Contrôle neurologique de l’éjaculation

The brain control of the genital tract and sexual behaviour remains poorly understood. Clinical results and basic research indicate that the neural control of ejaculation depends on three levels of organization. The first level consists of peripheral autonomic and somatic nerves. Leaving the spinal cord, these nerves control the motility, secretions and blood supply of the genital tract, and contractions of perineal striated muscles. Their path in the abdominal cavity and the effects of their neuro-transmitters on peripheral tissues have been established. These nerves also convey sensory information from the genital tract to the spinal cord. The second level is represented by the spinal cord. The thoracolumbar (sympathetic), and sacral (parasympathetic and pudendal) segments of the cord contain the somata of autonomic and somatic motoneurons, whose axons run in the above nerves. These motoneurons are part of a spinal network that likely organizes the activity of the whole genital tract in a given context such as copulation. The role of the different spinal cord segments in the control of ejaculation is mainly inferred from observations of the deleterious effects of spinal cord injury in human patients. A small population of galaninergic positive neurons has recently been identified in the lumbar segments of the rat spinal cord that plays a major role in ejaculation (Truitt and Coolen, 2003). Selective lesion of this population abolishes in copula ejaculations, but spares erection. Finally, the third level of organization is represented by supraspinal nervous structures. The spinal cord receives direct excitatory and inhibitory information from the brainstem, pons and hypothalamus. In turn, these structures receive sensory information from the genital tract. However, their role in the control of ejaculation remains poorly investigated. Again, it is mainly inferred from the observation of the deleterious effects of pharmacological treatments on brain neurotransmission. Positron emission tomography has recently been used to observe brain areas whose activity is enhanced during ejaculation in humans (Holstege et al., 2003). In this study, several areas of the right side of the cortex and the cerebellum were activated. The targets of future clinical and basic research include: the neural basis of the required coordination between spinal autonomic and somatic nuclei that innervate the genital tract, the role of sensory information from the genital tract in the recruitment and coordination of spinal and supraspinal nuclei, and finally the integration of descending excitatory and inhibitory influences onto the spinal cord. Both the organization during development and the activation at puberty of the spinal neural network that controls the genital tract are dependent on androgens. Future research should identify the regulatory factors that, in response to the action of androgens, provide neurons with the possibility of building their connexions and selecting their neurotransmitters and receptors.     

Vers une approche physiopathologique des troubles de l’éjaculation

Seminal emission and sperm expulsion are under the control of both the sympathetic and parasympathetic outflows and also of the somatic innervation conveyed by the pudendal nerve. The 2 phases of ejaculation are reflexive with the reflexes handled at the thoraco-lumbar and sacral levels of the spinal cord. Such a spinal organization remains widely unknown. The role of various peripheral neurotransmitters has been evidenced including norepinephrine and acetylcholine and also peptidergic, purinergic i.e. ATP and nitric oxide. Stimulation of the seminal tract afferents play a crucial in the onset of ejaculatory mechanisms. Except for the dorsal nerve of the penis, there is a lack of information concerning these afferents. Several supraspinal centers i.e. hypothalamus, medial amygdala, pons and nucleus paragigantocellularis exert descending and ascending inhibitory and excitatory influences on spinal nuclei controlling emission and expulsion of sperm. Central neurotransmission responsible for this supraspinal control could involve serotonin, oxytocin and norepinephrine. In the light of the available anatomical and neurophysiological data, pathophysiological aspects of ejaculatory disorders are futher discussed. Premature ejaculation could be related to a periheral and central hypersentivity. Most of the other ejaculation abnormalities are likely mainly related to an impairment of the central mechanisms.     

