Androgen control of penis development/growth is unclear. In rats, androgen action in a foetal 'masculinisation programming window' (MPW; e15.5-e18.5)' predetermines penile length and hypospadias occurrence. This has implications for humans (e.g. micropenis). Our studies aimed to establish in rats when androgen action/administration affects development/growth of the penis and if deficits in MPW androgen action were rescuable postnatally. Thus, pregnant rats were treated with flutamide during the MPW +/- postnatal testosterone propionate (TP) treatment. To assess penile growth responsiveness, rats were treated with TP in various time windows (late foetal, neonatal through early puberty, puberty onset, or combinations thereof). Phallus length, weight, and morphology, hypospadias and anogenital distance (AGD) were measured in mid-puberty (d25) or adulthood (d90) in males and females, plus serum testosterone in adult males. MPW flutamide exposure reduced adult penile length and induced hypospadias dose-dependently; this was not rescued by postnatal TP treatment. In normal rats, foetal (e14.5-e21.5) TP exposure did not affect male penis size but increased female clitoral size. In males, TP exposure from postnatal d1-24 or at puberty (d15-24), increased penile length at d25, but not ultimately in adulthood. Foetal + postnatal TP (e14-postnatal d24) increased penile size at d25 but reduced it at d90 (due to reduced endogenous testosterone). In females, this treatment caused the biggest increase in adult clitoral size but, unlike in males, phallus size was unaffected by TP during puberty (d15-24). Postnatal TP treatment advanced penile histology at d25 to more resemble adult histology. AGD strongly correlated with final penis length. It is concluded that adult penile size depends critically on androgen action during the MPW but subsequent growth depends on later androgen exposure. Foetal and/or postnatal TP exposure does not increase adult penile size above its 'predetermined' length though its growth towards this maximum is advanced by peripubertal TP treatment.

Peniform clitoris in 50 girls suffering from congenital adrenogenital syndrome were subtotally removed at the age of 4-6 years and studied by biopsy. A corpus spongiosum more or less developed was found in all cases beneath the corpora cavernosa in the bottom part of corpus clitoridis, epithelial urethral rudiments represented by single or multiple short tubules with transitional epithelium and mucinous glands were found in 46 cases; they were localized in corpus spongiosum or close to it in loose connective tissue. Other urethral rudiments occurring in glans clitoridis were represented by long slight pegs of squamous epithelium extending into corpus spongiosum glandis. Control samples from 20 4-6-year-old girls who had deceased from tumours showed but once heterotopic epithelial urethral rudiments-tubules with transitional epithelium and mucinous glands.

Premenstrual dysphoric disorder (PMDD) is a common, recently recognized, psychiatric condition among reproductive women, reflecting abnormal responsivity to ovarian steroids. Moreover, the potential organizational effect of prenatal sex hormones during PMDD has got attentions, but there have been considerably less of researches on this topic. The aim of this research was to investigate the possible role of prenatal androgen in the PMDD.

To investigate the therapeutic effect of clitoris exposure + episioplasty + dermabrasion + platelet-rich plasma (PRP) injection + chemexfoliation on vulvar lichen sclerosus (VLS).

At sex conversion operations on male transsexuals the glans penis is usually resected or used as a "portio" in the constructed artificial vagina. The glans penis and the clitoris are embryologically corresponding organs and it may be logical to conserve the glans as a clitoris in sex conversion operations. In one young male transsexual the glans penis was used as a substitute for clitoris. The result was good both cosmetically and functionally.

There has been an exponential increase in referrals for transmasculine patients seeking genital affirmation surgery. Despite transgender men's equal interest in metoidioplasty and phalloplasty, research has primarily focused on phalloplasty.

