Immunodetection of inhibin in the human testis and epididymis during normal development and in non-tumoural testicular lesions

2010 ◽  
Vol 22 (3) ◽  
pp. 558 ◽  
Author(s):  
Manuel Nistal ◽  
Pilar González-Peramato ◽  
Maria P. De Miguel
Keyword(s):  
Sertoli Cells ◽  
Leydig Cells ◽  
Staining Pattern ◽  
Hormonal Treatment ◽  
Human Testis ◽  
Seminiferous Tubules ◽  
Secretory Cells ◽  
Testicular Function ◽  
Human Epididymis ◽  
Efferent Ducts

Plasma concentrations of inhibin are correlated with spermatogenetic function. Inhibin is secreted mainly by the Sertoli and Leydig cells of the testis. In the human epididymis, the location and function of inhibin are contentious. Thus, the aim of the present study was to determine the location of inhibin in the human epididymis. Investigations were performed in samples with normal testicular function at different stages of development, as well as in samples in which testicular function or the testicular–epididymal connection were altered. In fetal, newborn and infant testes, Sertoli and Leydig cells stained positive for inhibin, whereas no such staining was detected in the epididymides. Inhibin was located in both the Sertoli and Leydig cells, as well as in the epididymis, in the apical pole of mainly secretory cells in the efferent ducts. This staining pattern was not correlated with the staining pattern for macrophages. The main duct of the epididymis was negative for inhibin staining. In ischaemic atrophic testes, the few tubules in which Sertoli cells were present stained positive for inhibin, whereas the epididymides stained negative. In paediatric cryptorchidism, Sertoli and Leydig cells stained positive for inhibin, whereas the epididymides were negative. In adult cryptorchidism, Sertoli and Leydig cells stained positive for inhibin, even in tubules containing Sertoli cells only. Interestingly, inhibin was absent from the efferent ducts. In three cases undergoing hormonal treatment prior to subsequent gender change, Sertoli and Leydig cells stained positive for inhibin. In contrast, the efferent ducts were negative or only faintly positive in cases of shorter hormonal treatment. In all cases studied, the presence of inhibin in the efferent ducts was associated with its production in the testis, suggesting that the epididymis is not responsible for the production of inhibin in men. The pattern of inhibin staining does not correlate with that of macrophages, suggesting that inhibin is not degraded in the human epididymis. The data suggest that, in humans, inhibin is secreted by Sertoli cells into the seminiferous tubules and then travels towards the efferent ducts, where it is reabsorbed into the bloodstream.

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.

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.

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 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.

1 XENOGRAFTING OF ADULT MAMMALIAN TESTIS TISSUE

2007 ◽  
Vol 19 (1) ◽  
pp. 119
Author(s):  
L. Arregui ◽  
R. Rathi ◽  
W. Zeng ◽  
A. Honaramooz ◽  
M. Gomendio ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Germ Cell ◽  
Germ Cells ◽  
Sertoli Cells ◽  
Human Testis ◽  
Seminiferous Tubules ◽  
Donor Tissue ◽  
Germ Cell Differentiation ◽  
Sexually Mature ◽  
Testis Tissue

Testis tissue grafting presents an option for preservation of genetic material when sperm recovery is not possible. Grafting of testis tissue from sexually immature males to immunodeficient mice results in germ cell differentiation and production of fertilization-competent sperm from different mammalian species (Honaramooz et al. 2002 Nature 418, 778–781). However, the efficiency of testis tissue xenografting from adult donors has not been critically evaluated. Spermatogenesis was arrested at meiosis in grafts from mature horses (Rathi et al. 2006 Reproduction 131, 1091–1098) and hamsters (Schlatt et al. 2002 Reproduction 124, 339–346), and no germ cell differentiation occurred in xenografts of adult human testis tissue (Schlatt et al. 2006 Hum. Reprod. 21, 384–389). The objective of this study was to investigate survival and germ cell differentiation of testis xenografts from sexually mature donors of different species. Small fragments of testis tissue from 10 donor animals of 5 species were grafted under the back skin of immunodeficient, castrated male mice (n = 37, 2–6/donor). Donors were pig (8 months old), goat (18 months old and 4 years old) (n = 2), bull (3 years old), donkey (13 months old), and rhesus monkey (3, 6, 11, and 12 years old). At the time of grafting, donor tissue contained elongated spermatids, albeit to different degrees (&gt;75% of seminiferous tubules in testis tissue from pig, goat, bull, and 6–12-year-old monkeys, and 33 or 66% of tubules in tissue from donkey or 3-year-old monkey, respectively). Grafts were recovered &lt;12 weeks (n = 14 mice), 12–24 weeks (n = 16 mice), and &gt;24 weeks (n = 7 mice) after grafting and classified histologically as completely degenerated (no tubules found), degenerated tubules (only hyalinized seminiferous tubules observed), or according to the most advanced type of germ cell present. Grafts from pig, goat, bull, and 6–12-year-old monkeys contained &gt;60% degenerated tubules or were completely degenerated at all time points analyzed. In contrast, in grafts from the 3-year-old monkey, only 18% of tubules were degenerated, 14% contained Sertoli cells only, 64% contained meiotic, and 4% haploid germ cells at 24 weeks after grafting. Similarly, donkey testis grafts recovered 12–24 weeks after grafting contained &lt;2% degenerated tubules, 46% of tubules had Sertoli cells only, 45% contained meiotic, and 7% haploid germ cells. These results show that survival and differentiation of germ cells in testis grafts from sexually mature mammalian donors is poor. However, better graft survival and maintenance of spermatogenesis occurred in donor tissue from donkey and 3-year-old monkey that were less mature at the time of grafting. Therefore, species and age-related differences appear to exist with regard to germ cell survival and differentiation in xenografts from adult donors. This work was supported by USDA/CSREES 03-35203-13486, NIH/NCRR 5-R01-RR17359-05, the Spanish Ministry of Education, and Science (BES-2004-4112).

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.

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