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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 3. Claudin-11 and Connexin 43 are disorganized in testicular dysgenesis. Confocal immunofluorescence of normal (A) and carcinoma in situ (B and C) human testis sections detecting claudin-11 (red, tight junctions, asterisks) and connexin 43 (green, gap junctions, open squares and triangles). Co-localization appears in yellow. Inserts are negative controls. (Bar = 50 µm).
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Figure 3: Figure 3. Claudin-11 and Connexin 43 are disorganized in testicular dysgenesis. Confocal immunofluorescence of normal (A) and carcinoma in situ (B and C) human testis sections detecting claudin-11 (red, tight junctions, asterisks) and connexin 43 (green, gap junctions, open squares and triangles). Co-localization appears in yellow. Inserts are negative controls. (Bar = 50 µm).

Mentions: In the normal seminiferous epithelium, claudin-11 reactivity was detected near the basement membrane luminal to pre-meiotic germ cells, in regions associated with inter-Sertoli cell tight junctions (Fig. 3A, red, asterisk). Connexin 43 reactivity was associated with Sertoli cells, spermatogonia and spermatocytes (Fig. 3A, open square) and colocalized with claudin-11 in regions associated with inter-Sertoli cell tight junctions (yellow). Connexin 43 reactivity was also present between Leydig cells of the interstitium (Fig. 3B and C, triangles). Unexpectedly, JAM-A was localized to basally located spermatogonia and spermatocytes (Fig. 4A, asterisk) in the normal testis, as well as being present at inter-Sertoli cell tight junctions. In the same regions, ZO-1 was detected extending from the basement membrane, encircling spermatogonia and spermatocytes (Fig. 5A, asterisk) and also in association with inter-Sertoli cell tight junctions.


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 3. Claudin-11 and Connexin 43 are disorganized in testicular dysgenesis. Confocal immunofluorescence of normal (A) and carcinoma in situ (B and C) human testis sections detecting claudin-11 (red, tight junctions, asterisks) and connexin 43 (green, gap junctions, open squares and triangles). Co-localization appears in yellow. 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 3: Figure 3. Claudin-11 and Connexin 43 are disorganized in testicular dysgenesis. Confocal immunofluorescence of normal (A) and carcinoma in situ (B and C) human testis sections detecting claudin-11 (red, tight junctions, asterisks) and connexin 43 (green, gap junctions, open squares and triangles). Co-localization appears in yellow. Inserts are negative controls. (Bar = 50 µm).
Mentions: In the normal seminiferous epithelium, claudin-11 reactivity was detected near the basement membrane luminal to pre-meiotic germ cells, in regions associated with inter-Sertoli cell tight junctions (Fig. 3A, red, asterisk). Connexin 43 reactivity was associated with Sertoli cells, spermatogonia and spermatocytes (Fig. 3A, open square) and colocalized with claudin-11 in regions associated with inter-Sertoli cell tight junctions (yellow). Connexin 43 reactivity was also present between Leydig cells of the interstitium (Fig. 3B and C, triangles). Unexpectedly, JAM-A was localized to basally located spermatogonia and spermatocytes (Fig. 4A, asterisk) in the normal testis, as well as being present at inter-Sertoli cell tight junctions. In the same regions, ZO-1 was detected extending from the basement membrane, encircling spermatogonia and spermatocytes (Fig. 5A, asterisk) and also in association with inter-Sertoli cell tight junctions.

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