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A survey of Sertoli cell differentiation in men after gonadotropin suppression and in testicular cancer.

Tarulli GA, Stanton PG, Loveland KL, Meyts ER, McLachlan RI, Meachem SJ - Spermatogenesis (2013)

Bottom Line: However, after long-term gonadotropin suppression, 1.7 ± 0.6% of Sertoli cells exhibited PCNA reactivity associated with a diminished immunoreactivity in androgen receptor, suggesting an undifferentiated phenotype.Tight junction protein localization (claudin 11, JAM-A and ZO-1) was altered in CIS, with a reduction in JAM-A reactivity in Sertoli cells from tubules with CIS and the emergence of strong JAM-A reactivity in seminoma.These findings indicate that adult human Sertoli cells exhibit characteristics of an undifferentiated state in oligospermic men and patients with CIS and seminoma in the presence of germ cell neoplasia.

View Article: PubMed Central - PubMed

Affiliation: Prince Henry's Institute of Medical Research; Clayton; Victoria, Australia ; Department of Anatomy & Developmental Biology; Monash University; Victoria, Australia.

ABSTRACT
It is widely held that the somatic cell population that is responsible for sperm development and output (Sertoli cells) is terminally differentiated and unmodifiable in adults. It is postulated, with little evidence, that Sertoli cells are not terminally differentiated in some phenotypes of infertility and testicular cancer. This study sought to compare markers of Sertoli cell differentiation in normospermic men, oligospermic men (undergoing gonadotropin suppression) and testicular carcinoma in situ (CIS) and seminoma samples. Confocal microscopy was used to assess the expression of markers of proliferation (PCNA and Ki67) and functional differentiation (androgen receptor). As additional markers of differentiation, the organization of Sertoli cell tight junction and associated proteins were assessed in specimens with carcinoma in situ. In normal men, Sertoli cells exhibited a differentiated phenotype (i.e., PCNA and Ki67 negative, androgen 40 receptor positive). However, after long-term gonadotropin suppression, 1.7 ± 0.6% of Sertoli cells exhibited PCNA reactivity associated with a diminished immunoreactivity in androgen receptor, suggesting an undifferentiated phenotype. Ki67-positive Sertoli cells were also observed. PCNA-positive Sertoli cells were never observed in tubules with carcinoma in situ, and only rarely observed adjacent to seminoma. Tight junction protein localization (claudin 11, JAM-A and ZO-1) was altered in CIS, with a reduction in JAM-A reactivity in Sertoli cells from tubules with CIS and the emergence of strong JAM-A reactivity in seminoma. These findings indicate that adult human Sertoli cells exhibit characteristics of an undifferentiated state in oligospermic men and patients with CIS and seminoma in the presence of germ cell neoplasia.

No MeSH data available.


Related in: MedlinePlus

Figure 1. Evidence for Sertoli cell proliferation in men. Confocal immunofluorescence of proliferation markers in testis tissue from normal (A and E) and gonadotropin suppressed men [2 wk, B; 12 wk, C and D (enlarged portion of C) and F and G (enlarged portion of panel F)], in testis with carcinoma in situ (H) and in a tubule adjacent to a seminoma (I). Sections were probed with a combination of either GATA4 (green, in the nuclei of Sertoli cells) within the seminiferous epithelium (asterisks), and PCNA antibodies (red, staining cells with proliferation capacity - triangles) (A–D, H–I), or GATA4 (red) and Ki67 (green, staining proliferating cells) (E–G). Colocalization of GATA4 and PCNA or GATA4 and Ki67 in Sertoli cell nuclei (indicating a proliferative state, arrows) is shown by a yellow color. Figure 1E–G includes a transmitted light channel to illustrate histological detail. Inserts are negative controls. (Bar = 50 µm).
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Figure 1: Figure 1. Evidence for Sertoli cell proliferation in men. Confocal immunofluorescence of proliferation markers in testis tissue from normal (A and E) and gonadotropin suppressed men [2 wk, B; 12 wk, C and D (enlarged portion of C) and F and G (enlarged portion of panel F)], in testis with carcinoma in situ (H) and in a tubule adjacent to a seminoma (I). Sections were probed with a combination of either GATA4 (green, in the nuclei of Sertoli cells) within the seminiferous epithelium (asterisks), and PCNA antibodies (red, staining cells with proliferation capacity - triangles) (A–D, H–I), or GATA4 (red) and Ki67 (green, staining proliferating cells) (E–G). Colocalization of GATA4 and PCNA or GATA4 and Ki67 in Sertoli cell nuclei (indicating a proliferative state, arrows) is shown by a yellow color. Figure 1E–G includes a transmitted light channel to illustrate histological detail. Inserts are negative controls. (Bar = 50 µm).

