scholarly journals Sox9 and Sox8 protect the adult testis from male-to-female genetic reprogramming and complete degeneration

eLife ◽  
2016 ◽  
Vol 5 ◽  
Author(s):  
Francisco J Barrionuevo ◽  
Alicia Hurtado ◽  
Gwang-Jin Kim ◽  
Francisca M Real ◽  
Mohammed Bakkali ◽  
...  
Keyword(s):  
Sertoli Cells ◽  
Male Fertility ◽  
Leydig Cells ◽  
Structural Proteins ◽  
Seminiferous Tubules ◽  
Adult Testis ◽  
Key Genes ◽  
Male To Female ◽  
Mutant Cells ◽  
Testis Regression

The new concept of mammalian sex maintenance establishes that particular key genes must remain active in the differentiated gonads to avoid genetic sex reprogramming, as described in adult ovaries after Foxl2 ablation. Dmrt1 plays a similar role in postnatal testes, but the mechanism of adult testis maintenance remains mostly unknown. Sox9 and Sox8 are required for postnatal male fertility, but their role in the adult testis has not been investigated. Here we show that after ablation of Sox9 in Sertoli cells of adult, fertile Sox8-/- mice, testis-to-ovary genetic reprogramming occurs and Sertoli cells transdifferentiate into granulosa-like cells. The process of testis regression culminates in complete degeneration of the seminiferous tubules, which become acellular, empty spaces among the extant Leydig cells. DMRT1 protein only remains in non-mutant cells, showing that SOX9/8 maintain Dmrt1 expression in the adult testis. Also, Sox9/8 warrant testis integrity by controlling the expression of structural proteins and protecting Sertoli cells from early apoptosis. Concluding, this study shows that, in addition to its crucial role in testis development, Sox9, together with Sox8 and coordinately with Dmrt1, also controls adult testis maintenance.

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.

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.

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.

Differentiation of Fetal Sertoli Cells in the Adult Testis

Reproduction ◽  
2021 ◽  
Author(s):  
Tetsuhiro Yokonishi ◽  
Blanche Capel
Keyword(s):  
Sertoli Cell ◽  
Sertoli Cells ◽  
Developmental Process ◽  
Ips Cells ◽  
Cell Maturation ◽  
Seminiferous Tubules ◽  
Fetal Life ◽  
Adult Testis ◽  
Testicular Cells

Sertoli cells proliferate and construct seminiferous tubules during fetal life, then undergo differentiation and maturation in the prepubertal testes. In the adult testes, mature Sertoli cells maintain spermatogonia and support spermatogenesis during the entire lifetime. Although Sertoli-like cells have been derived from iPS cells, they tend to remain immature. To investigate whether Sertoli cells can spontaneously acquire the ability to support spermatogenesis when transferred into the adult testis, we transplanted mouse fetal testicular cells into a Sertoli-depleted adult testis. We found that donor E12.5, E14.5 and E16.5 Sertoli cells colonized adult seminiferous tubules and supported host spermatogenesis two months after transplantation, demonstrating that immature fetal Sertoli cells can undergo sufficient maturation in the adult testis to become functional. This technique will be useful to analyze the developmental process of Sertoli cell maturation, and to investigate the potential of iPS-derived Sertoli cells to colonize, undergo maturation, and support spermatogenesis within the testis environment.

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.

Morphological study of the effects of an GnRH agonist on the canine testis after 4 months of treatment and recovery

1987 ◽  
Vol 116 (3) ◽  
pp. 413-417 ◽  
Author(s):  
D. Dubé ◽  
A. Assaf ◽  
G. Pelletier ◽  
F. Labrie
Keyword(s):  
Gnrh Agonist ◽  
Sertoli Cells ◽  
Leydig Cells ◽  
Lipid Droplets ◽  
Seminiferous Tubules ◽  
Testis Weight ◽  
Electron Microscope Level ◽  
Reversible Method ◽  
Normal Spermatogenesis ◽  
Cessation Of Treatment

Abstract. After 4 months of treatment of adult male dogs with the GnRH agonist (GnRH-A) [D-Trp6]GnRH ethylamide, the seminiferous tubules contained only type A and B spermatogonia, Sertoli cells, and rare primary spermatocytes, thus causing a 64% decrease in testis weight. At the electron microscope level, Sertoli cells showed an increase in phagosomes and lipid droplets. Leydig cells were markedly atrophied with the accumulation of lipid droplets and showed a pre-dominance of mitochondria with lamellar instead of vesicular cristae. Four months after cessation of treatment with GnRH-A, a complete return to normal spermatogenesis and Leydig cell morphology was observed. The full reversibility of spermatogenesis in the dog after chronic GnRH-A treatment suggests that this well-tolerated peptide could be used as a reversible method of male contraception.

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