Krause corpuscles, first discovered in the 1850s, are enigmatic sensory structures with unknown physiological properties and functions found within the genitalia and other mucocutaneous tissues. Here, we identified two distinct somatosensory neuron subtypes that innervate Krause corpuscles of the mouse penis and clitoris and project to a unique sensory terminal region of the spinal cord. Using in vivo electrophysiology and calcium imaging, we found that both Krause corpuscle afferent types are A-fiber rapid-adapting low-threshold mechanoreceptors, optimally tuned to dynamic, light touch and mechanical vibrations (40-80 Hz) applied to the clitoris or penis. Optogenetic activation of male Krause corpuscle afferent terminals evoked penile erection, while genetic ablation of Krause corpuscles impaired intromission and ejaculation of males as well as reduced sexual receptivity of females. Thus, Krause corpuscles, which are particularly dense in the clitoris, are vibrotactile sensors crucial for normal sexual behavior.

Rat somatosensory genital cortex contains a large sexually monomorphic representation of the penis in males and the clitoris in females. Genital cortex microstimulation-evoked movements of legs, trunk and genitals, which showed sex-specific differences related to mating behaviors and included thrusting in males and lordosis-like movements in females. Erections/tumescence of penis or clitoris could not be evoked, however. Anterograde tracer injections into penis/clitoris cortex revealed eleven corticocortical and 10 subcortical projection targets, which were qualitatively similar in both sexes. Corticocortical genital-cortex-projections innervated about 3% of the cortical surface and most were analog to other somatosensory projections targeting motor cortex, secondary somatosensory cortex, parietal cortex and perirhinal cortex. Corticocortical projections that differed from other parts of somatosensory cortex targeted male scrotum cortex, female vulva cortex, the somatosensory-ear-auditory-cortex-region and the caudal parietal area. Aligning cytoarchitectonic borders with motor topography, sensory genital responses and corticocortical projections identified a candidate region for genital motor cortex. Most subcortical genital-cortex-projections were analog to other thalamic, tectal or pontine projections of somatosensory cortex. Genital-cortex-specific subcortical projections targeted amygdala and nucleus submedius and accumbens. Microstimulation-effects and projections support a sexual function of genital cortex and suggest that genital cortex is a major hub of sexual sensorimotor processing in rodents.

Female sexual response involves a complex interplay between neurophysiological mechanisms and the nitric oxide (NO)-mediated relaxation of clitoris and vagina. The aim of this study was to evaluate sex steroids regulation of the relaxant pathway in vagina, using a validated animal model.

Background : Although genital sensations are an essential aspect of sexual behavior, the cortical somatosensory representation of genitalia in women and men remain poorly known and contradictory results have been reported. Objective : To conduct a systematic review of studies based on electrophysiological and functional neuroimaging studies, with the aim to identify insights brought by modern methods since the early descriptions of the sensory homunculus in the primary somatosensory cortex (SI). Results : The review supports the interpretation that there are two distinct representations of genital sensations in SI, one on the medial surface and the other on the lateral surface. In addition, the review suggests that the secondary somatosensory cortex and the posterior insula support a representation of the affective aspects of genital sensation. Conclusion : In view of the erogenous character of sensations originating in the genitalia, future studies on this topic should systematically assess qualitatively as well as quantitatively the sexually stimulating and/or sexually pleasurable characteristics of sensations felt by subjects in response to experimental stimuli.

Vaginoplasty aims to create a functional feminine vagina, sensate clitoris, and labia minora and majora with acceptable cosmesis. The upward trend in the number of transfemale vaginoplasties has impacted the number of published articles on this topic. Herein, we conducted an updated systematic review on complications and patient-reported outcomes.

External genital organs are among the most recognizable sexually dimorphic characters. The penis and clitoris develop from the embryonic genital tubercle, an outgrowth at the anterior margin of the cloaca that undergoes an extensive period of development in male and female embryos prior to the onset of sexual differentiation. In mice, differentiation into the penis and clitoris begins around embryonic day (E)15.5. Current knowledge of cell types that comprise the genital tubercle is limited to a few studies that have fate mapped derivatives of endoderm, mesoderm, and ectoderm. Here we use single cell transcriptomics to characterize the cell populations in the genital tubercles of male and female mouse embryos at E14.5, approximately 24 ​h before the onset of sexual differentiation, and we present the first comprehensive atlas of single-cell gene expression during external genital development. Clustering analyses and annotation using marker genes shows 19 distinct cell populations in E14.5 genital tubercles. Mapping of cell clusters to anatomical locations using in situ gene expression patterns revealed granularity of cellular specializations and positional identities. Although E14.5 precedes sexually dimorphic morphogenesis of the genital tubercle, comparative analysis of males and females identified sexual dimorphisms at the single cell level, including male-specific cell clusters with transcriptional signatures of smooth muscle and bone progenitors, both of which are known to be sexually dimorphic in adult genitalia, as well as immune cells. These results provide a new resource for classification of external genital cell types based on gene expression profiles and reveal sex-specific cellular specializations in the early genital tubercle.

