Sertoli Cells Are Susceptible to ZIKV Infection in Mouse Testis

GATA-1 is an essential factor for the transcriptional activation of erythroid-specific genes, and is also abundantly expressed in a discrete subset of cells bordering the seminiferous epithelium in tubules of the murine testis. In examining normal and germ-line defective mutant mice, we show here that GATA-1 is expressed only in the Sertoli cell lineage in mouse testis. GATA-1 expression in Sertoli cells is induced concomitantly with the first wave of spermatogenesis, and GATA-1-positive cells are uniformly distributed among all tubules during prepubertal testis development. However, the number of GATA-1-positive cells declines thereafter and were found only in the peripheral zone of seminiferous tubules in stages VII, VIII and IX of spermatogenesis in the adult mouse testis. In contrast, virtually every Sertoli cell in mutant W/Wv, jsd/jsd or cryptorchid mice (all of which lack significant numbers of germ cells) expresses GATA-1, thus showing that the expression of this transcription factor is negatively controlled by the maturing germ cells. These observations suggest that transcription factor GATA-1 is a developmental stage- and spermatogenic cycle-specific regulator of gene expression in Sertoli cells.

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Differential expression of placental (P)-cadherin in sertoli cells and peritubular myoid cells during postnatal development of the mouse testis

The Anatomical Record ◽

10.1002/(sici)1097-0185(199602)244:2<155::aid-ar3>3.0.co;2-0 ◽

1996 ◽

Vol 244 (2) ◽

pp. 155-164 ◽

Cited By ~ 19

Author(s):

Li-Hsien Lin ◽

Robert M. DePhilip

Keyword(s):

Differential Expression ◽

Postnatal Development ◽

Sertoli Cells ◽

Mouse Testis ◽

Myoid Cells

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RNA Synthetic Activities of Sertoli Cells in the Mouse Testis

Biology of Reproduction ◽

10.1095/biolreprod11.4.365 ◽

1974 ◽

Vol 11 (4) ◽

pp. 365-376 ◽

Cited By ~ 17

Author(s):

A. L. Kierszenbaum

Keyword(s):

Sertoli Cells ◽

Mouse Testis

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Differential expression of glucose transporter GLUT8 during mouse spermatogenesis

Reproduction ◽

10.1530/rep.1.00750 ◽

2006 ◽

Vol 131 (1) ◽

pp. 63-70 ◽

Cited By ~ 33

Author(s):

Olga Gómez ◽

Amparo Romero ◽

José Terrado ◽

José E Mesonero

Keyword(s):

Western Blot ◽

Differential Expression ◽

Germ Cells ◽

Sertoli Cells ◽

Glucose Transporter ◽

Mouse Testis ◽

Pivotal Role ◽

Interstitial Tissue ◽

Rt Pcr ◽

Fuel Supply

GLUT8 is a facilitative glucose transporter expressed at high levels in the testis. In this study, we analyzed the GLUT8 expression in mouse testis during spermatogenesis by RT–PCR, Western blot and immunohistochemistry methods. Our results show that GLUT8 expression is limited to spermatids and spermatozoa in the testis. Expression begins when round spermatids are formed at postnatal day 24. The expression persists throughout spermiogenesis, and it is also detected in spermatozoa, but it is absent in more immature germ cells, Sertoli cells and interstitial tissue. GLUT8 immunoreactivity is always restricted to the acrosomic system in a manner that matches the acrosome system formation. The GLUT8 expression is mainly associated with the acrosomic membrane in the acrosome, although significant immunoreactivity is also found inside the acrosomic lumen. The specific GLUT8 location suggests that this transporter plays a pivotal role in the fuel supply of spermatozoa, and in the traffic of sugars during the capacitation and fertilization processes.

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

mBio ◽

10.1128/mbio.01372-19 ◽

2019 ◽

Vol 10 (4) ◽

Cited By ~ 23

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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218. Expression of Wsb2 in the mouse testis

Reproduction Fertility and Development ◽

10.1071/srb05abs218 ◽

2005 ◽

Vol 17 (9) ◽

pp. 84

Author(s):

M. Sarraj ◽

P. J. McClive ◽

K. L. Loveland ◽

A. H. Sinclair

Keyword(s):

Sertoli Cells ◽

Leydig Cells ◽

Adult Mouse ◽

In Situ Hybridisation ◽

Mouse Testis ◽

Male Gonad ◽

Whole Mount ◽

Mantle Layer ◽

Pachytene Spermatocytes

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.

