scholarly journals Immunoexpression of Tyro 3 Family Receptors—Tyro 3, Axl, and Mer—and Their Ligand Gas6 in Postnatal Developing Mouse Testis

2005 ◽  
Vol 53 (11) ◽  
pp. 1355-1364 ◽  
Author(s):  
Huizhen Wang ◽  
Yongmei Chen ◽  
Yehua Ge ◽  
Pengpeng Ma ◽  
Quanhong Ma ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Leydig Cells ◽  
Cytoplasmic Membrane ◽  
Expression Patterns ◽  
Exact Expression ◽  
Seminiferous Tubules ◽  
Testicular Cells ◽  
Similar Expression Pattern ◽  
Weak Staining ◽  
Cell Processes

Tyro 3 family receptors contain three members—Tyro 3, Axl, and Mer—that are essential regulators of mammalian spermatogenesis. However, their exact expression patterns in testis are unclear. In this study, we examined the localizations of Tyro 3, Axl, Mer, and their ligand Gas6 in postnatal mouse testes by immunohistochemistry. All three members and their ligand were continuously expressed in different testicular cells during postnatal development. Tyro 3 was expressed only in Sertoli cells with a varied distribution during testis development. At day 3 postnatal, Tyro 3 was distributed in overall cytoplasmic membrane and cytoplasm of Sertoli cells. From day 14 to day 35 postnatal, Tyro 3 appeared on Sertoli cell processes toward the adlumenal compartment of seminiferous tubules. A stage-dependent Tyro 3 immunoexpression in Sertoli cells was shown by adulthood testis at day 56 postnatal with higher expression at stages I-VII and lower level at stages IX-XII. Axl showed a similar expression pattern to Tyro 3, except for some immunopositive Leydig cells detected in mature testis. In contrast, immunostaining of Mer was detected mainly in primitive spermatogonia and Leydig cells, whereas a relative weak signal was found in Sertoli cells. Gas6 was strongly expressed in Leydig cells, and a relative weak staining signal was seen in primitive spermatogonia and Sertoli cells. These immunoexpression patterns of Tyro 3 family receptors and ligand in testis provide a basis to further study their functions and mechanisms in regulating mammalian spermatogenesis.

METABOLIC CHANGES IN TESTICULAR CELLS FROM RATS AFTER LONG-TERM EXPOSURE TO 37 °C IN VIVO OR IN VITRO

1980 ◽  
Vol 85 (3) ◽  
pp. 471-479 ◽  
Author(s):  
F. F. G. ROMMERTS ◽  
F. H. DE JONG ◽  
J. A. GROOTEGOED ◽  
H. J. VAN DER MOLEN
Keyword(s):  
Sertoli Cells ◽  
Leydig Cells ◽  
Biochemical Properties ◽  
Effect Of Temperature ◽  
Seminiferous Tubules ◽  
Experimental Conditions ◽  
Testicular Cells ◽  
Old Rats

Biochemical properties of isolated Leydig cells, Sertoli cells and spermatocytes from rat testes have been investigated after in-vivo or in-vitro exposure of these cells to abdominal temperature (37 °C). The rate of production of testosterone and pregnenolone by isolated Leydig cells from cryptorchid and normal testes from mature rats was not different. Production of pregnenolone by mitochondria prepared from cryptorchid testes was 6·7 times higher than production by mitochondria from normal testes. Sertoli cells prepared from immature rats and incubated in vitro at 32 or 37 °C showed, on day 1 of the culture period, an initial twofold increase in the secretion of androgen-binding protein which was absent after 6 days in culture. In contrast, incorporation of [3H]leucine into secreted proteins was stimulated twofold on day 1 as well as by day 6 of culture. Secretion of oestradiol was increased 30-fold by day 6 when compared with the level found on day 1 when cells had been cultured at 37 °C and the increased secretion of oestradiol was maintained for approximately 2 days when the temperature of incubation was decreased to 32 °C Spermatocytes isolated from seminiferous tubules incubated for 20 h at 37 °C were active in the synthesis of RNA. No degeneration of these cells was observed in testes of 25-day-old rats 5 days after experimental cryptorchidism, whereas under similar conditions massive degeneration of spermatocytes was shown in the testes of mature rats. These results suggest that the effects of temperature on the different testicular cells greatly depend on the experimental conditions used to study the effect of temperature.

