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The testicular antiviral defense system: localization, expression, and regulation of 2'5' oligoadenylate synthetase, double-stranded RNA-activated protein kinase, and Mx proteins in the rat seminiferous tubule.

Dejucq N, Chousterman S, Jégou B - J. Cell Biol. (1997)

Bottom Line: Interestingly, IFN gamma had no effect on peritubular cells' 2'5' A synthetase and Mx production but it enhanced Mx proteins in Sertoli cells.In conclusion, this study reveals that the seminiferous tubules are particularly well equipped to react to a virus attack.The fact that the two key tubular elements of the blood-testis barrier, namely, Sertoli and peritubular cells, were found to assume this protection allows the extension of the concept of blood-testis barrier to the testicular antiviral defense.

View Article: PubMed Central - PubMed

Affiliation: Groupe d'Etude de la Reproduction chez le Mâle-Institut National de la Santé et de la Recherche Medicale, Unité 435, Université de Rennes I, Campus de Beaulieu, 35 042 Rennes Cedex, Bretagne, France.

ABSTRACT
Although the involvement of viruses in alterations of testicular function and in sexually transmitted diseases is well known, paradoxically, the testicular antiviral defense system has virtually not been studied. The well known antiviral activity of interferons (IFNs) occurs via the action of several IFN-induced proteins, among which the 2'5' oligoadenylate synthetase (2'5' A synthetase), the double-stranded RNA-activated protein kinase (PKR), and the Mx proteins are the best known. To explore the antiviral capacity of the testis and to study the testicular action of IFNs, we looked for the presence and regulation of these three proteins in isolated seminiferous tubule cells, cultured in the presence or in the absence of IFN alpha, IFN gamma, or Sendai virus. In all conditions tested, the meiotic pachytene spermatocytes and the post-meiotic early spermatids lacked 2'5' A synthetase, PKR, and Mx mRNAs and proteins. In contrast, Sertoli cells constitutively expressed these mRNAs and proteins, and their levels were greatly increased after IFN alpha or Sendai virus exposure. While peritubular cells were also able to markedly express 2'5' A synthetase, PKR, and Mx mRNA and proteins after IFN alpha or viral exposure, only PKR was constitutively present in these cells. Interestingly, IFN gamma had no effect on peritubular cells' 2'5' A synthetase and Mx production but it enhanced Mx proteins in Sertoli cells. In conclusion, this study reveals that the seminiferous tubules are particularly well equipped to react to a virus attack. The fact that the two key tubular elements of the blood-testis barrier, namely, Sertoli and peritubular cells, were found to assume this protection allows the extension of the concept of blood-testis barrier to the testicular antiviral defense.

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Mx mRNA expression in peritubular and Sertoli cells.  Mx mRNA expression was analyzed by Northern blot in peritubular cells (a, P) and in Sertoli cells (d, S) cultured in the presence or in the absence of IFN α (50, 275, and 500 U/ml) or IFN γ  (10 and 100 U/ml) for 14 h, or Sendai virus (V100 and V500 U/ml)  for 28 h. Hybridization of the blot with the actin probe is shown  (b and e). Blots shown are representative of three totally independent culture and Northern blot experiments. mRNA signals  were quantified by scanning densitometry and corrected relative  to actin signals for both peritubular (c) and Sertoli cells (f).
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Figure 6: Mx mRNA expression in peritubular and Sertoli cells. Mx mRNA expression was analyzed by Northern blot in peritubular cells (a, P) and in Sertoli cells (d, S) cultured in the presence or in the absence of IFN α (50, 275, and 500 U/ml) or IFN γ (10 and 100 U/ml) for 14 h, or Sendai virus (V100 and V500 U/ml) for 28 h. Hybridization of the blot with the actin probe is shown (b and e). Blots shown are representative of three totally independent culture and Northern blot experiments. mRNA signals were quantified by scanning densitometry and corrected relative to actin signals for both peritubular (c) and Sertoli cells (f).

Mentions: The rat lymphocytes used as positive controls revealed the two bands of 3.2 and 2.5 kb (Fig. 6, a and d) previously described in the rat and corresponding to Mx1 and Mx2 and/or Mx3 mRNAs, respectively (Meier et al., 1988). The 2.5-kb transcript was weakly expressed in untreated Sertoli cells (Fig. 6 d) but not in peritubular cells (Fig. 6 a). Exposure of both peritubular and Sertoli cells to IFN α or to Sendai virus resulted in a dramatic stimulation of both transcripts, while IFN γ had no effect on peritubular cells but induced Mx1 expression in Sertoli cells (Fig. 6, a and c, d and f, respectively). No Mx transcript was ever seen in germ cells (Table I).


