Title : Studies on microbial infections associated with azoospermia in male mouse model and multifaceted insights into the potential mechanisms of spermatogenic failure
Abstract:
Male infertility, an intricate interplay of genetic, anatomical, and environmental factors, underscores the notable influence of urogenital infections. Azoospermia, a multifactorial disorder characterized by absence of sperm in seminal plasma, silently challenges reproductive health, thwarting parenthood aspirations. It is categorized into obstructive azoospermia (OA) and non-obstructive azoospermia (NOA) and recent evidences highlight the substantial role of microbial infections in both OA and NOA development, with more attention traditionally given to OA. Notably, the etiological understanding of idiopathic NOA remains elusive despite extensive research. Focusing on this untapped scientific landscape, this study explores the relationship between uropathogens and NOA.
The representative sperm impairing uropathogens viz., sperm-agglutinating (SA) Escherichia coli, Klebsiella pneumoniae, and Serratia marcescens, and sperm-immobilizing (SI) Staphylococcus aureus, already available in the laboratory were used for intratesticular administration into male mice exclusively in the right testis with an inoculum of 108 cfu in 20 µl PBS and for control groups, 20 µl of PBS alone, was administered. On the 7th day, the mice were euthanized and the bacterial load within the reproductive tissues, namely the testis, epididymis, and vas deferens was quantified to discern the bacterial migration across these reproductive organs. Bacterial enumeration revealed a conspicuous pattern in the bacterial log cfu/g, displaying a descending sequence.
This progression was observed from the right set of tissues-specifically, from the right testis to right epididymis followed by the right vas deferens and reverse pattern was observed on the left side, from the left vas deferens to the left testis via left epididymis. Moreover, as expected, right set of reproductive organs showed higher bacterial count as compared to the left set. However, mice subjected to PBS administration exhibited a complete absence of viable counts. To illustrate the impact of uropathogens colonization on the spermiogram of mice from right and left vas deferens, fundamental parameters including sperm count, motility and viability % were evaluated. As compared to the control groups, right vas deferens of test groups inoculated with SA microorganisms exhibited zero sperm count as evident by the absence of spermatozoa (azoospermia) and, therefore, none of the seminal parameters could be evaluated.
However, for SI inoculated test group, significant reduction in the sperm count on the right side was observed exhibiting significantly reduced motility and viability percentages. Furthermore, only minimal presence of sperm count was observed on the left side for SA/SI inoculated test groups. The few sperms detected on the left side were predominantly immotile or nonviable. The histopathological examination of the testis of test groups showed altered histology indicating severe hypospermatogenesis and serum testosterone levels exhibited a prominent reduction.
To comprehend alternative mechanisms influenced by SA and SI on spermatogenesis, oxidative stress when evaluated through malondialdehyde (MDA) levels, catalase (CAT) activity, peroxidase (POD) activity, showed significantly high levels and glutathione (GSH) and superoxide dismutase (SOD) levels exhibited a decline. In conclusion, serum testosterone levels and ROS can act as important biomarkers in diagnosing azoospermia and may have promising implications for treatment strategies aimed at addressing male infertility caused by uropathogens.
Audience Take Away:
- The audience will learn that uropathogenic microorganisms can be one of the causative agents of azoospermia leading to male infertility.
- This study also provides the probable mechanism of azoospermia caused by microorganisms.
- Interventions that mitigate oxidative stress could offer new avenues for enhancing male fertility and improving the quality of life for affected individuals.