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At least 973 records · Page 54Linked to original sources
PubMed1992

Effects of a simulated microgravity model on cell structure and function in rat testis and epididymis.

A tail-suspension (TS) rat model used to simulate microgravity was tested for its effects on the anatomy, cell structure, and function of the testis and epididymis in sexually mature male rats. Rats suspended for 7 days without inguinal canal ligation exhibited a significant (P less than or equal to 0.05) reduction in testis weight compared with controls (1.55 +/- 0.04 to 1.1 +/- 0.02 g). Except for the liver, epididymis, and adrenals of TS rats and TS rats allowed to recover for 7 days, no significant (P less than or equal to 0.05) change was observed in the weight of other body and accessory sex organs. A histological examination of the testes and epididymides of model animals revealed disorganized seminiferous tubules and accumulation of large multinucleated cells and spermatids in the lumen of the epididymis. A significant (P less than or equal to 0.05) increase in serum luteinizing hormone (53.1 +/- 6.7 to 66.2 +/- 10.1 ng/ml) and follicle-stimulating hormone (257 +/- 25 to 305 +/- 38 ng/ml) was observed in TS nonligated rats, whereas serum prolactin and testosterone levels were observed to decline from 8.3 +/- 1.3 to 5.1 +/- 0.29 and 7.1 +/- 1.3 to 3.8 +/- 0.25 ng/ml, respectively. Decreases in testis protein content and testosterone levels of the testis, interstitial fluid, and epididymis were also observed in model animals. These data demonstrate that the suspension procedure used in the National Aeronautics and Space Administration TS model results in the testis and epididymis translocating into the abdominal cavity, causing cellular degeneration and organ dysfunction.

Animals↗
PubMed2002

Cell junction dynamics in the testis: Sertoli-germ cell interactions and male contraceptive development.

Spermatogenesis is an intriguing but complicated biological process. However, many studies since the 1960s have focused either on the hormonal events of the hypothalamus-pituitary-testicular axis or morphological events that take place in the seminiferous epithelium. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli-germ cell communication, and junction dynamics. In this review, we discuss the physiology and biology of junction dynamics in the testis, in particular how these events affect interactions of Sertoli and germ cells in the seminiferous epithelium behind the blood-testis barrier. We also discuss how these events regulate the opening and closing of the blood-testis barrier to permit the timely passage of preleptotene and leptotene spermatocytes across the blood-testis barrier. This is physiologically important since developing germ cells must translocate across the blood-testis barrier as well as traverse the seminiferous epithelium during their development. We also discuss several available in vitro and in vivo models that can be used to study Sertoli-germ cell anchoring junctions and Sertoli-Sertoli tight junctions. An in-depth survey in this subject has also identified several potential targets to be tackled to perturb spermatogenesis, which will likely lead to the development of novel male contraceptives.

Animals↗
PubMed2006

Testicular xenografts: a novel approach to study cytotoxic damage in juvenile primate testis.

The underlying primary damage to the testis caused by chemotherapeutic regimens during childhood is largely unknown. Xenografting of monkey testes was successfully applied in maturation of juvenile testis to the point of complete spermatogenesis. This allows us to manipulate developing primate testis without direct treatment of patients. This new model is validated establishing the effects of cytotoxic treatment in the immature primate testis. Male castrated nude mice received eight s.c. grafts of juvenile monkey testicular tissue and, 28 weeks later, were injected with busulfan (38 mg/kg, i.p.) or vehicle. Graft numbers, size, and histology were examined. Grafts showed pubertal induction of spermatogenesis to the level of pachytene spermatocytes at point of busulfan treatment and further progressed to the level of round spermatids in control samples at 4 weeks. Busulfan treatment caused a statistically significant decrease in the number of seminiferous tubules containing germ cells. Type B spermatogonia and more advanced stages of spermatogenesis were depleted. A statistically significant decrease to pretreatment level was observed in the number of type A pale and centrally located spermatogonia. Busulfan did not affect type A dark spermatogonia. Occasionally, elongating spermatids were detected in busulfan-treated grafts. Observations show that busulfan selectively destroys differentiating spermatogonia whereas some of the spermatocytes present at the moment of cytotoxic insult are able to continue differentiation. Data indicate that xenografting of testicular monkey tissue is a valid approach to detect the busulfan-induced germ cell damage and serves as a powerful experimental tool to study cytotoxic effects in developing primate testis.

