Mesonephric contribution to testis differentiation in the fetal mouse

Development ◽  
1993 ◽  
Vol 117 (1) ◽  
pp. 273-281 ◽  
Author(s):  
M. Buehr ◽  
S. Gu ◽  
A. McLaren

Testes from 11.5-day-old mouse embryos, with and without attached mesonephroi, were cultured for 7 days. Isolated testes failed to develop well-differentiated testis cords: however, when cultured attached to a mesonephros from either a male or a female donor embryo, testes developed cords that were normal in appearance. Testes cultured next to a mesonephric region but separated from it by a permeable filter, did not develop normal cords, nor did testes grafted to fragments of embryonic limb or heart. When testes were grafted to mesonephric regions from mice carrying a transgenic marker, the marker was found in some of the peritubular myoid cells and other interstitial cells of the testis, but not in the Sertoli cells or the germ cells. We conclude that after 11.5 days post coitum, cells can migrate from the mesonephric region into the differentiating testis and can contribute to the interstitial cell population, and that this contribution is necessary for the establishment of normal cord structure. The germ cells in all cultured testes, whether or not differentiated cords were present, were T1 prospermatogonia: no meiotic germ cells were seen.

1996 ◽  
Vol 8 (7) ◽  
pp. 1075 ◽  
Author(s):  
K Seidl ◽  
A Buchberger ◽  
C Erck

The present study was designed to clarify the non-neurotrophic role for neurotrophins in mouse testis. By means of SI nuclease protection assay we could demonstrate that the gene coding for the low-affinity nerve growth factor (NGF) receptor p75NGFR is transiently expressed during germ cell development. Gene expression for p75NGFR was detected in late-meiotic spermatocytes and early spermatids and was found to be co-expressed with trkB and trkC, two tyrosine kinase receptors, commonly regarded as the high-affinity receptors for brain-derived neurotrophic factor and neurotrophin-3. Gene transcripts for the high-affinity NGF receptor trkA were found exclusively in non-germ cells. Isolated Leydig cells, peritubular myoid cells and Sertoli cells, but not germ cells, could be identified as potential testicular NGF sources. Non-germ cells respond after incubation for several days with a sharp induction in NGF synthesis, which is accompanied by a loss of phenotypic expression patterns. The fact that p75NGFR mRNA expression was induced in cultured Sertoli cells and peritubular myoid cells suggests an autocrine mode of NGF action in these cells. Induction of NGF synthesis in cultured Leydig cells could be prevented by the glucocorticoid dexamethasone. Results indicate different roles for the individual neurotrophins in distinct testicular compartments and suggest that these neurotrophins might support testicular functions by signalling between individual cell types in an autocrine and paracrine manner.


2015 ◽  
Vol 2015 ◽  
pp. 1-8 ◽  
Author(s):  
Vincenza Ciaramella ◽  
Rosanna Chianese ◽  
Paolo Pariante ◽  
Silvia Fasano ◽  
Riccardo Pierantoni ◽  
...  

Hypothalamic Gonadotropin Releasing Hormone (GnRH),viaGnRH receptor (GnRHR), is the main actor in the control of reproduction, in that it induces the biosynthesis and the release of pituitary gonadotropins, which in turn promote steroidogenesis and gametogenesis in both sexes. Extrabrain functions of GnRH have been extensively described in the past decades and, in males, local GnRH activity promotes the progression of spermatogenesis and sperm functions at several levels. The canonical localization ofGnrh1andGnrhr1mRNA is Sertoli and Leydig cells, respectively, but ligand and receptor are also expressed in germ cells. Here, we analysed the expression rate ofGnrh1andGnrhr1in rat testis (180 days old) by quantitative real-time PCR (qPCR) and byin situhybridization we localizedGnrh1andGnrhr1mRNA in different spermatogenic cells of adult animals. Our data confirm the testicular expression ofGnrh1and ofGnrhr1in somatic cells and provide evidence that their expression in the germinal compartment is restricted to haploid cells. In addition, not only Sertoli cells connected to spermatids in the last steps of maturation but also Leydig and peritubular myoid cells expressGnrh1.


