantified per high-power field. RESULTS: The mean vaginal length was 7.45 cm, and the mean urethral length was 3.38 cm. A distinct vaginal fibromuscular layer was noted, without evidence of a dense sheet of continuous collagen. An epithelial, lamina propria, and muscular layer surrounded the urethral lumen. Adipose and loose fibroconnective tissue separated the urethra from the anterior vagina in 41% of slides. Nerves and vasculature were concentrated in the lamina propria. More small nerves and vessels were grossly seen compared with larger counterparts in both the vagina and urethra. No significant differences in layer thickness, innervation, or vasculature were observed along the vaginal length. The posterior urethra had greater innervation than did the anterior (P = 0.012). The distal posterior urethra had more large vessels than did the proximal posterior urethra (P = 0.03). No other differences were noted in urethral sections. CONCLUSIONS: A vaginal fibromuscular layer was confirmed, refuting a true fascia. Innervation and vasculature were quantitatively the same along the anterior vagina. However, the posterior urethra had greater innervation than did anterior and is most innervated proximally. Nerve and vascular histology may relate to pelvic floor disorder etiology.

Prostaglandin levels, vaginal innervation, and cyst innervation as peripheral contributors to endometriosis-associated vaginal hyperalgesia in rodents.

Endometriosis is a painful condition characterized by growth of endometrial cysts outside the uterus. Here, we tested the hypothesis that peripheral innervation and prostaglandin levels contribute to endometriosis-associated pain. Female Sprague-Dawley rats (n = 16) were surgically instrumented by transplanting uterine tissue onto mesenteric arteries within the peritoneal cavity to create a model of endometriosis which forms extra-uterine endometrial cysts and vaginal hyperalgesia. Our results describe a significant positive correlation between endometriosis-induced vaginal hyperalgesia and cyst innervation density (sensory, r = 0.70, p = 0.003; sympathetic, r = 0.55, p = 0.03), vaginal canal sympathetic innervation density (r = 0.80, p = 0.003), and peritoneal fluid levels of the prostaglandins PGE2 (r = 0.65, p = 0.01) and PGF2α (r = 0.63, p = 0.02). These results support the involvement of cyst innervation and prostaglandins in endometriosis-associated pain. We also describe how sympathetic innervation density of the vaginal canal is an important predictor of vaginal hyperalgesia.

Effect of Midurethral Sling Surgery on Vaginal Sensation.

INTRODUCTION: Previous studies have reported changes in the sensory functioning of the vagina in women with pelvic floor disorder. AIM: To evaluate vaginal and clitoral sensation before and after surgery with trans-obturator tape (TVT-O, Ethicon Johnson & Johnson). METHODS: Quantitative sensory thresholds for warm, cold, and vibratory sensations were measured at the vagina and clitoris 1 day before and 12 ± 4 months after surgery. MAIN OUTCOME MEASURES: Differences in thresholds to warm, cold, and vibratory sensations at a predetermined anatomic area of the genital region. RESULTS: Twenty-two women were admitted for midurethral sling surgery, and four were lost to follow-up. For the remaining 18 (mean age = 52 years, range = 37-65), we found a significant sensory decrease at the clitoral region to cold, warm, and vibratory stimuli after surgery. In contrast, in the anterior vaginal wall, there was a significant decrease only to warm stimuli after surgery. CONCLUSION: TVT-O can cause sensory loss in the clitoral and anterior vaginal wall region that can be measured and quantified. The effect of such sensory loss on sexual function and quality of sexual life needs further investigation.

Sensate Vagina Pedicled-Spot for Male-to-Female Transsexuals: The Experience in the First 50 Patients.

