Most gene functions have been discovered through phenotypic observations under loss of function experiments that lack temporal control. However, cell signaling relies on limited transcriptional effectors, having to be re-used temporally and spatially within the organism. Despite that, the dynamic nature of signaling pathways have been overlooked due to the difficulty on their assessment, resulting in important bottlenecks.
View Article and Find Full Text PDFPrenatal exposure to Di (2-ethylhexyl) phthalate (DEHP) impairs the reproductive system and causes fertility defects in male offspring. Additionally, high-fat (HF) diet is a risk factor for reproductive disorders in males. In this study, we tested the hypothesis that prenatal exposure to a physiologically relevant dose of DEHP in conjunction with HF diet synergistically impacts reproductive function and fertility in male offspring.
View Article and Find Full Text PDFUncovering the mechanisms regulating hematopoietic specification not only would overcome current limitations related to hematopoietic stem and progenitor cell (HSPC) transplantation, but also advance cellular immunotherapies. However, generating functional human induced pluripotent stem cell (hiPSC)-derived HSPCs and their derivatives has been elusive, necessitating a better understanding of the developmental mechanisms that trigger HSPC specification. Here, we reveal that early activation of the Nod1-Ripk2-NF-kB inflammatory pathway in endothelial cells (ECs) primes them to switch fate towards definitive hemogenic endothelium, a pre-requisite to specify HSPCs.
View Article and Find Full Text PDFRes Vet Sci
November 2023
While the importance of respiratory microbiota in maintaining respiratory health is increasingly recognized, we still lack a comprehensive understanding of the unique characteristics of respiratory microbiota specific to individual hosts. This study aimed to address this gap by analyzing publicly available 16S rRNA gene datasets from various domestic animals (cats, dogs, pigs, donkeys, chickens, sheep, and cattle) to identify host-specific signatures of respiratory microbiota. The findings revealed that cattle and pigs exhibited the highest Shannon diversity index and observed features, indicating a greater microbial variety compared to other animals.
View Article and Find Full Text PDFReproductive sterilization by surgical gonadectomy is strongly advocated to help manage animal populations, especially domesticated pets, and to prevent reproductive behaviors and diseases. This study explored the use of a single-injection method to induce sterility in female animals as an alternative to surgical ovariohysterectomy. The idea was based on our recent finding that repetitive daily injection of estrogen into neonatal rats disrupted hypothalamic expression of Kisspeptin (KISS1), the neuropeptide that triggers and regulates pulsatile secretion of GnRH.
View Article and Find Full Text PDFEstrogen is a disease-modifying factor in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE) via estrogen receptor alpha (ERα). However, the mechanisms by which ERα signaling contributes to changes in disease pathogenesis have not been completely elucidated. Here, we demonstrate that ERα deletion in dendritic cells (DCs) of mice induces severe neurodegeneration in the central nervous system in a mouse EAE model and resistance to interferon beta (IFNβ), a first-line MS treatment.
View Article and Find Full Text PDFCleavage Under Targets and Release Using Nuclease (CUT&RUN) has emerged as a chromatin profiling strategy that excels traditional methods. Although CUT&RUN has been widely utilized in mammalian cells, its use in the zebrafish is at its early stages. In this study, we have developed a protocol to successfully perform CUT&RUN to map transcription factor (TF) binding sites in embryonic, adult tissues, and FACS-sorted zebrafish cells.
View Article and Find Full Text PDFDi(2-ethylhexyl) phthalate (DEHP) is a chemical commonly used as a plasticizer to render polyvinyl chloride products more durable and flexible. Although exposure to DEHP has raised many health concerns due to the identification of DEHP as an endocrine disruptor, it is still used in consumer products, including polyvinyl chloride plastics, medical tubing, car interiors, and children's toys. To investigate the impact of early life exposure to DEHP on the ovary and testes, newborn piglets were orally dosed with DEHP (20 or 200 mg/kg/day) or vehicle control (tocopherol-stripped corn oil) for 21 days.
View Article and Find Full Text PDFGlobally, ischemic stroke is a leading cause of death and adult disability. Previous efforts to repair damaged brain tissue following ischemic events have been hindered by the relative isolation of the central nervous system. We have developed a gelatin nanoparticle-mediated intranasal drug delivery system as an efficient, non-invasive method for delivering 17β-estradiol (E2) specifically to the brain, enhancing neuroprotection, and limiting systemic side effects.
View Article and Find Full Text PDFBovine respiratory microbiota plays a significant role in bovine respiratory health. We conducted a meta-analysis using publicly available 16S rRNA gene datasets from the respiratory tract to characterize respiratory microbiota in feedlot cattle. Our aims were to determine the factors that influence microbiota development and to assess the differences in microbiota composition and diversity between healthy calves and those that developed bovine respiratory disease (BRD).