2009 ◽  
Vol 30 (2) ◽  
pp. 119-132 ◽  
Author(s):  
Ruey-Sheng Wang ◽  
Shuyuan Yeh ◽  
Chii-Ruey Tzeng ◽  
Chawnshang Chang

Abstract Androgens are critical steroid hormones that determine the expression of the male phenotype, including the outward development of secondary sex characteristics as well as the initiation and maintenance of spermatogenesis. Their actions are mediated by the androgen receptor (AR), a member of the nuclear receptor superfamily. AR functions as a ligand-dependent transcription factor, regulating expression of an array of androgen-responsive genes. Androgen and the AR play important roles in male spermatogenesis and fertility. The recent generation and characterization of male total and conditional AR knockout mice from different laboratories demonstrated the necessity of AR signaling for both external and internal male phenotype development. As expected, the male total AR knockout mice exhibited female-typical external appearance (including a vagina with a blind end and a clitoris-like phallus), the testis was located abdominally, and germ cell development was severely disrupted, which was similar to a human complete androgen insensitivity syndrome or testicular feminization mouse. However, the process of spermatogenesis is highly dependent on autocrine and paracrine communication among testicular cell types, and the disruption of AR throughout an experimental animal cannot answer the question about how AR in each type of testicular cell can play roles in the process of spermatogenesis. In this review, we provide new insights by comparing the results of cell-specific AR knockout in germ cells, peritubular myoid cells, Leydig cells, and Sertoli cells mouse models that were generated by different laboratories to see the consequent defects in spermatogenesis due to AR loss in different testicular cell types in spermatogenesis. Briefly, this review summarizes these results as follows: 1) the impact of lacking AR in Sertoli cells mainly affects Sertoli cell functions to support and nurture germ cells, leading to spermatogenesis arrest at the diplotene primary spermatocyte stage prior to the accomplishment of first meiotic division; 2) the impact of lacking AR in Leydig cells mainly affects steroidogenic functions leading to arrest of spermatogenesis at the round spermatid stage; 3) the impact of lacking AR in the smooth muscle cells and peritubular myoid cells in mice results in similar fertility despite decreased sperm output as compared to wild-type controls; and 4) the deletion of AR gene in mouse germ cells does not affect spermatogenesis and male fertility. This review tries to clarify the useful information regarding how androgen/AR functions in individual cells of the testis. The future studies of detailed molecular mechanisms in these in vivo animals with cell-specific AR knockout could possibly lead to useful insights for improvements in the treatment of male infertility, hypogonadism, and testicular dysgenesis syndrome, and in attempts to create safe as well as effective male contraceptive methods.


1963 ◽  
Vol 44 (4) ◽  
pp. 536-544 ◽  
Author(s):  
Ardis J. Lostroh ◽  
Ruth Johnson ◽  
C. W. Jordan

ABSTRACT Rabbit antiserum to ovine ICSH was administered to male Sprague-Dawley rats 2 months after hypophysectomy; further atrophy of the testis ensued. The interstitial tissue, the Sertoli cells, and the germ cells were adversely affected by the treatment. In the absence of gonadotrophins and exogenous androgen, spermatogenesis was nearly arrested. Ovine ICSH repaired the interstitial tissue and stimulated mitotic activity among the spermatogonia. Ovine FSH (NIH-FSH-S-1), containing approximately 1% ICSH activity, stimulated spermatid formation. When antiserum to ICSH was injected together with the FSH, no maturation divisions or spermatids were observed. The combination of FSH and ICSH, 100 μg of each per day injected for a period of 21 days, stimulated extensive and uniform tubular repair and advanced spermiogenesis to the acrosome phase; an enhancement in the secretion of androgen also was effected when FSH was given in combination with ICSH.


Author(s):  
Rita Meyer ◽  
Zoltan Posalaky ◽  
Dennis Mcginley

The Sertoli cell tight junctional complexes have been shown to be the most important structural counterpart of the physiological blood-testis barrier. In freeze etch replicas they consist of extensive rows of intramembranous particles which are not only oriented parallel to one another, but to the myoid layer as well. Thus the occluding complex has both an internal and an overall orientation. However, this overall orientation to the myoid layer does not seem to be necessary to its barrier function. The 20 day old rat has extensive parallel tight junctions which are not oriented with respect to the myoid layer, and yet they are inpenetrable by lanthanum. The mechanism(s) for the control of Sertoli cell junction development and orientation has not been established, although such factors as the presence or absence of germ cells, and/or hormones, especially FSH have been implicated.