Mammalian external genitals show sexual dimorphism [1, 2] and can change size and shape upon sexual arousal. Genitals feature prominently in the oldest pieces of figural art [3] and phallic depictions of penises informed psychoanalytic thought about sexuality [4, 5]. Despite this longstanding interest, the neural representations of genitals are still poorly understood [6]. In somatosensory cortex specifically, many studies did not detect any cortical representation of genitals [7-9]. Studies in humans debate whether genitals are represented displaced below the foot of the cortical body map [10-12] or whether they are represented somatotopically [13-15]. We wondered what a high-resolution mapping of genital representations might tell us about the sexual differentiation of the mammalian brain. We identified genital responses in rat somatosensory cortex in a region previously assigned as arm/leg cortex. Genital responses were more common in males than in females. Despite such response dimorphism, we observed a stunning anatomical monomorphism of cortical penis and clitoris input maps revealed by cytochrome-oxidase-staining of cortical layer 4. Genital representations were somatotopic and bilaterally symmetric, and their relative size increased markedly during puberty. Size, shape, and erect posture give the cortical penis representation a phallic appearance pointing to a role in sexually aroused states. Cortical genital neurons showed unusual multi-body-part responses and sexually dimorphic receptive fields. Specifically, genital neurons were co-activated by distant body regions, which are touched during mounting in the respective sex. Genital maps indicate a deep homology of penis and clitoris representations in line with a fundamentally bi-sexual layout [16] of the vertebrate brain.

Female social dominance (FSD) over males is unusual in mammals, yet characterizes most Malagasy lemurs, which represent almost 30% of all primates. Despite its prevalence in this suborder, both the evolutionary trajectory and proximate mechanism of FSD remain unclear. Potentially associated with FSD is a suite of behavioural, physiological and morphological traits in females that implicates (as a putative mechanism) 'masculinization' via androgen exposure; however, relative to conspecific males, female lemurs curiously show little evidence of raised androgen concentrations. By observing mixed-sex pairs of related Eulemur species, we identified two key study groups--one comprised of species expressing FSD and increased female scent marking, the other comprised of species (from a recently evolved clade) showing equal status between the sexes and the more traditional pattern of sexually dimorphic behaviour. Comparing females from these two groups, we show that FSD is associated with more masculine androgen profiles. Based on the widespread prevalence of male-like features in female lemurs and a current phylogeny, we suggest that relaxation of hormonally mediated FSD emerged only recently and that female masculinization may be the ancestral lemur condition, an idea that could revolutionize our understanding of the ancient socioecology and evolution of primate social systems.

The aim of this study is to estimate trends in incidence and relative survival in women diagnosed with invasive squamous cell vulvar cancer in the United States (U.S.) and Canada over the periods of 1973-2010 for U.S. and 1992-2008 for Canada.

