Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination

It has long been assumed that the mammalian Y chromosome either encodes, or controls the production of, a diffusible testis-determining molecule, exposure of the embryonic gonad to this molecule being all that is required to divert it along the testicular pathway. My recent finding that Sertoli cells in XX ↔ XY chimeric mouse testes are exclusively XY has led me to propose a new model in which the Y acts cell-autonomously to bring about Sertoli-cell differentiation. I have suggested that all other aspects of foetal testicular development are triggered by the Sertoli cells without further Y-chromosome involvement. This model thus equates mammalian sex determination with Sertoli-cell determination. Examples of natural and experimentally induced sex reversal are discussed in the context of this model.

Download Full-text

Di(2-Ethylhexyl) Phthalate ExposureIn UteroDamages Sertoli Cell Differentiation Via Disturbance of Sex Determination Pathway in Fetal and Postnatal Mice

Toxicological Sciences ◽

10.1093/toxsci/kfw063 ◽

2016 ◽

Vol 152 (1) ◽

pp. 53-61 ◽

Cited By ~ 9

Author(s):

Yongan Wang ◽

Qing Yang ◽

Wei Liu ◽

Mingxi Yu ◽

Zhou Zhang ◽

...

Keyword(s):

Cell Differentiation ◽

Sex Determination ◽

Sertoli Cell ◽

Ethylhexyl Phthalate

Download Full-text

209. The absence of betaglycan affects Sox9 m RNA expression at the time of sex determination in a mouse model

Reproduction Fertility and Development ◽

10.1071/srb08abs209 ◽

2008 ◽

Vol 20 (9) ◽

pp. 9

Author(s):

M. A. Sarraj ◽

H. Chua ◽

A. Umbers ◽

R. Escalona ◽

K. L. Loveland ◽

...

Keyword(s):

Cell Differentiation ◽

Sex Determination ◽

Sertoli Cell ◽

Leydig Cell ◽

Cell Biology ◽

Leydig Cells ◽

Cell Marker ◽

Sox9 Expression ◽

And Function ◽

The Impact

Betaglycan is a co-receptor that binds both TGF-β and inhibin, and thereby acts as a modulator of the activities of multiple members of the TGF-β superfamily. We have previously shown that the murine betaglycan gene is expressed in somatic cells within the interstitium of the fetal testis from 12.5 dpc-16.5 dpc. Betaglycan protein was predominantly localised to the interstitial cells surrounding the developing seminiferous cords which stained positive for Cyp11a (p450 Scc), a Leydig cell marker. In order to determine the impact of this receptor on fetal Leydig cell biology, RNA was extracted from two independently collected sets of betaglycan knockout and wildtype male and female gonads at 12.5 dpc and 13.5 dpc (n = 4 gonad pairs/set), and quantitative real time PCR was performed to determine changes in the expression levels of key genes involved in fetal Leydig cell differentiation and function. This analysis revealed that the levels of mRNA expression of SF1, Cyp11a and Cyp17a1 were downregulated between 12.5–13.5 dpc in the betaglycan knockout embryos compared with wildtype embryos immediately after the time of sex determination. Interestingly, the expression level of the key Sertoli cell marker SRY-(sex determining region Y)-box 9 (Sox9) was transiently decreased at 12.5 dpc by 50% in the knockout testis in comparison with that of the wildtype testis. No significant change was found one day later at 13.5 dpc. Our data show that betaglycan is predominantly expressed in the fetal Leydig cells of the murine testis and that the presence of this receptor is required for normal fetal Leydig cell differentiation. Furthermore, the transient downregulation of Sox9 expression in null testis suggests that Sertoli cell differentiation may also be affected in betaglycan knockout mice, and that this defect may precede the defect in Leydig cell development. Supported by: the NHMRC Australia (RegKeys 338516; 241000).

Download Full-text

SRY Induced TCF21 Genome-Wide Targets and Cascade of bHLH Factors During Sertoli Cell Differentiation and Male Sex Determination in Rats1

Biology of Reproduction ◽

10.1095/biolreprod.112.099663 ◽

2012 ◽

Vol 87 (6) ◽

Cited By ~ 18

Author(s):

Ramji K. Bhandari ◽

Ellyn N. Schinke ◽

Md. M. Haque ◽

Ingrid Sadler-Riggleman ◽

Michael K. Skinner

Keyword(s):

Cell Differentiation ◽

Sex Determination ◽

Sertoli Cell ◽

Genome Wide ◽

Bhlh Factors ◽

Male Sex

Download Full-text

Changes in Expression of Specific mRNA Transcripts after Single- or Re-Irradiation in Mouse Testes

Genes ◽

10.3390/genes13010151 ◽

2022 ◽

Vol 13 (1) ◽

pp. 151

Author(s):

Kenta Nagahori ◽

Ning Qu ◽

Miyuki Kuramasu ◽

Yuki Ogawa ◽

Daisuke Kiyoshima ◽

...