2021 ◽  
pp. 1-14
Author(s):  
Yuanyuan Li ◽  
Jinbo Li ◽  
Man Cai ◽  
Zhanfen Qin

The knowledge of testis development in amphibians relative to amniotes remains limited. Here, we used Xenopus laevis to investigate the process of testis cord development. Morphological observations revealed the presence of segmental gonomeres consisting of medullary knots in male gonads at stages 52–53, with no distinct gonomeres in female gonads. Further observations showed that cell proliferation occurs at specific sites along the anterior-posterior axis of the future testis at stage 50, which contributes to the formation of medullary knots. At stage 53, adjacent gonomeres become close to each other, resulting in fusion; then (pre-)Sertoli cells aggregate and form primitive testis cords, which ultimately become testis cords when germ cells are present inside. The process of testis cord formation in X. laevis appears to be more complex than in amniotes. Strikingly, steroidogenic cells appear earlier than (pre-)Sertoli cells in differentiating testes of X. laevis, which differs from earlier differentiation of (pre-)Sertoli cells in amniotes. Importantly, we found that the mesonephros is connected to the testis gonomere at a specific site at early larval stages and that these connections become efferent ducts after metamorphosis, which challenges the previous concept that the mesonephric side and the gonadal side initially develop in isolation and then connect to each other in amphibians and amniotes.


2009 ◽  
Vol 296 (3) ◽  
pp. R743-R762 ◽  
Author(s):  
R.-Marc Pelletier ◽  
Suk Ran Yoon ◽  
Casimir D. Akpovi ◽  
Emil Silvas ◽  
María Leiza Vitale

We identified aberrations leading to spontaneous autoimmune orchitis (AIO) in mink, a seasonal breeder and natural model for autoimmunity. This study provides evidence favoring the view that a malfunction of the clearance mechanisms for apoptotic cell debris arising from imbalances in phagocyte receptors or cytokines acting on Sertoli cells constitutes a major factor leading to breakdown of self-tolerance during spontaneous AIO. Serum anti-sperm antibody titers measured by ELISA reflected spermatogenic activity without causing immune inflammatory responses. Orchitic mink showed excess antibody production accompanied by spermatogenic arrest, testicular leukocyte infiltration, and infertility. AIO serum labeled the postacrosomal region, the mid and end piece of mink sperm, whereas normal mink serum did not. Normal serum labeled plasma membranes, whereas AIO serum reacted with germ cell nuclei. Western blot analyses revealed that AIO serum reacted specifically to a 23- and 50-kDa protein. The number of apostain-labeled apoptotic cells was significantly higher in orchitic compared with normal tubules. However, apoptosis levels measured by ELISA in seminiferous tubular fractions (STf) were not significantly different in normal and orchitic tubules. The levels of CD36, TNF-α, TNF-α RI, IL-6, and Fas but not Fas-ligand (L), and ATP-binding cassette transporter ABCA1 were changed in AIO STf. TNF-α and IL-6 serum levels were increased during AIO. Fas localized to germ cells, Sertoli cells, and the lamina propria of the tubules and Fas-L, to germ cells. Fas colocalized with Fas-L in residual bodies in normal testis and in giant cells and infiltrating leukocytes in orchitic tubules.


2007 ◽  
Vol 292 (2) ◽  
pp. E513-E522 ◽  
Author(s):  
Andrii Domanskyi ◽  
Fu-Ping Zhang ◽  
Mirja Nurmio ◽  
Jorma J. Palvimo ◽  
Jorma Toppari ◽  
...  

Androgen receptor-interacting protein 4 (ARIP4) belongs to the SNF2 family of proteins involved in chromatin remodeling, DNA excision repair, and homologous recombination. It is a DNA-dependent ATPase, binds to DNA and mononucleosomes, and interacts with androgen receptor (AR) and modulates AR-dependent transactivation. We have examined in this study the expression and cellular localization of ARIP4 during postnatal development of mouse testis. ARIP4 was detected by immunohistochemistry in Sertoli cell nuclei at all ages studied, starting on day 5, and exhibited the highest expression level in adult mice. At the onset of spermatogenesis, ARIP4 expression became evident in spermatogonia, pachytene, and diplotene spermatocytes. Immunoreactive ARIP4 antigen was present in Leydig cell nuclei. In Sertoli cells ARIP4 was expressed in a stage-dependent manner, with high expression levels at stages II–VI and VII–VIII. ARIP4 expression patterns did not differ significantly in testes of wild-type, follicle-stimulating hormone receptor knockout, and luteinizing hormone receptor knockout mice. In testes of hypogonadal mice, ARIP4 was found mainly in interstitial cells and exhibited lower expression in Sertoli and germ cells. In vitro stimulation of rat seminiferous tubule segments with testosterone, FSH, or forskolin did not significantly change stage-specific levels of ARIP4 mRNA. Heterozygous ARIP4+/− mice were haploinsufficient and had reduced levels of Sertoli-cell specific androgen-regulated Rhox5 (also called Pem) mRNA. Collectively, ARIP4 is an AR coregulator in Sertoli cells in vivo, but the expression in the germ cells implies that it has also AR-independent functions in spermatogenesis.


