An insight into testis and gubernaculum dynamics of INSL3 - RXFP2 signalling during testicular descent in the dog

2010 ◽  
Vol 22 (5) ◽  
pp. 751 ◽  
Author(s):  
S. Arrighi ◽  
G. Bosi ◽  
D. Groppetti ◽  
M. Aralla ◽  
F. Cremonesi
Keyword(s):  
Sertoli Cells ◽  
Leydig Cells ◽  
Feedback Loop ◽  
Testicular Descent ◽  
Fetal Period ◽  
Male Development ◽  
Dog Testis ◽  
Gubernaculum Testis ◽  
Insight Into ◽  
Different Tissues

Insulin-like 3 (INSL3) plays a prominent role in male development and is supposed to induce the growth of the gubernaculum testis (g.t.), thus being directly involved in testicular descent in humans and rodents. This happens through activation of the RXFP2 receptor (GREAT or LGR8). The INSL3–RXFP2 complex is reputed to play an additional paracrine role in the testis, possibly acting as part of an autocrine feedback loop. The present work provides evidence of the immunolocalisation of INSL3 in the Leydig cells of canine fetuses and of the expression of RXFP2 receptor in different tissues of the g.t. of the same specimens. RXFP2 was localised at the cell membrane of g.t. muscle and connective cells, as well as in the epithelial cells of the developing excurrent ducts. Notably, RXFP2 immunoreactivity of the g.t. was limited to fetuses at ~35–45 days of gestation, which is also the fetal period when the endocrine compartment of the dog testis is active endocrinologically, as confirmed by the anti-P450c17 and anti-INSL3 immunoreactivities of the fetal Leydig cells, and by anti-Müllerian hormone immunoreactivity of the Sertoli cells. The same immunoreactivities were also evaluated in the testes of cryptorchid dogs of different ages. RXFP2 immunoreactivity was absent from genital tracts of cryptorchid testes and g.t. remnants.

scholarly journals Functions of TAM RTKs in regulating spermatogenesis and male fertility in mice

Reproduction ◽  
2009 ◽  
Vol 138 (4) ◽  
pp. 655-666 ◽  
Author(s):  
Yongmei Chen ◽  
Huizhen Wang ◽  
Nan Qi ◽  
Hui Wu ◽  
Weipeng Xiong ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Tyrosine Kinases ◽  
Male Fertility ◽  
Leydig Cells ◽  
Seminiferous Tubules ◽  
Wild Type ◽  
Male Sterile ◽  
Triple Mutant ◽  
Insight Into

Mice lacking TYRO3, AXL and MER (TAM) receptor tyrosine kinases (RTKs) are male sterile. The mechanism of TAM RTKs in regulating male fertility remains unknown. In this study, we analyzed in more detail the testicular phenotype of TAM triple mutant (TAM−/−) mice with an effort to understand the mechanism. We demonstrate that the three TAM RTKs cooperatively regulate male fertility, and MER appears to be more important than AXL and TYRO3. TAM−/− testes showed a progressive loss of germ cells from elongated spermatids to spermatogonia. Young adult TAM−/− mice exhibited oligo-astheno-teratozoospermia and various morphological malformations of sperm cells. As the mice aged, the germ cells were eventually depleted from the seminiferous tubules. Furthermore, we found that TAM−/− Sertoli cells have an impaired phagocytic activity and a large number of differentially expressed genes compared to wild-type controls. By contrast, the function of Leydig cells was not apparently affected by the mutation of TAM RTKs. Therefore, we conclude that the suboptimal function of Sertoli cells leads to the impaired spermatogenesis in TAM−/− mice. The results provide novel insight into the mechanism of TAM RTKs in regulating male fertility.