Animals↗
PubMed1999

Traumatic dislocation of the testis.

We report on a patient having testis dislocated into the superficial crus caused by an accident on a fishing boat. On physical examination, the left hemiscrotum was empty, and a painful mass was palpable inside the left thigh. On sonography, the testis appeared to be normal. Magnetic resonance imaging showed that the mass was located between subcutaneous tissue and muscle layer of the thigh. Surgical intervention was performed, and the left testis was found within the subcutaneous tissue inside the thigh, with slight torsion of the spermatic cord. The testis was fixed in the left hemiscrotum. To our knowledge, traumatic dislocation of the testis into the superficial crus is rare, and only 2 cases have been reported.

Adult↗
PubMed1990

Histochemistry and ultrastructure of nerve fibres and contractile cells in the tunica albuginea of the rat testis.

Whole-mounted preparations of the tunica albuginea of the rat testis were studied using light microscopy techniques for demonstration of cholinergic nerve fibres (Karnovski-Root method), catecholaminergic nerve fibres (De la Torre's method) and actin filaments (avidin-biotin-peroxidase method). An ultrastructural study of different regions of the albuginea was also performed. Cholinergic fibres were seen to penetrate into the albuginea with the testicular artery to form a broad network in the mediastinum testis, many fibres ending beneath the rete testis epithelium. Catecholaminergic fibres penetrated through the middle part of the cauda epididymis and formed a plexus in the albuginea covering the inferior testicular pole. This plexus gave rise to straight fibres which formed varicosities, some of them appeared related with mast cells. Actin-containing cells were only found beneath the rete testis epithelium. These cells were similar to myofibroblasts. The location of both cholinergic fibres and contractile cells among the rete testis channels suggests that these cells may be involved in the pumping of semen towards the ductuli efferentes and that their contractility may be regulated by cholinergic fibres.

Acetylcholine↗
PubMed1987

Unilaterally impalpable testis.

Thirty children presenting with a unilateral impalpable testis and a normally descended contralateral testis underwent surgical exploration. The testis was absent ('vanishing testis') in 12 cases (40%) and orchidectomy for a dysgenetic testis was performed in a further 5 cases. The overall rate of monorchism following surgery was therefore 56%. It is desirable that parents be advised of this possibility pre-operatively.

Adolescent↗
PubMed2003

Adhering junction dynamics in the testis are regulated by an interplay of beta 1-integrin and focal adhesion complex-associated proteins.

During spermatogenesis, the movement of developing germ cells across the seminiferous epithelium associates with extensive restructuring of cell-cell actin-based adherens junctions (AJs), such as ectoplasmic specialization (ES, a testis-specific AJ junction), between Sertoli and germ cells. Although this event of germ cell movement is essential to the completion of spermatogenesis, the mechanism(s) that regulates AJ restructuring is largely unknown. Using Sertoli-germ cells cocultured in vitro to study the regulation of AJ assembly, it was shown that this event associated with a transient induction of beta 1-integrin, vinculin, p-FAK-Tyr(397), and phosphatidylinositol 3-kinase (PI3K) but not the nonphosphorylated form of focal adhesion kinase (FAK), paxillin, and p130 Cas. Furthermore, p-FAK-Tyr(397) was shown to coimmunoprecipitate with beta 1-integrin, vinculin, and c-Src both in vitro and in vivo using Sertoli-germ cell cocultures and seminiferous tubules, respectively. These results seemingly suggest that the testis is using constituent proteins of the focal adhesion complex (FAC) found in other epithelia between cell and extracellular matrix to regulate AJ dynamics. To further confirm that p-FAK, a putative FAC protein in other epithelia, is indeed present at the site of ES, immunohistochemistry and immunofluorescent microscopy were used. The p-FAK-Tyr(397) and p-FAK-Tyr(576) were found to localize almost exclusively at the site of apical ES with weak staining at the basal ES in the seminiferous epithelium in a stage-specific manner, being highest at stages VI-VIII. In contrast, FAK was largely restricted to the basal compartment but with weak staining at the apical compartment. When rats were treated with 1-(2,4-dichlorobenzyl)-indazole-3-carbohydrazide (AF-2364) to perturb Sertoli-germ cell AJs, an induction of beta 1-integrin, vinculin, p-FAK-Tyr(397), PI3K, and p130 Cas but not the nonphosphorylated form of FAK and paxillin was also detected in the testis, coinciding with the time spermatids began to deplete from the epithelium, indicating their involvement in AJ disassembly. Thereafter, the levels of vinculin, p-FAK-Tyr(397), PI3K, and p130 Cas in the testis plunged, coinciding with the declining events of AJ disruption when virtually all spermatids were depleted from the epithelium. Taken collectively, these results suggest a bifunctional role of p-FAK, being involved in the events of Sertoli-germ cell AJ assembly and disassembly. In summary, the events of AJ dynamics in the testis, in particular at the site of ES, are regulated, at least in part, by proteins that are found in the FAC in other epithelia, such as beta1-integrin, vinculin, and FAK utilizing the integrin/pFAK/PI3K/p130 Cas signaling pathway.

