Autophagy: A Double-Edged Sword in Male Reproduction

Abstract

Autophagy, an evolutionarily conserved cell reprogramming mechanism, exists in all eukaryotic organisms. It is a fundamental and vital degradation/recycling pathway that removes undesirable components, such as cytoplasmic organelles, misfolded proteins, viruses, and intracellular bacteria, to provide energy and essential materials for organisms. The success of male reproduction depends on healthy testes, which are mainly composed of seminiferous tubules and mesenchyme. Seminiferous tubules are composed of Sertoli cells (SCs) and various germ cells, and the main functional part of mesenchyme are Leydig cells (LCs). In recent years, a large amount of evidence has confirmed that autophagy is active in many cellular events associated with the testes. Autophagy is not only important for testicular spermatogenesis, but is also an essential regulatory mechanism for the ectoplasmic specialization (ES) integrity of SCs, as well as for the normal function of the blood–testes barrier (BTB). At the same time, it is active in LCs and is crucial for steroid production and for maintaining testosterone levels. In this review, we expanded upon the narration regarding the composition of the testes; summarized the regulation and molecular mechanism of autophagy in SCs, germ cells, and LCs; and concluded the roles of autophagy in the process of spermatogenesis and testicular endocrinology. Through integrating the latest summaries and advances, we discuss how the role of autophagy is a double-edged sword in the testes and may provide insight for future studies and explorations on autophagy in male reproduction.

Octanoic acid mitigates busulfan-induced blood-testis barrier damage by alleviating oxidative stress and autophagy

“…Contrary to the results presented in this study, Wei and colleagues observed that busulfan suppresses autophagy by halting the breakdown of autophagosomes, leading to the impairment of spermatogonial cells [ 39 ]. However, this finding does not contradict this study, as the effect of autophagy on male fertility is twofold [ 40 ]. Optimal autophagy can shield cells effectively from unfavorable environmental conditions, such as hypoxia, a lack of nutrients, oxidative stress, or the buildup of misfolded proteins.…”

Gut microbiota and its metabolic products in acute respiratory distress syndrome

“…Cellular autophagy is often characterized as a 'double-edged sword' in various diseases and biological processes. It serves a protective role when functioning within normal limits but can become detrimental when overactivated (84,85). The alteration of gut microbiota interacts with cellular autophagy, contributing to disease development.…”

Potential role of autophagy in the male reproductive system

“…Understanding the particular autophagic responses to various stressors in the male reproductive system sheds light on prospective therapeutic techniques for reducing the negative effects of environmental insults on fertility. The male reproductive system, which includes the testes and epididymis, is a dynamic environment in which autophagy helps to regulate cellular remodeling and energy balance [3,52,53]. Autophagy in the testes helps to remove damaged or extra organelles, allowing for the creation of high-quality sperm.…”

“…Autophagy, a conserved catabolic mechanism necessary for the maintenance of cellular equilibrium, has emerged as an important factor in a variety of physiological and pathological conditions [1,2]. While autophagy has been extensively investigated in the context of cellular maintenance and stress response, it has recently received a lot of attention for its role in the male reproductive system [3,4]. Understanding the complex connection between autophagy and male reproductive systems holds the prospect of yielding new insights into fertility, sperm production, and testicular health.…”