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[Inhibin: new gonadal hormone (author's transl)].

There are many convincing arguments to accept the existence of inhibin. This hormone is produced inside the seminiferous tubules by the Sertoli cells in males and by the granulosa cells of the follicule in females. The biological, immunological and chemical characteristics of testicular and ovarian inhibin are identical so that it could be speculated the same molecule is secreted by both organs. This hormone is not a knownsteroid but is a protein substance. Thus, its biological activity is destroyed by trypsin and pepsin digestion and by heating at 60 degrees for 30 minutes. Furthermore, immunization with inhibin from rete testis fluid induces antibodies capable of neutralizing endogenous inhibin of adult male and female rats. This polypeptide hormone is not identical neither to ABP nor to a fragment of gonadotrophins. The molecular weight is not yet exactly defined and the possibility exists that two forms of inhibin are present in RTF: one of high (greater than 10,000 Daltons) and the other of low molecular weight. The high M.W. species could be a polymer or alternatively the combination of native inhibin and a carrier substance or unique precursor molecule. Inhibin preparations selectively depress the synthesis and the release of FSH in pituitary cell culture. The threshold dose to affect the LH production is higher than that active on FSH secretion. Furthermore, they reduce LH-RH content of hypothalamus maintained in organ culture. In animals, inhibin induced effects are depending on both hypothalamus and pituitary actions according to the functions of these two structures. In that sense, apparently contradictory results are obtained in short and long term castrated animals. Inhibin does not modify TSH, GH and prolactin in vivo and in vitro. This substance displays an inhibition on the synthesis of DNA in the testis of pubertal male rats and depresses the maturation of follicle in female.

Animals↗

[ABP: the testicular protein that binds androgens].

ABP is a protein found in the testicular cytosol or secreted by Sertoli cells in the rete testis fluid. It has a high affinity for androgers and binds specifically 5 alpha-DHT and testosterone (but to a lesser extent). The binding capacity is saturable. ABP is measured by steady state polyacrylamide gel electrophoresis or by separation on dextran coated charcoal. ABP moves from testis to epididymis where its binding activity is totally or partially destroyed from caput to cauda epididymis. In some species (ram, bull, billy goat) but not in others (human, boar, stallion) ABP is present in the seminal plasma of the ejaculate. In some species like the rat, ABP is also secreted in the testicular blood stream by Sertoli cells through the basement membrane of the seminiferous tubules. ABP varies with age and with season. Its production is under separate endocrine control of FSH and testosterone and its transport from testis to epididymis is specifically controlled by FSH. Through its binding activity, ABP may play a role in spermatogenesis and epididymal sperm maturation by enhancing the local concentration of androgens around the germinal cells and the male gametes. However ABP is not present in some species, like the pig, although their spermatogenesis and epididymal sperm maturation are normal.

Age Factors↗

[Congenital or acquired obstructions of the human epididymis: study of the motility of the spermatozoa above the obstruction].

Azoospermia is frequently due to an obstruction of genital pathways. In this work, concerning 22 patients submitted to surgical investigation for sterility, we made a systematic histological investigation of the lesions, and we studied the motility of epididymal spermatozoa. We observed with an unexpected frequency abnormalities of junctions either between seminiferous tubules and efferents ducts - leading to disappearance of rete testis - or between efferent ducts and epididymis. In each case a fibrosis of the epididymis was discovered, the consequence was either an interruption or, more frequently a simple narrowing of the lumen of the epididymal duct. The presence of spermiophages which destroyed all spermatozoa, was also systematically observed. The origin of the lesions (congenital, inflammatory, ischemic... ) could not be determined by simple histological study. Motility of spermatozoa was generally observed in the initial portion of the epididymal duct, but motile spermatozoa were sometimes still observed in the efferent tubules. Motility could be initiated by caffeine while other compounds as albumin, seminal plasma and different organic substrates, had no effects.

Epididymis↗

On the ultrastructure of modified Sertoli cells in the terminal segment of seminiferous tubules in the boar.

The seminiferous tubules are linked to the tubuli recti by a short terminal segment which is lined by a single layer of modified Sertoli cells whose long cytoplasmic processes occlude the lumen and form a plug-like structure in the 'receptacle. The main features of the modified Sertoli cells are: enormous numbers of microtubules and microfilaments, many crystalloids, abundance of rough endoplasmic reticulum, and paucity of smooth endoplasmic reticulum. The intercellular spaces are considerably dilated, and the cells posses intracellular spaces having well developed microvilli. Degenerated spermatozoa were seen engulfed by the modified Sertoli cells. Desmosome-like devices and tight junctions were observed joining adjacent cells. The configuration of the epithelium and the fine structure of the cells of the terminal segment are discussed in relationship to their possible roles as modifiers of the seminiferous tubule fluid and as regulators of fluid reflux from the rete testis into the seminiferous tubules.

