Surgical therapy in infertile men with ejaculatory duct obstruction: technique and outcome of a standardized surgical approach.
In severe oligozoospermia or azoospermia, low ejaculate volume, low ejaculate pH and little or no fructose in seminal plasma suggest an obstruction of the seminal pathways at the level of the prostate gland, when vasal aplasia and ejaculatory disorders are excluded. We report on our standardized surgical approach in 16 consecutive patients with this condition after clinical evaluation, semen analysis, endocrine assessment, testicular biopsy and transrectal ultrasonography. Pre-operatively, sperm analysis demonstrated typical low-volume ejaculates with azoospermia in 12 and severe oligozoospermia in four cases. Ultrasonography demonstrated seven central (Mullerian) and five lateral cystic lesions. Four cases with central obstruction revealed no ultrasonographic pathology. After intra-operative vasopuncture and vasography for definite localization of the level of obstruction, transurethral incision and/or resection of ejaculatory ducts (TURED) was performed. Patency was proven in 15 out of 16 cases by 'intra-operative chromotubation'. In nine out of 12 patients, spermatozoa could be harvested intra-operatively from the vas. During the follow-up of 12 months, post-operative ejaculates showed persistent patency in six out of seven Mullerian cysts with concomitant improvement of sperm quality. Only three of the other nine cases remained patent with the worst results in lateral cystic lesions. Only two of the patients with Mullerian cysts have fathered a child so far. The data provide evidence for the effectiveness of surgical treatment of ejaculatory duct obstruction, especially in the case of central cystic lesions. The combination of surgery, cryostoring of spermatozoa retrieved intra-operatively and the possible storage of ejaculated spermatozoa post-operatively creates the possibility of subsequently using reproductive techniques if pregnancy is not achieved. (+info)
Oestrogen in fluid transport in efferent ducts of the male reproductive tract.
This review focuses on the importance of oestrogen and oestrogen receptors in the male reproductive system, with a special interest in the newly discovered role of oestrogen in the regulation of fluid reabsorption in the efferent ductules of the testis. Early work on oestrogen synthesis indicated that Leydig and Sertoli cells were the only important cells in the production of this steroid in the adult testis. However, more recent work has shown that germ cells and spermatozoa also contain aromatase and produce oestrogen. The observation that germ cells synthesize oestrogen contributed to a new hypothesis that oestrogen in the lumen of the male reproductive tract targets the epithelial lining of efferent ductules and the epididymis. The location of nuclear oestrogen receptors in the male reproductive tract has also been investigated and it has been found that oestrogen receptor alpha is more abundant in the efferent ductules of the testis than in any other tissue of the male or female. In all species examined to date, oestrogen receptor alpha has been found to be abundant in the efferent ductules. The structure and function of the efferent ductules are taken into account as these tubules are responsible for the reabsorption of almost 90% of the luminal rete testis fluid. Thus, it was logical to hypothesize that oestrogen receptors play a role in the regulation of fluid reabsorption in efferent ductules. The oestrogen receptor alpha knockout mouse was used to help define this role of the receptor in males. In this animal model, the efferent ductules are altered markedly from a reabsorptive epithelium to a squamous epithelium devoid of lysosomes and endocytotic organelles. Although the separate roles for oestrogens and androgens in the regulation of fluid reabsorption are controversial and remain to be resolved, it is now established that loss of oestrogen receptor function in males interferes with the resorptive function of efferent ductules, a function that is essential for fertility. Future studies will focus on the biochemical and physiological mechanisms involved in the regulation of water and ion movement by oestrogen in the male reproductive tract. (+info)
Human ejaculatory duct: parameters of smooth muscle motor activity and modulatory role of autonomic drugs.
