Necrosis Is the Dominant Cell Death Pathway in Uropathogenic Escherichia coli Elicited Epididymo-Orchitis and Is Responsible for Damage of Rat Testis

Abstract

Male infertility is a frequent medical condition, compromising approximately one in twenty men, with infections of the reproductive tract constituting a major etiological factor. Bacterial epididymo-orchitis results in acute inflammation most often caused by ascending canalicular infections from the urethra via the continuous male excurrent ductal system. Uropathogenic Escherichia coli (UPEC) represent a relevant pathogen in urogenital tract infections. To explore how bacteria can cause damage and cell loss and thus impair fertility, an in vivo epididymo-orchitis model was employed in rats by injecting UPEC strain CFT073 into the vas deference in close proximity to the epididymis. Seven days post infection bacteria were found predominantly in the testicular interstitial space. UPEC infection resulted in severe impairment of spermatogenesis by germ cell loss, damage of testicular somatic cells, a decrease in sperm numbers and a significant increase in TUNEL (+) cells. Activation of caspase-8 (extrinsic apoptotic pathway), caspase-3/−6 (intrinsic apoptotic pathway), caspase-1 (pyroptosis pathway) and the presence of 180 bp DNA fragments, all of which serve as indicators of the classical apoptotic pathway, were not observed in infected testis. Notably, electron microscopical examination revealed degenerative features of Sertoli cells (SC) in UPEC infected testis. Furthermore, the passive release of high mobility group protein B1 (HMGB1), as an indication of necrosis, was observed in vivo in infected testis. Thus, necrosis appears to be the dominant cell death pathway in UPEC infected testis. Substantial necrotic changes seen in Sertoli cells will contribute to impaired spermatogenesis by loss of function in supporting the dependent germ cells.

Ability of Escherichia coli to produce hemolysis leads to a greater pathogenic effect on human sperm

“…In fact, an experimental infection with E. coli in the epididymis of rats impaired even spermatogenesis (39), with cell-death pathways and necrosis involved (40). Therefore, a bacterial infection would be expected to have an effect on mature sperm stored in the epididymis.…”

The role of the prostate in male fertility, health and disease

“…However, although a direct relationship between E. coli infection and male infertility has been clearly demonstrated, it should be noted that in everyday clinical practice, even after eradication of the patho gen by antibiotic treatment, about 50% of men do not recover normal sperm counts 37 . This finding is prob ably the result of asymptomatic continuation of inflammation that can affect both testes, causing permanent impairment to fertility as a result of germ cell loss or duct obstruction 38,39 .…”

The Impact of Bacterial Infections on Human Spermatozoa

“…In rats, infection with uropathogenic E. coli (UPEC) results in severely impaired spermatogenesis, characterized by, for example hypospermatogenesis, germ cell loss and reduced sperm number (79). Kaur and Prabha (69) isolated Sperm agglutination factor from S. aureus which showed sperm agglutinating and spermicidal properties in vitro.…”