Expression profile of Toll‐like receptor 4 in rat testis and epididymis throughout postnatal development

Toll‐like receptors (TLRs) belonging to pattern recognition receptors are involved in maintaining testicular and epididymal immune homeostasis. The purpose of the current study was to investigate TLR4 expression in rat testis and epididymis throughout postnatal development. Weak staining was detected in peritubular myoid cells and immature Sertoli cells while no staining was observed in gonocytes during prepubertal period. However, TLR4 expression began to appear in spermatocytes in pubertal period and gradually increased in spermatids. An intense staining was observed in steps 5–19 spermatids in post pubertal and mature periods. Similarly, TLR4 expression in the testes steadily increased from pubertal period to mature period. Puberty also caused a significant increase in TLR4 expression in epididymis. TLR4 expression in cauda epididymis was lower as compared to those of other epididymal segments. The majority of epididymal epithelial cells exhibited apical TLR4 expression, whereas basal cells showed intense intracytoplasmic immunoreaction. We detected an intense staining in epididymal smooth muscle cells. The expression levels of TLR4 showed dynamic changes in both spermatogenic cells, and entire testicular and epididymal tissues during postnatal development. These results suggest that TLR4 expression contributes not only to inflammation but also to the development of spermatogenic cells.

[1]  M. Hitit,et al.  Spatiotemporal expression patterns of natriuretic peptides in rat testis and epididymis during postnatal development , 2019, Andrologia.

[2]  N. Liman,et al.  The expression and localization of Toll-like receptors 2, 4, 5 and 9 in the epididymis and vas deferens of a adult tom cats. , 2019, Theriogenology.

[3]  H. Altunay,et al.  Expression pattern of galectin-1 and galectin-3 in rat testes and epididymis during postnatal development. , 2018, Acta histochemica.

[4]  G. Barton,et al.  A Map of Toll‐like Receptor Expression in the Intestinal Epithelium Reveals Distinct Spatial, Cell Type‐Specific, and Temporal Patterns , 2018, Immunity.

[5]  K. Tung,et al.  Infectious, inflammatory and ‘autoimmune’ male factor infertility: how do rodent models inform clinical practice? , 2018, Human reproduction update.

[6]  R. M. Romano,et al.  Lipopolysaccharide and lipotheicoic acid differentially modulate epididymal cytokine and chemokine profiles and sperm parameters in experimental acute epididymitis , 2018, Scientific Reports.

[7]  G. Rhodes,et al.  The effects of sex hormones on immune function: a meta‐analysis , 2017, Biological reviews of the Cambridge Philosophical Society.

[8]  M. Hedger,et al.  Epididymitis: revelations at the convergence of clinical and basic sciences , 2015, Asian journal of andrology.

[9]  Shutao Zhao,et al.  Pattern Recognition Receptor–Initiated Innate Antiviral Responses in Mouse Epididymal Epithelial Cells , 2015, The Journal of Immunology.

[10]  M. L. Simons,et al.  Postnatal Development of the Testis in the Rat , 2015, Toxicologic pathology.

[11]  S. Arrighi.  Are the basal cells of the mammalian epididymis still an enigma? , 2014, Reproduction, fertility, and development.

[12]  C. Rathke,et al.  H3K79 methylation directly precedes the histone‐to‐protamine transition in mammalian spermatids and is sensitive to bacterial infections , 2014, Andrology.

[13]  N. Kotaja,et al.  Epigenetic regulation of male germ cell differentiation. , 2013, Sub-cellular biochemistry.

[14]  Daishu Han,et al.  Structural, cellular and molecular aspects of immune privilege in the testis , 2012, Front. Immun..

[15]  M. Hedger.  Immunophysiology and Pathology of Inflammation in the Testis and Epididymis , 2011, Journal of andrology.

[16]  Daishu Han,et al.  Toll-like receptor-initiated testicular innate immune responses in mouse Leydig cells. , 2011, Endocrinology.

[17]  M. Hedger,et al.  Differential responses of epithelial Sertoli cells of the rat testis to Toll-like receptor 2 and 4 ligands: Implications for studies of testicular inflammation using bacterial lipopolysaccharides , 2011, Innate immunity.