The contractile behaviour and effects of several autonomic drugs on the motor activity of human isolated ejaculatory ducts were investigated. Ejaculatory ducts exhibited spontaneous contractions characterised by an amplitude of 2.35 +/- 0.28 mN, a duration of 62. 9 +/- 3.72 s and a frequency of 0.64 +/- 0.014 waves min-1. Acetylcholine (10-5-10-4 m) induced a slight increase in basal tone and in the frequency of the contraction waves. These effects were suppressed by atropine (10-4 m). Noradrenaline (norepinephrine) increased the basal tone and frequency of spontaneous contractions in a dose-dependent manner. These responses were competitively inhibited by HEAT, a selective a1-adrenoceptor antagonist. These preliminary functional findings, indicating the presence of spontaneous motor activity of human ejaculatory ducts and its possible control by adrenergic agonists, suggests a physiological role for human ejaculatory duct in the propulsion of semen from the seminal vesicle towards the urethra. (+info)
Estrogen receptor alpha has a functional role in the mouse rete testis and efferent ductules.
Previous studies of the estrogen receptor-alpha knockout (alpha ERKO) in the male mouse demonstrate that the rete testis and efferent ductules are targets of estrogen. Because the alpha ERKO mouse lacks a functional estrogen receptor alpha (ER alpha) throughout development, it was not known whether the morphological and physiological abnormalities observed in the alpha ERKO male were due to developmental defects or to dysfunctions concurrent with the lack of ER alpha in the tissue. This study was designed to determine if treatment of normal wild-type (WT) mice with the pure antiestrogen, ICI 182,780, (ICI) could reproduce the morphological characteristics seen in alpha ERKO mice. Thirty-day-old male mice were treated for 35 days with either castor oil or ICI. Age-equivalent alpha ERKO mice were used for comparison. Light microscopic examinations of the reproductive tracts revealed dramatic changes in the efferent ductules of treated mice: a 1.7-fold increase in luminal diameter, a 56% reduction in epithelial cell height, a 60% reduction in brush boarder height of nonciliated cells, and an apparent reduction of the number of observable lysosomes and endocytotic vesicles. Testes of ICI-treated mice showed swollen rete testes area (6.5 times larger than control) and a 65% reduction in rete testis epithelium height. However, there were no significant changes in body and testis weights. These results indicate that ER blockage with ICI in WT mice results in morphological changes of the efferent ductules resembling those seen in alpha ERKO siblings of the same age. Based on this study, we conclude that ER alpha has a functional role in the mouse reproductive tract and the aberrant morphology observed in the efferent ductules of the alpha ERKO mouse is likely the result of a concurrent response to the lack of functional ER alpha, and not solely due to the lack of ER alpha during early developmental times. (+info)
Effect of vasectomy on P34H messenger ribonucleic acid expression along the human excurrent duct: a reflection on the function of the human epididymis.
Sperm surface proteins involved in fertilization can be added or modified during epididymal transit. P34H, a human epididymal-sperm protein, appears on the sperm acrosomal cap in the distal caput-proximal corpus epididymis. In previous studies, it was shown that P34H is present on spermatozoa in men of proven fertility, is absent in 50% of men presenting with idiopathic infertility, and that a high proportion of men with normospermic vasovasectomy produce spermatozoa deficient in this sperm surface protein. P34H mRNA was expressed in the principal cells of the epididymis of normal men, predominantly in the corpus region. Recently, results coming from the assisted reproductive technologies have questioned the importance of the human epididymis in sperm maturation. In order to understand the effect of obstruction on the physiological state of the human epididymis and its function in sperm maturation, we have analyzed the expression of P34H mRNA at the level of the vas deferens and along the epididymis of normal and vasectomized men. In situ hybridization experiments showed that obstruction of the vas deferens alters the pattern of P34H mRNA expression compared with the tract of normal tissues. The P34H transcript was detected in the proximal caput epididymis of vasectomized men at a much higher intensity than that observed in the same region of normal tissues, being restricted to the principal cells of the epididymal epithelium. Compared with the normal duct, the lumen of vasectomized men was distended throughout the duct and the height of the epithelium was maximal in the caput. P34H mRNA was detectable in vas deferens, was not affected by vasectomy, and a 912-base pair P34H transcript was restricted to the epithelial cells of the vas deferens. Thus, using P34H as a marker, these results show that vasectomy alters the pattern of gene expression along the human epididymis, and suggest that the vas deferens can be a major contributor to sperm maturation in certain situations. (+info)
Dual role of the Pax gene paired in accessory gland development of Drosophila.
