The Biology of Blood–Testis Barrier Dynamics
Population Council researchers have been investigating innovative ways to regulate the blood–testis barrier in spermatogenesis, which will likely lead to the development of novel male contraceptives.
Spermatogenesis is an intriguing but complicated biological process. Recent advances in biochemistry, cell biology, and molecular biology have shifted attention to understanding some of the key events that regulate spermatogenesis, such as germ cell apoptosis, cell cycle regulation, Sertoli–germ cell communication, and junction dynamics. As part of spermatogenesis, developing germ cells must translocate across the blood–testis barrier (BTB) as well as traverse the seminiferous epithelium during their development. Without this timely movement of developing germ cells across the BTB, spermatogenesis will be disrupted, leading to infertility. While the concept of the BTB has been known for more than a century and its significance to spermatogenesis discerned for more than five decades, its regulation has remained largely unknown.
The tight junctions, anchoring junctions (known as basal ectoplasmic specialization), and desmosome-gap junctions between Sertoli cells, which make up the BTB, play a major role in keeping the developing spermatozoa and immune system separate. During spermatogenesis, such as meiosis, many sperm-specific antigens, which are highly immunogenic to the host immune system, express themselves transiently. To avoid the production of antisperm antibodies, autoantigenic germ cells must be sequestered from the immune system by the BTB. In addition, other immunosuppressive mechanisms are necessary to suppress antigenic responses behind the BTB, such as via secretions from Sertoli cells (e.g., growth factors, bioactive peptides, and lipids).
The Council has published important findings in this field over the last decade that provide a solid basis for this expanded line of research. Council researchers have used in vitro and in vivo models for studying tight junction dynamics and their regulation, which has revealed many targets that can be tackled to compromise the BTB function and to perturb spermatogenesis, forming the basis of new approaches for male contraceptive development. The Council is investigating the role of focal adhesion kinase (FAK), specifically, in regulating the timely "opening" and "closing" of the BTB.
Spermatogonial stem cells alone are not sufficient to re-initiate spermatogenesis in the rat testis following adjudin-induced infertility (abstract)
Mok,Ka-Wai; Mruk,Dolores D.; Lee,Will M.; Cheng,Chuen-yan
International Journal of Andrology 35(1): 86-101
Publication date: 2012
The biology of interleukin-1: Emerging concepts in the regulation of the actin cytoskeleton and cell junction dynamics (abstract)
Lie,Pearl P.Y.; Cheng,Chuen-yan; Mruk,Dolores D.
Cellular and Molecular Life Sciences 69(4): 487-500
Publication date: 2012
The blood-testis barrier and its implications for male contraception (abstract)
Cheng,Chuen-yan; Mruk,Dolores D.
Pharmacological Reviews 64(1): 16-64
Publication date: 2012
A study to assess the assembly of a functional blood-testis barrier in developing rat testes (abstract) (PDF)
Mok,Ka-Wai; Mruk,Dolores D.; Lee,Will M.; Cheng,Chuen-yan
Spermatogenesis 1(3): 270-280
Publication date: 2011
Actin-binding protein drebrin E is involved in junction dynamics during spermatogenesis (abstract) (PDF)
Li,Michelle W.M.; Xiao,Xiang; Mruk,Dolores D.; Lam,Yee-ling; Lee,Will M.; Lui,Wing-Yee; Bonanomi,Michele; Silvestrini,Bruno; Cheng,Chuen-yan
Spermatogenesis 1(2): 123-136
Publication date: 2011
Adjudin disrupts spermatogenesis via the action of some unlikely partners: Eps8, Arp2/3 complex, drebrin E, PAR6 and 14-3-3 (abstract) (PDF)
Cheng,Chuen-yan; Lie,Pearl P.Y.; Wong,Elissa W.P.; Mruk,Dolores D.; Silvestrini,Bruno
Spermatogenesis 1(4): 291-291
Publication date: 2011
Adjudin, a potential male contraceptive, exerts its effects locally in the seminiferous epithelium of mammalian testes (abstract) (HTML)
Mok,Ka-Wai; Mruk,Dolores D.; Lie,Pearl P.Y.; Lui,Wing-Yee; Cheng,Chuen-yan
Reproduction 141(5): 571-580
Publication date: 2011
Cancer/testis (CT) antigens, carcinogenesis and spermatogenesis (abstract) (PDF)
Cheng,Yan Ho; Wong,Elissa W.P.; Cheng,Chuen-yan
Spermatogenesis 1(3): 209-220
Publication date: 2011
Characterization and functionality of proliferative human Sertoli cells (abstract)
Chui,Kitty; Trivedi,Alpa; Cheng,Chuen-yan; Cherbavaz,Diana B.; Dazin,Paul F.; Huynh,Ai Lam Thu; Mitchell,James B.; Rabinovitch,Gabriel A.; Noble-Haeusslein,Linda J.; John,Constance M.