Somatic genital reflexes in rats with a nod to humans: anatomy, physiology, and the role of the social neuropeptides

Somatic genital reflexes such as ejaculation and vaginocervical contractions are produced through the striated muscles associated with the genitalia. The coordination of these reflexes is surprisingly complex and involves a number of lumbosacral spinal and supraspinal systems. The rat model has been proven to be an excellent source of information regarding these mechanisms, and many parallels to research in humans can be drawn. An understanding of the spinal systems involving the lumbosacral spinal cord, both efferent and afferent, has been generated through decades of research. Spinal and supraspinal mechanisms of descending excitation, through a spinal ejaculation generator in the lumbar spinal cord and thalamus, and descending inhibition, through the ventrolateral medulla, have been identified and characterized both anatomically and physiologically. In addition, delineation of the neural circuits whereby ascending genitosensory information regarding the regulation of somatic genital reflexes is relayed supraspinally has also been the topic of recent investigation. Lastly, the importance of the “social neuropeptides” oxytocin and vasopressin in the regulation of somatic genital reflexes, and associated sociosexual behaviors, is emerging. This work not only has implications for understanding how nervous systems generate sexual behavior but also provides treatment targets for sexual dysfunction in people.     

The regulation of male sexual behavior by the sex hormones

The article provides a review of the clinical and experimental data, both published and the author's own observations. They demonstrate that the hormone regulation of sex behaviour takes place at the central and the peripheral levels. The major role is played by androgenes, of which testosterone is the main regulator of sex appeal (libido, courtship behaviour in animals), while the most important regulator of ejaculation, in particular, of the time of ejaculation, is the non-aromatized androgene dihydrotestosterone (DHT). There is no rigid correlation between the level of sex activity and the level of androgenes, if the latter are within the normal individual and physiological range. However, both in case of hypo- and hyperendrogeny, the observations indicate depression of sexuality, though the mechanism of the depression are different. The author established the optimal levels of androgenes, which maintain the individual elements of the sexual act. The role of estrogene in regulation of the male sex appeal is not yet clear. As a rule, use of estrogenes results in depression of the male sexuality. At the same time, combination of DHT and estradiole (in laboratory and productive animals) leads to normalisation of erection and ejaculation disorders. These result is, probably, due to the central effect of estrogene, which prolongs the DHT effect and censures its accelerated penetration into cellular neuronal structures, as well as to the peripheral effect of DHT.     

Characterization of p-chloroamphetamine-induced penile erection and ejaculation in anesthetized rats

Methodological shortcomings present in elicitation of male sexual reflexes in anesthetized animals. The present study has demonstrated, however, that intraperitoneal (i.p.) injection of p-chloroamphetamine (PCA), an indirect serotonin (5-HT) agonist, elicited simultaneously both penile erection and ejaculation in anesthetized rats. PCA (2.5-10.0 mg/kg, i.p.) caused an intermittent cluster of genital responses consisting of penile erection, glans erections, and penile cups, which closely resembles the response observed during the ex copula tests in unanesthetized rats. Measurements of intracavernous penile pressure showed that rhythmic changes in penile pressure were produced by PCA, together with glans erections and penile cups. PCA also caused a frequent ejaculations and the weighing of ejaculate accumulated over 0.5 hr was increased in a bell-shaped pattern, and the maximum effect was observed at 5.0 mg/kg. Pretreatment with p-chlorophenylalanine, a serotonin (5-HT)-synthesis inhibitor, significantly inhibited the expression of PCA-induced penile erection and ejaculation, while acute spinal transection at thoracic level did not affect the sexual responses. These results indicate that PCA-induced penile erection and ejaculation in anesthetized rats are mainly produced by the release of 5-HT, which is limited to the lower spinal cord and/or the peripheral sites. Furthermore, the sexual responses can be easily and reliably elicited by administration of PCA, which may be useful for the study of the mechanisms underlying male sexual functions.     

