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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 2. Downregulation of androgen receptor immunoreactivity in PCNA-positive Sertoli cells. Confocal immunofluorescence of human testis sections from normal (A) or gonadotropin-suppressed men (B, 2 wk; C–I, 12 wk). Sections were probed for GATA-4 [green, Sertoli cells within the seminiferous epithelium, asterisks), androgen receptor (blue, Sertoli (asterisks), Leydig and peritubular cells], and PCNA (red, labeling predominantly germ cells, triangles). Colocalization of GATA-4 and PCNA in Sertoli cells indicated by yellow (arrows). G–I are individual channels of the merged image in F, highlighting a GATA4 and PCNA-positive, AR-negative Sertoli cell (arrow) and a GATA4 and AR-positive, PCNA-negative Sertoli cell (asterisk). Inserts are controls where primary antibody was substituted for non-specific antibody of the same isotype. (Bar = 50 µm).
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Figure 2: Figure 2. Downregulation of androgen receptor immunoreactivity in PCNA-positive Sertoli cells. Confocal immunofluorescence of human testis sections from normal (A) or gonadotropin-suppressed men (B, 2 wk; C–I, 12 wk). Sections were probed for GATA-4 [green, Sertoli cells within the seminiferous epithelium, asterisks), androgen receptor (blue, Sertoli (asterisks), Leydig and peritubular cells], and PCNA (red, labeling predominantly germ cells, triangles). Colocalization of GATA-4 and PCNA in Sertoli cells indicated by yellow (arrows). G–I are individual channels of the merged image in F, highlighting a GATA4 and PCNA-positive, AR-negative Sertoli cell (arrow) and a GATA4 and AR-positive, PCNA-negative Sertoli cell (asterisk). Inserts are controls where primary antibody was substituted for non-specific antibody of the same isotype. (Bar = 50 µm).

Mentions: Androgen receptor immunoreactivity appeared lower in PCNA-positive Sertoli cells. AR expression was detected in all somatic cells (Leydig, peritubular myoid and Sertoli cells; as indicated by colocalization with GATA4) of normal men (Fig. 2A, light blue, asterisk), though expression of AR by Sertoli cells was variable, even within a single tubule. This expression pattern persisted after T+DPMA treatment for 2 wk (Fig. 2B) and 12 wk (Fig. 2C–F) though PCNA-positive Sertoli cells consistently appeared to express lower AR reactivity (Fig. 2D–I, yellow, arrow). In Figure 2F–I, a direct comparison of a PCNA-positive, AR low Sertoli cell (arrow) with a PCNA-negative AR-positive Sertoli cell (asterisk) can be seen. Expression of PCNA was detected in germ cells of all assessed groups (Fig. 2A–D, triangles). Samples of tissue from men with testicular cancer could not be reliably assessed with this combination of markers due to their highly variable immunoreactivity.


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 2. Downregulation of androgen receptor immunoreactivity in PCNA-positive Sertoli cells. Confocal immunofluorescence of human testis sections from normal (A) or gonadotropin-suppressed men (B, 2 wk; C–I, 12 wk). Sections were probed for GATA-4 [green, Sertoli cells within the seminiferous epithelium, asterisks), androgen receptor (blue, Sertoli (asterisks), Leydig and peritubular cells], and PCNA (red, labeling predominantly germ cells, triangles). Colocalization of GATA-4 and PCNA in Sertoli cells indicated by yellow (arrows). G–I are individual channels of the merged image in F, highlighting a GATA4 and PCNA-positive, AR-negative Sertoli cell (arrow) and a GATA4 and AR-positive, PCNA-negative Sertoli cell (asterisk). Inserts are controls where primary antibody was substituted for non-specific antibody of the same isotype. (Bar = 50 µm).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 2: Figure 2. Downregulation of androgen receptor immunoreactivity in PCNA-positive Sertoli cells. Confocal immunofluorescence of human testis sections from normal (A) or gonadotropin-suppressed men (B, 2 wk; C–I, 12 wk). Sections were probed for GATA-4 [green, Sertoli cells within the seminiferous epithelium, asterisks), androgen receptor (blue, Sertoli (asterisks), Leydig and peritubular cells], and PCNA (red, labeling predominantly germ cells, triangles). Colocalization of GATA-4 and PCNA in Sertoli cells indicated by yellow (arrows). G–I are individual channels of the merged image in F, highlighting a GATA4 and PCNA-positive, AR-negative Sertoli cell (arrow) and a GATA4 and AR-positive, PCNA-negative Sertoli cell (asterisk). Inserts are controls where primary antibody was substituted for non-specific antibody of the same isotype. (Bar = 50 µm).
Mentions: Androgen receptor immunoreactivity appeared lower in PCNA-positive Sertoli cells. AR expression was detected in all somatic cells (Leydig, peritubular myoid and Sertoli cells; as indicated by colocalization with GATA4) of normal men (Fig. 2A, light blue, asterisk), though expression of AR by Sertoli cells was variable, even within a single tubule. This expression pattern persisted after T+DPMA treatment for 2 wk (Fig. 2B) and 12 wk (Fig. 2C–F) though PCNA-positive Sertoli cells consistently appeared to express lower AR reactivity (Fig. 2D–I, yellow, arrow). In Figure 2F–I, a direct comparison of a PCNA-positive, AR low Sertoli cell (arrow) with a PCNA-negative AR-positive Sertoli cell (asterisk) can be seen. Expression of PCNA was detected in germ cells of all assessed groups (Fig. 2A–D, triangles). Samples of tissue from men with testicular cancer could not be reliably assessed with this combination of markers due to their highly variable immunoreactivity.

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