Recurrent photic zone euxinia limited ocean oxygenation and animal evolution during the Ediacaran.

The Ediacaran Period (~635-539 Ma) is marked by the emergence and diversification of complex metazoans linked to ocean redox changes, but the processes and mechanism of the redox evolution in the Ediacaran ocean are intensely debated. Here we use mercury isotope compositions from multiple black shale sections of the Doushantuo Formation in South China to reconstruct Ediacaran oceanic redox conditions. Mercury isotopes show compelling evidence for recurrent and spatially dynamic photic zone euxinia (PZE) on the continental margin of South China during time intervals coincident with previously identified ocean oxygenation events. We suggest that PZE was driven by increased availability of sulfate and nutrients from a transiently oxygenated ocean, but PZE may have also initiated negative feedbacks that inhibited oxygen production by promoting anoxygenic photosynthesis and limiting the habitable space for eukaryotes, hence abating the long-term rise of oxygen and restricting the Ediacaran expansion of macroscopic oxygen-demanding animals.

Altered local RAS in the liver increased the risk of NAFLD in male mouse offspring produced by in vitro fertilization.

BACKGROUND: Assisted reproductive technology (ART) is associated with an increased risk of adverse metabolic health in offspring, and these findings have been demonstrated in animal models without parental infertility issues. However, it is unclear what changes lead to abnormal metabolism. The activation of the renin-angiotensin system (RAS) has been related to various aspects of metabolic syndrome. Thus, we focused on the local RAS of the liver, which is the central organ for glucose and lipid metabolism in offspring conceived by in vitro fertilization (IVF), and studied the role of local liver RAS in metabolic diseases. METHODS: Male C57BL/6 mouse offspring obtained by natural pregnancy and IVF were fed a standard chow diet or a high-fat diet (HFD) from 4 weeks of age through 16 weeks of age. We assessed glucose and lipid metabolism, hepatic histopathology, and the gene and protein expression of key RAS components. In addition, the blocker losartan was used from 4 weeks of age through 16 weeks of age to investigate the regulatory mechanisms of abnormal local RAS on metabolic activity in the IVF offspring liver. RESULTS: The growth trajectories of IVF offspring body and liver weights were different from those of naturally pregnant offspring. Impaired glucose tolerance (IGT) and insulin resistance (IR) occurred in IVF-conceived male offspring. After continuous HFD feeding, male offspring in the IVF group underwent earlier and more severe IR. Furthermore, there was a trend of lipid accumulation in the livers of chow-fed IVF offspring. Hepatic steatosis was also more serious in the IVF offspring after HFD treatment. Type 1 receptor (AT1R), which is the primary receptor mediating the action of angiotensin (Ang) II, has been confirmed to be upregulated in IVF offspring livers. Losartan reduced or even eliminated most of the significant differences between the IVF and NC groups after HFD consumption. CONCLUSIONS: The upregulation of AT1R expression in the liver increased the activity of the local RAS, resulting in abnormal glucose and lipid metabolism and lipid accumulation in the liver, significantly increasing the risk of nonalcoholic fatty liver disease (NAFLD) in IVF offspring.

WT1 influences apoptosis and proliferation of immature mice granular cells through regulation of the wnt/ß-catenin signal pathway.

It was to study the influence of Wilms tumor suppressor gene (WT1) on ovarian granular cells (GCs) in mice, and the molecular mechanism involved. LV-WT1 short hairpin ribonucleic acid (shRNA) vector was used to downregulate WT1 expression in granular cells (GCs). The effects of WTI on proliferation and apoptosis of GCs were investigated. Western blot and qRT-PCR were used to assay the mRNA and protein expressions of Bax/bcl-2 in GCs transfected with LV-WT1-RNAi. The expression levels of SUZ12, Wnt5a, Wnt11, Wnt4, Wnt3a, Wnt2 mRNA in GCs were also determined. LV-WT1-RNAi significantly reduced WT1 expression, increased apoptosis and inhibited proliferation of GCs. The inhibition of WT1 had no significant effect on the expression of bcl-2 in GCs. The expressions of Wnt2, Wnt4 and Wnt5a were augmented in WT1-knockdown GCs, relative to non-transfected cells. WT1 activation is necessary for maintaining early survival of GCs in follicles via activation of the Wnt/ß-catenin signal pathway.

Hypothetical protein Cpn0423 triggers NOD2 activation and contributes to Chlamydia pneumoniae-mediated inflammation.