Reproduction ◽  
2013 ◽  
Vol 146 (5) ◽  
pp. 471-480 ◽  
Author(s):  
Gerardo M Oresti ◽  
Jesús García-López ◽  
Marta I Aveldaño ◽  
Jesús del Mazo

Male germ cell differentiation entails the synthesis and remodeling of membrane polar lipids and the formation of triacylglycerols (TAGs). This requires fatty acid-binding proteins (FABPs) for intracellular fatty acid traffic, a diacylglycerol acyltransferase (DGAT) to catalyze the final step of TAG biosynthesis, and a TAG storage mode. We examined the expression of genes encoding five members of the FABP family and two DGAT proteins, as well as the lipid droplet protein perilipin 2 (PLIN2), during mouse testis development and in specific cells from seminiferous epithelium.Fabp5expression was distinctive of Sertoli cells and consequently was higher in prepubertal than in adult testis. The expression ofFabp3increased in testis during postnatal development, associated with the functional differentiation of interstitial cells, but was low in germ cells.Fabp9, together withFabp12, was prominently expressed in the latter. Their transcripts increased from spermatocytes to spermatids and, interestingly, were highest in spermatid-derived residual bodies (RB). Both Sertoli and germ cells, which produce neutral lipids and store them in lipid droplets, expressedPlin2. Yet, whileDgat1was detected in Sertoli cells,Dgat2accumulated in germ cells with a similar pattern of expression asFabp9. These results correlated with polyunsaturated fatty acid-rich TAG levels also increasing with mouse germ cell differentiation highest in RB, connecting DGAT2 with the biosynthesis of such TAGs. The age- and germ cell type-associated increases inFabp9,Dgat2, andPlin2levels are thus functionally related in the last stages of germ cell differentiation.


Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1532-1540 ◽  
Author(s):  
Anne Florin ◽  
Magali Maire ◽  
Aline Bozec ◽  
Ali Hellani ◽  
Sonia Chater ◽  
...  

In the present study we investigated whether fetal exposure to flutamide affected messenger and protein levels of claudin-11, a key Sertoli cell factor in the establishment of the hemotesticular barrier, at the time of two key events of postnatal testis development: 1) before puberty (postnatal d 14) during the establishment of the hemotesticular barrier, and 2) at the adult age (postnatal d 90) at the time of full spermatogenesis. The data obtained show that claudin-11 expression was inhibited in prepubertal rat testes exposed in utero to 2 and 10 mg/kg·d flutamide. However, in adult testes, the inhibition was observed only with 2, and not with 10, mg/kg·d of the antiandrogen. It is shown here that these differences between prepubertal and adult testes could be related to dual and opposed regulation of claudin-11 expression resulting from positive control by androgens and an inhibitory effect of postmeiotic germ cells. Indeed, testosterone is shown to stimulate claudin-11 expression in cultured Sertoli cells in a dose- and time-dependent manner (maximum effect with 0.06 μm after 72 h of treatment). In contrast, postmeiotic germ cells potentially exert a negative effect on claudin-11 expression, because adult rat testes depleted in spermatids (after local irradiation) displayed increased claudin-11 expression, whereas in a model of cocultured Sertoli and germ cells, spermatids, but not spermatocytes, inhibited claudin-11 expression. The apparent absence of claudin-11 expression changes in adult rat testes exposed to 10 mg/kg·d flutamide therefore could result from the antagonistic effects of 1) the inhibitory action of the antiandrogen and 2) the stimulatory effect of the apoptotic germ cells on claudin-11 expression. Together, due to the key role of claudin-11 in the hemotesticular barrier, the present findings suggest that such regulatory mechanisms may potentially affect this barrier (re)modeling during spermatogenesis.


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