Adherens Junctions↗
PubMed2004

Blood-testis barrier dynamics are regulated by {alpha}2-macroglobulin via the c-Jun N-terminal protein kinase pathway.

The blood-testis barrier (BTB), in contrast to the blood-brain and blood-retina barriers, is composed of coexisting tight junctions, gap junctions, and basal ectoplasmic specializations, a testis-specific type of adherens junction. Recent studies showed that BTB restructuring that facilitates germ cell migration during spermatogenesis involves proteolysis, an event that is usually restricted to the cell-matrix interface in other epithelia. For instance, a surge in alpha(2)-macroglobulin (alpha(2)-MG), a protease inhibitor produced by Sertoli cells, was detected at the Sertoli-Sertoli and Sertoli-germ cell interface in the epithelium during cadmium chloride-induced BTB disruption in adult rats. It is thus proposed that the increase in alpha(2)-MG is crucial for protecting the epithelium from unwanted proteolysis as well as regulating the availability of cytokines that affect junction turnover. Although both tight junction and adherens junction dynamics at the BTB are regulated via the p38 MAPK signaling pathway, the mechanism(s) that regulates alpha(2)-MG is entirely unknown. In this study, we have shown that by administering dimethylaminopurine, a c-Jun N-terminal protein kinase (JNK) inhibitor, to the testis, JNK activity was blocked specifically and alpha(2)-MG production was inhibited, worsening the cadmium chloride-induced damage to the epithelium. Studies coupled with inhibitors, immunoblottings, and immunofluorescent and electron microscopy have unequivocally demonstrated that the JNK signaling pathway is a putative regulatory pathway for alpha(2)-MG production in the testis. This finding illustrates for the first time that a cell-matrix restructuring event occurs in normal cell physiology at the cell-cell interface in the testis, highlighting the significance of alpha(2)-MG in the regulation of BTB function.

Adenine↗
PubMed2006

Sprouty2 is involved in male sex organogenesis by controlling fibroblast growth factor 9-induced mesonephric cell migration to the developing testis.

Fibroblast growth factor 9 (FGF9) signal has a role in organogenesis of the mammalian testis by controlling migration of mesonephric cells to the XY gonad, but neither it nor the FGF receptors is expressed sex-specifically. Of the Sprouty genes encoding antagonists of receptor tyrosine kinases including FGFr, mSprouty2 expression was confined to the developing testis and mesonephros. Gain of SPROUTY2 function in the male genital ridge and mesonephros malformed the vas deferens and epididymis, and diminished the number of seminiferous tubules and interstitium associating with reduced mesonephric cell migration and Fgf9 expression in embryonic testis, whereas exogenous FGF9 signaling recovered mesonephric cell migration inhibited by SPROUTY2. These phenotypes associated also with the decreased expression of Sox9, Desert hedgehog, Hsd3beta, Platelet/endothelial cell adhesion molecule, and alpha-smooth muscle actin, which are markers of the Sertoli, Leydig, endothelial, and peritubular myoid cells of the developing testis. Based on these data, we propose that the Sprouty proteins are involved normally in mediating the sexually dimorphic signaling of FGF9 and controlling cell migration from the mesonephros during testis development.