Changes of the neuropeptides content and gene expression in spinal cord and dorsal root ganglion after noxious colorectal distension

Visceral pain/hypersensitivity is a cardinal symptom of functional gastrointestinal disorders. With their peripheral and central (spinal) projections, sensory neurons in the dorsal root ganglia (DRG) are the "gateway" for painful signals emanating from both somatic and visceral structures. In contrast to somatic pain, the neurochemical pathways involved in visceral pain/hypersensitivity have not been well studied. We hypothesized the neuropeptide changes in spinal cord and DRG during visceral pain would mirror similar changes in somatic nociception. Noxious (painful) colorectal distension (CRD) was done by distending a rectal balloon up to 60 mm Hg phasically for 1 h in Sprague-Dawley rats. The spinal content of calcitonin gene-related peptide (CGRP), substance P (SP), galanin and vasoactive intestinal peptide (VIP) as well as their mRNAs in DRG were measured at 0, 4 and 24 h after the CRD. Visceromotor reflex (VMR) was measured by recording the electromyogram at the abdominal muscle in response to CRD. Distal colorectum was removed for evaluating the presence of inflammation. No significant evidence of histological inflammation was seen in the colonic mucosa/submucosa after repeated CRD, which is confirmed by myeloperoxidase assay. The spinal content of CGRP and SP decreased significantly 4 h after CRD, while galanin and VIP levels increased gradually and reached highest level at 24 h (p<0.05). The mRNAs in DRG of the neuropeptides were significantly upregulated after CRD (p<0.05). VMR recording showed the rat's colon became hypersensitive 4 h after CRD, a sequence parallel to the spinal changes of CGRP and SP in timeframe. Noxious mechanical distension of the colorectum causes an acute change in the spinal levels of excitatory neurotransmitters (CGRP and SP), probably reflecting central release of these peptides from sensory neurons and contributing to the hypersensitivity following the noxious CRD. This is followed by a slower change in the levels of the inhibitory neurotransmitter galanin and VIP. Such stimulation results in significant alternation of the gene expression in DRG, reflecting the plasticity of the neuronal response. In the absence of visceral inflammation, the aforementioned neuropeptides are important mediators in the processing of visceral pain/hypersensitivity.     

The organizational hypothesis and final common pathways: Sexual differentiation of the spinal cord and peripheral nervous system

In honor of the 50th anniversary of the “organizational hypothesis,” this paper reviews work on sexual differentiation of the spinal cord and peripheral nervous system. Topics considered include the spinal nucleus of the bulbocavernosus, the ejaculation center, the cremaster nucleus, sensory and autonomic neurons, and pain. These relatively simple neural systems offer ample confirmation that early exposure to testicular hormones masculinizes the nervous system, including final common pathways. However, I also discuss findings that challenge, or at least stretch, the organizational hypothesis, with important implications for understanding sex differences throughout the nervous system.     

Commande nerveuse peripherique de l’erection

Local mechanisms causing penile erection and detumescence result from variation in tone of vascular and trabecular smooth muscles and in a lesser part of striated muscles around the crura penis. All these events are neurally mediated. We reviewed human and animal data concerning the functional peripheral neuroanatorny of erection. General organization of peripheral nervous system is recalled. Somatic efferents of the pudendal nerve, originating in the sacral spinal cord, innervate the striated musculature of the perineum. Somatic afferents of the penis are conveyed by the dorsal penile nerve, a branch of the pudendal nerve. Afferent terminations project into the spinal cord, their role is discussed. Parasympathetic pathways are involved in the reflexogenic erections. Sympathetic pathways destinated to the erectile structures are more complex. They are issued from thoracolumbar spinal cord and travel through the hypogastric nerve or the lumbosacral sympathetic chain. Sympathetic fibers originating in the sacral sympathetic chain are present in both pelvic and pudendal nerves. Inhibitory role on the erection of the sympathetic nervous system is well-known, it could be also responsible for psychogenic erections. Parasympathetic and sympathetic fibees are mixed in the pelvic plexus and the cavernous nerves which are described. Relations between the four sets of peripheral nerves (somatic efferents, penile afferents, thoracolumbar sympathetic sacral parasympathetic and sympathetic) are discussed.     