scholarly journals Stage-Dependent Expression of Protein Gene Product 9.5 in Donkey Testes

Animals ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 2169
Author(s):  
Yeonju Choi ◽  
Youngwook Jung ◽  
Seongmin Kim ◽  
Junyoung Kim ◽  
Heejun Jung ◽  
...  
Keyword(s):  
Gene Product ◽  
Western Blotting ◽  
Leydig Cells ◽  
Protein Gene ◽  
Expression Patterns ◽  
Seminiferous Tubules ◽  
Pubertal Stage ◽  
Protein Gene Product ◽  
Testicular Cells ◽  
Pubertal Stages

Molecular markers can be used to identify and isolate specific developmental stages of germ cells and Leydig cells. Protein gene product (PGP)9.5 expression in spermatogonia and Leydig cells has been reported in several species. The stages of spermatogonia and Leydig cells expressing PGP9.5 vary depending on the species and reproductive stages. Thus, the objectives of this study were (1) to identify the localization of PGP9.5 in donkey testicular cells, and (2) to compare the expression patterns of PGP9.5 in donkey testicular cells between pre- and post-pubertal stages. Testes samples were collected following the routine field castration of six donkeys. Western blotting was performed to verify the cross-reactivity of the rabbit anti-human PGP9.5 antibody to donkey testes. Immunofluorescence was performed to investigate the expression pattern of PGP9.5 in testicular tissues at different reproductive stages. In Western blotting, the protein band of the PGP9.5 antibody appeared at approximately 27 kDa, whereas the band was not observed in the negative control treated with normal mouse IgG. In the pre-pubertal stage, the expression of deleted in azoospermia-like (DAZL) was found in some spermatogonia in pre-pubertal testicular tissues. However, the immunolabeling of PGP9.5 in testicular tissue was not observed in the seminiferous tubules. In stages 1 and 2, spermatogonia were immunolabeled with either PGP9.5 or DAZL. In contrast, PGP9.5 and DAZL were co-immunolabeled in some of the spermatogonia in stages 3 to 8. Interestingly, some Leydig cells were immunolabeled with PGP9.5 in both pre- and post-pubertal stages. In conclusion, the PGP9.5 antibody can be used as a tool to identify and isolate spermatogonia from seminiferous tubules.

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 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.

Results of study on changes in the body of livestock castrated by unopened method

2014 ◽  
Vol 11 (2) ◽  
pp. 43-48
Author(s):  
D Alimaa ◽  
S Byambatsogt ◽  
TS Enkhbaatar
Keyword(s):  
Sertoli Cells ◽  
Spermatic Cord ◽  
Leydig Cells ◽  
The Body ◽  
Seminiferous Tubules ◽  
Cremaster Muscle ◽  
Connective Tissues ◽  
Cellular Division ◽  
Ductus Deferens ◽  
Frontal Wall

"Tartu-SHAB" emasculator for unopened castration of male calf, lamb and kids is used to break ductus deferens and blood vessels and damage cremaster muscle after detecting outside the spermatic cord via palpation of scrotal neck skin. Movement of castrated animal becomes slower, hind legs are slightly spread, animal steps on frontal wall of its hind leg hooves and lifts one of hind legs in turn, and superficial, small, painful, differently sized, and warmer swelling appears. Cremaster fascia of testicle tissue castrated animals (at day 30) divides testicle parenchyma into lobules and there are epithelial cells producing spermatozoa at various stages of development in the wall of seminiferous tubules, Sertoli cells and Leydig cells in reticular and soft connective tissues between seminiferous tubules. But at day 60, thickened outer layer of testicle, larger gaps between tubules, structural change of primary and secondary spermatozoa, ceased cellular division cellular division and absence of Leydig cells reveal the process of atrophy. DOI: http://dx.doi.org/10.5564/mjas.v11i2.215 Mongolian Journal of Agricultural Sciences Vol.11(2) 2013 pp.43-48

scholarly journals Curcumin Effectivity on Hepar and Reproductive Organ Recovery Male Mice (Mus musculus L) after Methoxychlor Exposure

