Barry T. Hinton

Primary Appointment

  • Professor, Cell Biology

Contact

Research Interest(s)

Cell And Molecular Biology of Epididymal Function

Research Description

Wolffian/Epididymal duct Morphogenesis. The formation of tubes is a fundamental biological process during the genesis of many organs, for example, kidney, intestine, brain, heart, and lungs. In fact, very few organs do not form tubular structures at some point in their development. Formation of the tubular structure is then followed by unique morphogenic events in each organ to generate their final adult structure. The morphogenesis of the Wolffian/epididymal duct is unusual in that it exhibits a unique pattern in that it forms a simple tube and then systematically elongates and coils dramatically. Surprisingly, the fully developed epididymis is 1.2 meters long in the mouse, 3 meters long in the rat and a remarkable 6 meters long in the human. The goal of this laboratory is to understand the mechanisms by which this important biological tube elongates and coils because without a fully developed and functional epididymis, male infertility will result. We are especially interested in the contribution of cell proliferation and cell rearrangements towards duct elongation. Data obtained from using mice that are null for protein tyrosine kinase 7 supports the hypothesis that cell rearrangements are under the regulation of the planar cell polarity/non-canonical Wnt pathway. It appears that signal transduction pathways involving MAPK, PTEN and Src regulate cell proliferation. Regulation of epididymal initial segment function. The initial segment region of the epididymis has been clearly shown to play a major role in male fertility because without an initial segment, infertility results. Therefore, we are very much interested in the mechanisms by which this important region of the epididymis is regulated. Androgens clearly play a role in the regulation of epididymal function but we, and others, have shown that testicular luminal fluid factors, lumicrine factors, play a major role also. We have identified a number of growth factors as candidate lumicrine factors that regulate cell proliferation and survival of the initial segment. We are currently identifying the downstream signaling pathways and genes that are regulated by lumicrine factors. C-ros, an orphan tyrosine kinase receptor is highly expressed in the initial segment and C-ros null male mice are infertile. Therefore, we are examining the manner by which this important gene plays a role in male fertility and also examining this gene as a potential target for the development of a male contraceptive.

Selected Publications

  • Xu B, Yang L, Hinton B. The Role of fibroblast growth factor receptor substrate 2 (FRS2) in the regulation of two activity levels of the components of the extracellular signal-regulated kinase (ERK) pathway in the mouse epididymis. Biology of reproduction. 2013;89(2): 48. PMID: 23782834 | PMCID: PMC4076368
  • Hinton B, Galdamez M, Sutherland A, Bomgardner D, Xu B, Abdel-Fattah R, Yang L. How do you get six meters of epididymis inside a human scrotum? Journal of andrology. 2011;32(6): 558-64. PMID: 21441421
  • Mital P, Hinton B, Dufour J. The blood-testis and blood-epididymis barriers are more than just their tight junctions. Biology of reproduction. 2011;84(5): 851-8. PMID: 21209417
  • Xu B, Abdel-Fattah R, Yang L, Crenshaw S, Black M, Hinton B. Testicular lumicrine factors regulate ERK, STAT, and NFKB pathways in the initial segment of the rat epididymis to prevent apoptosis. Biology of reproduction. 2011;84(6): 1282-91. PMID: 21311037 | PMCID: PMC3099589
  • Hinton B, Cooper T. The epididymis as a target for male contraceptive development. Handbook of experimental pharmacology. 2010; 117-37. PMID: 20839090
  • Snyder E, Small C, Bomgardner D, Xu B, Evanoff R, Griswold M, Hinton B. Gene expression in the efferent ducts, epididymis, and vas deferens during embryonic development of the mouse. Developmental dynamics : an official publication of the American Association of Anatomists. 2010;239(9): 2479-91. PMID: 20652947 | PMCID: PMC2939230
  • Xu B, Yang L, Lye R, Hinton B. p-MAPK1/3 and DUSP6 regulate epididymal cell proliferation and survival in a region-specific manner in mice. Biology of reproduction. 2010;83(5): 807-17. PMID: 20650883 | PMCID: PMC2959110
  • Cotton L, Rodriguez C, Suzuki K, Orgebin-Crist M, Hinton B. Organic cation/carnitine transporter, OCTN2, transcriptional activity is regulated by osmotic stress in epididymal cells. Molecular reproduction and development. 2009;77(2): 114-25. PMID: 19899138
  • Januszewicz E, Pajak B, Gajkowska B, Samluk L, Djavadian R, Hinton B, Nałecz K. Organic cation/carnitine transporter OCTN3 is present in astrocytes and is up-regulated by peroxisome proliferators-activator receptor agonist. The international journal of biochemistry & cell biology. 2009;41(12): 2599-609. PMID: 19735737
  • Archambeault D, Tomaszewski J, Joseph A, Hinton B, Yao H. Epithelial-mesenchymal crosstalk in Wolffian duct and fetal testis cord development. Genesis (New York, N.Y. : 2000). 2008;47(1): 40-8. PMID: 18979542 | PMCID: PMC2877590
  • Cotton L, O'Bryan M, Hinton B. Cellular signaling by fibroblast growth factors (FGFs) and their receptors (FGFRs) in male reproduction. Endocrine reviews. 2008;29(2): 193-216. PMID: 18216218 | PMCID: PMC2528845
  • Joseph A, Yao H, Hinton B. Development and morphogenesis of the Wolffian/epididymal duct, more twists and turns. Developmental biology. 2008;325(1): 6-14. PMID: 18992735 | PMCID: PMC2639655
  • Miecz D, Januszewicz E, Czeredys M, Hinton B, Berezowski V, Cecchelli R, Nałecz K. Localization of organic cation/carnitine transporter (OCTN2) in cells forming the blood-brain barrier. Journal of neurochemistry. 2007;104(1): 113-23. PMID: 17995936
  • Fox S, Yang L, Hinton B. Identifying putative contraceptive targets by dissecting signal transduction networks in the epididymis using an in vivo electroporation (electrotransfer) approach. Molecular and cellular endocrinology. 2006;250(1): 196-200. PMID: 16423449
  • Yang L, Fox S, Kirby J, Troan B, Hinton B. Putative regulation of expression of members of the Ets variant 4 transcription factor family and their downstream targets in the rat epididymis. Biology of reproduction. 2006;74(4): 714-20. PMID: 16394217
  • Kirby J, Yang L, Labus J, Lye R, Hsia N, Day R, Cornwall G, Hinton B. Characterization of epididymal epithelial cell-specific gene promoters by in vivo electroporation. Biology of reproduction. 2004;71(2): 613-9. PMID: 15115732
  • Lye R, Hinton B. Technologies for the study of epididymal-specific genes. Molecular and cellular endocrinology. 2004;216(1): 23-30. PMID: 15109741