Exogenous androgens reduce the expression of INSL3, a hormone involved in normal testicular descent, in fetal Leydig cells

2014 ◽  
Author(s):  
W Colin Duncan ◽  
Fiona Connolly ◽  
Lyndsey Boswell ◽  
Graeme Burt ◽  
Alan S McNeilly ◽  
...  
Keyword(s):  
Leydig Cells ◽  
Testicular Descent ◽  
Fetal Leydig Cells

Sex chimaerism, fertility and sex determination in the mouse

Development ◽  
1991 ◽  
Vol 113 (1) ◽  
pp. 311-325 ◽  
Author(s):  
C.E. Patek ◽  
J.B. Kerr ◽  
R.G. Gosden ◽  
K.W. Jones ◽  
K. Hardy ◽  
...  
Keyword(s):  
Sex Determination ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Sex Chromosome ◽  
Tunica Albuginea ◽  
In Situ Hybridisation ◽  
Ovarian Surface Epithelium ◽  
Surface Epithelium ◽  
Seminiferous Tubules ◽  
Coelomic Epithelium

Adult intraspecific mouse chimaeras, derived by introducing male embryonal stem cells into unsexed host blastocysts, were examined to determine whether gonadal sex was correlated with the sex chromosome composition of particular cell lineages. The fertility of XX in equilibrium XY and XY in equilibrium XY male chimaeras was also compared. The distribution of XX and XY cells in 34 XX in equilibrium XY ovaries, testes and ovotestes was determined by in situ hybridisation using a Y-chromosome-specific probe. Both XX and XY cells were found in all gonadal somatic tissues but Sertoli cells were predominantly XY and granulosa cells predominantly XX. The sex chromosome composition of the tunica albuginea and testicular surface epithelium could not, in general, be fully resolved, owing to diminished hybridisation efficiency in these tissues, but the ovarian surface epithelium (which like the testicular surface epithelium derives from the coelomic epithelium) was predominantly XX. These findings show that the claim that Sertoli cells were exclusively XY, on which some previous models of gonadal sex determination were based, was incorrect, and indicate instead that in the mechanism of Sertoli cell determination there is a step in which XX cells can be recruited. However, it remains to be established whether the sex chromosome constitution of the coelomic epithelium lineage plays a causal role in gonadal sex determination. Male chimaeras with XX in equilibrium XY testes were either sterile or less fertile than chimaeras with testes composed entirely of XY cells. This impaired fertility was associated with the loss of XY germ cells in atrophic seminiferous tubules. Since this progressive lesion was correlated with a high proportion of XX Leydig cells, we suggest that XX Leydig cells are functionally defective, and unable to support spermatogenesis.

scholarly journals 3D micro-environment regulates NF–κβ dependent adhesion to induce monocyte differentiation

2018 ◽  
Author(s):  
Anindita Bhattacharya ◽  
Mahesh Agarwal ◽  
Rachita Mukherjee ◽  
Prosenjit Sen ◽  
Deepak Kumar Sinha
Keyword(s):  
Positive Feedback ◽  
Feedback Loop ◽  
The Novel ◽  
Monocyte Adhesion ◽  
Cellular Functions ◽  
Monocyte Differentiation ◽  
Summary Statement ◽  
Necessary And Sufficient ◽  
Multiple Signaling ◽  
Insight Into

AbstractDifferentiation of monocytes entails their relocation from blood to the tissue, hence accompanied by an altered physicochemical micro-environment. While the mechanism by which the biochemical make-up of the micro-environment induces differentiation is known, the fluid-like to gel-like transition in the physical micro-environment is not well understood. Monocytes maintain non-adherent state to prevent differentiation. We establish that irrespective of the chemical makeup, a 3D gel-like micro-environment induces a positive-feedback loop of adhesion-MAPK-NF-κβ activation to facilitate differentiation. In 2D fluid-like micro-environment, adhesion alone is capable of inducing differentiation via the same positive-feedback signalling. Chemical inducer treatment in fluid-like micro-environment, increases the propensity of monocyte adhesion via a brief pulse of p-MAPK. The adhesion subsequently elicit differentiation, establishing that adhesion is both necessary and sufficient to induce differentiation in 2D/3D micro-environment. Our findings challenge the notion that adhesion is a result of monocyte differentiation. Rather it’s the adhesion which triggers the differentiation of monocytes. MAPK, and NF-κβ being key molecules of multiple signaling pathways, we hypothesize that biochemically inert 3D gel-like micro-environment would also influence other cellular functions.Summary statementThis article brings out a new insight into the novel mechanisms of monocyte differentiation solely driven by physical micro-environment and adhesion.

