Highlights d RNA-seq of oocytes and granulosa cells mapped transcriptome and signature genes d KEGG/GSEA analysis uncovered pathways involved in primordial follicle activation d Oocyte-granulosa cell interactions exhibit stage-and species-specific patterns d RNA-seq analysis identified candidate secretory biomarkers of ovarian reserve
In this work, a carbon nanotube (CNT) electrochemical filter was investigated for treatment of aqueous antibiotics using tetracycline (TC) as a model compound. Electrochemical filtration of 0.2 mM TC at a total cell potential of 2.5 V and a flow rate of 1.5 mL min(-1) (hydraulic residence time <2 s) resulted in an oxidative flux of 0.025 ± 0.001 mol h(-1) m(-2). Replacement of the perforated Ti cathode with a CNT cathode increased the TC oxidative flux by 2.3-fold to 0.020 ± 0.001 mol h(-1) m(-2) at a total cell potential of 1.0 V. Effluent analysis by liquid chromatography-mass spectrometry and disk agar biocidal diffusion tests indicate that the electrochemical filtration process can degrade the TC molecular structure and significantly decrease its antimicrobial activity, respectively. Addition of dissolved natural organic matter (NOM) negatively affected the TC electrooxidation because of competition for CNT sorption and electrooxidation sites. At 2.0 V total cell potential, TC spiked (0.2 mM) into drinking water reservoir and wastewater treatment plant effluent samples had an oxidative flux of 0.015 ± 0.001 and 0.022 ± 0.001 mol h(-1) m(-2), respectively, and an energy requirement of 0.7 kWh kgCOD(-1) or 0.084 kWh m(-3). These results indicate a CNT electrochemical filter may have potential to effectively and efficiently treat antibiotics in water and wastewater effluent.
SummaryCaseinolytic peptidase P mediates degradation of unfolded mitochondrial proteins and activates mitochondrial unfolded protein response (mtUPR) to maintain protein homeostasis. Clpp −/− female mice generate a lower number of mature oocytes and two‐cell embryos, and no blastocysts. Clpp −/− oocytes have smaller mitochondria, with lower aspect ratio (length/width), and decreased expression of genes that promote fusion. A 4‐fold increase in atretic follicles at 3 months, and reduced number of primordial follicles at 6–12 months are observed in Clpp −/− ovaries. This is associated with upregulation of p‐S6, p‐S6K, p‐4EBP1 and p‐AKT473, p‐mTOR2481 consistent with mTORC1 and mTORC2 activation, respectively, and Clpp −/− oocyte competence is partially rescued by mTOR inhibitor rapamycin. Our findings demonstrate that CLPP is required for oocyte and embryo development and oocyte mitochondrial function and dynamics. Absence of CLPP results in mTOR pathway activation, and accelerated depletion of ovarian follicular reserve.
Weaver syndrome (WS), an overgrowth/intellectual disability syndrome (OGID), is caused by pathogenic variants in the histone methyltransferase EZH2 , which encodes a core component of the Polycomb repressive complex-2 (PRC2). Using genome-wide DNA methylation (DNAm) data for 187 individuals with OGID and 969 control subjects, we show that pathogenic variants in EZH2 generate a highly specific and sensitive DNAm signature reflecting the phenotype of WS. This signature can be used to distinguish loss-of-function from gain-of-function missense variants and to detect somatic mosaicism. We also show that the signature can accurately classify sequence variants in EED and SUZ12 , which encode two other core components of PRC2, and predict the presence of pathogenic variants in undiagnosed individuals with OGID. The discovery of a functionally relevant signature with utility for diagnostic classification of sequence variants in EZH2 , EED , and SUZ12 supports the emerging paradigm shift for implementation of DNAm signatures into diagnostics and translational research.
