| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Medical Research Council Human Reproductive Sciences Unit, Centre for Reproductive Biology, The University of Edinburgh Academic Centre, Edinburgh EH16 4SB, United Kingdom
Address all correspondence and requests for reprints to: Richard M. Sharpe, Medical Research Center Human Reproductive Sciences Unit, Centre for Reproductive Biology, The University of Edinburgh Academic Centre, 49 Little France Crescent, Edinburgh EH16 4SB, United Kingdom. E-mail: r.sharpe{at}hrsu.mrc.ac.uk.
Fetal exposure of male rats to di (n-butyl) phthalate (DBP) induces testicular changes remarkably similar to testicular dysgenesis syndrome in humans; these include induction of focal areas of dysgenetic tubules in otherwise normal testes. In searching for the fetal origins of the latter, we used image analysis to show that exposure to 500 mg/kg DBP [embryonic day (E)13.5–20.5)] caused abnormal aggregation of Leydig cells centrally in the fetal testis. This aggregation was not due to increase in Leydig cell number, and Leydig cell size was significantly reduced in DBP-exposed animals, as were testosterone levels and immunoexpression of P450 side-chain cleavage enzyme. The Leydig cell aggregates did not exhibit evidence of focal proliferation at E17.5–19.5. Using confocal microscopy and Leydig (3ß-hydroxysteroid dehydrogenase) and Sertoli (anti-Mullerian hormone) cell-specific markers, we show that fetal Leydig cell aggregates in DBP-exposed animals trap isolated Sertoli cells within them at E21.5. These areas of intermingled cells are still apparent on postnatal d 4, after cessation of DBP treatment, when they may form misshapen seminiferous cords that trap (intratubular) Leydig cells within them. These centrally located dysgenetic tubules contain germ cells in early puberty, but by adulthood they are Sertoli cell only, implying that presence of intratubular Leydig cells interferes with spermatogenesis. It is concluded that DBP-induced fetal Leydig cell aggregation may be a key event in formation of focal dysgenetic areas in the testis, and identification of the mechanisms underlying these events may give new insights into the fetal origins of testicular dysgenesis syndrome disorders in the human.
This article has been cited by other articles:
 |
|
 |
|
  C. McKinnell, R. T. Mitchell, M. Walker, K. Morris, C. J.H. Kelnar, W H. Wallace, and R. M. Sharpe Effect of fetal or neonatal exposure to monobutyl phthalate (MBP) on testicular development and function in the marmoset Hum. Reprod., June 2, 2009; (2009) dep200v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Welsh, R. M. Sharpe, M. Walker, L. B. Smith, and P. T. K. Saunders New Insights into the Role of Androgens in Wolffian Duct Stabilization in Male and Female Rodents Endocrinology, May 1, 2009; 150(5): 2472 - 2480. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Wilkens, A.R.W. Williams, K. Chwalisz, C. Han, I.T. Cameron, and H.O.D. Critchley Effect of asoprisnil on uterine proliferation markers and endometrial expression of the tumour suppressor gene, PTEN Hum. Reprod., May 1, 2009; 24(5): 1036 - 1044. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Lin, Q.-Q. Lian, G.-X. Hu, Y. Jin, Y. Zhang, D. O. Hardy, G.-R. Chen, Z.-Q. Lu, C. M. Sottas, M. P. Hardy, et al. In Utero and Lactational Exposures to Diethylhexyl-Phthalate Affect Two Populations of Leydig Cells in Male Long-Evans Rats Biol Reprod, May 1, 2009; 80(5): 882 - 888. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Scott, G. R. Hutchison, M. S. Jobling, C. McKinnell, A. J. Drake, and R. M. Sharpe Relationship between Androgen Action in the "Male Programming Window," Fetal Sertoli Cell Number, and Adult Testis Size in the Rat Endocrinology, October 1, 2008; 149(10): 5280 - 5287. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. M. Onorato, P. W. Brown, and P. L. Morris Mono-(2-ethylhexyl) Phthalate Increases Spermatocyte Mitochondrial Peroxiredoxin 3 and Cyclooxygenase 2 J Androl, May 1, 2008; 29(3): 293 - 303. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Gunnarsson, P. Leffler, E. Ekwurtzel, G. Martinsson, K. Liu, and G. Selstam Mono-(2-ethylhexyl) phthalate stimulates basal steroidogenesis by a cAMP-independent mechanism in mouse gonadal cells of both sexes Reproduction, May 1, 2008; 135(5): 693 - 703. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. E. Walker, G. P. Lutz, and C. J. Alvarez Development of a Cross-Disciplinary Investigative Model for the Introduction of Microarray Techniques at Non-R1 Undergraduate Institutions CBE Life Sci Educ, March 1, 2008; 7(1): 118 - 131. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. R Hutchison, H. M Scott, M. Walker, C. McKinnell, D. Ferrara, I. K. Mahood, and R. M Sharpe Sertoli Cell Development and Function in an Animal Model of Testicular Dysgenesis Syndrome Biol Reprod, February 1, 2008; 78(2): 352 - 360. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J Johnson, J. B Hensley, M. D Kelso, D. G Wallace, and K. W Gaido Mapping Gene Expression Changes in the Fetal Rat Testis Following Acute Dibutyl Phthalate Exposure Defines a Complex Temporal Cascade of Responding Cell Types Biol Reprod, December 1, 2007; 77(6): 978 - 989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. L. Howdeshell, J. Furr, C. R. Lambright, C. V. Rider, V. S. Wilson, and L. E. Gray Jr Cumulative Effects of Dibutyl Phthalate and Diethylhexyl Phthalate on Male Rat Reproductive Tract Development: Altered Fetal Steroid Hormones and Genes Toxicol. Sci., September 1, 2007; 99(1): 190 - 202. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. M. Scott, G. R. Hutchison, I. K. Mahood, N. Hallmark, M. Welsh, K. De Gendt, G. Verhoeven, P. O'Shaughnessy, and R. M. Sharpe Role of Androgens in Fetal Testis Development and Dysgenesis Endocrinology, May 1, 2007; 148(5): 2027 - 2036. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Ferrara, N. Hallmark, H. Scott, R. Brown, C. McKinnell, I. K. Mahood, and R. M. Sharpe Acute and Long-Term Effects of in Utero Exposure of Rats to Di(n-Butyl) Phthalate on Testicular Germ Cell Development and Proliferation Endocrinology, November 1, 2006; 147(11): 5352 - 5362. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. Lahousse, D. G. Wallace, D. Liu, K. W. Gaido, and K. J. Johnson Testicular Gene Expression Profiling following Prepubertal Rat Mono-(2-ethylhexyl) Phthalate Exposure Suggests a Common Initial Genetic Response at Fetal and Prepubertal Ages Toxicol. Sci., October 1, 2006; 93(2): 369 - 381. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Hamers, J. H. Kamstra, E. Sonneveld, A. J. Murk, M. H. A. Kester, P. L. Andersson, J. Legler, and A. Brouwer In Vitro Profiling of the Endocrine-Disrupting Potency of Brominated Flame Retardants Toxicol. Sci., July 1, 2006; 92(1): 157 - 173. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. M. David Proposed Mode of Action for In Utero Effects of Some Phthalate Esters on the Developing Male Reproductive Tract Toxicol Pathol, April 1, 2006; 34(3): 209 - 219. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. McKinnell, R. M. Sharpe, K. Mahood, N. Hallmark, H. Scott, R. Ivell, C. Staub, B. Jegou, F. Haag, F. Koch-Nolte, et al. Expression of Insulin-Like Factor 3 Protein in the Rat Testis during Fetal and Postnatal Development and in Relation to Cryptorchidism Induced by in Utero Exposure to Di (n-Butyl) Phthalate Endocrinology, October 1, 2005; 146(10): 4536 - 4544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. L. Tan, K. De Gendt, N. Atanassova, M. Walker, R. M. Sharpe, P. T. K. Saunders, E. Denolet, and G. Verhoeven The Role of Androgens in Sertoli Cell Proliferation and Functional Maturation: Studies in Mice with Total or Sertoli Cell-Selective Ablation of the Androgen Receptor Endocrinology, June 1, 2005; 146(6): 2674 - 2683. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
