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The morbidity of polycystic ovary syndrome (PCOS) is in highly increasing rate nowadays. PCOS not only affects the fertility in women, but also threatens the health of whole life. Hence, to find the prognostic risk factors is of great value. However, the effective predictors in clinical practice of PCOS are still in blackness. In this study, we found Klotho (KL) was increased in follicular fluid (FF) and primary luteinized granulosa cells (GCs) from PCOS patients with hyperandrogenism. Furthermore, we found follicular KL was negatively correlated with numbers of mature oocytes, and positively correlated with serum testosterone, LH, and LH/FSH levels menstrual cycle and number of total antral follicles in PCOS patients. In primary luteinized GCs, the increased KL was accompanied with upregulation of cell apoptosis and inflammation-related genes. In ovaries of PCOS mice and cultured human KGN cell line, KL was up-regulated and accompanied by apoptosis, inflammation, and mitochondrial dysfunction. Therefore, our findings suggest new mechanisms for granulosa cell injury and revealed to target inhibit KL maybe a new therapeutic strategy for treatment of PCOS., (© The Author(s) 2024. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Ovarian endometrioma (OE) is a common gynecological condition characterized by the formation of "chocolate cysts". Recent research indicates that the cyst fluid acts as a "toxic environment" for the ovary and plays a significant role in the development of OE, with macrophages being pivotal. However, the specific molecular and cellular mechanisms of it are not fully understood. In this study, clinical samples are integrated, single-cell sequencing, in vivo and in vitro experimental models to comprehensively investigate the effects of OE fluid on ovarian function and the mechanisms of it. Combined with bioinformatics analysis and experimental validation, the findings demonstrate that OE fluid can cause ovarian function decline, which associated with inflammatory response, and mitochondrial dysfunction and cellular senescence, while activating the cGAS/STING signaling pathway. As a STING inhibitor, H-151 effectively alleviates ovarian dysfunction, inflammatory state and cell apoptosis induced by OE fluid. Furthermore, it is also discovered that H-151 can inhibit OE fluid-induced mitochondrial dysfunction and cellular senescence. These findings provide important theoretical and experimental foundations for further research and development of STING inhibitors as potential drugs for treating ovarian dysfunction., (© 2024 Wiley‐VCH GmbH.)

Background: Diabetic peripheral neuropathy (DPN) is considered one of the most common chronic complications of diabetes. Impairment of mitochondrial function is regarded as one of the causes. Iron–sulfur clusters are essential cofactors for numerous iron–sulfur (Fe-S)-containing proteins/enzymes, including mitochondrial electron transport chain complex I, II, and III and aconitase. Methods: To determine the impact of hyperglycemia on peripheral nerves, we used Schwann-like RSC96 cells and classical db/db mice to detect the expression of Fe-S-related proteins, mitochondrially enzymatic activities, and iron metabolism. Subsequently, we treated high-glucose-induced RSC96 cells and db/db mice with pioglitazone (PGZ), respectively, to evaluate the effects on Fe-S cluster biogenesis, mitochondrial function, and animal behavior. Results: We found that the core components of Fe-S biogenesis machinery, such as frataxin (Fxn) and scaffold protein IscU, significantly decreased in high-glucose-induced RSC96 cells and db/db mice, accompanied by compromised mitochondrial Fe-S-containing enzymatic activities, such as complex I and II and aconitase. Consequently, oxidative stress and inflammation increased. PGZ not only has antidiabetic effects but also increases the expression of Fxn and IscU to enhance mitochondrial function in RSC96 cells and db/db mice. Meanwhile, PGZ significantly alleviated sciatic nerve injury and improved peripheral neuronal behavior, accompanied by suppressed oxidative stress and inflammation in the sciatic nerve of the db/db mice. Conclusions: Iron–sulfur cluster deficiency may contribute to hyperglycemia-mediated DPN. [ABSTRACT FROM AUTHOR]

[Display omitted] • The first single-cell transcriptomic atlases of testes of young and old mice were constructed. • Revealed aging-associated heterogenous differentially expressed genes in mouse testes. • Discovered aging-associated dysregulation of multiple biological processes in mouse testes. • Aging disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia. • Aging increased a subtype of aging-specific macrophages. Advanced paternal age of reproduction is an increasing trend, especially in developed countries and areas. This trend results in elevated risks of adverse reproductive outcomes such as reduced fertility rates, increased pregnancy loss, and poor childhood health. Yet, a systematic profiling of aging-associated molecular and cellular alterations in testicular tissue is still missing. We aimed to dissect aging-associated molecular characteristics in testes of mice. Single-cell transcriptomic sequencing and analysis were conducted in testes of young (2 months old) and old mice (24 months old). Immunofluorescences and immunochemistry were used to characterize aging-associated phenotypes and verify single cell sequence results. Here, we constructed the first single-cell transcriptomic atlases of testes of young and old mice. In-depth dissection of aging-dependent transcriptional alterations in specific cell types revealed multiple dysregulated biological processes such as increased 'senescence-associated secretory phenotype' and 'inflammation', which were major aging-associated characteristics. Further analysis of aging-related differentially expressed genes uncovered a disrupted balance of undifferentiated and differentiated spermatogonia stem cells in spermatogonia, indicative of a potential role of spermatogonia stem cells in aging-associated subfertility. Importantly, for the first time, our results identified an increased subtype of aging-specific macrophages, which may contribute to a hostile proinflammatory microenvironment during testicular aging. Taken together, our findings depict the distinct single-cell transcriptional features of the aged mouse testes and provide enormous resources for a comprehensive understanding of the cell-type-specific molecular mechanisms underlying mouse testicular aging, which may shed light on developing novel potential diagnostic biomarkers and therapeutic targets for age-associated male subfertility. [ABSTRACT FROM AUTHOR]