Animals↗

[Distribution of ABH substances in normal secretor human tissue cells by avidin-biotin complex method].

The distribution and location of ABH substances in 54 various kinds of normal secretor human tissue cell of known ABO type were studied by Avidin-Biotin complex (ABC) method. It was firstly demonstrated that 18 different kinds of tissue cells contained ABH substances, which were as follows: neuron and nerve fiber, astrocyte, oligodendrocyte, ependyma epithelial cells, epithelial cells of soft meninges, epithelial cells of parotid gland duct, taste bud cells of tongue, acinar and epithelial cells of duct of buccal gland, epithelial cells of rectal mucous membrane gland, regenerated liver cells of hepatocirrhosis, basal cells of stratified aquamous epithelium of epiglottis, spermiogenesis and spermatozoa of seminiferous tubules, epithelial cells of tubuli reti, rete testis and tubuli epididymis, both primary and secondary follicles of ovary and decidua cells of endometrium. Some new phenomena were observed as follows: ABH substances in chief cells more than those in parietal cells of gastric gland, locally distributed ABH positive cells in stratum spinosum of stratified squamous epithelium of skin, segmentally distributed ABH positive cells in pseudostratified ciliated columanal epithelium of epiglottis. The ABH substances were located at the infranuclear and/or supranuclear region and/or brush border of the epithelial cells of submaxillary gland, mosaic distributed ABH substances were found in the epithelia of both sweat and submaxillary glandular ducts. A few controversies about distribution of ABH substances were solved. The relationship between H and A, B substances, origin of ABH substances, source of ABH substances in body fluids. Production of ABH substances and cell differentiation, mosaicism and inconsistency of ABH distribution are discussed and compared with other reports.(ABSTRACT TRUNCATED AT 250 WORDS)

ABO Blood-Group System↗

Epithelial monolayers from human epididymal and efferent duct tubules; testosterone metabolism and effects of culture conditions on cell height and confluence.

Corpus epididymal and efferent duct epithelial cells on permeable supports formed confluent monolayers that resisted hydrodynamic equilibrium and created electrical resistance. Monolayers were formed sooner and were of better quality when fetal bovine serum (FBS), rather than bovine serum albumin (BSA), was present in glucose-free, rather than glucose-containing, media. Testosterone was converted to androstenedione by both cell types and conversion of both steroids to 5 alpha-reduced metabolites was higher in cells from the corpus epididymidis than from efferent ducts. Addition of heat-treated human spermatocoele fluid (similar to rete testis fluid) to the apical aspects of the cells increased cell heights when they were initially low, but some cytoplasmic damage was observed. New serum-free media (especially those designed for keratinocytes and mammary epithelial cells) could maintain cultured cells at heights found in situ.

Aged↗

Epididymal cribriform hyperplasia. A variant of normal epididymal histology.

We describe a case of orchiectomy for testicular germ cell neoplasm with a peculiar associated cribriform hyperplasia of the epididymis. The process, which we have termed epididymal cribriform hyperplasia (ECH), is tantalizingly akin to patterns of cribriform ductal carcinoma in situ of the female breast and is characterized by complex arcades and cellular bridges spanning dilated epididymal lumina. The cells lining these interconnecting arches have hyperchromatic nuclei, but lack significant atypia or mitotic activity. A limited search of the Vanderbilt University Medical Center (Nashville, Tenn) surgical pathology files produced 30 cases with evaluable epididymis, 15 of which had some degree of ECH. The ECH occurred in a broad age range with a mean of 40 years. No association of ECH with testicular germ cell neoplasia, adenomatous hyperplasia of the rete testis, or parenchymal atrophy could be documented. We conclude that ECH is a seldom recognized variant of normal epididymal histologic appearance that may be present in up to half of epididymides.

Adolescent↗

[Epididymal fine needle aspiration replacing vasography].