Cell Transplant 20(5): 619-635
Publication date: 2011
c-Yes regulates cell adhesion at the blood-testis barrier and the apical ectoplasmic specialization in the seminiferous epithelium of rat testes. (abstract)
Xiao,Xiang; Mruk,Dolores D.; Lee,William M.; Cheng,Chuen-yan
International Journal of Biochemistry and Cell Biology 43(4): 651-665
Publication date: 2011
Desmosomes in the testis: Moving into an unchartered territory (abstract) (HTML)
Mruk,Dolores D.; Cheng,Chuen-yan
Spermatogenesis 1(1): 47-51
Publication date: 2011
Drug transporters and blood-testis barrier function (abstract)
Su,Linlin; Mruk,Dolores D.; Lee,William M.; Cheng,Chuen-yan
Journal of Endocrinology 209(3): 337-351
Publication date: 2011
Drug transporters, the blood-testis barrier, and spermatogenesis (abstract) (HTML)
Su,Linlin; Mruk,Dolores D.; Cheng,Chuen-yan
Journal of Endocrinology 208(3): 207-223
Publication date: 2011
Emerging role for drug transporters at the blood-testis barrier (abstract)
Mruk,Dolores D.; Su,Linlin; Cheng,Chuen-yan
Trends in Pharmacological Science 32(2): 99-106
Publication date: 2011
Enhanced chemiluminescence (ECL) for routine immunoblotting. An inexpensive alternative to commercially available kits (abstract) (PDF)
Mruk,Dolores D.; Cheng,Chuen-yan
Spermatogenesis 1(2): 121-122
Publication date: 2011
Environmental contaminants: Is male reproductive health at risk? (abstract) (PDF)
Mruk,Dolores D.; Cheng,Chuen-yan
Spermatogenesis 1(4): 283-290
Publication date: 2011
Environmental toxicants and male reproductive function (abstract) (HTML)
Cheng,Chuen-yan; Wong,Elissa W.P.; Lie,Pearl P.Y.; Li,Michelle W.M.; Su,Linlin; Siu,Erica R.; Yan,Helen H.N.; Mannu,J.; Mathur,Premendu P.; Bonanomi,Michele; Silvestrini,Bruno; Mruk,Dolores D.
Spermatogenesis 1(1): 2-13
Publication date: 2011
Impacts of environmental toxicants on male reproductive dysfunction (abstract)
Wong,Elissa W.P.; Cheng,Chuen-yan
Trends in Pharmacological Science 32(5): 290-299
Publication date: 2011
Interleukin-1alpha is a regulator of the blood-testis barrier (abstract)
Lie,Pearl P.Y.; Cheng,Chuen-yan; Mruk,Dolores D.