Mentions: No PCNA reactivity was detectable in Sertoli cells of sections from untreated normal men (Fig. 1A, green, asterisk) and after treatment of normal men with T and DPMA for 2 wk (Fig. 1B, asterisk). When treatment was extended to 12 wk, PCNA reactivity was detected in 1.7% ± 0.6 of Sertoli cells (Fig. 1C and D, arrows). To verify the proliferating state of Sertoli cells after gonadotropin suppression, an additional marker of proliferation believed to be more specific for the actual growth fraction of a cell population was employed; Ki67.45 No Ki67-positive Sertoli cells were present in untreated normal men (Fig. 1E, red, asterisk); however, positive Sertoli cells were observed after 12 wk of T + DMPA treatment [Fig. 1F and G (enlarged image of IF), green, arrow]. No PCNA was detectable in Sertoli cells of testis sections with CIS (Fig. 1H, asterisk). In the vicinity of seminoma, PCNA-positive Sertoli cells were identified (albeit infrequently) in tubules with a highly abnormal morphology. PCNA reactivity was detectable in germ cells of all assessed groups (Fig. 1A, 1I, triangles). In all sections analyzed, notable non-specific reactivity was observed in the interstitium, making it impossible to assess PCNA and Ki67 reactivity in these regions.


A survey of Sertoli cell differentiation in men after gonadotropin suppression and in testicular cancer.

Tarulli GA, Stanton PG, Loveland KL, Meyts ER, McLachlan RI, Meachem SJ - Spermatogenesis (2013)

Figure 1. Evidence for Sertoli cell proliferation in men. Confocal immunofluorescence of proliferation markers in testis tissue from normal (A and E) and gonadotropin suppressed men [2 wk, B; 12 wk, C and D (enlarged portion of C) and F and G (enlarged portion of panel F)], in testis with carcinoma in situ (H) and in a tubule adjacent to a seminoma (I). Sections were probed with a combination of either GATA4 (green, in the nuclei of Sertoli cells) within the seminiferous epithelium (asterisks), and PCNA antibodies (red, staining cells with proliferation capacity - triangles) (A–D, H–I), or GATA4 (red) and Ki67 (green, staining proliferating cells) (E–G). Colocalization of GATA4 and PCNA or GATA4 and Ki67 in Sertoli cell nuclei (indicating a proliferative state, arrows) is shown by a yellow color. Figure 1E–G includes a transmitted light channel to illustrate histological detail. Inserts are negative controls. (Bar = 50 µm).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3644048&req=5