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Sertoli Cells of the Mouse Testis Originate from the Coelomic Epithelium

Developmental Biology ◽

10.1006/dbio.1998.9068 ◽

1998 ◽

Vol 203 (2) ◽

pp. 323-333 ◽

Cited By ~ 262

Author(s):

Jeannie Karl ◽

Blanche Capel

Keyword(s):

Sertoli Cells ◽

Mouse Testis ◽

Coelomic Epithelium

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Sertoli cell replacement in explanted mouse testis tissue supporting host spermatogenesis

Biology of Reproduction ◽

10.1093/biolre/ioab104 ◽

2021 ◽

Author(s):

Kazusa Higuch ◽

Takafumi Matsumura ◽

Haruhiko Akiyama ◽

Yoshiakira Kanai ◽

Takehiko Ogawa ◽

...

Keyword(s):

Sertoli Cell ◽

Germ Cells ◽

Sertoli Cells ◽

Diphtheria Toxin ◽

Mouse Testis ◽

Seminiferous Tubules ◽

Functional Assay ◽

Cell Replacement ◽

Replacement Method ◽

Toxin Receptor

Abstract Spermatogenesis takes place in the seminiferous tubules, starting from the spermatogonial stem cell and maturing into sperm through multiple stages of cell differentiation. Sertoli cells, the main somatic cell constituting the seminiferous tubule, are in close contact with every germ cell and play pivotal roles in the progression of spermatogenesis. In this study, we developed an in vitro Sertoli cell replacement method by combining an organ culture technique and a toxin receptor-mediated cell knockout (Treck) system. We used Amh- diphtheria toxin receptor (DTR) transgenic mice, whose Sertoli cells specifically express human DTR, which renders them sensitive to diphtheria toxin (DT). An immature Amh-DTR testis was transplanted with donor testis cells followed by culturing in a medium containing DT. This procedure successfully replaced the original Sertoli cells with the transplanted Sertoli cells, and spermatogenesis originating from resident germ cells was confirmed. In addition, Sertoli cells in the mouse testis tissues were replaced by transplanted rat Sertoli cells within culture conditions, without requiring immunosuppressive treatments. This method works as a functional assay system, making it possible to evaluate any cells that might function as Sertoli cells. It would also be possible to investigate interactions between Sertoli and germ cells more closely, providing a new platform for the study of spermatogenesis and its impairments.

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Retinoic Acid Metabolism and Signaling Pathways in the Adult and Developing Mouse Testis

Endocrinology ◽

10.1210/en.2005-0953 ◽

2006 ◽

Vol 147 (1) ◽

pp. 96-110 ◽

Cited By ~ 156

Author(s):

Nadège Vernet ◽

Christine Dennefeld ◽

Cécile Rochette-Egly ◽

Mustapha Oulad-Abdelghani ◽

Pierre Chambon ◽

...

Keyword(s):

Cytochrome P450 ◽

Retinoic Acid ◽

Vitamin A ◽

Signaling Pathways ◽

Sertoli Cells ◽

Vitamin A Deficiency ◽

Expression Patterns ◽

Mouse Testis ◽

Cytochrome P450 Hydroxylase ◽

Lecithin:Retinol Acyltransferase

As a first step in investigating the role of retinoic acid (RA) in mouse testis, we analyzed the distribution pattern of the enzymes involved in vitamin A storage (lecithin:retinol acyltransferase), RA synthesis (β-carotene 15,15′-monoxygenase and retinaldehyde dehydrogenases) and RA degradation (cytochrome P450 hydroxylases) as well as those of all isotypes of receptors transducing the RA signal [RA receptors (RARs) and rexinoid receptors (RXRs)]. Our data indicate that in adult testis 1) cytochrome P450 hydroxylase enzymes may generate in peritubular myoid cells a catabolic barrier that prevents circulating RA and RA synthesized by Leydig cells to enter the seminiferous epithelium; 2) the compartmentalization of RA synthesis within this epithelium may modulate, through paracrine mechanisms, the coupling between spermatogonia proliferation and spermatogenesis; 3) retinyl esters synthesized in round spermatids by lecithin:retinol acyltransferase may be transferred and stored in Sertoli cells, in the form of adipose differentiation-related protein-coated lipid droplets. We also show that RARα and RXRβ are confined to Sertoli cells, whereas RARγ is expressed in spermatogonia and RARβ, RXRα, and RXRγ are colocalized in step 7–8 spermatids. Correlating these expression patterns with the pathological phenotypes generated in response to RAR and RXR mutations and to postnatal vitamin A deficiency suggests that spermiation requires RXRβ/RARα heterodimers in Sertoli cells, whereas spermatogonia proliferation involves, independently of RXR, two distinct RAR-mediated signaling pathways in both Sertoli cells and spermatogonia. Our data also suggest that the involvement of RA in testis development starts when primary spermatogonia first appear.

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