Blessé médullaire: prise en charge en andrologie

Sexual reactions are under neurological control. Spinal cord trauma alters neurological structure and induces sexual dysfunction. Pharmacological drugs used currently allow erectile function to be recovered in spinal cord-injured men, an essential step towards the resumption of a sex life. Triggering of ejaculation is often difficult. Perineal stimulation techniques, used either in isolation or in association with pharmacological treatment, promote ejaculation and allow sperm collection and freezing. The possibility of achieving ejaculation during sexual intercourse in spinal cord-injured men remains rare and there is as yet no real therapy available. Despite poor semen quality, spinal cord-injured men maintain reproductive possibilities in 40 to 60% of couples. The use of assisted reproductive technologies is often required. Management of sexual dysfunction in spinal cord-injured men must be integrated into a rehabilitation and re-insertion programme.     

Physiology and physiopathology of somatic sensations studied in man by the method of evoked potentials

The physiology of somatic sensation can be investigated noninvasively in man by recording the electric activity of peripheral nerves, spinal cord and brain. Since these responses have a small voltage, it is necessary to use electronic averaging methods for improving the signal-to-noise ratio. These methods are described and discussed, as well as principles of interpretation of somatosensory evoked potentials. It is agreed that the traces thus obtained involve a series of components (extracellular potentials) which reflect distinct neural generators. These generators have been identified and localized at different levels of the subcortical somatosensory pathway and in different cortical areas. Several components reflect generators located under the recording electrodes (nearfield potentials), while other reflect extracellular potentials diffusing at a distance in the volume conductor of the neck and head (farfield potentials). The analysis of these components provides a wealth of new data for the physiology and pathophysiology of the somatic sensory system in man. Besides so-called "obligatory" components that are present irrespective of the attention of the subject, the studies have uncovered "cognitive" components which reflect neural mechanisms involved in the intellectual processus of perception and decision.     

Characterization of somatic embryo attached structures in Feijoa sellowiana Berg. (Myrtaceae)

The presence of an attached organ to somatic embryos of angiosperms connecting the embryo to the supporting tissue has been a subject of controversy. This study shows that 67% of the morphologically normal somatic embryos of Feijoa sellowiana possess this type of organ and that its formation was not affected by culture media composition. Histological and ultrastructural analysis indicated that the attached structures of somatic embryos displayed a great morphological diversity ranging from a few cells to massive and columnar structures. This contrast with the simple suspensors observed in zygotic embryos which were only formed by five cells. As well as the suspensor of zygotic embryos, somatic embryo attached structures undergo a process of degeneration in later stages of embryo development. Other characteristic shared by zygotic suspensors and somatic embryo attached structures was the presence of thick cell walls surrounding the cells. Elongated thin filaments were often associated with the structures attached to somatic embryos, whereas in other cases, tubular cells containing starch grains connected the embryo to the supporting tissue. These characteristics associated with the presence of plasmodesmata in the cells of the attached structures seem to indicate a role on embryo nutrition. However, cell proliferation in the attached structures resulting into new somatic embryos may also suggest a more complex relationship between the embryo and the structures connecting it to the supporting tissue.     

Localization and interaction of N-methyl-D-aspartate and non-N-methyl-D-aspartate receptors of lamprey spinal neurons.

Small volumes of N-Methyl-D-Aspartate (NMDA) and non-NMDA excitatory amino acid receptor agonists were applied to localized regions of the dendritic trees of lamprey spinal neurons along their medial-lateral axis to obtain a spatial map of glutamate receptor distribution. Voltage clamp and frequency domain methods were used to obtain quantitative kinetic data of the voltage dependent ionic channels located both on the soma and on highly branched dendritic membranes. Pressure pulses of NMDA applied to the most peripheral regions of the dendritic tree elicited large somatic impedance increases, indicating that the most peripheral dendrites are well supplied with NMDA receptors. Experiments done with kainate did not elicit somatic responses to agonist applications on peripheral dendrites. The data obtained are consistent with the hypothesis that the activation of NMDA receptors by exogenous glutamate is significantly modified by the simultaneous activation of non-NMDA receptors, which shunts the NMDA response. The non-NMDA shunting hypothesis was tested by a combined application of kainate and NMDA to mimic the action of glutamate showing that the shunting effect of non-NMDA receptor activation virtually abolished the marked voltage dependency typical of NMDA receptor activation. These data were interpreted with a compartmental neuronal model having both NMDA and non-NMDA receptors.     