The Drosophila Pax gene paired encodes a transcription factor that is required for the activation of segment-polarity genes and proper segmentation of the larval cuticle, postembryonic viability and male fertility. We show that paired executes a dual role in the development of male accessory glands, the organ homologous to the human prostate. An early function is necessary to promote cell proliferation, whereas a late function, which regulates the expression of accessory gland products such as the sex peptide and Acp26Aa protein, is essential for maturation and differentiation of accessory glands. The late function exhibits in main and secondary secretory cells of accessory glands dynamic patterns of Paired expression that depend in both cell types on the mating activity of adult males, possibly because Paired expression is regulated by negative feedback. The early Paired function depends on domains or motifs in its C-terminal moiety and the late function on the DNA-binding specificity of its N-terminal paired-domain and/or homeodomain. Both Paired functions are absolutely required for male fertility, and both depend on an enhancer located within 0.8 kb of the downstream region of paired. (+info)
We have characterized a glycosylated, 31 amino-acid peptide of 4932 Da isolated from Drosophila melanogaster males. The mature peptide contains a sugar moiety of 1184 Da at a NDT consensus glycosylation site and a disulfide bond. It is synthesized in the male ejaculatory duct via a 54 amino-acid precursor containing an N-terminal signal peptide and Arg-Lys at the C-terminus which is cleaved off during maturation. The gene contains an intron of 53 bp and is localized in the cytological region 99B of the D. melanogaster genome. The peptide is therefore named DUP99B (for ductus ejaculatorius peptide, cytological localization 99B). The C-terminal parts of mature DUP99B and D. melanogaster sex-peptide (ACP70A) are highly homologous. Injected into virgin females, DUP99B elicits the same postmating responses as sex-peptide (increased oviposition, reduced receptivity). These effects are also induced by de-glycosylated native peptide or synthetic DUP99B lacking the sugar moiety. Presence of the glycosyl group, however, decreases the amount needed to elicit the postmating responses. Homologies in the coding regions of the two exons of DUP99B and sex-peptide, respectively, suggest that the two genes have evolved by gene duplication. Thus, we consider these two genes to be members of the new sex-peptide gene family. (+info)
Osteopontin expression and regulation in the testis, efferent ducts, and epididymis of rats during postnatal development through to adulthood.
Osteopontin (OPN), a multifunctional phosphoprotein found in both hard and soft tissues, was examined in the male reproductive tract. The expression and regulation of OPN in the rat testis, efferent ducts, and epididymis was examined during postnatal development through to adulthood using immunocytochemistry at the light- and electron-microscopic level. Immunoblot analysis revealed a major 30-kDa band for epididymal tissue and a major 60-kDa band for the testis. In the testis, immunostaining of OPN was noted in early germ cells from spermatogonia to early pachytene spermatocytes, suggesting a role for OPN as an adhesive protein binding these cells to the basement membrane and adjacent Sertoli cells. Nonciliated cells of the efferent ducts expressed OPN, whereas a cell- and region-specific distribution of OPN was observed in the epididymis. Reactivity of OPN in the apical region of the cell corresponded to labeling of microvilli, small endocytic vesicles, and endosomes, where OPN may serve to remove calcium from the epididymal lumen and, thus, prevent mineral accumulation and subsequent decrease in sperm fertility. Regulation and postnatal studies revealed that circulating androgens regulate OPN expression in principal cells of the epididymis only. Taken together, the data reveal cell- and region-specific expression and regulation of OPN in the epididymis. (+info)