The testicular antiviral defense system: localization, expression, and regulation of 2'5' oligoadenylate synthetase, double-stranded RNA-activated protein kinase, and Mx proteins in the rat seminiferous tubule.

Dejucq N, Chousterman S, Jégou B - J. Cell Biol. (1997)

Mx mRNA expression in peritubular and Sertoli cells.  Mx mRNA expression was analyzed by Northern blot in peritubular cells (a, P) and in Sertoli cells (d, S) cultured in the presence or in the absence of IFN α (50, 275, and 500 U/ml) or IFN γ  (10 and 100 U/ml) for 14 h, or Sendai virus (V100 and V500 U/ml)  for 28 h. Hybridization of the blot with the actin probe is shown  (b and e). Blots shown are representative of three totally independent culture and Northern blot experiments. mRNA signals  were quantified by scanning densitometry and corrected relative  to actin signals for both peritubular (c) and Sertoli cells (f).
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2139956&req=5

Figure 6: Mx mRNA expression in peritubular and Sertoli cells. Mx mRNA expression was analyzed by Northern blot in peritubular cells (a, P) and in Sertoli cells (d, S) cultured in the presence or in the absence of IFN α (50, 275, and 500 U/ml) or IFN γ (10 and 100 U/ml) for 14 h, or Sendai virus (V100 and V500 U/ml) for 28 h. Hybridization of the blot with the actin probe is shown (b and e). Blots shown are representative of three totally independent culture and Northern blot experiments. mRNA signals were quantified by scanning densitometry and corrected relative to actin signals for both peritubular (c) and Sertoli cells (f).
Mentions: The rat lymphocytes used as positive controls revealed the two bands of 3.2 and 2.5 kb (Fig. 6, a and d) previously described in the rat and corresponding to Mx1 and Mx2 and/or Mx3 mRNAs, respectively (Meier et al., 1988). The 2.5-kb transcript was weakly expressed in untreated Sertoli cells (Fig. 6 d) but not in peritubular cells (Fig. 6 a). Exposure of both peritubular and Sertoli cells to IFN α or to Sendai virus resulted in a dramatic stimulation of both transcripts, while IFN γ had no effect on peritubular cells but induced Mx1 expression in Sertoli cells (Fig. 6, a and c, d and f, respectively). No Mx transcript was ever seen in germ cells (Table I).

Bottom Line: Interestingly, IFN gamma had no effect on peritubular cells' 2'5' A synthetase and Mx production but it enhanced Mx proteins in Sertoli cells.In conclusion, this study reveals that the seminiferous tubules are particularly well equipped to react to a virus attack.The fact that the two key tubular elements of the blood-testis barrier, namely, Sertoli and peritubular cells, were found to assume this protection allows the extension of the concept of blood-testis barrier to the testicular antiviral defense.

View Article: PubMed Central - PubMed

Affiliation: Groupe d'Etude de la Reproduction chez le Mâle-Institut National de la Santé et de la Recherche Medicale, Unité 435, Université de Rennes I, Campus de Beaulieu, 35 042 Rennes Cedex, Bretagne, France.

ABSTRACT
Although the involvement of viruses in alterations of testicular function and in sexually transmitted diseases is well known, paradoxically, the testicular antiviral defense system has virtually not been studied. The well known antiviral activity of interferons (IFNs) occurs via the action of several IFN-induced proteins, among which the 2'5' oligoadenylate synthetase (2'5' A synthetase), the double-stranded RNA-activated protein kinase (PKR), and the Mx proteins are the best known. To explore the antiviral capacity of the testis and to study the testicular action of IFNs, we looked for the presence and regulation of these three proteins in isolated seminiferous tubule cells, cultured in the presence or in the absence of IFN alpha, IFN gamma, or Sendai virus. In all conditions tested, the meiotic pachytene spermatocytes and the post-meiotic early spermatids lacked 2'5' A synthetase, PKR, and Mx mRNAs and proteins. In contrast, Sertoli cells constitutively expressed these mRNAs and proteins, and their levels were greatly increased after IFN alpha or Sendai virus exposure. While peritubular cells were also able to markedly express 2'5' A synthetase, PKR, and Mx mRNA and proteins after IFN alpha or viral exposure, only PKR was constitutively present in these cells. Interestingly, IFN gamma had no effect on peritubular cells' 2'5' A synthetase and Mx production but it enhanced Mx proteins in Sertoli cells. In conclusion, this study reveals that the seminiferous tubules are particularly well equipped to react to a virus attack. The fact that the two key tubular elements of the blood-testis barrier, namely, Sertoli and peritubular cells, were found to assume this protection allows the extension of the concept of blood-testis barrier to the testicular antiviral defense.

Show MeSH
Related in: MedlinePlus