3-Hydroxysteroid Dehydrogenases↗
PubMed1978

Binding of bovine thyrotropin to receptors in rat testis and its interaction with gonadotropins.

Previously, we have shown that preparations of hCG bind to bovine thyroid membranes, as judged from their ability both to inhibit the binding of 125I-labeled bovine TSH (bTSH) and to activate adenylate cyclase (Amir, S.M., H. Uchimura, and S.H. Ingbar, J Clin Endocrinol Metab 45: 280, 1977). In the present studies, 125I-labeled, highly purified bTSH ([125I]bTSH) has been shown to bind specifically and saturably to receptors in a particulate fraction from rat testis. At 37 C, binding was rapid, reaching a maximum level in less than 15 min, but then declining markedly during the next several hours. At 22 C, binding reached a steady state after 2 h and remained unchanged for another 22 h. Binding of [125I]bTSH was greatest at pH 5.5, at which pH more than 50% of [125I]bTSH was bound in the presence of 330 microgram/ml particulate protein, the concentration of protein that yielded maximum binding. Nevertheless, the majority of experiments were conducted at lesser protein concentrations and at physiological pH (7.45), under which conditions total binding was only 25% of that measured at pH 5.5. Scatchard plots indicated the presence of a single binding site with a dissociation constant of 5.8 X 10(-8) M and a binding capacity of 0.22 nmol/mg protein on the basis of data obtained at 22 C and pH 7.45. Both crude and highly purified preparations of hCG inhibited the binding of [125I]bTSH to testis particulate fraction; crude hCG had 46 times the activity, and purified hCG had only one-tenth the activity of bTSH itself in this respect. This was true despite the fact that with respect to the displacement of [125I]hCG, crude and purified hCG were almost equally active. Bovine LH had one-third the activity of bTSH in displacing [125I]bTSH. Human FSH inhibited [125I]bTSH binding only slightly at the highest concentration tested, while glucagon, insulin, PRL, and GH were inactive. Purified bTSH inhibited the binding of [125I]hCG to testis particulate fraction but contained only about 2% of the activity of purified hCG. Lineweaver-Burk analysis suggested that inhibition of [125I]hCG binding by bTSH was competitive in nature. Purified bTSH stimulated cAMP production in Leydig cells, but with only about 0.1% of the activity of purified hCG. It is concluded that bTSH binds reversibly, saturably, and with relatively high affinity to receptors in rat testis that are either the same as receptors for hCG and LH or that interact therewith. bTSH, like hCG, is capable of stimulating the production of cAMP in rat Leydig cells, but is much less potent than hCG in this regard. Preparations of crude hCG contain a factor lacking hCG activity in bioassay, immunoassay, and receptor assay that is especially potent in displacing [125I]bTSH from receptors in testis, as has earlier been described for bTSH receptors in bovine thyroid membranes.

Animals↗
PubMed1988

Effect of long term deprivation of luteinizing hormone on Leydig cell volume, Leydig cell number, and steroidogenic capacity of the rat testis.