Keyword(s):

Cell Differentiation ◽

Germ Cell ◽

Sertoli Cell ◽

Alkylating Agents ◽

Mrna Species ◽

Germ Cell Differentiation ◽

Targeted Treatments ◽

Mrna Transcripts ◽

Specific Mrna

Alkylating agents and irradiation induce testicular damage, which results in prolonged azoospermia. Even very low doses of radiation can significantly impair testis function. However, re-irradiation is an effective strategy for locally targeted treatments and the pain response and has seen important advances in the field of radiation oncology. At present, little is known about the relationship between the harmful effects and accumulated dose of irradiation derived from continuous low-dose radiation exposure. In this study, we examined the levels of mRNA transcripts encoding markers of 13 markers of germ cell differentiation and 28 Sertoli cell-specific products in single- and re-irradiated mice. Our results demonstrated that re-irradiation induced significantly decreased testicular weights with a significant decrease in germ cell differentiation mRNA species (Spo11, Tnp1, Gfra1, Oct4, Sycp3, Ddx4, Boll, Crem, Prm1, and Acrosin). In the 13 Sertoli cell-specific mRNA species decreased upon irradiation, six mRNA species (Claudin-11,Espn, Fshr, GATA1, Inhbb, and Wt1) showed significant differences between single- and re-irradiation. At the same time, different decreases in Sertoli cell-specific mRNA species were found in single-irradiation (Aqp8, Clu, Cst12, and Wnt5a) and re-irradiation (Tjp1, occludin,ZO-1, and ZO-2) mice. These results indicate that long-term aspermatogenesis may differ after single- and re-irradiated treatment.

Download Full-text

CX43 expression, phosphorylation, and distribution in the normal and autoimmune orchitic testis with a look at gap junctions joining germ cell to germ cell

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00500.2010 ◽

2011 ◽

Vol 300 (1) ◽

pp. R121-R139 ◽

Cited By ~ 13

Author(s):

R.-Marc Pelletier ◽

Casimir D. Akpovi ◽

Li Chen ◽

Robert Day ◽

María L. Vitale

Keyword(s):

Cell Differentiation ◽

Gap Junctions ◽

Germ Cell ◽

Sertoli Cell ◽

Sertoli Cells ◽

Seminiferous Tubule ◽

Connexin 43 ◽

Cx43 Expression ◽

Cx43 Protein ◽

Cx43 Mrna

Spermatogenesis requires connexin 43 (Cx43).This study examines normal gene transcription, translation, and phosphorylation of Cx43 to define its role on germ cell growth and Sertoli cell's differentiation, and identifies abnormalities arising from spontaneous autoimmune orchitis (AIO) in mink, a seasonal breeder and a natural model for autoimmunity. Northern blot analysis detected 2.8- and a 3.7-kb Cx43 mRNA bands in seminiferous tubule-enriched fractions. Cx43 mRNA increased in seminiferous tubule-enriched fractions throughout development and then seasonally with the completion of spermatogenesis. Cx43 protein levels increased transiently during the colonization of the tubules by the early-stage spermatocytes. Cx43 phosphorylated (PCx43) and nonphosphorylated (NPCx43) in Ser368 decreased during the periods of completion of meiosis and Sertoli cell differentiation, while Cx43 mRNA remained elevated throughout. PCx43 labeled chiefly the plasma membrane except by stage VII when vesicles were also labeled in Sertoli cells. Vesicles and lysosomes in Sertoli cells and the Golgi apparatus in the round spermatids were NPCx43 positive. A decrease in Cx43 gene expression was matched by a Cx43 protein increase in the early, not the late, phase of AIO. Total Cx43 and PCx43 decreased with the advance of orchitis. The study makes a novel finding of gap junctions connecting germ cells. The data indicate that Cx43 protein expression and phosphorylation in Ser368 are stage-specific events that may locally influence the acquisition of meiotic competence and the Sertoli cell differentiation in normal testis. AIO modifies Cx43 levels, suggesting changes in Cx43-mediated intercommunication and spermatogenic activity in response to cytokines imbalances in Sertoli cells.

Download Full-text