231. Sertoli cells de-differentiate in men after chronic gonadotrophin suppression
G. A. Tarulli A B , P. G. Stanton A , K. Loveland C , E. Rajpert De Meyts D , R. I. McLachlan A E and S. J. Meachem A BA Male Reproductive Endocrinology and Metabolism, Prince Henry's Institute, Clayton, Vic., Australia.
B Anatomy and Developmental Biology, Monash University, Clayton, Vic., Australia.
C Monash Institute of Medical Research, Monash University, Clayton, Vic., Australia.
D Growth and Reproduction, University of Copenhagen (Rigshospitalet), Copenhagen, DK-1017, Denmark.
E Obstetrics and Gynaecology, Monash University, Clayton, Vic., Australia.
Reproduction, Fertility and Development 20(9) 31-31 https://doi.org/10.1071/SRB08Abs231
Published: 28 August 2008
Abstract
Recent studies suggest that adult Sertoli cells are not part of a homogenous and terminally differentiated population in phenotypes infertility1–4. The aims of this study were to compare the differentiation status of Sertoli cells from normal men undergoing gonadotrophin suppression by hormonal-based contraception (androgen plus progestin), as well as in pre-malignant and malignant testicular cancer. Confocal microscopy was performed to assess the expression of markers of cell proliferation (PCNA) and differentiation (androgen receptor) in Sertoli cells in all tissues. As additional markers of differentiation, Sertoli cell tight junction (claudin-11, JAM-A) and associated proteins (ZO-1) were assessed in men with testicular cancer. Samples from five different men were assessed in each group. In normal men, Sertoli cells exhibited a differentiated phenotype (i.e. PCNA negative, androgen receptor positive). However, after gonadotrophin suppression, 1.7 ± 0.6% of Sertoli cells exhibited intense PCNA reactivity and a reduction in androgen receptor immunoreactivity, demonstrating an undifferentiated phenotype. PCNA-positive Sertoli cells were never observed in pre-malignancy, and were only rarely observed in malignant testicular cancer, indicating a potential change in differentiation. Tight junction protein localisation was disrupted in pre-malignant cancer, with a reduction in JAM-A reactivity in Sertoli cells from pre-malignancy and strong JAM-A reactivity in malignant cancer; suggesting a potential role for JAM-A expression in the progression of testicular cancer. We conclude that Sertoli cells are not a homogenous and terminally differentiated population in men and their differentiation is modifiable by hormones and in the disease state.
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(2) Tarulli et al. 2006, Biol Reprod. 74:798–806
(3) Donner et al. 2004, APMIS. 112:79–88
(4) Brehm et al. 2006, Anat Embryol (Berl). 211(3):223–36