Leydig cells atrophy, losing cytoplasmic volume and the capacity for testosterone secretion, within 1-2 weeks of LH deprivation. We investigated the effects of long term (0-16 weeks) LH deprivation on the volume of an average Leydig cell, the volume of Leydig cells per testis, the number of Leydig cells per testis, and testosterone secretion by in vitro perfused testes. Endogenous LH was suppressed in adult rats by testosterone/estradiol-filled (TE) Silastic implants. The presence of Leydig cells in testes was verified by 1) morphological examination using light and electron microscopy, 2) histochemical localization of 3 beta-hydroxysteroid dehydrogenase activity (3 beta HSD), and 3) conversion of pregnenolone to progesterone by in vitro perfused testes. Marked quantitative differences existed in Leydig cell morphology among control and treated rats. The volume of an average Leydig cell and the total volume of Leydig cells per testis decreased (P less than 0.01) rapidly and progressively after TE implantation. At 16 weeks, the average Leydig cell lost 90% of its cytoplasmic volume and 65% of its nuclear volume. Analysis of variance failed to detect a significant decline in Leydig cell number per testis, despite a 16% reduction from the value in control rats (22.2 +/- 1.5 x 10(6)) in rats treated for 16 weeks (18.7 +/- 1.5 x 10(6)). After TE implantation, LH-stimulated testosterone secretion by in vitro perfused testes diminished (P less than 0.01) rapidly to 5% of the control values at 1 week and less than 0.3% of the control value from 4-16 weeks. In contrast, 25% of 3 beta HSD activity was retained (P less than 0.01 vs. controls) at 16 weeks, based on the rate of pregnenolone conversion to progesterone. Moreover, testes of treated rats secreted progesterone at a rate twice that of controls, when the steroid secretion rates were expressed per volume of Leydig cell cytoplasm. Loss of the testosterone-secreting capacity of testes after LH withdrawal was associated with a loss in the volume, but not a significant loss in the number, of Leydig cells. Thus, LH was required to maintain the differentiated structure and function of Leydig cells, but was not required to maintain the overwhelming majority of Leydig cells in the adult rat testis through 16 weeks. Moreover, at least one steroidogenic enzyme, 3 beta HSD, was retained by Leydig cells after long term LH deprivation.

3-Hydroxysteroid Dehydrogenases↗
PubMed1990

To what extent can spermatogenesis be maintained in the hypophysectomized adult rat testis with exogenously administered testosterone?

In a previous study it was demonstrated that spermatogenesis can be maintained quantitatively with exogenously administered testosterone in adult intact rats that lack LH. The studies described herein were designed to examine the extent to which spermatogenesis can be maintained quantitatively with exogenously administered testosterone in adult rats that lack all pituitary hormones. Adult male rats were hypophysectomized and testosterone was administered at the time of hypophysectomy via sustained release polydimethylsiloxane (PDS) capsules of increasing lengths. We used the PDS capsules to clamp testosterone at defined concentrations within the seminiferous tubule fluid over a 2- to 3-month treatment period. Mean testis weights and advanced spermatid numbers per testis stabilized by 8 weeks of testosterone treatment regardless of testosterone dose. Both testis weight and advanced spermatid number responded to testosterone dose, reaching plateaus of 1.2 g and 170 x 10(6) per testis, respectively. These values were 60% of, and significantly less than, the respective control values. This result was in striking contrast to the results of our previous study of LH-suppressed intact rats, in which exogenously administered testosterone resulted in testis weights and advanced spermatid numbers that plateaued at values not significantly different from those in controls. These different effects of testosterone in intact and hypophysectomized rats occurred despite the fact that the seminiferous tubule fluid testosterone concentrations achieved in the hypophysectomized rats (up to 25 ng/ml) were greater than the minimal testosterone concentration found previously to be required to maintain spermatogenesis quantitatively in LH-suppressed intact rats (13 ng/ml). Taken together, these results demonstrate clearly that intratesticular testosterone doses that are as high as or higher than those that maintain spermatogenesis quantitatively in intact rats lacking LH fail to maintain spermatogenesis quantitatively in rats lacking all pituitary hormones.

Animals↗
PubMed1990

Identification of interleukin-1 receptors in mouse testis.