Biota ◽  
2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Mahriani Mahriani ◽  
Susantin Fajariyah ◽  
Eva Tyas Utami
Keyword(s):  
Mus Musculus ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Reproductive Organ ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Disruptive Effect ◽  
Curcumin Treatment ◽  
Cell Counts ◽  
Male Reproductive Organ

Methoxychlor (MXC) is an insecticide (DDT derivates) that has the potential for bioaccumulation in mammal and causes a disruptive effect on the hepar and reproductive system. This study was done to find out the benefits of curcumin as a natural ingredient to overcome the negative impact of Methoxychlor (MXC) on hepar and male reproductive organ of Balb’C mice (Mus musculus L). The study was carried out in a Completely Randomized Design (CRD) Posttest Only Control Group Design used four treatments and six replications. The curcumin treatment after administration of MXC was carried out by gavage with curcumin doses: 0.05; 0,1; and 0.2 mg/g body weight, every day for two weeks, respectively. Histological observations of the liver, and testis was performed using the paraffin method and Hematoxylin Eosin stained. The results showed that MXC exposure caused liver disruption by increasing the number of pycnotic necrotic hepatocytes and hydrophic degeneration hepatocytes. On the male reproductive organ, MXC caused testis impairment by reducing the number of Sertoli cells and Leydig cells, spermatogenic cell counts, and the diameter of seminiferous tubules. The administration of curcumin at doses of 0.1 mg/g bw in mice exposed to methoxychlor can reduce the number of hydrophic degeneration hepatocytes and tend to reduce the number of pycnotic hepatocytes; and also increase the number of Sertoli cells, the number of spermatogenic cells, and the diameter of the seminiferous tubules, and tend to reduce the amount of Leydig cells. Curcumin treatment tends to recover hepar dan testis disruption of mice that were exposed by MXC.

scholarly journals Health concerns regarding the effect of the COVID-19 pandemic on male fertility

2021 ◽  
Author(s):  
Hamidreza Mosleh ◽  
Fatemeh Moradi ◽  
Mehdi Mehdizadeh ◽  
Marziyeh Ajdary ◽  
Alaa Moeinzadeh ◽  
...  
Keyword(s):  
Male Infertility ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Renin Angiotensin System ◽  
High Expression ◽  
Angiotensin System ◽  
Angiotensin Converting Enzyme 2 ◽  
Testicular Cells ◽  
Novel Coronavirus ◽  
High Expression Level

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus found in China in 2019. The disease caused by SARS-CoV-2, coronavirus disease 2019 (COVID-19), has been found to be closely related to the cells that secrete angiotensin-converting enzyme 2 (ACE2). ACE2 is involved in the renin-angiotensin system and is widely secreted in several tissues, including the testis, which has raised concerns because organs with high expression of the ACE2 receptor are susceptible to infection. Analyses have shown that in testicular cells, such as spermatogonia, seminiferous duct cells, Sertoli cells, and Leydig cells, there is a high expression level of ACE2. Therefore, SARS-CoV-2 may damage male reproductive tissues and cause infertility. Since male infertility is an important problem, scientists are evaluating whether COVID-19 may influence male infertility through the ACE2 receptor.

scholarly journals Autologous transplantation of spermatogonial stem cells restores fertility in congenitally infertile mice

2020 ◽  
Vol 117 (14) ◽  
pp. 7837-7844
Author(s):  
Mito Kanatsu-Shinohara ◽  
Narumi Ogonuki ◽  
Shogo Matoba ◽  
Atsuo Ogura ◽  
Takashi Shinohara
Keyword(s):  
Stem Cells ◽  
Sertoli Cells ◽  
Expression Patterns ◽  
Autologous Transplantation ◽  
Spermatogonial Stem Cells ◽  
Congenital Defects ◽  
Seminiferous Tubules ◽  
Special Environment ◽  
Deficient Mice