Background: We measured changes in resting brain functional connectivity, with blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMRI), associated with a creative meditation practice that is augmented by clitoral stimulation and is designed to not only achieve a spiritual experience but to help individuals manage their most intimate personal relationships. Briefly, the meditative state is attained by both the male and female participants while the male stimulates the woman's clitoris. The goal of this practice, called orgasmic meditation (OM), according to the practitioners is not sexual, but to use the focus on clitoral stimulation to facilitate a meditative state of connectedness and calm alertness between the two participants. Methods: fMRI was acquired on 20 pairs of subjects shortly following one of two states that were randomized in their order - during the OM practice or during a neutral condition. The practice is performed while the female is lying down on pillows with the clitoris exposed. During the practice, the male performs digital stimulation of the clitoris for 15 min. Resting BOLD image acquisition was performed at completion of the practice to assess changes in functional connectivity associated with the performance of the practice. Results: The results demonstrated significant changes (p < 0.05) in functional connectivity associated with the OM compared to the neutral condition. For the entire group there was altered connectivity following the OM practice involving the left superior temporal lobe, the frontal lobe, anterior cingulate, and insula. In female subjects, there was altered connectivity involving the cerebellum, thalamus, inferior frontal lobe posterior parietal lobe, angular gyrus, amygdala and middle temporal gyrus, and prefrontal cortex. In males, functional connectivity changes involved the supramarginal gyrus, cerebellum, and orbitofrontal gyrus, cerebellum, parahippocampus, inferior temporal gyrus, and anterior cingulate. Conclusion: Overall, these findings suggest a complex pattern of functional connectivity changes occurring in both members of the couple pair that result from this unique meditation practice. The changes represent a hybrid of functional connectivity findings with some similarities to meditation based practices and some with sexual stimulation and orgasm. This study has broader implications for understanding the dynamic relationship between sexuality and spirituality.

Catheter-related bladder discomfort (CRBD) to an indwelling urinary catheter is defined as a painful urethral discomfort, resistant to conventional opioid therapy, decreasing the quality of postoperative recovery. According to anatomy, the branches of sacral somatic nerves form the afferent nerves of the urethra and bladder triangle, which deriving from the ventral rami of the second to fourth sacral spinal nerves, innervating the urethral muscles and sphincter of the perineum and pelvic floor; as well as providing sensation to the penis and clitoris in males and females, which including the urethra and bladder triangle. Based on this theoretical knowledge, we formed a hypothesis that CRBD could be prevented by pudendal nerve block.

Klippel-Trénaunay Syndrome (KTS) is a genetic vascular malformation involving the capillary, lymphatic, and venous channels. Prenatal sonographic diagnosis of KTS with an enlarged fetal limb is well-known; however, postnatal gynecologic manifestations are rarely reported. KTS can cause clitoromegaly, vulvovaginal hemangioma, and heavy menstrual bleeding. Somatic mosaicism of the PIK3CA gene is considered as responsible for KTS but reports based on whole-genome sequencing are limited. A 31-year-old woman with KTS presented with bulging of the clitoris and vagina. Analysis of whole-genome sequencing variant data revealed that gene ontology terms related to development and differentiation such as 'skeletal system morphogenesis', 'embryonic morphogenesis', and 'sensory organ development' were nominally significant in non-coding regions. Variants in non-coding genes may be responsible for this phenotype.

We report on seven Iraqi patients with 46,XY karyotype and ambiguous genitalia characterized by perineo-scrotal hypospadias, bifid scrotum, clitoris like phallus, palpable testes in inguinal canal and pseudovagina. Patients were raised five as females and two as males. They are all unrelated with the exception of two couples of brothers. The diagnosis of 5-α-reductase-2 deficiency syndrome was first hypothesized on clinical grounds and then confirmed by molecular analysis. Direct sequencing analysis of the SRD5A2 gene revealed in five patients a novel homozygous frame-shift mutation (c.453delC) and in two related patients a previous reported missense mutation. The presence of the same mutation in unrelated patients of the same population suggests a possible founder effect. This report brings the 5-α-reductase-2 deficiency syndrome to the attention of clinical geneticists and child surgeons and discusses the appropriate clinical and surgical strategies for treating these patients.

Pubococcygeus muscle reflex activity has been reported to be driven by specialized neuronal circuitry, including the participation of spinal cord interneurons. Both the reflex and elements of the circuit are known to be sensitive to gonadal hormones, but studies using female rats have not considered the potential effects of estrous phase. Hence, in the present study we used mechanical stimulation of the clitoris to produce reflex activity, and recorded across the different phases of the estrous cycle, including the dark and light periods during each phase. Afterdischarge activity was observed only during the light and dark periods of proestrus, and during the light period of estrus coincident with the receptivity period in the rat́s reproductive behavior. Moreover, this reflex activity comprises at least five different motor unit groups with different firing patterns that are dependent on gonadal hormones variation.