Remodeling of Gut Microbiota by Probiotics Alleviated Heat Stroke-Induced Necroptosis in Male Germ Cells.

SCOPE: Systemic heat stress (or heatstroke; HS) induces germ cell death and spermatogenesis disorders in men and male mammals. Also, it affects the immune environment of the circulatory system promoting gut inflammation and intestinal permeability, leading to pathogenic infection. In this study, the crosstalk between the gut and testis (gut-testis axis) under HS is explored, by examining the effects of intestinal immune status on the health of the male reproductive system in mice. METHODS AND RESULTS: A mouse model of systemic heat stress is established to investigate the effect of probiotics on testis health. The results reveal that pro-inflammatory factor receptor activation pathway and pathogen infection response pathway are significantly upregulated in HS testes, leading to necroptosis, while pro-inflammatory factor and endotoxin are detected locally in the intestine and then entered the blood. The study then uses probiotics to intervene in gut microbiota, which results in milder gut microbial changes, lower inflammatory responses in the HS gut, and less necroptosis in the HS testes. CONCLUSION: Probiotics-based remodeling of gut microbiota (GM) reduces the proliferation of abnormal bacteria and decreases the spread of gut-derived inflammatory mediators into the blood circulation under long-term systemic heat stress, which relieves inflammation on germ cells.

Gut microbiota supports male reproduction via nutrition, immunity, and signaling.

Gut microbiota (GM) is a major component of the gastrointestinal tract. Growing evidence suggests that it has various effects on many distal organs including the male reproductive system in mammals. GM and testis form the gut-testis axis involving the production of key molecules through microbial metabolism or de novo synthesis. These molecules have nutrition, immunity, and hormone-related functions and promote the male reproductive system via the circulatory system. GM helps maintain the integral structure of testes and regulates testicular immunity to protect the spermatogenic environment. Factors damaging GM negatively impact male reproductive function, however, the related mechanism is unknown. Also, the correlation between GM and testis remains to be yet investigated. This review discusses the complex influence of GM on the male reproductive system highlighting the impact on male fertility.

Melatonin alleviates heat stress-induced testicular damage in dairy goats by inhibiting the PI3K/AKT signaling pathway.

Current measures mainly focus on how melatonin reduces physiological heat stress in animals, but its effects on reproductive damage to male dairy goats have been neglected. This study aimed to determine the protective effect of melatonin on male reproduction during heat stress in dairy goats and to further explore its mechanisms. A natural heat stress model of Saanen dairy goats was used to assess testicular tissue damage 7 days after heat stress and to examine semen quality changes during a spermatogenic cycle. RNA-seq, Western blot, RT-qPCR, and immunofluorescence staining were used to explore the mechanism by which melatonin protects against heat stress-induced reproductive damage and to validate the results. The data suggested that melatonin significantly alleviated the heat stress-induced decrease in sperm quality, protected varicose tubule structure, reduced the levels of heat shock proteins and apoptotic proteins and protected the spermatocytes and round spermatozoa, which are mainly affected by heat stress. RNA-seq results suggest that melatonin inhibits the PI3K/AKT signaling pathway, reduces the level of p-AKT, and promotes elevated BCL-2. In addition, melatonin treatment could upregulate the gene expression of MT2 which was downregulated by heat stress and improve the change in extracellular matrix components and restore serum testosterone levels. Our results suggest that melatonin can protect against testicular and spermatogenic cell damage and improve semen quality in male dairy goats under heat stress. This study provides an important reference for subsequent studies on the molecular mechanisms of melatonin in protecting male reproductive processes under heat stress and using exogenous melatonin to prevent heat stress.

Nrf2 activation mediates the protection of mouse Sertoli Cells damage under acute heat stress conditions.

Heat stress is known to negatively impact the reproductive process of livestock, which inevitably leads to a decline in animal fertility. Nuclear factor E2-related factor 2 (Nrf2) is an inducible transcription factor, which is essential for maintaining redox signal transmission against oxidative stress. However, there is no reliable research on the response mechanism of Sertoli Cells (SCs) against heat stress and the activation of Nrf2 when SCs are exposed to heat stress. Here, we used primary mouse SCs and SCs line TM4, along with Nrf2 specific inhibitor to determine the reaction mechanism of SCs to maintain intracellular redox homeostasis and self-survival by activating Nrf2. We found that acute heat stress only affected the vitality of SCs and the expression of functional molecules (tight junction-associated proteins and lactate dehydrogenase A [LDHA]) but did not cause cell apoptosis. When Nrf2 was inhibited, more cell death occurred in TM4 cells post heat stress treatment, along with a greater decrease in cell viability and a significant increase in intracellular ROS levels. Our study clarified for the first time the protective effect of Nrf2 activation on heat stress-induced SCs damage. It explained the possible reasons or mechanisms involved in the survival of SCs, the critical protective cells in the testis, which were not affected by heat stress. This study further improved the response mechanism of SCs in the reproductive injury caused by a high-temperature environment.