1-Nitropyrene exposure induces mitochondria dysfunction and impairs oocyte maturation in mice.

Oocyte quality is essential for a successful pregnancy. 1-Nitropyrene (1-NP) is a widely distributed pollutant in the environment and is well-known for its mutagenicity and carcinogenicity. However, whether 1-NP has toxic effects on mammalian oocyte quality remains unknown. In the present study, we focused on the effect of 1-NP on oocyte maturation using mouse oocytes as an in vitro model. Our study showed that 1-NP exposure disrupted the meiotic spindle assembly and caused chromosome misalignment, further impaired first polar body extrusion, and significantly decreased the fertilization capability in mouse oocytes. Further investigation showed that the mitochondrial membrane potential (MMP) and ATP levels were decreased, and the expression of genes encoding components of the mitochondrial respiratory chain was inhibited in 1-NP exposed oocytes. Meanwhile, 1-NP exposure increased the levels of reactive oxygen species (ROS), inhibited the expression of genes encoding antioxidant enzymes, and increased the frequency of early apoptotic oocytes. Overall, our data suggest that 1-NP exposure disrupts mitochondrial function and intracellular redox balance, ultimately impairing oocyte maturation. These findings reveal the adverse effect of 1-NP exposure on oocyte quality.

RNAi-Related Dicer and Argonaute Proteins Play Critical Roles for Meiocyte Formation, Chromosome-Axes Lengths and Crossover Patterning in the Fungus Sordaria macrospora.

RNA interference (RNAi) is a cellular process involving small RNAs that target and regulate complementary RNA transcripts. This phenomenon has well-characterized roles in regulating gene and transposon expression. In addition, Dicer and Argonaute proteins, which are key players of RNAi, also have functions unrelated to gene repression. We show here that in the filamentous Ascomycete Sordaria macrospora, genes encoding the two Dicer (Dcl1 and Dcl2) and the two Argonaute (Sms2 and Qde2) proteins are dispensable for vegetative growth. However, we identified roles for all four proteins in the sexual cycle. Dcl1 and Sms2 are essential for timely and successful ascus/meiocyte formation. During meiosis per se, Dcl1, Dcl2, and Qde2 modulate, more or less severely, chromosome axis length and crossover numbers, patterning and interference. Additionally, Sms2 is necessary both for correct synaptonemal complex formation and loading of the pro-crossover E3 ligase-protein Hei10. Moreover, meiocyte formation, and thus meiotic induction, is completely blocked in the dcl1 dcl2 and dcl1 sms2 null double mutants. These results indicate complex roles of the RNAi machinery during major steps of the meiotic process with newly uncovered roles for chromosomes-axis length modulation and crossover patterning regulation.

Variants in Homologous Recombination Genes EXO1 and RAD51 Related with Premature Ovarian Insufficiency.

CONTEXT: Premature ovarian insufficiency (POI) is characterized by cessation of menstruation before 40 years of age and elevated serum level of FSH (>25 IU/L). Recent studies have found a few causative genes responsible for POI enriched in meiotic recombination and DNA damage repair pathways. OBJECTIVE: To investigate the role of variations in homologous recombination genes played in POI pathogenesis. METHODS: The whole exome sequencing was performed in 50 POI patients with primary amenorrhea. Functional characterizations of the novel variants were carried out in budding yeast and human cell line. RESULTS: We identified 8 missense variants in 7 homologous recombination genes, including EXO1, RAD51, RMI1, MSH5, MSH2, MSH6, and MLH1. The mutation p.Thr52Ser in EXO1 impaired the meiotic process of budding yeast and p.Glu68Gly in RAD51-altered protein localization in human cells, both of them impaired the efficiency of homologous recombination repair for DNA double-stranded breaks in human cells. CONCLUSIONS: Our study first linked the variants of EXO1 and RAD51 with POI and further highlighted the role of DNA repair genes in ovarian dysgenesis.

Glycyrrhizin attenuates histamine-mediated MUC5AC upregulation, inflammatory cytokine production, and aquaporin 5 downregulation through suppressing the NF-κB pathway in human nasal epithelial cells.

Allergic rhinitis (AR) is a chronic respiratory inflammatory disease. Glycyrrhizin is a main bioactive component of the licorice root extract and exhibits anti-inflammatory activity. However, the role of glycyrrhizin in AR has not been studied. The aim of the present study was to investigate the effect of glycyrrhizin on histamine-induced human nasal epithelial cells (HNEpCs). Here, we found that glycyrrhizin (20 or 40 µM) inhibited histamine-induced the mRNA expression and secretion of mucin 5 subtype AC (MUC5AC), interleukin (IL)-6 and IL-8 in HNEpCs. The expression levels of aquaporin 5 (AQP5) and phosphorylated cyclic adenosine monophosphate-responsive element binding protein (p-CREB) were decreased by histamine in HNEpCs and increased in cells treated with glycyrrhizin. The glycyrrhizin treatment inhibited histamine-induced expressions of p-NF-κB p65 and p-IκBα in HNEpCs, indicating that glycyrrhizin inhibited the activation of NF-κB pathway in histamine-induced HNEpCs. In addition, inhibition of the NF-κB pathway exhibited the similar effect with glycyrrhizin on histamine-induced HNEpCs. In summary, the results showed that glycyrrhizin reversed the effect of histamine on MUC5AC expression, inflammatory cytokine production, and AQP5 expression in HNEpCs, and the NF-κB pathway was involved in the effect. Glycyrrhizin might be used for complementary and alternative therapeutics of AR.

The rice OsRad21-4, an orthologue of yeast Rec8 protein, is required for efficient meiosis.

In yeast, Rad21/Scc1 and its meiotic variant Rec8 are key players in the establishment and subsequent dissolution of sister chromatid cohesion for mitosis and meiosis, respectively, which are essential for chromosome segregation. Unlike yeast, our identification revealed that the rice genome has 4 RAD21-like genes that share lower than 21% identity at polypeptide levels, and each is present as a single copy in this genome. Here we describe our analysis of the function of OsRAD21-4 by RNAi. Western blot analyses indicated that the protein was most abundant in young flowers and less in leaves and buds but absent in roots. In flowers, the expression was further defined to premeiotic pollen mother cells (PMCs) and meiotic PMCs of anthers. Meiotic chromosome behaviors were monitored from male meiocytes of OsRAD21-4-deficient lines mediated by RNAi. The male meiocytes showed multiple aberrant events at meiotic prophase I, including over-condensation of chromosomes, precocious segregation of homologues and chromosome fragmentation. Fluorescence in situ hybridization experiments revealed that the deficient lines were defective in homologous pairing and cohesion at sister chromatid arms. These defects resulted in unequal chromosome segregation and aberrant spore generation. These observations suggest that OsRad21-4 is essential for efficient meiosis.