Epididymal fine needle aspirations (EFNA) were performed on 29 epididymides of 17 infertile, azoospermic men in whom testicular cytology revealed adequate spermatogenesis. Sonograms confirmed the presence of all the excretory male organs. EFNA was performed to diagnose and locate the site of genital tract occlusion. The presence of cuboidal epithelial cells in the aspirate was the sole indication that epididymal content was aspirated. In 10 (34%) of the 29 aspirates there were only cuboidal epithelial cells and no spermatozoa, indicating proximal occlusion in the rete testis, in the canaliculi efferents or in the most proximal segment of the epididymis itself. Occlusion in the distal segments of the epididymis or in the vas deferens was diagnosed in 13 epididymal aspirates (45%) which contained both cuboidal cells and spermatozoa. In 6 epididymides (21%) no conclusion could be reached because of failed aspirations. There are a variety of treatment modalities available for male genital tract obstruction, such as reconstructive surgery or IVF. The success rate of treatment is mainly dependent on the site of obstruction. Since vasography has its own limitations and hazards, diagnostic EFNA should be performed before treatment in men in whom genital obstruction is suspected.

Biopsy, Needle↗

Target sites for suppressing fertility in the male.

The present status and perspectives in the control of fertility in the male have been reviewed. There are two potential sites in the male reproductive processes that can be used as targets for regulation of fertility in the male: (1) inhibition of spermatogenesis, and (2) interference with sperm maturation in the epididymis. A variety of compounds tested for their antispermatogenic action in laboratory animals have no future for the control of fertility in the human male because of a number of undesirable side effects (cf. Prasad, 1973). Progestational compounds inhibit spermatogenesis by affecting the hypothalamo-hypophysial system and result in impairment of libido. The possibility of adjustment of the minimal dose of progestational compounds required to induce suppression of spermatogenesis and reduction of plasma testosterone to a level compatible with the maintenance of normalcy of libido and potency needs to be studied. A new approach to contraception in the male involves the use of a combination of progestational compounds for suppression of spermatogenesis along with testosterone (administered through silastic capsule implants or as intramuscular injections) for maintenance of libido and accessory sex gland function. A number of such combinations have been tested clinically with some success. However, the limitations of side effects, such as weight gain, gynecomastia, and psychological complications preclude their long-term use for contraception in man. Short-term use of these combination regimens by the male for 1 year followed by use of a contraceptive method by the female may be desirable to encourage partnership in family planning. Although testosterone and other androgens suppress spermatogenesis in man, the feasibility of their use for contraception depends on the establishment of a dosage and mode of adminstration that provide antispermatogenic action without causing more general metabolic alterations. Inhibition of spermatogenesis by selective interference with the action of FSH on the Sertoli cells by active or passive immunization or by selective suppression of synthesis and release of FSH by administration of "Inhibin" offers exciting possibilities in the control of fertility in the male. Studies on the physiology of the rete testis highlight its importance as a post-tubular site of action of antifertility agents in conveying (to the epididymis) compounds interfering with epididymal functions and/or viability of spermatozoa. A new approach to the induction of functional sterility in the male by selective alteration of epididymal function by a local androgen deprivation effect has been successfully tested in clinical trials. Small doses of cyproterone acetate, administered orally, result in maintenance of libido and accessory sex gland function accompanied by a decrease in the motility of ejaculated spermatozoa and incomplete inhibition of spermatogenesis...

Androgen Antagonists↗

Pregnancy caused by sperm from vasa efferentia.

Pregnancies induced by sperm from the vasa efferentia are extremely rare. We report on a 37-year-old male with obstructive azoospermia. An anastomosis between the vas and the rete testis region was carried out by microsurgery on the left side. A healthy male baby was born in March 1993. Paternity was proved by DNA fingerprinting.

Adult↗

Retiform hemangioendothelioma. A distinctive form of low-grade angiosarcoma delineated in a series of 15 cases.

Fifteen cases of a distinctive type of low-grade angiosarcoma of the skin are described. Most tumors presented in the second to fourth decades of life, the youngest patient being 9 years old and the oldest 78 (mean age, 36 years). There was no sex predilection. Six tumors arose on the lower limb, four on the upper limb, three on the trunk, and one each on the penis and the scalp. One case arose in the setting of chronic lymphedema and another following radiotherapy for carcinoma of the uterine cervix. Distinctive morphologic features were the presence of long arborizing blood vessels arranged in a retiform pattern (reminiscent of normal rete testis) lined by monomorphic hobnail endothelial cells, a very prominent lymphocytic infiltrate in most cases, and the focal presence of papillae with hyaline collagenous cores, similar to those seen in malignant endovascular papillary angioendothelioma (Dabska's tumor). With a median follow-up of 7.25 years in 14 cases, retiform hemangioendothelioma has proved to be a low-grade neoplasm that recurs frequently but has a very low metastatic rate. The single regional lymph node metastasis in this series was from a case with a biphasic pattern in which only the spindle cell component was represented in the metastasis. There have been no tumor-related deaths, underlining the importance of accurate distinction from conventional angiosarcoma. This distinction is facilitated principally by the absence of dissection between individual collagen bundles and the absence of endothelial atypia or mitotic activity. The precise relationship between retiform hemangioendothelioma and Dabska's tumor is uncertain, possibly because cases of the latter may not be homogeneous.