scholarly journals Minireview: Transcriptional Regulation of Gonadal Development and Differentiation

Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1035-1042 ◽  
Author(s):  
Susan Y. Park ◽  
J. Larry Jameson
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Cell Types ◽  
Gonadal Development ◽  
Targeted Mutagenesis ◽  
Seminiferous Tubules ◽  
Molecular Pathways ◽  
Theca Cells ◽  
Main Cell

The embryonic gonad is undifferentiated in males and females until a critical stage when the sex chromosomes dictate its development as a testis or ovary. This binary developmental process provides a unique opportunity to delineate the molecular pathways that lead to distinctly different tissues. The testis comprises three main cell types: Sertoli cells, Leydig cells, and germ cells. The Sertoli cells and germ cells reside in seminiferous tubules where spermatogenesis occurs. The Leydig cells populate the interstitial compartment and produce testosterone. The ovary also comprises three main cell types: granulosa cells, theca cells, and oocytes. The oocytes are surrounded by granulosa and theca cells in follicles that grow and differentiate during characteristic reproductive cycles. In this review, we summarize the molecular pathways that regulate the distinct differentiation of these cell types in the developing testis and ovary. In particular, we focus on the transcription factors that initiate these cascades. Although most of the early insights into the sex determination pathway were based on human mutations, targeted mutagenesis in mouse models has revealed key roles for genes not anticipated to regulate gonadal development. Defining these molecular pathways provides the foundation for understanding this critical developmental event and provides new insight into the causes of gonadal dysgenesis.

Expression of nerve growth factor and neurotrophin receptors in testicular cells suggest novel roles for neurotrophins outside the nervous system

1996 ◽  
Vol 8 (7) ◽  
pp. 1075 ◽  
Author(s):  
K Seidl ◽  
A Buchberger ◽  
C Erck
Keyword(s):  
Nerve Growth Factor ◽  
Growth Factor ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Expression Patterns ◽  
Myoid Cells ◽  
Nerve Growth ◽  
High Affinity ◽  
Ngf Receptor

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.

scholarly journals Bovine fetal testicular development in the Nellore breed

2017 ◽  
Vol 38 (4Supl1) ◽  
pp. 2551
Author(s):  
Juliana Stephany de Souza ◽  
Maria Carolina Villani Miguel ◽  
Marcos Antônio Maioli ◽  
Arthur Nelson Trali Neto ◽  
David Giraldo Arana ◽  
...  
Keyword(s):  
Germ Cells ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Principal Component ◽  
Gonadal Development ◽  
Cell Number ◽  
Testicular Development ◽  
Testosterone Concentration ◽  
Testicular Weight ◽  
Bovine Fetuses

The study of gonadal development improves the understanding of factors that can influence the reproductive development process. This study aims to characterize bovine fetal testicular development and the testosterone level in the Nellore breed. For the study, 162 bovine fetuses aged between 3 and 8 months were collected from Nellore cows at a local abattoir. The fetal age was estimated by DP=8.4+0.087L+5.46?L, where DP is the estimated pregnancy day and L represents fetal length. The fetal gonadal weight (g), width (cm), and thickness (cm) were measured. Thereafter, the gonads were submitted to classic histology processes in 3-µm-thick slices cut at 210 µm intervals. The Sertoli cells, Leydig cells, and germ cells were counted. Blood samples were collected from umbilical cords for testosterone levels. The data were analyzed using the Spearman correlation test followed by Principal Component Analysis and one-way ANOVA to compare the averages between months. The testicular weight and volume were found to have a positive correlation with the numbers of Sertoli cells (r = 0.84; p < 0.0001 and r = 0.92; p < 0.0001, respectively), Leydig cells (r = 0.80; p < 0.0001 and r = 0.90; p < 0.0001, respectively), and germ cells (r = 0.84; p < 0.0001 and r = 0.93; p < 0.0001, respectively) and to be negatively correlated with testosterone plasmatic concentration (r = -0.31; p = 0.0001 and r = -0.22; p = 0.006, respectively) during pregnancy. After the fifth month, the numbers of Sertoli cells, Leydig cells and germ cells differed (p < 0.0001) from the following gestational months. The highest testosterone concentration (p = 0.007) was observed in the fifth month of gestation and was followed by a concentration decrease in the seventh and eighth months. The increase in cell quantity was responsible for the increase in testicular weight and volume during fetal development. On the other hand, the testosterone concentration followed the increase in testicular weight and volume until the 7th month of gestation and regressed during the 8th and 9th months, in addition to the increase in cell number.