Seminal plug expulsion induced by electrical stimulation of the intermesenteric nerve in anesthetized rats

Synchronized activation of autonomic and somatic divisions of the nervous system respectively destined to the seminal tract, including the bladder neck and the pelvi-perineal striated musculature, is necessary for anterograde ejaculation. We aimed at investigating the role of intermesenteric nerves (IMNs) in ejaculation in anesthetized rats. Electrical stimulation of intact IMNs and distal and proximal stumps of the sectioned IMN were tested in isoflurane-anesthetized male rats. Electrical stimulation of the intact IMN was also applied to rats with acute spinal transection at the T8 level. The effects of IMN electrical stimulation on emission and expulsion phases of ejaculation were evaluated by measuring seminal vesicle pressure (SVP) and bulbospongiosus (BS) muscle contractions, respectively. IMN electrical stimulation could induce SVP increase and rhythmic contractions of BS muscle concomitantly with expulsion of the seminal plug. When compared with intact IMN electrical stimulation, the occurrence of ejaculation and rhythmic BS muscle contractions, but not SVP increase, was reduced in response to electrical stimulation of the distal stump of the sectioned IMN. In comparison to intact IMN electrical stimulation, the occurrence of ejaculation and rhythmic BS muscle contractions was not significantly modified, whereas the increase in SVP was diminished when the proximal stump of the sectioned IMN was stimulated. Spinalization abolished ejaculation and rhythmic BS muscle contraction but did not impair SVP increase. It is concluded that both afferents conveyed by IMN and relaying supraspinally and efferents of IMN are involved in IMN electrical stimulation-induced ejaculation. We propose that the IMN electrical stimulation paradigm can be used to investigate physiological and pharmacologic aspects of ejaculation.     

Diversity of neurohormonal release sites in insects: Neurohemal areas associated with peripheral neurosecretory cells in Periplaneta americana L. (Dictyoptera: Blattidae) and Locusta migratoria R. & F. (Orthoptera : Locustidae)

Neurohemal areas are located on the distal region of the transverse nerve and on the link nerve of the cockroach, Periplaneta americana (Dictyoptera : Blattidae) and the locust, Locusta migratoria (Orthoptera : Locustidae). They constitute the sites at which the peripheral neurosecretory cells on these nerves discharge their products. Histological and ultrastructural studies suggest that, at least in Periplaneta, these areas also serve to release neurosecretory products different from those found in the perisympathetic organs (POs). These products come from the ganglion cells, some of them via the transverse nerve, and others, via the somatic nerves. The existence of these neurohemal areas broadens the problem of the release zones and shows that the POs are not the only neurohemal structures associated with ventral ganglion cells. An attempt is made to explain the reason for the existence of these different release sites, as well as the role of the peripheral cells.     

Expression of the QrCPE gene is associated with the induction and development of oak somatic embryos

Somatic embryogenesis is a powerful tool for plant regeneration and also provides a suitable material for investigating the molecular events that control the induction and development of somatic embryos. This study focuses on expression analysis of the QrCPE gene (which encodes a glycine-rich protein) during the initiation of oak somatic embryos from leaf explants and also during the histodifferentiation of somatic embryos. Northern blot and in situ hybridization were used to determine the specific localisation of QrCPE mRNA. The results showed that the QrCPE gene is developmentally regulated during the histodifferentiation of somatic embryos and that its expression is tissue- and genotype-dependent. QrCPE was strongly expressed in embryogenic cell aggregates and in embryogenic nodular structures originated in leaf explants as well as in the protodermis of somatic embryos from which new embryos are generated by secondary embryogenesis. This suggests a role for the gene during the induction of somatic embryos and in the maintenance of embryogenic competence. The QrCPE gene was highly expressed in actively dividing cells during embryo development, suggesting that it participates in embryo histodifferentiation. The localised expression in the root cap initial cells of cotyledonary somatic embryos and in the root cap of somatic seedlings also suggests that the gene may be involved in the fate of root cap cells.     