Figure 1: Figure 1. Evidence for Sertoli cell proliferation in men. Confocal immunofluorescence of proliferation markers in testis tissue from normal (A and E) and gonadotropin suppressed men [2 wk, B; 12 wk, C and D (enlarged portion of C) and F and G (enlarged portion of panel F)], in testis with carcinoma in situ (H) and in a tubule adjacent to a seminoma (I). Sections were probed with a combination of either GATA4 (green, in the nuclei of Sertoli cells) within the seminiferous epithelium (asterisks), and PCNA antibodies (red, staining cells with proliferation capacity - triangles) (A–D, H–I), or GATA4 (red) and Ki67 (green, staining proliferating cells) (E–G). Colocalization of GATA4 and PCNA or GATA4 and Ki67 in Sertoli cell nuclei (indicating a proliferative state, arrows) is shown by a yellow color. Figure 1E–G includes a transmitted light channel to illustrate histological detail. Inserts are negative controls. (Bar = 50 µm).
Mentions: No PCNA reactivity was detectable in Sertoli cells of sections from untreated normal men (Fig. 1A, green, asterisk) and after treatment of normal men with T and DPMA for 2 wk (Fig. 1B, asterisk). When treatment was extended to 12 wk, PCNA reactivity was detected in 1.7% ± 0.6 of Sertoli cells (Fig. 1C and D, arrows). To verify the proliferating state of Sertoli cells after gonadotropin suppression, an additional marker of proliferation believed to be more specific for the actual growth fraction of a cell population was employed; Ki67.45 No Ki67-positive Sertoli cells were present in untreated normal men (Fig. 1E, red, asterisk); however, positive Sertoli cells were observed after 12 wk of T + DMPA treatment [Fig. 1F and G (enlarged image of IF), green, arrow]. No PCNA was detectable in Sertoli cells of testis sections with CIS (Fig. 1H, asterisk). In the vicinity of seminoma, PCNA-positive Sertoli cells were identified (albeit infrequently) in tubules with a highly abnormal morphology. PCNA reactivity was detectable in germ cells of all assessed groups (Fig. 1A, 1I, triangles). In all sections analyzed, notable non-specific reactivity was observed in the interstitium, making it impossible to assess PCNA and Ki67 reactivity in these regions.

Bottom Line: However, after long-term gonadotropin suppression, 1.7 ± 0.6% of Sertoli cells exhibited PCNA reactivity associated with a diminished immunoreactivity in androgen receptor, suggesting an undifferentiated phenotype.Tight junction protein localization (claudin 11, JAM-A and ZO-1) was altered in CIS, with a reduction in JAM-A reactivity in Sertoli cells from tubules with CIS and the emergence of strong JAM-A reactivity in seminoma.These findings indicate that adult human Sertoli cells exhibit characteristics of an undifferentiated state in oligospermic men and patients with CIS and seminoma in the presence of germ cell neoplasia.

View Article: PubMed Central - PubMed

Affiliation: Prince Henry's Institute of Medical Research; Clayton; Victoria, Australia ; Department of Anatomy & Developmental Biology; Monash University; Victoria, Australia.

ABSTRACT
It is widely held that the somatic cell population that is responsible for sperm development and output (Sertoli cells) is terminally differentiated and unmodifiable in adults. It is postulated, with little evidence, that Sertoli cells are not terminally differentiated in some phenotypes of infertility and testicular cancer. This study sought to compare markers of Sertoli cell differentiation in normospermic men, oligospermic men (undergoing gonadotropin suppression) and testicular carcinoma in situ (CIS) and seminoma samples. Confocal microscopy was used to assess the expression of markers of proliferation (PCNA and Ki67) and functional differentiation (androgen receptor). As additional markers of differentiation, the organization of Sertoli cell tight junction and associated proteins were assessed in specimens with carcinoma in situ. In normal men, Sertoli cells exhibited a differentiated phenotype (i.e., PCNA and Ki67 negative, androgen 40 receptor positive). However, after long-term gonadotropin suppression, 1.7 ± 0.6% of Sertoli cells exhibited PCNA reactivity associated with a diminished immunoreactivity in androgen receptor, suggesting an undifferentiated phenotype. Ki67-positive Sertoli cells were also observed. PCNA-positive Sertoli cells were never observed in tubules with carcinoma in situ, and only rarely observed adjacent to seminoma. Tight junction protein localization (claudin 11, JAM-A and ZO-1) was altered in CIS, with a reduction in JAM-A reactivity in Sertoli cells from tubules with CIS and the emergence of strong JAM-A reactivity in seminoma. These findings indicate that adult human Sertoli cells exhibit characteristics of an undifferentiated state in oligospermic men and patients with CIS and seminoma in the presence of germ cell neoplasia.

No MeSH data available.


Related in: MedlinePlus