BACKGROUND: The cosmetic and functional results of vaginoplasty by inversion of penile and scrotal skin in male-to-female transsexuals are, in general, satisfactory. The sexual arousal function of the neo-female genitalia depends mainly on the clitoris. Due to the lack of a sexual arousal organ within the neo-vagina, patients are denied sexual arousal during penetration of the neo-vagina. This necessitated improvement of sexual innervation within the neo-vagina. METHODS: A new technique to create a sexual arousal organ in the anterior wall of the neo-vagina by creation of a sensate pedicled-spot, in combination with the neo-clitoroplasty. RESULTS: In this paper, this new technique and part of the long-term results in the first 50 patients with a sensate pedicled-spot plasty are presented and discussed. CONCLUSIONS: Sensate pedicled-spot plasty has proven to be a safe innovative technique which lead to adequate sexual functionality in all patients. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.

The impact of prolapse mesh on vaginal smooth muscle structure and function.

OBJECTIVE: To evaluate the impact of prolapse meshes on vaginal smooth muscle structure (VaSM) and function, and to evaluate these outcomes in the context of the mechanical and textile properties of the mesh. DESIGN: Three months following the implantation of three polypropylene prolapse meshes with distinct textile and mechanical properties, mesh tissue explants were evaluated for smooth muscle contraction, innervation, receptor function, and innervation density. SETTING: Magee-Womens Research Institute at the University of Pittsburgh. POPULATION: Thirty-four parous rhesus macaques of similar age, parity, and pelvic organ prolapse quantification (POP-Q) scores. METHODS: Macaques were implanted with mesh via sacrocolpopexy. The impact of Gynemesh(™)  PS (Ethicon; n = 7), Restorelle(®) (Coloplast; n = 7), UltraPro(™) parallel and UltraPro(™) perpendicular (Ethicon; n = 6 and 7, respectively) were compared with sham-operated controls (n = 7). Outcomes were analysed by Kruskal-Wallis ANOVA, Mann-Whitney U-tests and multiple regression analysis (P < 0.05). MEAN OUTCOME MEASURES: Vaginal tissue explants were evaluated for the maximum contractile force generated following muscle, nerve, and receptor stimulation, and for peripheral nerve density. RESULTS: Muscle myofibre, nerve, and receptor-mediated contractions were negatively affected by mesh only in the grafted region (P < 0.001, P = 0.002, and P = 0.008, respectively), whereas cholinergic and adrenergic nerve densities were affected in the grafted (P = 0.090 and P = 0.008, respectively) and non-grafted (P = 0.009 and P = 0.005, respectively) regions. The impact varied by mesh property, as mesh stiffness was a significant predictor of the negative affect on muscle function and nerve density (P < 0.001 and P = 0.013, respectively), whereas mesh and weight was a predictor of receptor function (P < 0.001). CONCLUSIONS: Mesh has an overall negative impact on VaSM, and the effects are a function of mesh properties, most notably, mesh stiffness. TWEETABLE ABSTRACT: Prolapse mesh affects vaginal smooth muscle.

Female rats express a conditioned object preference for receipt of sexual stimulation.

Female rats alternately approach and avoid the male rat during copulation, potentially reflecting appetitive and aversive aspects of mating, respectively. We developed a novel classical conditioning procedure, conditioned object preference (COP), to test whether female rats show increased approach toward a conditioned stimulus associated directly with receipt of sexual stimulation. During conditioning, one scented object was paired with an appetitive stimulus and a different object plus scent was paired with a control stimulus on a separate day. After conditioning, preference for each object was evaluated with a choice task. Experiment 1 was conducted to verify the procedure. Rats exhibited a significant COP for 1mg/kg amphetamine, indicating that the conditioned object preference procedure is an effective tool for evaluating the rewarding nature of a treatment. In Experiment 2, paced mating to one ejaculation and experimenter-delivered artificial vaginocervical stimulation (aVCS) each induced a COP. The robust COPs for paced mating and aVCS support the notion that female rats experience a reward state during receipt of sexual stimulation. Moreover, the data suggest that any aversive aspects of receipt of sexual stimulation do not overshadow the appetitive effects.