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The development of life beyond planet Earth is a long-standing quest of the human race, but whether normal mammalian embryonic development can occur in space is still unclear. Here, we show unequivocally that preimplantation mouse embryos can develop in space, but the rate of blastocyst formation and blastocyst quality are compromised. Additionally, the cells in the embryo contain severe DNA damage, while the genome of the blastocysts developed in space is globally hypomethylated with a unique set of differentially methylated regions. The developmental defects, DNA damage and epigenetic abnormalities can be largely mimicked by the treatment with ground-based low-dose radiation. However, the exposure to simulated microgravity alone does not cause major disruptions of embryonic development, indicating that radiation is the main cause for the developmental defects. This work advances the understanding of embryonic development in space and reveals long-term extreme low-dose radiation as a hazardous factor for mammalian reproduction.

Purpose of the study: To observe the dynamic changes in monocyte subsets during septic lung injury and to assess the anti-inflammatory role of the sulfotransferase homolog 2 (ST2) receptor. Materials and Methods: Dynamic changes of monocyte subsets from patients with septic lung injury and mice post-cecal ligation and puncture (CLP) were monitored. ST2 receptors on mice monocytes and concentrations of IL-33, IL-1β, IL-12, and IL-27 from peripheral blood or culture supernatant were detected. Results: CD14lowCD16− (Mo0) and CD14++CD16+ (Mo2) monocyte subsets were significantly expanded in patients with sepsis-related acute respiratory distress syndrome. In sepsis model mice, monocyte counts, particularly of Ly6Cint and CDLy6Cint+hi monocytes, were significantly increased. The mean optical density value of TNF-α after CLP mainly increased after 24 h, whereas that of IL-6 was significantly increased at all time points assessed after CLP. The levels of IL-1β, IL-12, IL-27, and IL-33 increased to variable degrees at 6, 12, 24, and 48h after CLP, and ST2+ monocytes were significantly expanded in sepsis model mice compared to sham-operated mice. ST2 receptor blockade suppressed IL-1β and IL-12 production in cell culture. Conclusions: Changes in monocyte subsets expressing the ST2 receptor play an important role in septic lung injury by modulating inflammatory cytokine secretion. [ABSTRACT FROM AUTHOR]

Adipose tissue formation and moderate fat deposition are important for the production performance and eating quality of livestock meats. The self-renewal and adipogenic differentiation of adipose-derived stem cells are responsible for the formation and development of adipose tissue. In addition, estrogen targeting G protein-coupled estrogen receptor 1 (GPER1) has been reported to modulate cell proliferation and differentiation during tissue and organ development. However, the potential correlation among estrogen, GPER1, proliferation, and adipogenic differentiation in goat adipose-derived stem cells (gADSCs) is still unclear. Herein, we demonstrated that 17β-estradiol enhances the proliferative ability of gADSCs, indicated by the increased cell number and cell viability, accompanied by up-regulated expressions of cyclin D1 and PCNA. Meanwhile, the adipogenic differentiation is promoted by 17β-estradiol, supported by higher ccumulation of intracellular lipids and increased expressions of PPARγ, ACC, and FABP4. Notably, these activities are all obviously reduced by administration with GPER1 antagonist G15, but GPER1 agonist G1 enhances cell proliferation and adipogenic differentiation. Moreover, GPER1 silencing diminishes cell proliferation and adipogenic differentiation. In parallel, 17β-estradiol elevates the protein level of nuclear p-p65. Furthermore, the phosphorylation of p65 is enhanced by G1 but inhibited by G15 and GPER1 silencing. In addition, the phosphorylation of p65 is mediated by ERK1/2, suggesting that estrogen targeting GPER1 regulates cell proliferation and adipogenic differentiation of gADSCs through the ERK1/2-NF-κB signaling pathway. This study may provide a strong theoretical basis for improving meat quality, flavor, and cold resistance of livestock.

Estrogen is a steroid hormone that plays a key role in regulating many physiological processes, such as follicle activation and development and oocyte maturation in mammals. Ca2+ is crucial in oogenesis, oocyte maturation, ovulation, and fertilization. However, the mechanism by which estrogen regulates Ca2+ during oocyte maturation in mice has not been reported. This study revealed that Ca2+ levels in oocytes significantly increase during the 4–12 h period in vitro. Oocytes treated with 0.1 µM estrogen and 1 µM G1, a G-protein-coupled estrogen receptor (GPER) agonist, showed significantly increased Ca2+ levels, while treatment with 1 µM G15, an antagonist of GPER, significantly decreased Ca2+ levels. Notably, estrogen regulates Ca2+ in oocytes through the GPER pathway and promotes the expression of the Ca2+-producing protein EPAC1. In addition, estrogen alleviates the inhibitory effect of the Ca2+ chelator BAPTA-AM during oocyte maturation by promoting Ca2+ production. Furthermore, estrogen can promote the expression of the mitochondrial generation-associated protein SIRT1 through the GPER pathway, alleviate mitochondrial oxidative damage caused by BAPTA-AM, and restore the mitochondrial membrane potential level. Collectively, this study demonstrates that estrogen can regulate Ca2+ through the GPER-EPAC1 pathway and promote the expression of SIRT1, which promotes oocyte mitochondrial function during oocyte maturation. [ABSTRACT FROM AUTHOR]

Estrogen has been implicated in multiple biological processes, but the variation underlying estrogen‐mediated primordial follicle (PF) formation remains unclear. Here, we show that 17β‐estradiol (E2) treatment of neonatal mice led to the inhibition of PF formation and cell proliferation. Single‐cell RNA sequencing (scRNA‐seq) revealed that E2 treatment caused significant changes in the transcriptome of oocytes and somatic cells. E2 treatment disrupted the synchronised development of oocytes, pre‐granulosa (PG) cells and stromal cells. Mechanistically, E2 treatment disrupted several signalling pathways critical to PF formation, especially down‐regulating the Kitl and Smad1/3/4/5/7 expression, reducing the frequency and number of cell communication. In addition, E2 treatment influenced key gene expression, mitochondrial function of oocytes, the recruitment and maintenance of PG cells, the cell proliferation of somatic cells, as well as disordered the ovarian microenvironment. This study not only revealed insights into the regulatory role of estrogen during PF formation, but also filled in knowledge of dramatic changes in perinatal hormones, which are critical for the physiological significance of understanding hormone changes and reproductive protection. [ABSTRACT FROM AUTHOR]