Preclinical models and evaluation criteria of prostatitis

Abstract

Prostatitis is a common urological condition that affects almost half of all men at some point in their life. The prostate gland has a dense nerve supply that contributes to the production of fluid to nourish sperm and the mechanism to switch between urination and ejaculation. Prostatitis can cause frequent urination, pelvic pain, and even infertility. Long-term prostatitis increases the risk of prostate cancer and benign prostate hyperplasia. Chronic non-bacterial prostatitis presents a complex pathogenesis, which has challenged medical research. Experimental studies of prostatitis require appropriate preclinical models. This review aimed to summarize and compare preclinical models of prostatitis based on their methods, success rate, evaluation, and range of application. The objective of this study is to provide a comprehensive understanding of prostatitis and advance basic research.

Keywords: animal models; chronic non-bacterial prostatitis; evaluation criteria; infectious prostatitis; prostatitis.

Figure 1

The anatomy of normal prostate and microscopic changes of prostatitis in a man and rodent. (A) is the schema human prostate. It consists of the central zone (CZ), the peripheral zone (PZ) and the transitional zone (TZ). (B) is the schema of rodents’ prostate. It consists of four distinct lobular structures: the anterior lobe the dorsal lobe, the ventral lobe and the lateral lobe, distributed on the left and right flanks. (C) shows the typical histology of prostatitis from a biopsy specimen, with inflammatory cell infiltration between the epithelial cells and in the interstitium. (D) shows the typical histology of prostatitis in a gonadectomized rats, with inflammatory cells in the interstitium and lumen.

Figure 2

The pathogenesis of chronic prostatitis.

Figure 3

Mechanism of prostatitis induced by thymectomy. CD4+ T cells are crucial in the development of prostatitis. CD4+ CD25- T cells recognize prostate tissue-specific antigens and produce autoimmunity to attack prostate tissue. CD4+CD25+ T cells, on the other hand, inhibit this autoimmune response and only appear in the peripheral immune system 3 days after birth, stimulated by prostate tissue-specific antigens and promoted by the thymus. Prostate tissue-specific suppressor T cells are generated to suppress prostate tissue-specific antigens induced autoimmunity and produce immune tolerance. Moreover, the prostate tissue-specific suppressor T cells inhibit CD4+ CD25- T cells. Removal of the thymus at 3 days of life leads to an increase in CD4+CD25+ T cells, and a relative increase in CD4+CD25- T cells, which leads to an imbalance and the development of prostatitis.

Figure 4

Mechanism of prostatitis induced by injection of prostatic antigen or adoptive immune cells. The principle of the EAP model is that proteins extracted from rat or mouse prostate tissue are injected subcutaneously to stimulate the mouse’s autoimmune response to produce inflammatory cells such as B cells and T cells associated with the injected prostate proteins, which migrate to the prostate tissue, infiltrate, and attack the prostate tissue, causing prostate damage and prostatitis. Cell transplantation-related prostatitis models are based on the principle that relevant immune cells are extracted from a model that has already produced prostatitis and injected into new mice, and that these adaptive immune cells may be specific enough to specifically travel to prostate tissue and attack it, causing damage and prostatitis.