Background Recently, human infertility incidence is increasing in obese women causing it to become an emerging global health challenge requiring improved treatment. There is extensive evidence that obesity caused female reproductive dysfunction is accompanied by an endocrinological influence. Besides, systemic and tissue-specific chronic inflammatory status are common characteristics of obesity. However, the underlying molecular mechanism is unclear linking obesity to infertility or subfertility. Methods To deal with this question, we created an obese mouse model through providing a high fat diet (HFD) and determined the fertility of the obese mice. The morphological alterations were evaluated in both the reproductive glands and tracts, such as uterus, ovary and oviduct. Furthermore, to explore the underlying mechanism of these functional changes, the expressions of pro-inflammatory cytokines as well as the activations of MAPK signaling and NF-κB signaling were detected in these reproductive tissues. Results The obese females were successful construction and displayed subfertility. They accumulated lipid droplets and developed morphological alterations in each of their reproductive organs including uterus, ovary and oviduct. These pathological changes accompanied increases in pro-inflammatory cytokine expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in all of these sites. Such effects also accompanied increases in nuclear factor kappa B (NF-kB) expression and mitogen-activated protein kinase (MAPK) signaling pathway stimulation based on uniform time dependent increases in the NF-κB (p-NF-κB), JNK (p-JNK), ERK1/2 (p-ERK) and p38 (p-p38) phosphorylation status. Conclusions These HFD-induced increases in pro-inflammatory cytokine expression levels and NF-κB and MAPKs signaling pathway activation in reproductive organs support the notion that increases of adipocytes resident and inflammatory status are symptomatic of female fertility impairment in obese mice.
Background Mammalian sperm maturation in the epididymis is mainly modulated by exosomes that are secreted into the epididymal lumen from epididymal epithelial cells (EECs). Exposure to oxidative stress (OS) resulting from being fed a high fat diet (HFD) reduces sperm fertility, which is one of the cause inducing male infertility. Thus, we hypothesize that stress-induced changes in exosome content play a critical role in mediating this detrimental process. Methods An obese mouse model was established by feeding a HFD. Then oxidative stress status was measured in the mouse caput epididymis, epididymal fluid and spermatozoa. Meanwhile, epididymis-derived purified exosomes were isolated and validated. Subsequently, liquid chromatography tandem mass spectrometry (LC-MS) was used to perform proteomic analysis of purified exosomes. Gene Ontology (GO) analysis was performed along with pathway enrichment to identify differentially expressed proteins (DEPs). Results Two hundred and two DEPs mostly related to endoplasmic reticulum (ER) function were identified in the exosomes separated from the epididymis of control mice and obese mice. The ER stress and CD63 (an exosome marker), both increased in the caput epididymis of obese mice. Furthermore, an in vitro study showed that palmitic acid (PA), an-oxidative stress inducer, increased exosome biogenesis and secretion in the EECs. Conclusion Oxidative stress in the epididymal microenvironment induces ER stress in the EECs. This effect alters the epididymis-derived exosome content, profile and amounts of their differentially expressed ER proteins. Such changes may affect exosome biogenesis and cargo packaging, finally leading to abnormalities in sperm maturation and fertility.
Background: Recently, human infertility incidence is increasing in obese women causing it to become an emerging global health challenge requiring improved treatment. There is extensive evidence that obesity caused female reproductive dysfunction is accompanied by an endocrinological influence. Besides, systemic and tissue-specific chronic inflammatory status are common characteristics of obesity. However, the underlying molecular mechanism is unclear linking obesity to infertility or subfertility.Methods: To deal with this question, we created an obese mouse model through providing a high fat diet (HFD) and determined the fertility of the obese mice. The morphological alterations were evaluated in both the reproductive glands and tracts, such as uterus, ovary and oviduct. Furthermore, to explore the underlying mechanism of these functional changes, the expressions of pro-inflammatory cytokines as well as the activations of MAPK signaling and NF-κB signaling were detected in these reproductive tissues. Results: The obese females were successful construction and displayed subfertility. They accumulated lipid droplets and developed morphological alterations in each of their reproductive organs including uterus, ovary and oviduct. These pathological changes accompanied increases in pro-inflammatory cytokine expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in all of these sites. Such effects also accompanied increases in nuclear factor kappa B (NF-kB) expression and mitogen-activated protein kinase (MAPK) signaling pathway stimulation based on uniform time dependent increases in the NF-κB (p-NF-κB), JNK (p-JNK), ERK1/2 (p-ERK) and p38 (p-p38) phosphorylation status. Conclusions: These HFD-induced increases in pro-inflammatory cytokine expression levels and NF-κB and MAPKs signaling pathway activation in reproductive organs support the notion that increases of adipocytes resident and inflammatory status are symptomatic of female fertility impairment in obese mice.
Background Over the past few decades, global maternal obesity prevalence has rapidly increased. This condition may induce long-lasting pathophysiological effects on either fetal or infant health that could be attributable to unknown unique changes in the umbilical blood composition. Methods A total of 34 overweight/obese and 32 normal-weight pregnant women were recruited. Fifteen umbilical blood samples including 8 overweight/obese subjects and 7 normal weight women were sequenced using Targeted Bisulfite Sequencing technology to detect the average methylation level of cytosine and identify the differentially methylated region (DMR). GO and KEGG analyses were then employed to perform pathway enrichment analysis of DMR-related genes and promoters. Moreover, the mRNA levels of methylation-related genes histone deacetylases (HDACs) and DNA methyltransferases (DNMTs) were characterized in the samples obtained from these two groups. Results Average methylated cytosine levels in both the CpG islands (CGI) and promoter significantly decreased in overweight/obese groups. A total of 1669 DMRs exhibited differences in their DNA methylation status between the overweight/obese and control groups. GO and KEGG analyses revealed that DMR-related genes and promoters were enriched in the metabolism, cancer and cardiomyopathy signaling pathways. Furthermore, the HDACs and DNMTs mRNA levels trended to decline in overweight/obese groups. Conclusions Decreased methylated cytosine levels in overweight/obese women induce the gene expression activity at a higher level than in the control group. DMRs between these two groups in the fetal blood may contribute to the changes in gene transcription that underlie the increased risk of metabolic disorders, cancers and cardiomyopathy in their offspring.
In order to solve the environmental problems caused by landfilling and incineration of Fenton sludge, realize the recycling of papermaking solid waste. In this paper, we explored the formation of a layer of calcium carbonate coating on the surface of Fenton sludge by crystallization coating in the Fenton sludge-[Ca(OH)2/H2O]-CO2 three-phase reaction system to improve the brightness of Fenton sludge and apply it to the filling of paper. The effects of particle size, temperature, stirring rate and calcium hydroxide addition on crystallization coating effect were studied. The advantages and disadvantages of the coating effect are mainly judged by the brightness and dustiness of the powder material. The research results show that when the particle size is 38–48 μm, the temperature is 25 °C, the stirring speed is 600 r/min, and the ratio of calcium hydroxide to Fenton sludge is 2:1, the brightness of the composite can be increased from 3.56 % ISO to 64.24 % ISO.
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