View Article and Find Full Text PDFOvulation is triggered by the gonadotropin surge that induces the expression of two key genes, progesterone receptor (Pgr) and prostaglandin-endoperoxide synthase 2 (Ptgs2), in the granulosa cells of preovulatory follicles. Their gene products PGR and PTGS2 activate two separate pathways that are both essential for successful ovulation. Here, we show that the PGR plays an additional essential role: it attenuates ovulatory inflammation by diminishing the gonadotropin surge-induced Ptgs2 expression.
View Article and Find Full Text PDFIn males, defective reproductive traits induced by an exposure to an endocrine disruptor are transmitted to future generations via epigenetic modification of the germ cells. Interestingly, the impacted future generations display a wide range of heterogeneity in their reproductive traits. In this study, the role that the Y chromosome plays in creating such heterogeneity is explored by testing the hypothesis that the Y chromosome serves as a carrier of the exposure impact to future generations.
View Article and Find Full Text PDFEndocrine disrupting chemicals (EDCs) in the environment are considered to be a contributing factor to the decline in the sperm quality. With growing evidence of the harmful effects of EDCs on the male reproductive system, we tested the hypothesis that prenatal exposure to an environmentally relevant phthalate mixture adversely affects reproductive outcomes and androgen synthesis. In this study, an environmentally relevant composition of phthalates (15% DiNP, 21% DEHP, 36% DEP, 15% DBP, 8% DiBP, and 5% BBzP) that were detected in urine samples of pregnant women in Illinois, United States, was used.
View Article and Find Full Text PDFSanitary pads and diapers are made of synthetic plastic materials that can potentially be released while being used. This study measured the amounts of volatile organic compounds (VOCs) (methylene chloride, toluene, and xylene) and phthalates (DBP, DEHP, DEP, and BBP) contained in sanitary pads and diapers. In sanitary pads, 5,900- and 130-fold differences of VOC and phthalate concentrations were seen among the brands.
View Article and Find Full Text PDFHost-rumen-microbe interactions are essential components of many physiological processes, and therefore can affect ruminant health. Classical knowledge of rumen microbiology is based on culture-dependent methodologies, which only account for 10-20% of the rumen bacterial communities. While, the advancement in DNA sequencing and bioinformatics platforms provide novel approaches to investigate the composition and dynamics of the rumen microbiota.
View Article and Find Full Text PDFPhthalates are a family of synthetic chemicals that are used in producing a variety of consumer products. Di-(2-ethylhexyl) phthalate (DEHP) is an widely used phthalate and poses a public health concern. Prenatal exposure to DEHP has been shown to induce premature reproductive senescence in animal studies.
View Article and Find Full Text PDFEstradiol (17β-estradiol) is synthesized primarily in the gonads of both sexes and regulates the development and function of reproductive organs. Recently, we reported that intestinal lymphocyte homeostasis is regulated by estradiol synthesized in the endothelial cells of the high endothelial venules (HEVs) of mesenteric lymph nodes and Peyer's patches in mice. This observation prompted us to hypothesize that HEVs of intestinal lymphoid tissues are sites of estradiol synthesis across species.
View Article and Find Full Text PDFDi-(2-ethylhexyl) phthalate (DEHP) is the most commonly used phthalate, and it is an endocrine-disrupting chemical. This study tested a hypothesis that prenatal exposure to DEHP lays the foundation for premature gonadal dysfunction and subsequent reproductive senescence in male mice. Pregnant female CD-1 mice were orally dosed with vehicle control (tocopherol-stripped corn oil) or with 20 μg/kg/day, 200 μg/kg/day, 500 mg/kg/day, or 750 mg/kg/day of DEHP from gestational day 11 to birth.
View Article and Find Full Text PDF17β-estradiol is a potent sex hormone synthesized primarily by gonads in females and males that regulates development and function of the reproductive system. Recent studies show that 17β-estradiol is locally synthesized in nonreproductive tissues and regulates a myriad of events, including local inflammatory responses. In this study, we report that mesenteric lymph nodes (mLNs) and Peyer's patches (Pps) are novel sites of de novo synthesis of 17β-estradiol.
View Article and Find Full Text PDFEstrogens are the key hormones regulating the development and function of reproductive organs in all vertebrates. Recent evidence indicates that estrogens play important roles in the immune system, cancer development, and other critical biological processes related to human well-being. Obviously, the gonads (ovary and testis) are the primary sites of estrogen synthesis, but estrogens synthesized in extra- gonadal sites play an equally important role in controlling biological activities.
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