Semen samples from men after a short ejaculatory abstinence show improved sperm quality and result in increased pregnancy rates, but the underlying mechanisms remain unclear. Herein, we report that ejaculates from short (1-3 hours) compared with long (3-7 days) periods of abstinence showed increases in motile sperm count, sperm vitality, normal sperm morphology, acrosome reaction capacity, total antioxidant capacity, sperm mitochondrial membrane potential, high DNA stainability, and a decrease in the sperm DNA fragmentation index (P < 0.05). Sperm proteomic analysis showed 322 differentially expressed proteins (minimal fold change of ±1.5 or greater and P < 0.05), with 224 up-regulated and 98 down-regulated. These differentially expressed proteins are profoundly involved in specific cellular processes, such as motility and capacitation, oxidative stress, and metabolism. Interestingly, protein trimethyllysine modification was increased, and butyryllysine, propionyllysine, and malonyllysine modifications were decreased in ejaculates from a short versus long abstinence (P < 0.05). Finally, the rates of implantation, clinical pregnancy, and live births from in vitro fertilization treatments were significantly increased in semen samples after a short abstinence. Our study provides preliminary mechanistic insights into improved sperm quality and pregnancy outcomes associated with spermatozoa retrieved after a short ejaculatory abstinence.
Hybrid composites with great potential for white light LED and temperature sensing obtained through a simple, low cost, and environmental benign way is highly desirable and remains a challengeable task. Herein we present luminescent hybrid composites both in the form of powder and transparent film by simply mixing organic sensitizer, aminoclay (AC), and lanthanide (Ln(3+)) in aqueous solution, the emission color of which can be fine-tuned by changing various parameters such as the molar ratio of Eu(3+) to Tb(3+), excitation wavelength, and the temperature. White lights with satisfied color coordinates have been achieved. The emission intensity ratio of (5)D4 → (7)F5 transition (Tb(3+)) to (5)D0 → (7)F2 transition (Eu(3+)) of the composite containing both Eu(3+) and Tb(3+) can be linearly related to temperature in the range from 78 K to 288 K. These characteristics make the composites suitable for optoelectronic devices such as thermosensors and white light LED.
Maternal effect genes play essential roles in early embryonic development. However, the mechanisms by which maternal effect genes regulate mammalian early embryonic development remain largely unknown. Recently, we identified a subcortical maternal complex (SCMC) that is composed of at least four proteins encoded by Mater, Floped, Tle6 and Filia and is critical for mouse preimplantation development. The present study demonstrates that human SCMC homologous genes (NLRP5, OOEP, TLE6 and KHDC3L) are specifically expressed in the oocytes of human fetal ovaries. The proteins of this complex co-localize in the subcortex of human oocytes and early embryos. Furthermore, the SCMC proteins physically interact with each other when they are co-expressed in cell lines. These results indicate that human NLRP5, OOEP, TLE6 and KHDC3L function as a complex in the oocytes and early embryos of Homo sapiens. Considering the important roles of the SCMC in mouse early embryogenesis, the characterization of the human SCMC will provide a basis for investigating human early embryonic development and will have clinical implications in human female infertility or recurrent spontaneous abortion.
Mitochondria affect numerous aspects of mammalian reproduction. We investigated whether the decrease in oocyte quality associated with aging is related to altered mitochondria. Oocytes from old (12 months) and young (9 weeks) C57BL/6J mice were compared in relation to: mitochondria morphology and dynamics (mitochondria density, coverage, size and shape) throughout folliculogenesis; levels of mitochondrial DNA (mtDNA); mitochondrial stress reflected in the expression of mitochondrial unfolded protein response (mt-UPR) genes; and levels of reactive oxygen species (ROS) under baseline conditions and following H2O2 treatment. In old mice, mitochondria of primary follicle-enclosed oocytes were smaller, with lower mitochondria coverage (total mitochondria µm2/µm2 cytosol area) (p<0.05). Other follicular stages showed a similar trend, but the changes were not significant. Mature oocytes (Metaphase II – MII) from old mice had significantly less mtDNA (p<0.01), and elevated mt-UPR gene Hspd1 expression (p<0.05), compared with those from young mice. ROS levels in aged MII oocytes were also higher following pretreatment with H2O2 (p<0.05). Aging is associated with altered mitochondrial morphological parameters and decreased mtDNA levels in oocytes, as well as an increase in ROS under stressful conditions and elevated expression of mitochondrial stress response gene Hspd1. Delineation of the mechanisms underlying mitochondrial changes associated with ageing may help in the development of diagnostic and therapeutic tools in reproductive medicine.
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