The cytokine interleukin-1 (IL-1) has been reported to alter reproductive functions through both effects in brain and direct actions at the level of the gonads. To further define the role of IL-1 at the gonads, we have used 125I-labeled recombinant human IL-1 to identify and characterize IL-1 receptors in crude membrane preparations of mouse (C57BL/6) testis and to study the distribution of IL-1-binding sites using autoradiography. In preliminary homogenate binding and autoradiographic studies, [125I]IL-1 alpha showed significantly higher specific binding than [125I]IL-1 beta. Thus, [125I]IL-1 alpha was used in all subsequent assays. The binding of [125I]IL-1 alpha was linear over a broad range of membrane protein concentrations, saturable, and reversible, and on Scatchard analysis revealed an equilibrium dissociation constant (Kd) of 82 +/- 4 pM and a maximum number of binding sites (Bmax) of 10.8 +/- 1.5 fmol/mg protein. In competition studies, IL-1 alpha, IL-1 beta, and a weak IL-1 beta analog IL-1 beta+ inhibited [125I]IL-1 alpha binding to mouse testis in parallel with their relative bioactivities in immune assays, with inhibitory binding affinity constant (Ki) values of 14.2 +/- 1.7, 88.8 +/- 5.7, and 7183.3 +/- 603 pM, respectively; rat/human CRF and human tumor necrosis factor showed no effect on [125I]IL-1 alpha binding. In autoradiographic studies, IL-1 receptors were heterogeneously distributed, with highest densities present in the luminal border of the epididymis and interstitial areas of the testis. After hypophysectomy, the testes were significantly atrophied, and homogenate binding and autoradiographic studies showed that while the total number of binding sites per testis was significantly decreased in hypophysectomized mice in proportion to the reduction in testicular mass, there was no apparent change in the relative density of IL-1 receptors. These data provide the first identification of IL-1 receptors in testis and provide further support for a physiological role for IL-1 to alter reproductive functions through a direct effect at the gonads.

Animals↗
PubMed1991

Early hypothyroidism in rats causes increased adult testis and reproductive organ size but does not change testosterone levels.

The role of thyroid hormones in the testis is unclear, although recent evidence indicates they may be important for testicular development. Here we describe a novel method for increasing adult testicular size in the rat by induction of transient hypothyroidism during neonatal life. Rats were treated with a reversible goitrogen, 6-propyl-2-thiouracil from birth to day 25 when treatment was stopped, allowing return to a euthyroid state. At days 90, 135, 160, and 180, wt and DNA content of the testis, epididymis, ventral prostate, seminal vesicle, and those of some nonreproductive organs were determined, as well as serum levels of testosterone (T) and thyroid hormones. Despite decreased body wts in 90-day and older 6-propyl-2-thiouracil-treated rats, testis wt was increased by 40% and 60% at 90 and 135 days, respectively; maximal increase (80%) occurred at 160 days. These wt increases were accompanied by proportional changes in DNA content. Significant enlargements were also seen in other reproductive organs, but they occurred after a time lag and were smaller in magnitude. Interestingly, serum T levels showed no increase at any age. Weight and DNA content of nonreproductive organs, like body wts, were less than controls at all ages but thyroid hormone levels were normal. Thus, transient hypothyroidism in neonatal rats is associated with lasting enlargements in the ultimate size of testis and other reproductive organs in the adult. These changes are not related to excess T levels. The results indicate early critical influences of thyroid hormones on growth and development of the reproductive system and suggest an experimental model for inducing lasting enlargements in testis and reproductive organs. The model may also be useful for studying regulation of reproductive growth and final size.

Animals↗
PubMed2000

Expression of the leptin receptor during germ cell development in the mouse testis.

Leptin, a recently identified hormonal product of the ob gene, is known to regulate appetite, body metabolism, and reproductive functions. We investigated the expression of the leptin receptor (Ob-R) in testes from different age groups. The messenger RNA for Ob-R was found in testes from all age groups using RT-PCR. Using immunohistochemistry, we observed age- and stage-dependent distribution of the Ob-R in mouse testis. In testis of 5-day-old mice, its expression was mainly in type A spermatogonia. In the 20- and 30-day-old testis, Ob-R expression was in the spermatocytes; in the adult testis, it was specific to spermatocytes in stages IX and X of the cycle of the seminiferous epithelium. Five main immunoreactive proteins were detected using Western blot (220, 120, 90, 66, and 46 kDa). The 120-kDa protein was evident only in 20-day-old and older testes, whereas the 90-kDa band was present only in the 5- and 10-day-old testis. Leptin treatment induced phosphorylation of signal transducer and activator of transcription-3 in cultured seminiferous tubules from adult and 5-day-old testes. Our results show for the first time age- and stage-specific localization of a functional Ob-R in testicular germ cells. We hypothesize a direct role for leptin, through phosphorylation of signal transducer and activator of transcription-3, in proliferation and differentiation of germ cells, which may partially explain the infertility observed in leptin-deficient mice.

Aging↗
PubMed2001

Blockage of the rete testis and efferent ductules by ectopic Sertoli and Leydig cells causes infertility in Dax1-deficient male mice.

