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.

Urethral regions with differential tissular composition may underlie urinary continence and voiding function in female rats.

AIMS: To analyze, in female rats, the anatomical and histological features of the urethra and its relationship with the vagina and clitoris, and its innervation. METHODS: Seventeen adult female Wistar rats were used. Gross anatomy and acetylcholinesterase (AchE) histochemistry were performed to describe the urethral features, adjacent structures, and innervation. The histomorphometric characteristics of the urethra were determined in transversal, longitudinal, or coronal sections stained with Masson's Trichrome. RESULTS: The female rat urethra is not a homogeneous tubular organ. The pre-pelvic and pelvic regions are firmly attached to the vagina with belt-like striated fibers forming a urethra-vaginal complex. The bulbar regions have curved segments and a narrow lumen. The clitoral region is characterized by a urethra-clitoral complex surrounded by a vascular plexus. The lumen area and thickness of the urethral layers significantly varied between regions (P < 0.05). Innervation of the urethra arrives from the major pelvic ganglion, the dorsal nerve of the clitoris (DNC), and the motor branch of the sacral plexus (MBSP). CONCLUSIONS: Differential tissular composition of the urethra may underlie urinary continence and voiding dysfunction through different physiological mechanisms. The urethra-vagina complex seems to be the main site controlling urinary continence through active muscular mechanisms, while the bulbar urethra provides passive mechanisms and the urethra-clitoris complex seems to be crucial for distal urethral closure by means of a periurethral vascular network.

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.

Neuronal Nitric Oxide Synthase Expression in the Anterior Vaginal Wall of Patients with Stress Urinary Incontinence.

PURPOSE: Stress urinary incontinence (SUI) and pelvic organ prolapse (POP) are common medical problems, particularlyamong older women. In this study, we aim to explore the relationship between the neurotransmitter nNOS in the vaginal epithelium, and the occurrence of SUI and changes of nNOS levels according to menopausal status.Matherials and Methods: Fourty women were enrolled. The patients were divided into four groups according to menstruaiton status and SUI. The vagina specimens were taken during transobturator tape application. The specimens were examined pathologically in terms of n-NOS expression. nNOS expression was compared between SUI and control groups. The results were evaluated statistically. RESULT: Epithelial total nNOS score in group 1 and group 3 were 2.4 ± 0.5 and 1.4 ± 0.5 respectively (P = .003). Stromal total nNOS score was found 2.2 ± 0.4 in group 1 and 1.3 ± 0.5 in group 3 (P = .001). Epithelial total nNOS score in group 2 and group 4 were 4.4 ± 0.5 and 3.5 ± 0.5 respectively (P = .003). Stromal total nNOS score was found 4.4 ± 0.5 in group 2 and 3.6 ± 0.5 in group 4 ( P = .006). CONCLUSION: Our results show that expression of nNOs in the anterior vaginal epithelium decreased significantly in the SUI group. Altough our findings indicate important results, well designed further studies are needed to comprehend the role of NOS pathways better in SUI pathophysiology.

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.

The Vaginal Pressure Inducer: A New Device to Test the (Un)pleasurableness and Tolerance of Vaginal Pressure and the Influence of Sexual Stimuli.

To better understand the impact of sexual stimuli on genital pain, a new instrument was developed: the Vaginal Pressure Inducer (VPI). We administered gradually increasing vaginal pressure with the VPI to sexually functional women as they watched a neutral, erotic, or explicit sex film. Women had higher unpleasantness thresholds in a sexual context compared to a nonsexual context. Moreover, ratings of pleasurableness were higher in the sexual compared to neutral context and most so during the explicit sexual film. These results provide initial support for the suitability of the VPI to study determinants of pleasant and unpleasant appraisal of vaginal pressure.

Interoception and Awareness of Physiological Sexual Arousal in Women With Sexual Arousal Concerns.

Laboratory studies assessing physiological genital arousal have largely failed to find differences between women with and without female sexual arousal disorder (FSAD). Therefore, it is possible that women with FSAD may be unaware of their genital arousal response. The present study examined the extent to which women with FSAD can report their genital arousal response, as well as the role of interoception (body awareness) in this relationship. Additionally, this study examined the influence of interoception on the relationship between subjective and genital arousal. Twenty-six women who met criteria for FSAD (M age = 29.5, SD = 8.1 years) watched an erotic film and completed a series of questionnaires. Physiological (i.e., genital) and perceived genital arousal were measured continuously throughout the film. Results indicated women were able to perceive their level of physiological arousal. Greater levels of interoception were linked with stronger relationships between perceived and physiological arousal, but not between subjective and genital arousal. Methodological and clinical implications are discussed.