Adolescent↗

[Organ saving therapy of bilateral testicular tumor].

Of 368 patients with unilateral testicular cancer, 12 (3.3%) suffered from a second malignant germ cell tumor; five tumors occurred synchronously, seven were treated by bilateral orchiectomy, five were treated by unilateral organ sparing surgery with enucleation of the germ cell tumor in a pilot study. Enucleation was performed for four seminomas and one embryonal carcinoma; an associated carcinoma was found in situ in three cases. The average follow-up time for patients treated conservatively is 22 months; no local recurrence has been detected. Testosterone synthesis is sufficient to obtain normal serum androgen levels. Organ sparing surgery for testicular cancer is possible if the following prerequisites are met: pT 1-tumor, no infiltration of the rete testis, biopsies of the tumor bed are negative, biopsies from peripheral parenchyma are taken and any associated carcinoma in situ is irradiated with 20 Gy.

Combined Modality Therapy↗

Organ-specific binding system for beta-galactosidase in the male reproductive tract.

This study reports on the binding of beta-galactosidase obtained from different organs of the rat urogenital tract to membranes of these organs. Homologous and cross binding saturation assays indicated that: (1) high-affinity sites that recognize fructose-6-phosphate derivates (FPR) are present in spermatozoa from the rete testis, epididymal membranes and testes, although the latter may reflect binding to testicular spermatozoa; (2) the membranes of the other organs studied do not have FPR; (3) the FPR of the epididymis does not recognize enzymes purified from other organs of the reproductive tract. These results suggest that the FPR-binding system belongs to a peculiar transport route that permits maturing spermatozoa to acquire hydrolytic enzymes secreted by the epididymal epithelium. In the epididymis and seminal vesicles more than 50% of the enzymatic activity of beta-galactosidase was recovered in cytosol, suggesting that the enzyme is located mainly in the secretory fluid of these organs.

Animals↗

The use of epididymal fine-needle aspiration for the diagnosis of male genital tract obstruction.

Epididymal fine-needle aspirations (EFNA) were performed on 29 epididymides of 17 infertile, azoospermic men in whom testicular cytology revealed adequate spermatogenesis. Sonograms confirmed the presence of all the excretory male organs. EFNA was performed to diagnose and locate the site of genital tract occlusion. The presence of cuboidal epithelial cells in the aspirate was the sole indication that epididymal content was aspirated. In 10 (34%) of the 29 aspirates there were only cuboidal epithelial cells and no spermatozoa, indicating proximal occlusion in the rete testis, in the canaliculi efferentes or in the most proximal segment of the epididymis itself. Occlusion in the distal segment of the epididymis or in the vas deferens was diagnosed in 13 epididymal aspirates (45%) which contained both cuboidal cells and spermatozoa. From 6 epididymides (21%) no conclusion could be reached because of failed aspirations. There are a variety of treatment modalities available for male genital tract obstruction, such as reconstructive surgery or assisted reproductive technology using sperm aspiration technique. The success rate of treatment is mainly dependent on the site of obstruction. Since vasography has its own limitations and hazards, diagnostic EFNA should be performed before treatment in men in whom genital obstruction is suspected.

Biopsy, Needle↗

[Indication and clinical value of vesiculodeferentography concerning urologic-andrologic diseases (author's transl)].

There are 29 cases of vesiculodeferentography (VDG) (1962-1975) presented. The very indication of VDG was the evaluation of azoospermia due to occlusion of the vas deferens, in addition to other urologic diseases. Especially from the andrologic point of view the various forms of occlusion-azoospermia are classified and analyzed. It is pointed out, that the rete testis region is not to be elucidated by VDG.

Blood↗

Estrogen receptor (alpha and beta) expression in the excurrent ducts of the adult male rat reproductive tract.