The blood–testis barrier (BTB) is thought to be indispensable for spermatogenesis because it creates a special environment for meiosis and protects haploid cells from the immune system. The BTB divides the seminiferous tubules into the adluminal and basal compartments. Spermatogonial stem cells (SSCs) have a unique ability to transmigrate from the adluminal compartment to the basal compartment through the BTB upon transplantation into the seminiferous tubule. Here, we analyzed the role ofCldn11, a major component of the BTB, in spermatogenesis using spermatogonial transplantation.Cldn11-deficient mice are infertile due to the cessation of spermatogenesis at the spermatocyte stage.Cldn11-deficient SSCs failed to colonize wild-type testes efficiently, andCldn11-deficient SSCs that underwent double depletion ofCldn3andCldn5showed minimal colonization, suggesting that claudins on SSCs are necessary for transmigration. However,Cldn11-deficient Sertoli cells increased SSC homing efficiency by >3-fold, suggesting that CLDN11 in Sertoli cells inhibits transmigration of SSCs through the BTB. In contrast to endogenous SSCs in intactCldn11-deficient testes, those from WT orCldn11-deficient testes regenerated sperm inCldn11-deficient testes. The success of this autologous transplantation appears to depend on removal of endogenous germ cells for recipient preparation, which reprogrammed claudin expression patterns in Sertoli cells. Consistent with this idea, in vivo depletion ofCldn3/5regenerated endogenous spermatogenesis inCldn11-deficient mice. Thus, coordinated claudin expression in both SSCs and Sertoli cells expression is necessary for SSC homing and regeneration of spermatogenesis, and autologous stem cell transplantation can rescue congenital defects of a self-renewing tissue.

scholarly journals Axl Promotes Zika Virus Entry and Modulates the Antiviral State of Human Sertoli Cells

mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Daniel P. Strange ◽  
Boonyanudh Jiyarom ◽  
Nima Pourhabibi Zarandi ◽  
Xuping Xie ◽  
Coleman Baker ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Zika Virus ◽  
Leydig Cells ◽  
Virus Entry ◽  
Seminiferous Epithelium ◽  
Seminiferous Tubules ◽  
Type I ◽  
Cell Type ◽  
Zikv Infection ◽  
Antiviral State

ABSTRACT Zika virus (ZIKV) is unique among mosquito-borne flaviviruses in its ability to be sexually transmitted. Persistent ZIKV infection in the testes, which are immune privileged organs, long after peripheral clearance suggests involvement of immunosuppressive pathways; however, the underlying mechanisms remain undetermined. We recently demonstrated that ZIKV infects human Sertoli cells (SC), the major cell type of the seminiferous epithelium responsible for maintaining the immune privileged compartment of seminiferous tubules. Recent reports have identified the TAM (Tyro3, Axl, Mer) receptor tyrosine kinase Axl as an entry receptor and/or immune modulator for ZIKV in a cell type-specific manner. Interestingly, the seminiferous epithelium exhibits high basal expression of the Axl receptor where it is involved in clearance of apoptotic germ cells and immunosuppression. Here, we show that Axl was highly expressed in SC compared to Leydig cells (LC) that correlated with robust ZIKV infection of SC, but not LC. Further, neutralization of Axl receptor and its ligand Gas6 strongly attenuated virus entry in SC. However, inhibition of Axl kinase did not affect ZIKV entry but instead led to decreased protein levels of suppressor of cytokine signaling 1 (SOCS1) and SOCS3, increased expression of interferon-stimulated genes (ISGs), and reduced ZIKV replication. Similarly, treatment of multicellular human testicular organoids with an Axl kinase inhibitor attenuated ZIKV replication and increased ISG expression. Together, our data demonstrate that Axl promotes ZIKV entry and negatively regulates the antiviral state of SC to augment ZIKV infection of the testes and provides new insights into testis antiviral immunity and ZIKV persistence. IMPORTANCE Recent Zika virus (ZIKV) outbreaks have identified sexual transmission as a new route of disease spread not reported for other flaviviruses. ZIKV crosses the blood-testis barrier and establishes infection in seminiferous tubules, the site for spermatozoa development. Currently, there are no therapies to treat ZIKV infection, and the immune mechanisms underlying testicular persistence are unclear. We found that multiple human testicular cell types, except Leydig cells, support ZIKV infection. Axl receptor, which plays a pivotal role in maintaining the immunosuppressive milieu of the testis, is highly expressed in Sertoli cells and augments ZIKV infection by promoting virus entry and negatively regulating the antiviral state. By using testicular organoids, we further describe the antiviral role of Axl inhibition. The significance of our research lies in defining cross talk between Axl and type I interferon signaling as an essential mechanism of immune control that can inform therapeutic efforts to clear ZIKV from the testis.

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