Time-Frequency Analysis of Increases in Vaginal Blood Perfusion Elicited by Long-Duration Pudendal Neuromodulation in Anesthetized Rats.

OBJECTIVES: Female sexual dysfunction (FSD) affects a significant portion of the population. Although treatment options for FSD are limited, neuromodulation for bladder dysfunction has improved sexual function in some women. A few studies have investigated peripheral neuromodulation for eliciting changes in vaginal blood flow, as a proxy for modulating genital sexual arousal, however results are generally transient. Our central hypothesis is that repeated or extended-duration pudendal nerve stimulation can elicit maintained vaginal blood flow increases. MATERIALS AND METHODS: Under ketamine anesthesia, the pudendal nerve of 14 female rats was stimulated at varying frequencies (1-100 Hz) and durations (0.15-60 min). Vaginal blood perfusion was measured with a laser Doppler flowmetry probe. Changes in blood perfusion were determined through raw signal analysis and increases in the energy of neurogenic (0.076-0.200 Hz) and myogenic (0.200-0.740 Hz) frequency bands through wavelet analysis. Additionally, a convolution model was developed for a carry-over stimulation effect. RESULTS: Each experiment had significant increases in vaginal blood perfusion due to pudendal nerve stimulation. In addition, there were large concurrent increases in neurogenic and myogenic frequency-band energy in 11/14 experiments, with an average maximal response at 31.3 min after stimulation initiation. An effective stimulation model with a 30-min carry-over effect had a stronger correlation to blood perfusion than the stimulation period itself. CONCLUSIONS: Repeated or extended-duration pudendal nerve stimulation can elicit maintained increases in vaginal blood perfusion. This work indicates the potential for pudendal neuromodulation as a method for increasing genital arousal as a potential treatment for FSD.

Clinical relevance of neurological evaluation in patients suffering urinary retention in the absence of subvesical obstruction.

PURPOSE: Clinical relevance of neurological evaluation in patients suffered urinary retention in the absence of subvesical obstruction. Determining whether (1) women complaining residual bladder volume without prolapse and obstruction always suffer pudendal nerve damage; (2) neurogenic damage can be linked to patients history/clinical examination; (3) therapy alters regarding to neurological findings; and (4) electromyography (EMG) of musculus sphincter ani externus (MSAE) can be omitted with electronically stimulated pudendal nerve latency (ESPL) as the standard investigation. METHODS: Women with urinary retention without ≥stage 2 prolapse or obstruction have neurological investigation including vaginally and anally pudendal terminal nerve latency (PTNL) (>2.4 ms considered abnormal) and EMG seen 7/2005-04/2010. RESULTS: (1) 148/180 (82.2%) suffered at least moderate neurogenic damage and (2) severe neurogenic damage occurs with urge odds ratio (OR) = 3.1 or age (OR = 3.2). Correlations: spasticity with therapy changes (OR = 11.1), latencies. (a) Anally: (i) right and peripheral neuropathy (PNP) (OR = 2.5), chemotherapy (OR = 5.0); (ii) left and PNP (OR = 3.9), chemotherapy (OR = 4.8); (iii) left or right with PNP (OR = 3.9), chemotherapy (OR = 6.8); and (iv) left and right with chemotherapy (OR = 5.0). (b) Vaginally: (i) right with age >60 (OR = 3.2), radical operation (OR = 10.6); (ii) left with diabetes mellitus (OR = 2.5); and (iii) left or right with age (OR = 3.3), radical operation (OR = 8.7). (3) 19.6% therapy changes (36 patients). (4) Neither EMG nor ESPL can be replaced one by another (p = 0.12 anal, p = 0.05 vaginal). CONCLUSION: Red flags are neurogenic damage, age >60, chemotherapy, PNP, radical operation or diabetes. In unclear situations, EMG and ESPL need to be performed to gain relevant information.

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.