The understanding of estrogen's function in the male reproductive tract is limited, and estrogen receptor (ER) localization in the reproductive tract of the adult male rat has not been described. In the present study, ERalpha was localized by immunohistochemistry using ER21 antibody, which recognizes only ERalpha. Strongest immunoreactivity was seen in epithelia of ductuli efferentes and the initial segment of the epididymis. Nuclei of both ciliated and nonciliated cells were positive. The epithelium of the rete testis, and caput, corpus, and cauda epididymides stained less intensely for ERalpha. The vas deferens epithelium was ERalpha-negative. Stromal tissue in the excurrent ducts was also ERalpha-positive. Using 3H-estradiol autoradiography, specific binding of estradiol was seen in nuclei of ductuli efferentes. Estrogen receptor alpha mRNA expression was greatly enhanced in ductuli efferentes compared to other regions of the male tract and was 3.5x greater than in the uterus. For comparison, the presence of ERalpha was determined using reverse transcription-polymerase chain reaction (RT-PCR) amplification. Estrogen receptor beta mRNA was expressed throughout the male tract and in the prostate. These results indicate that all organs in the male excurrent ductal system of the rat express ERalpha and are potential targets of estrogen. However, the ductuli efferentes are the site of the most intense ERalpha expression. The role of ERbeta remains to be determined, but its expression appears ubiguitous in the male tract.

Animals↗

Cytoplasmic extrusion and the switch from creatine kinase B to M isoform are completed by the commencement of epididymal transport in human and stallion spermatozoa.

Although in several species there is a relationship between epididymal sperm transport and fertility, in human in vitro fertilization (IVF), spermatozoa recovered from the caput epididymidis or even the rete testis are fertile. We studied two objective markers of sperm maturity in the sperm of men and stallions: creatine kinase (CK) concentrations, which are a measure of cytoplasmic retention in immature spermatozoa, and the ratio of CK-M and CK-B isoforms (% CK-M/[CK-M + CK-B]), which is proportional to the incidence of mature sperm. The CK markers and the fertilizing function are closely related: Immature sperm with cytoplasmic retention do not bind to the zona, because during cytoplasmic extrusion, the sperm plasma membrane is also remodeled. We examined whether changes in sperm CK values are still ongoing during epididymal transport, or if cellular maturation is completed prior to the arrival of sperm in the caput epididymidis. The incidences of mature sperm in human caput and corpus epididymidis (studied in six men with obstructive azoospermia of various pathogeneses) were (mean+/-SEM) 55.7+/-2.2 and 49.3+/-7.6%, respectively; and the sperm CK-M ratios in the caput epididymidis of three men were 72, 75, and 70%, values that are similar to those of ejaculated sperm. In four segments of the proximal and distal epididymis of three stallions (the origin of sperm was also verified by the position of the cytoplasmic droplet) and in ejaculate of five stallions, the incidences of mature sperm were 88.2+/-6.2, 89.0+/-6.7, 90.3+/-7.8, 87.6+/-5.9, and 86.7+/-0.8%, and the respective CK-M ratios were 75.0+/-8.7, 84.2+/-2.9, 87.9+/-1.2, 92.5+/-1.5, and 69.3+/-3.5%. There were no differences in the incidences of mature and immature spermatozoa or in CK-M ratios among sperm arising from the various epididymal regions or from the ejaculate in men or stallions. Thus, the cellular maturation events in sperm, as detected by the CK markers, are completed by the time the sperm commences epididymal transport. These findings are in agreement with the IVF fertility of sperm aspirated from the male reproductive tract. The data may also suggest that the primary role of sperm epididymal transport in men is to remodel the plasma membrane to enhance sperm functional integrity in the diverse environments of the male and female reproductive tracts prior to fertilization.

Animals↗

Male germ cell transplantation: present achievements and future prospects.

Germ cells are unique, since their surviving descendants can undergo meiosis and differentiate into gametes, which transmit genetic material from one generation to another. We now know that male germ cells, whether they be primordial germ cells in gonadal ridges, gonocytes, or stem spermatogonia, are transplantable. The donor cells can be transferred by direct microinjection into the seminiferous tubules, rete testis or efferent ducts, depending on the recipient species. Following transplantation, the donor cells undergo spermatogenesis in the host's seminiferous tubules in rats and mice, and have even sired offspring in mice. Interspecific germ cell transfer is possible if the recipient's immune system is defective; nude or SCID mice can even produce rat spermatozoa. However, the major obstacle restricting widespread use of this new technology is its extremely low success rate. This article discusses some ideas for improving the success rate of the transfer technique, and considers several potential applications.

Animals↗