[18]  M. Hedger,et al.  Immunological, paracrine and endocrine aspects of testicular immune privilege , 2011, Molecular and Cellular Endocrinology.

[19]  M. Hedger.  Toll-like receptors and signalling in spermatogenesis and testicular responses to inflammation—a perspective , 2011, Journal of Reproductive Immunology.

[20]  Daishu Han,et al.  Sertoli cell-initiated testicular innate immune response through toll-like receptor-3 activation is negatively regulated by Tyro3, Axl, and mer receptors. , 2010, Endocrinology.

[21]  S. Akira,et al.  Pattern Recognition Receptors and Inflammation , 2010, Cell.

[22]  G. Cornwall.  New insights into epididymal biology and function. , 2008, Human reproduction update.

[23]  M. Mckee,et al.  Transepithelial Projections from Basal Cells Are Luminal Sensors in Pseudostratified Epithelia , 2008, Cell.

[24]  M. Palladino,et al.  ORIGINAL ARTICLE: Localization of Toll‐Like Receptors on Epididymal Epithelial Cells and Spermatozoa , 2008, American journal of reproductive immunology.

[25]  A. Filippini,et al.  Toll-Like Receptor 3 Activation Induces Antiviral Immune Responses in Mouse Sertoli Cells1 , 2008, Biology of reproduction.

[26]  H. Schuppe,et al.  Chronic orchitis: a neglected cause of male infertility? , 2008, Andrologia.

[27]  A. Fuso,et al.  Sertoli Cells Initiate Testicular Innate Immune Responses through TLR Activation1 , 2006, The Journal of Immunology.

[28]  B. Robaire,et al.  CHAPTER 22 – The Epididymis , 2006 .

[29]  S. Akira,et al.  TLR signaling , 2006, Cell Death and Differentiation.

[30]  A. Kaur,et al.  The evolution of vertebrate Toll-like receptors. , 2005, Proceedings of the National Academy of Sciences of the United States of America.

[31]  T. Baba,et al.  Gene expression in spermiogenesis , 2005, Cellular and Molecular Life Sciences CMLS.

[32]  Shizuo Akira,et al.  Toll-like receptor signalling , 2004, Nature Reviews Immunology.

[33]  N. Schultz,et al.  A multitude of genes expressed solely in meiotic or postmeiotic spermatogenic cells offers a myriad of contraceptive targets , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[34]  J. Gatti,et al.  Contribution of epididymal secretory proteins for spermatozoa maturation , 2003, Microscopy research and technique.

[35]  D. Cyr,et al.  Expression of multiple connexins in the rat epididymis indicates a complex regulation of gap junctional communication. , 2003, American journal of physiology. Cell physiology.

[36]  M. Ohkawa,et al.  Neonatally administered diethylstilbestrol retards the development of the blood-testis barrier in the rat. , 2001, Journal of andrology.

[37]  P. D. Ekwere.  Immunological infertility among Nigerian men: incidence of circulating antisperm auto-antibodies and some clinical observations: a preliminary report. , 1995, British journal of urology.

[38]  L. Hermo,et al.  Developmental expression of the Yf subunit of glutathione S‐transferase P in epithelial cells of the testis, efferent ducts, and epididymis of the rat , 1994, The Anatomical Record.

[39]  B. Jégou,et al.  Lipopolysaccharide, latex beads and residual bodies are potent activators of Sertoli cell interleukin-1 alpha production. , 1992, Biochemical and biophysical research communications.

[40]  K. Tung,et al.  Autoantigenic germ cells exist outside the blood testis barrier. , 1988, Journal of immunology.

[41]  J. Orth.  Proliferation of sertoli cells in fetal and postnatal rats: A quantitative autoradiographic study , 1982, The Anatomical record.

[42]  C. Flickinger,et al.  Proliferative activity in the rat epididymis during postnatal development , 1982, The Anatomical record.

[43]  C. Flickinger,et al.  Development of cell types and of regional differences in the postnatal rat epididymis. , 1979, The American journal of anatomy.