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 ◽  
...  

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.

1970 ◽  
Vol 6 (1) ◽  
pp. 67-74 ◽  
Author(s):  
MR Gofur ◽  
MZI Khan ◽  
MR Karim ◽  
MN Islam

Histomorphological and histochemical features of testes were studied in six adult indigenous bulls (Bos indicus) of two different age groups, 1 year 9 months to 2 years of age (group A) and 2 years 3 months to 2 years 6 months of age (group B) during the period from September 2006 to April 2007 by using Hematoxylin and Eosin (H&E) stain, Verhoeff's stain, Van Gieson's stain and Periodic Acid-Schiff Reaction (PAS) stain. The testes were surrounded by visceral layer of tunica vaginalis (consisted of mesothelium and connective tissue) and tunica albugenia mainly composed of collagen fibers. The seminiferous tubules were tortuous, two ended loops and varying in appearance and the wall of tubules consisted of lamina propria, basement membrane supported by reticular fibers and a lining of complex stratified epithelium consisted of sertoli cells and spermatogenic cells. The sertoli cells are irregulary columnar cells, extended from basal lamina to lumen of tubules and the spermatogenic cells situated between the sertoli cells in an orderly manner with four to eight layers occupying the space between the basal lamina and the lumen of the tubules. There was presence of both spermatid and spermatozoa in the lumen of some seminiferous tubules of testes of bulls of both age groups. The spermatogonia, primary spermatocytes and secondary spermatocytes showed more staining affinity than the spermatid in routine staining technique. The basement membrane of tubules, spermatid and spermatozoa showed positive affinity whereas spermatogonia, primary spermatocytes and secondary spermatocytes showed negative affinity to PAS stain. The interstitial tissues located between the sminiferous tubules, consisted of connective tissue network, mainly composed of collagenous and reticular fibers; blood and lymph vessels with Leydig cells. The Leydig cells were present as single or groups within intertubular spaces. It was concluded that the thickness of tunica albuginea, the stratification of growing spermatogenic cells and cross sectional length and breadth of the seminiferous tubules of testes were higher in the bull of group B than group A and the number of Leydig cells were more in the testis of group A than group B and in between left and right testes, the thickness of tunica albuginea and cross sectional length and breadth of the seminiferous tubules were higher in the left testis but the number of Leydig cells was higher in right testis in both age groups. Key words: Testis, seminiferous tubule, Leydig cell, indigenous bull DOI = 10.3329/bjvm.v6i1.1341 Bangl. J. Vet. Med. (2008). 6 (1): 67-74


Endocrinology ◽  
2005 ◽  
Vol 146 (3) ◽  
pp. 1035-1042 ◽  
Author(s):  
Susan Y. Park ◽  
J. Larry Jameson

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.


2014 ◽  
Vol 11 (2) ◽  
pp. 43-48
Author(s):  
D Alimaa ◽  
S Byambatsogt ◽  
TS Enkhbaatar

"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


Biota ◽  
2020 ◽  
Vol 13 (1) ◽  
Author(s):  
Mahriani Mahriani ◽  
Susantin Fajariyah ◽  
Eva Tyas Utami

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.


mBio ◽  
2019 ◽  
Vol 10 (4) ◽  
Author(s):  
Daniel P. Strange ◽  
Boonyanudh Jiyarom ◽  
Nima Pourhabibi Zarandi ◽  
Xuping Xie ◽  
Coleman Baker ◽  
...  

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.


2005 ◽  
Vol 17 (9) ◽  
pp. 84
Author(s):  
M. Sarraj ◽  
P. J. McClive ◽  
K. L. Loveland ◽  
A. H. Sinclair

We present a detailed study on the expression pattern of Wsb2 in the mouse foetal and adult gonad. Wsb2 expression was analysed during mouse embryogenesis by whole-mount, section in situ hybridisation and immunohistochemistry. Wsb2 was found to be expressed in the developing mouse gonads from 11.5 dpc to 16.5 dpc. Expression is initially equal in both sexes from 10.5 dpc until 12.0 dpc, then it persists in the male gonad. Wsb2 expression was confined to the cords in both Sertoli cell and germ cells. Other sites of Wsb2 embryonic expression were the somites, dorsal root ganglia and the lateral mantle layer of the neural tube. mRNA encoding Wsb2 and Wsb2 protein has been detected in the newborn testis in both gonocytes and Sertoli cells. Wsb2 mRNA in the adult mouse testis was observed in Sertoli cells, spermatogonia, spermatocytes and the corresponding Wsb2 protein expression was in pachytene spermatocytes, round and elongated spermatids, Sertoli cells and Leydig cells. The differential expression of Wsb2 in male versus female embryonic gonads suggests it may play a role in mammalian sex determination during embryonic development and its expression in the first wave of spermatogenesis and in the adult suggests a later role in spermatogenesis.


Development ◽  
1986 ◽  
Vol 95 (1) ◽  
pp. 261-277
Author(s):  
C. J. A. H. V. van Vorstenbosch ◽  
C. M. J. E. van Rossum-Kok ◽  
B. Colenbrander ◽  
C. J. G. Wensing

Testes of foetal pigs between 26 to 35 days post coitum (p.c.) were investigated histochemically and ultrastructurally. Diaphorase and Δ5-3β-hydroxysteroid dehydrogenase activities were studied using, respectively, NADH and pregnenolone and dihydroxy androsterone as substrates. Ultrastructurally, attention was focused on the development of mesenchymal cells and on the sustentacular cells in the primitive sex cords in an attempt to detect the origin of Ley dig cells. Histochemically there is a concentration of activity toward the interstitium with increasing age. Also the reactions increase in intensity. Ultrastructurally no evidence for Leydig cell development from Sertoli cells could be observed. Mesenchymal cells between the sex cords show a development toward Leydig cells. This is absent in mesenchymal cells in the future tunica albuginea. Before 30 days p.c. no ‘true’ Leydig cells can be observed morphologically. The role of the rough endoplasmic reticulum/mitochondrial complex, which is present in many mesenchymal and sustentacular cells, is discussed.


Reproduction ◽  
2009 ◽  
Vol 138 (4) ◽  
pp. 655-666 ◽  
Author(s):  
Yongmei Chen ◽  
Huizhen Wang ◽  
Nan Qi ◽  
Hui Wu ◽  
Weipeng Xiong ◽  
...  

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.


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

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.


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