BACKGROUND: Chlamydia pneumoniae (C. pneumoniae) is pathogenic to humans, by causing pulmonary inflammation or bronchitis in both adolescents and young adults. However, the molecular signals linking C. pneumoniae components to inflammation remain elusive. This study was to investigate the effect of Chlamydia-specific Cpn0423 of C. pneumoniae on C. pneumoniae-mediated inflammation. RESULTS: Cpn0423 was detected outside of C. pneumoniae inclusions, which induced production of several cytokines including macrophage inflammatory protein-2 (MIP-2) and interleukins (ILs). Production of the Cpn0423-induced cytokines was markedly reduced in cells pretreated with NOD2-siRNA, but not with negative control oligonucleotides. Mice treated with Cpn0423 through intranasal administration exhibited pulmonary inflammation as evidenced by infiltration of inflammatory cells, increased inflammatory scores in the lung histology, recruitment of neutrophils and increased cytokines levels in the BALF. CONCLUSION: Cpn0423 could be sensed by NOD2, which was identified as an essential element in a pathway contributing to the development of C. pneumoniae -mediated inflammation.

Maternal high-salt diets affected pressor responses and microvasoconstriction via PKC/BK channel signaling pathways in rat offspring.

SCOPE: High-salt (HS) intake is linked to hypertension, and prenatal exposure to maternal HS diets may have long-term impact on cardiovascular systems. The relationship between HS diets and cardiovascular disease has received extensive attention. This study determined pressor responses and microvessel functions in the adult offspring rats exposed to prenatal HS. METHODS AND RESULTS: The offspring of 5-month old as young adults in rats were used. Blood pressure, vascular tone, intracellular Ca(2+), and BK channels in mesenteric arteries were measured in the offspring. Phenylephrine (Phe)-induced pressor responses were significantly higher in the prenatal HS offspring. Vessel tension and intracellular Ca(2+) concentrations associated with Phe-induced pressor responses were increased in the mesenteric arteries of the HS offspring. PKC α- and δ-isoforms were upregulated in mesenteric arteries of the HS offspring. The enhanced Phe-mediated vascular activity was linked to the altered PKC-modulated BK channel functions. CONCLUSION: The results suggested that prenatal exposure to HS altered microvascular activity probably via changes in PKC/BK signaling pathways, which may lead to increased risks of hypertension in the offspring.

Intake of high sucrose during pregnancy altered large-conductance Ca2+-activated K+ channels and vessel tone in offspring's mesenteric arteries.

Antenatal malnutrition could be linked to hypertension and vascular diseases in fetal origins. This study determined the influence of maternal intake of high sucrose (HS) during pregnancy on vessel tone, intracellular Ca(2+) ([Ca(2+)](i)), K(+) channels, especially large-conductance Ca(2+)-activated K(+) channels (BK), in mesenteric arteries in the offspring rats exposed to prenatal HS. Vessel tension and [Ca(2+)](i) induced by angiotensin II were higher in the small mesenteric arteries of the HS offspring. In the vascular smooth muscle cells (VSMCs) from the HS offspring, electrophysiological studies showed depressed BK current density and depolarized membrane. Western blot showed altered expressions of BK α-subunits, AT1 and AT2 receptors in mesenteric arteries. The results suggest that decreased BK channel activity and depolarized membrane potential in the VSMCs partly contributed to the increased vessel tone and [Ca(2+)](i) in the HS offspring, adding new information for understanding mechanisms in vascular malfunctions in fetal origins, and novel insights for early prevention and treatments against such vascular diseases.

The effect of folic acid on ovine fetuses in utero during late gestation.

To investigate whether folic acid would have toxic effects on fetal cardiac, hepatic, and renal functions, this was the first in utero fetal study testing acute effects of folic acid at the last third of gestation. Folic acid (5 mg/day) or 0.9% saline as the control was intragastricly administrated into pregnant ewes. Both maternal and fetal blood were analyzed for pH, PO(2), PCO(2), SO(2)%, hemoglobin, hematocrit, glucose, lactic acid, osmolality, Na(+), and K(+) concentrations. Maternal and fetal cardiovascular functions were assessed by examining cardiac enzymes and cardiovascular responses in vivo. Fetal hepatic and renal functions were examined by analysis of biochemistry index and renal excretion. Folic acid did not alter the blood values in both ewes and fetuses. Cardiac enzyme activities remained unchanged, and no alteration in cardiovascular responses was observed. Folic acid did not affect fetal urine volume, urine electrolytes, and osmolality. Enzyme activities related to hepatic and renal functions were not changed. In addition, maternal application of folic acid had no effect on maternal and fetal lipid profile. The results showed that folic acid used (5 mg/day) during the last third of gestation did not cause biochemical changes related to cardiac, hepatic, and renal functions in both maternal and fetal sheep, providing new information for use of folic acid during late pregnancy.