Spontaneous Occurrence of Vasculitis-Like Lesions in Male Reproductive Tissues

Itoh, Masahiro; Miyamoto, Kensaku; Ohga, Tatsujiroh; Takeuchi, Yoshiki

doi:10.1080/014850199262814

Cited by 11 publications

(8 citation statements)

References 18 publications

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“…For example, infiltration of lymphocytes and neutrophils into the interstitial tissue are frequently observed in the epididymis and vas deferens, but rarely in the testis, of aging mice. 913 In mice injected intravenously with Bordetella pertussis and adjuvant, neutrophils invade the stroma of the epididymis, vas deferens and accessory glands, but the testis is not affected. 914 In the alymphoplastic (aly) mouse, eosinophils and macrophages spontaneously accumulate in the stroma of the epididymis and vas deferens, but not the testis.…”

Section: Autoimmunity In the Epididymis Vas Deferens And Prostatementioning

confidence: 99%

“…Immune cell infiltrates are much more likely to appear in the epididymis than the testis in aging mice, in mice injected with B. pertussis and adjuvant, in mice with the alymphoplasia mutation, and in mice with a deletion of the AIRE transcription factor. [913][914][915]923 In addition, epididymitis or epididymovasitis precedes orchitis in the day 3 thymectomized mouse model, and following transfer of lymphocytes from mice immunized against spermatogenic cell antigens. 267,874,876 These observations suggest that the epididymis and vas deferens may be much more reliant on maintenance of tolerance to protect the sperm from immunological damage, compared with the testis.…”

Section: Immunology Of the Epididymis And Vas Deferensmentioning

confidence: 99%

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The Immunophysiology of Male Reproduction

Hedger

2015

Knobil and Neill's Physiology of Reproduction

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Section: Autoimmunity In the Epididymis Vas Deferens And Prostatementioning

confidence: 99%

Section: Immunology Of the Epididymis And Vas Deferensmentioning

confidence: 99%

The Immunophysiology of Male Reproduction

Hedger

2015

Knobil and Neill's Physiology of Reproduction

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“…However, experimental evidence is considerable that the epididymis might be much more susceptible to inflammation and subsequent leukocytic infiltration than is the testis. Interstitial tissue infiltrates of lymphocytes and neutrophils are frequently observed in the epididymis and vas deferens, but rarely in the testis, of aging mice (Itoh et al, 1999a). Similarly, in mice injected (IV) with Bordetella pertussis and adjuvant, neutrophils invade the stroma of the epididymis and vas deferens, as well as the accessory organs, but the testis is not affected (Itoh et al, 1995).…”

Section: Immune Privilege In the Testis And Epididymismentioning

confidence: 99%

Immunophysiology and Pathology of Inflammation in the Testis and Epididymis

Hedger

2011

Journal of Andrology

178

155

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The ability of spermatogenic cells to evade the host immune system and the ability of systemic inflammation to inhibit male reproductive function represent two of the most intriguing conundrums of male reproduction. Clearly, an understanding of the underlying immunology of the male reproductive tract is crucial to resolving these superficially incompatible observations. One important consideration must be the very different immunological environments of the testis, where sperm develop, and the epididymis, where sperm mature and are stored. Compared with the elaborate blood-testis barrier, the tight junctions of the epididymis are much less effective. Unlike the seminiferous epithelium, immune cells are commonly observed within the epithelium, and can even be found within the lumen, of the epididymis. Crucially, there is little evidence for extended allograft survival (immune privilege) in the epididymis, as it exists in the testis, and the epididymis is much more susceptible to loss of immune tolerance. Moreover, the incidence of epididymitis is considerably greater than that of orchitis in humans, and susceptibility to sperm antibody formation after damage to the epididymis or vas deferens increases with increasing distance of the damage from the testis. Although we still know relatively little about testicular immunity, we know less about the interactions between the epididymis and the immune system. Given that the epididymis appears to be more susceptible to inflammation and immune reactions than the testis, and thereby represents the weaker link in protecting developing sperm from the immune system, it is probably time this imbalance in knowledge was addressed.

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“…Spontaneous vascular lesions have also been seen in the epididymis and vas deferens in aging BALB/c mice and are of unknown pathogenesis (Itoh et al 1999). In both rats and mice, lesions of PAN may be noted more commonly in animals with concurrent chronic progressive nephropathy.…”

Section: Differentiation From Spontaneous Vascular Disease In Laboratmentioning

confidence: 84%

Scientific and Regulatory Policy Committee Points-to-consider Paper*

Frazier

Engelhardt

Fant³

et al. 2015

Toxicol Pathol

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Drug-induced vascular injury (DIVI) is a recurrent challenge in the development of novel pharmaceutical agents. Although DIVI in laboratory animal species has been well characterized for vasoactive small molecules, there is little available information regarding DIVI associated with biotherapeutics such as peptides/proteins or antibodies. Because of the uncertainty about whether DIVI in preclinical studies is predictive of effects in humans and the lack of robust biomarkers of DIVI, preclinical DIVI findings can cause considerable delays in or even halt development of promising new drugs. This review discusses standard terminology, characteristics, and mechanisms of DIVI associated with biotherapeutics. Guidance and points to consider for the toxicologist and pathologist facing preclinical cases of biotherapeutic-related DIVI are outlined, and examples of regulatory feedback for each of the mechanistic types of DIVI are included to provide insight into risk assessment.

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Spontaneous Occurrence of Vasculitis-Like Lesions in Male Reproductive Tissues

Cited by 11 publications

References 18 publications

The Immunophysiology of Male Reproduction

The Immunophysiology of Male Reproduction

Immunophysiology and Pathology of Inflammation in the Testis and Epididymis

Scientific and Regulatory Policy Committee Points-to-consider Paper*

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