Activation of Mu or Delta Opioid Receptors in the Lumbosacral Spinal Cord Is Essential for Ejaculatory Reflexes in Male Rats

Ejaculation is controlled by a spinal ejaculation generator located in the lumbosacral spinal cord, consisting in male rats of lumbar spinothalamic (LSt) cells and their inter-spinal projections to autonomic and motor centers. LSt cells co-express several neuropeptides, including gastrin releasing peptide (GRP) and enkephalin. We previously demonstrated in rats that GRP regulates ejaculation by acting within the lumbosacral spinal cord. In the present study, the hypothesis was tested that enkephalin controls ejaculation by acting on mu (MOR) or delta opioid receptors (DOR) in LSt target areas. Adult male rats were anesthetized and spinalized and received intrathecal infusions of vehicle, MOR antagonist CTOP (0.4 or 4 nmol), DOR antagonist (TIPP (0.4, 4 or 40 nmol), MOR agonist DAMGO (0.1 or 10 nmol), or DOR agonist deltorphin II (1.3 or 13 nmol). Ejaculatory reflexes were triggered by stimulation of the dorsal penile nerve (DPN) and seminal vesicle pressure and rhythmic contractions of the bulbocavernosus muscle were analyzed. Intrathecal infusion of MOR or DOR antagonists effectively blocked ejaculatory reflexes induced by DPN stimulation. Intrathecal infusion of DAMGO, but not deltorphin II triggered ejaculation in absence of DPN stimulation. Both MOR and DOR agonists facilitated ejaculatory reflexes induced by subthreshold DPN stimulation in all animals. Overall, these results support the hypothesis that enkephalin plays a critical role in the control of ejaculation in male rats. Activation of either MOR or DOR in LSt target areas is required for ejaculation, while MOR activation is sufficient to trigger ejaculation in the absence of sensory stimulation.     

Electromyography of pelvic floor muscles

Pelvic floor muscles (PFM) are intimately involved in function of lower urinary tract, the anorectum and sexual functions, therefore their neural control transcends the primarily important somatic innervation of striated muscle, as they are directly involved in “visceral activity”. Neural control of pelvic organs is affected by a unique co-ordination of somatic and autonomic motor nervous systems. Visceral and somatic sensory fibres supply sensory information from pelvic organs; their input influences through central integrative mechanisms also pelvic floor muscle activity. Anatomically, somatic afferent and efferent nerves of the sacral cord segments, reflexly integrated at the spinal cord and brainstem level, conduct neural control of PFM. The inputs from several higher centres influence the complex reflex control and are decisive for voluntary control, and for socially adapted behaviour related to excretory functions.     

Genotype-phenotype correlations for nervous system tumors in neurofibromatosis 2: a population-based study

Neurofibromatosis 2 (NF2) is an autosomal dominant disease that is characterized by tumors on the vestibular branch of the VIII cranial nerve, but other types of nervous system tumors usually occur as well. Genotype-phenotype correlations are well documented for overall NF2 disease severity but have not been definitively evaluated for specific types of non-VIII nerve tumors. We evaluated genotype-phenotype correlations for various types of non-VIII nerve tumors in 406 patients from the population-based United Kingdom NF2 registry, using regression models with the additional covariates of current age and type of treatment center (specialty or nonspecialty). The models also permitted consideration of intrafamilial correlation. We found statistically significant genotype-phenotype correlations for intracranial meningiomas, spinal tumors, and peripheral nerve tumors. People with constitutional NF2 missense mutations, splice-site mutations, large deletions, or somatic mosaicism had significantly fewer tumors than did people with constitutional nonsense or frameshift NF2 mutations. In addition, there were significant intrafamilial correlations for intracranial meningiomas and spinal tumors, after adjustment for the type of constitutional NF2 mutation. The type of constitutional NF2 mutation is an important determinant of the number of NF2-associated intracranial meningiomas, spinal tumors, and peripheral nerve tumors.