FASEB Journal 25(4): 1244-1253
Publication date: 2011
P-glycoprotein regulates blood-testis barrier dynamics via its effects on the occludin/zonula occludens 1 (ZO-1) protein complex mediated by focal adhesion kinase (FAK) (abstract)
Su,Linlin; Mruk,Dolores D.; Lui,Wing-Yee; Lee,William M.; Cheng,Chuen-yan
Proceedings of the National Academy of Sciences of the United States of America 108(49): 19623-19628
Publication date: 2011
Polarity proteins and actin regulatory proteins are unlikely partners that regulate cell adhesion in the seminiferous epithelium during spermatogenesis (abstract)
Cheng,Chuen-yan; Wong,Elissa W.P.; Lie,Pearl P.Y.; Mruk,Dolores D.; Xiao,Xiang; Li,Michelle W.M.; Lui,Wing-Yee; Lee,Will M.
Histology and Histopathology 26(11): 1465-1474
Publication date: 2011
Regulation of spermiogenesis, spermiation and blood-testis barrier dynamics: Novel insights from studies on Eps8 and Arp3 (abstract) (HTML)
Cheng,Chuen-yan; Mruk,Dolores D.
Biochemical Journal 435(3): 553-562
Publication date: 2011
Testin and actin are key molecular targets of adjudin, an anti-spermatogenic agent, in the testis (abstract) (PDF)
Mruk,Dolores D.; Cheng,Chuen-yan
Spermatogenesis 1(2): 137-146
Publication date: 2011
The biology of the desmosome-like junction a versatile anchoring junction and signal transducer in the seminiferous epithelium (abstract)
Lie,Pearl P.Y.; Cheng,Chuen-yan; Mruk,Dolores D.
International Review of Cell and Molecular Biology 286: 223-269
Publication date: 2011
The myotubularin family of lipid phosphatases in disease and in spermatogenesis (abstract) (PDF)
Mruk,Dolores D.; Cheng,Chuen-yan
Biochemical Journal 433(2): 253-262
Publication date: 2011
Disruption of the blood-testis barrier integrity by bisphenol A in vitro: Is this a suitable model for studying blood-testis barrier dynamics? (abstract)
Li,Michelle W.M.; Mruk,Dolores D.; Lee,Will M.; Cheng,Chuen-yan
International Journal of Biochemistry and Cell Biology 41(11): 2302-2314
Publication date: 2009
Regulation of blood-testis barrier dynamics by focal adhesion kinase (FAK): An unexpected turn of events (abstract)
Cheng,Chuen-yan; Mruk,Dolores D.
Cell Cycle 8(21): 3493-3499
Publication date: 2009
Blood-testis barrier dynamics are regulated by testosterone and cytokines via their differential effects on the kinetics of protein endocytosis and recycling in Sertoli cells (abstract)
Yan,Helen H.N.; Mruk,Dolores D.; Lee,Will M.; Cheng,Chuen-yan
FASEB Journal 22(6): 1945-1959
Publication date: 2008
Blood-testis barrier dynamics are regulated by an engagement/disengagement mechanism between tight and adherens junctions via peripheral adaptors (abstract)
Yan,Helen H.N.; Cheng,Chuen-yan
Proceedings of the National Academy of Sciences of the United States of America 102(33): 11722-11727
Publication date: 2005
Blood-testis barrier dynamics are regulated by α2-macroglobulin via the c-Jun N-terminal protein kinase pathway (abstract)
Wong,Ching-hang; Mruk,Dolores D.; Siu,Michelle K.Y.; Cheng,Chuen-yan
Endocrinology 146(4): 1893-1908
Publication date: 2005
Regulation of blood-testis barrier dynamics: An in vivo study (abstract)
Wong,Ching-hang; Mruk,Dolores D.; Lui,Wing-Yee; Cheng,Chuen-yan
Journal of Cell Science 117(5): 783-798
Publication date: 2004
Project Stats
Location: United States
Program(s):
Reproductive Health
Topic(s):
Reproductive health biomedical research
Duration: 2/2009 - 3/2014
Population Council researchers:
C. Yan Cheng
Donors:
US National Institutes of Health
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