Passage of leptin across the blood-testis barrier

1999 ◽  
Vol 276 (6) ◽  
pp. E1099-E1104 ◽  
Author(s):  
William A. Banks ◽  
Robert N. McLay ◽  
Abba J. Kastin ◽  
Ulla Sarmiento ◽  
Sheila Scully
Keyword(s):  
Central Nervous System ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Reproductive Function ◽  
Multiple Time ◽  
Testicular Function ◽  
Leptin Receptors ◽  
The Central Nervous System ◽  
Significant Expression ◽  
Blood Testis Barrier

Leptin is a 17-kDa protein, secreted by fat, that controls adiposity and has been proposed to have numerous effects on reproduction in the mouse. To assess whether the effects of leptin on testicular function are direct, we determined whether leptin can cross the murine blood-testis barrier. Multiple time regression analysis showed that a small amount of blood-borne leptin is able to enter the testis but does so by a nonsaturable process. In addition, no significant expression of leptin receptors was found at the Leydig cells or Sertoli cells of the testis. This compares with the presence of a saturable transport system for leptin at the blood-brain barrier and abundant receptors for leptin at the leptomeninges, neurons, and choroid plexus of the central nervous system (CNS). These results support the hypothesis that the effects of leptin on reproductive function are not mediated at the level of the testis but indirectly, probably through the CNS.

scholarly journals Testicular expression of NGF, TrkA and p75 during seasonal spermatogenesis of the wild ground squirrel (Citellus dauricus Brandt)

2015 ◽  
Vol 59 (3) ◽  
Author(s):  
H. Zhang ◽  
Y. Wang ◽  
J. Zhang ◽  
L. Wang ◽  
Q. Li ◽  
...  
Keyword(s):  
Breeding Season ◽  
Sertoli Cells ◽  
Seasonal Changes ◽  
Ground Squirrel ◽  
Leydig Cells ◽  
Testicular Function ◽  
Nonbreeding Season ◽  
Function Change ◽  
The Mean ◽  
Neuronal Systems

The nerve growth factor (NGF) not only has an essential effect on the nervous system, but also plays an important role in a variety of non-neuronal systems, such as the reproductive system. The aim of this study was to investigate the seasonal changes in<strong> </strong>expression of NGF and its receptors (TrkA and p75) in testes of the wild ground squirrel during the breeding and nonbreeding seasons.<strong> </strong>Immunolocalization for NGF was detected mainly in Leydig cells and Sertoli cells in testes of the breeding and nonbreeding seasons. The immunoreactivity of TrkA was highest in the elongated spermatids, whereas p75 in spermatogonia and spermatocytes in testes of the breeding season. In the nonbreeding season testes, TrkA showed positive immunostainings in Leydig cells, spermatogonia and primary spermatocytes, while p75 showed positive signals in spermatogonia and primary spermatocytes. Consistent with the immunohistochemical results, the mean mRNA and protein level of NGF and TrkA were higher in the testes of the breeding season, and then decreased to a relatively low level in the nonbreeding season. In addition, the concentration of plasma gonadotropins and testosterone were assayed by radioimmunoassay (RIA), and the results showed a significant seasonal change between the breeding and nonbreeding seasons. To conclude, these results of this study provide the first evidence on the potential involvement of NGF and its receptor, TrkA and p75 in the seasonal spermatogenesis and testicular function change of the wild ground squirrel.

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