Induction of experimental autoimmune orchitis in mice: responses to elevated circulating levels of the activin-binding protein, follistatin

Reproduction ◽  
2017 ◽  
Vol 154 (3) ◽  
pp. 293-305 ◽  
Author(s):  
Nour Nicolas ◽  
Julie A Muir ◽  
Susan Hayward ◽  
Justin L Chen ◽  
Peter G Stanton ◽  
...  

Experimental autoimmune orchitis (EAO) is a rodent model of chronic testicular inflammation that mimics the pathology observed in some types of human infertility. In a previous study, testicular expression of the inflammatory/immunoregulatory cytokine, activin A, was elevated in adult mice during the onset of EAO, indicating a potential role in the regulation of the disease. Consequently, we examined the development of EAO in mice with elevated levels of follistatin, an endogenous activin antagonist, as a potential therapeutic approach to testicular inflammation. Prior to EAO induction, mice received a single intramuscular injection of a non-replicative recombinant adeno-associated viral vector carrying a gene cassette of the circulating form of follistatin, FST315 (FST group). Serum follistatin levels were increased 5-fold in the FST group compared with the control empty vector (EV) group at 30 and 50 days of EAO, but intra-testicular levels of follistatin or activin A were not significantly altered. Induction of EAO was reduced, but not prevented, with mild-to-severe damage in 75% of the EV group and 40% of the FST group, at 50 days following immunisation with testicular homogenate. However, the EAO damage score (based on disruption of the blood–testis barrier, apoptosis, testicular damage and fibrosis) and extent of intratesticular inflammation (expression of inflammatory mediators) were directly proportional to the levels of activin A measured in the testis at 50 days. These data implicate activin A in the progression of EAO, thereby providing a potential therapeutic target; however, elevating circulating follistatin levels were not sufficient to prevent EAO development.

2014 ◽  
Vol 30 (2) ◽  
pp. 417-431 ◽  
Author(s):  
Ferial Aslani ◽  
Hans-Christian Schuppe ◽  
Vanesa A. Guazzone ◽  
Sudhanshu Bhushan ◽  
Eva Wahle ◽  
...  

2001 ◽  
pp. 425-429 ◽  
Author(s):  
S Muttukrishna ◽  
A Farouk ◽  
S Sharma ◽  
L Evans ◽  
N Groome ◽  
...  

OBJECTIVE: Inhibin, activin and follistatin are glycoprotein hormones produced by the gonads. Recent studies have shown that inhibin B is the predominant form of inhibin in the circulation in men. The objective of this study was to investigate circulating levels of activin A and follistatin in disorders of spermatogenesis in men and their relationship with FSH and inhibin B. DESIGN AND METHOD: Serum from five different groups of men was prospectively collected and stored at -20 degrees C. The groups were men with: (i) proven fertility (controls) (n=20), (ii) primary testicular failure (n=15), (iii) obstructive azoospermia (n=10), (iv) oligospermia (n=10) and (v) miscellaneous sperm dysfunction (n=40). WHO criteria (1992) were used for semen characterisation. Serum concentrations of 'total' activin A, follistatin, FSH and inhibin B were measured using specific two-site enzyme immunoassays. RESULTS: Activin A levels were significantly lower than in the controls in the obstructive azoospermia group and higher in the miscellaneous sperm dysfunction group. Serum follistatin levels did not significantly vary in any group compared with the controls. Circulating levels of FSH were higher than in the controls in the primary testicular failure and obstructive azoospermic group. Levels of inhibin B were lower than in the controls in all disorders of spermatogenesis studied. CONCLUSION: This study demonstrates that activin A and follistatin are in the circulation in males and activin A levels are significantly lower in obstructive azoospermia and higher in miscellaneous sperm dysfunction than in controls. The mechanism involved in altering the levels of activin A in these conditions is not clear. However, high follistatin:activin A molar ratios (>2.5) in all groups suggests that all activin A in the circulation is bound to follistatin in males.


Reproduction ◽  
2008 ◽  
Vol 135 (6) ◽  
pp. 859-866 ◽  
Author(s):  
Ning Qu ◽  
Hayato Terayama ◽  
Munekazu Naito ◽  
Yuki Ogawa ◽  
Shuichi Hirai ◽  
...  

Immunization of mice with viable syngeneic testicular germ cells (TGC) alone can induce autoimmune responses against autoantigens of both round and elongating spermatids, resulting in the development of experimental autoimmune orchitis (EAO). Histological lesions in this EAO model without an adjuvant are characterized by lymphocytic infiltration into the testes, spermatogenic disturbance, and a complete lack of epididymitis. In this study, we investigated the effects of vasectomy (Vx) on TGC-induced EAO expecting that Vx augments the severity of testicular inflammation in A/J mice. The results showed that mice receiving Vx alone exhibited no significant inflammatory cell response in either the testes or epididymides, and mice receiving shamVx+TGC immunization had EAO with no epididymitis. In sharp contrast, no EAO was found in the testes of any mice receiving Vx+TGC immunization. Instead, caput epididymitis involving CD4+T cells, CD8+T cells, B cells, and macrophages were induced in them with striking elevation of the tissue levels of bothIL6andIL10mRNA. Furthermore, serum autoantibodies induced by shamVx+TGC immunization were reactive with both round (immature) and elongating (mature) spermatids; however, those induced by Vx+TGC immunization were specific to acrosomes of mature spermatids and spermatozoa. These unexpected results indicate that Vx may induce the mode by which autoreactive lymphocytes gain access to TGC autoantigens in the epididymides, leading to autoimmune responses against the autoantigens of mature rather than immature spermatids.


2005 ◽  
Vol 173 (4S) ◽  
pp. 409-409
Author(s):  
Masami Watanabe ◽  
Atsushi Nagai ◽  
Norihiro Kusumi ◽  
Yasutomo Nasu ◽  
Hiromi Kumon ◽  
...  

1983 ◽  
Vol 5 ◽  
pp. 84
Author(s):  
Enia Comini Andrada ◽  
María del C. Samaniego ◽  
Grato E. Bur ◽  
Esteban Montuori ◽  
Juan A. Andrada

2015 ◽  
Vol 92 (3) ◽  
Author(s):  
Zhenghui Liu ◽  
Shutao Zhao ◽  
Qiaoyuan Chen ◽  
Keqin Yan ◽  
Peng Liu ◽  
...  

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