DAX-1, an X-linked member of the orphan nuclear receptor superfamily of transcription factors, plays a key role in sex determination and gonadal differentiation. Dax1-deficient male mice are infertile and have small testes despite normal serum levels of T and gonadotropins. Examination of Dax1-deficient testes reveals dilated seminiferous tubules and abnormal parameters of sperm fertilizing capability consistent with a possible obstruction in the testis. To test this hypothesis, we performed a comprehensive evaluation of the male reproductive tract in Dax1-deficient mice. Light and electron microscopic examination revealed the rete testis is blocked by aberrantly located Sertoli cells, creating a tailback of necrosing sperm in the testis. Sertoli cells also obstruct the proximal and middle efferent ductules, and this is accompanied by an overgrowth of the efferent duct epithelium. Seminiferous tubules close to the rete testis contain ectopic Leydig cells, distinct from the hyperplastic Leydig cells present in the interstitial space. The peritubular tissue surrounding these tubules is frequently abnormal, containing relatively undifferentiated myoid cells and no basement membrane between the myoid cells and Sertoli cells. A third of aged (>1-yr-old) Dax1-deficient male mice develop sex cord-stromal tumors, derived from cells of the Sertoli/granulosa cell or Leydig cell lineages. Combined, these observations reveal abnormal differentiation and proliferation of Leydig cells and Sertoli cells in Dax1-deficient male mice, leading to obstruction of the rete testis and infertility.

Animals↗
PubMed2003

Transcription factor GATA-6, cell proliferation, apoptosis, and apoptosis-related proteins Bcl-2 and Bax in human fetal testis.

The GATA family of transcription factors have been implicated in regulating the development and function of many organs. Furthermore, they have been linked to signaling cascades regulating cell fate through apoptosis. GATA-6 has been shown to be expressed in the gonads, but its cell-specific expression in the testis has remained unclear. We have studied GATA-6 expression in human fetal testis using in situ hybridization and immunohistochemistry and compared these results with the expression of the apoptosis-related proteins Bcl-2 and Bax. Furthermore, apoptosis was studied by thymidine deoxyribose-mediated deoxy-UTP nick end labeling assay, and cell proliferation by Ki-67 immunohistochemistry. GATA-6 mRNA and protein were expressed in Sertoli and Leydig cells early in gestation. Apoptotic cells were scanty between wk 16 and 40, and proliferation significantly ceased during the third trimester, supporting the view that only a little tissue remodeling occurs in the late fetal testis. Bax was present throughout the fetal period, whereas Bcl-2 expression decreased toward term. Neither of these factors correlated to the extent of apoptosis, and thus their role in the regulation of apoptosis in the fetal testis remains open. Despite strong expression, GATA-6 did not correlate with apoptosis or cell proliferation and is therefore unlikely to be directly involved in these processes in the human fetal testis.

Apoptosis↗
PubMed2003

The human fetal testis is a site of expression of neurotrophins and their receptors: regulation of the germ cell and peritubular cell population.

In the fetal testis, organization of the tissue into two compartments consisting of cords containing Sertoli and germ cells surrounded by peritubular cells and of other cells within the interstitium is essential for subsequent function. Neurotrophins (NTs) act as survival and differentiation factors in the nervous system and have been detected in the developing rodent testis. Expression of mRNA for nerve growth factor; NTs 3 and 4 and brain-derived neurotrophic factor; the high-affinity receptors TrkA, TrkB, and TrkC; and the low-affinity p75 receptor were detected in the human testis between 14 and 19 wk gestation. NT4 mRNA and protein were predominantly localized to the peritubular cells. These cells were also the site of expression of p75. By contrast, nerve growth factor and NT3 were mainly expressed in Sertoli and interstitial cells. Treatment of testis organ cultures with the Trk-specific kinase inhibitor K252a resulted in a marked decrease in both gonocyte and peritubular cell number and proliferation with little effect on Sertoli cells. These data demonstrate the expression of NTs and their receptors in the human fetal testis during the second trimester and indicate possible roles in the regulation of proliferation and survival of germ cells and peritubular cells.

Adult↗