Estrogen targets genes involved in protein processing, calcium homeostasis, and Wnt signaling in the mouse uterus independent of estrogen receptor-alpha and -beta

Estrogen actions in target organs are normally mediated via activation of nuclear estrogen receptors (ERs). By using mRNA differential display technique, we show, herein, that estradiol-17beta (E(2)) and its catechol metabolite 4-hydroxy-E(2) (4OHE(2)) can modulate uterine gene expression in ERalpha(-/-) mice. Whereas administration of E(2) or 4OHE(2) rapidly up-regulated (4-8-fold) the expression of immunoglobulin heavy chain binding protein (Bip), calpactin I (CalP), calmodulin (CalM), and Sik similar protein (Sik-SP) genes in ovariectomized wild-type or ERalpha(-/-) mice, the expression of secreted frizzled related protein-2 (SFRP-2) gene was down-regulated (4-fold). Bip, CalP, and CalM are calcium-binding proteins and implicated in calcium homeostasis, whereas SFRP-2 is a negative regulator of Wnt signaling. Bip and Sik-SP also possess chaperone-like functions. Administration of ICI-182,780 or cycloheximide failed to influence these estrogenic responses, demonstrating that these effects occur independent of ERalpha, ERbeta, or protein synthesis. In situ hybridization showed differential cell-specific expression of these genes in wild-type and ERalpha(-/-) uteri. Although progesterone can antagonize or synergize estrogen actions, it had minimal effects on these estrogenic responses. Collectively, the results demonstrate that estrogens have a unique ability to influence specific genes in the uterus not involving classical nuclear ERs.     

Ligand-receptor signaling with endocannabinoids in preimplantation embryo development and implantation

Although adverse effects of cannabinoids on pregnancy have been indicated for many years, the mechanisms by which they exert their actions were not clearly understood. Only recently, molecular and biochemical approaches have led to the identification of two types of cannabinoid receptors, brain-type receptors (CB1-R) and spleen-type receptors (CB2-R), which mediate cannabinoid effects. These findings were followed by the discovery of endocannabinoids, anandamide and 2-arachidonoylglycerol (2-AG). The natural cannabinoids and endocannabinoids exert their effects via cannabinoid receptors and share similar pharmacological and physiological properties. Recent demonstration of expression of functional CB1-R in the preimplantation embryo and synthesis of anandamide in the pregnant uterus of mice suggests that cannabinoid ligand-receptor signaling is operative in the regulation of preimplantation embryo development and implantation. This review describes recent observations and their significance in embryo-uterine interactions during implantation and future research directions in this emerging area of interest.     

Differential expression of VEGF isoforms and VEGF(164)-specific receptor neuropilin-1 in the mouse uterus suggests a role for VEGF(164) in vascular permeability and angiogenesis during implantation

The mechanism(s) by which localized vascular permeability and angiogenesis occur at the sites of implantation is not clearly understood. Vascular endothelial growth factor (VEGF) is a key regulator of vasculogenesis during embryogenesis and angiogenesis in adult tissues. VEGF is also a vascular permeability factor. VEGF acts via two tyrosine kinase family receptors: VEGFR1 (Flt-1) and VEGFR2 (KDR/Flk-1). Recent evidence suggests that neuropilin-1 (NRP1), a receptor involved in neuronal cell guidance, is expressed in endothelial cells, binds to VEGF(165) and enhances the binding of VEGF(165) to VEGFR2. We examined the spatiotemporal expression of vegf isoforms, nrp1 and vegfr2 as well as their interactions in the periimplantation mouse uterus. We observed that vegf(164) is the predominant isoform in the mouse uterus. vegf(164) mRNA accumulation primarily occurred in epithelial cells on days 1 and 2 of pregnancy. On days 3 and 4, the subepithelial stroma in addition to epithelial cells exhibited accumulation of this mRNA. After the initial attachment reaction on day 5, luminal epithelial and stromal cells immediately surrounding the blastocyst exhibited distinct accumulation of vegf(164) mRNA. On days 6-8, the accumulation of this mRNA occurred in both mesometrial and antimesometrial decidual cells. These results suggest that VEGF(164) is available in mediating vascular changes and angiogenesis in the uterus during implantation and decidualization. This is consistent with coordinate expression of vegfr2, and nrp1, a VEGF(164)-specific receptor, in uterine endothelial cells. Their expression was low during the first 2 days of pregnancy followed by increases thereafter. With the initiation and progression of implantation (days 5-8), these genes were distinctly expressed in endothelial cells of the decidualizing stroma. Expression was more intense on days 6-8 at the mesometrial pole, the presumptive site of heightened angiogenesis and placentation. However, the expression was absent in the avascular primary decidual zone immediately surrounding the implanting embryo. Crosslinking experiments showed that (125)I-VEGF(165) binds to both NRP1 and VEGFR2 present in decidual endothelial cells. These results suggest that VEGF(164), NRP1 and VEGFR2 play a role in VEGF-induced vascular permeability and angiogenesis in the uterus required for implantation. genesis 26:213-224, 2000.     

Endocannabinoid signaling in synchronizing embryo development and uterine receptivity for implantation

There are reports of adverse effects of cannabinoids on pregnancy outcome including retarded embryo development and pregnancy failure. Thus, discoveries of endogenous cannabinoid-like lipid mediators and cannabinoid receptors raise questions about their pathophysiological roles during normal pregnancy. We previously reported that anandamide, an endogenously produced arachidonate derivative (endocannabinoid), is synthesized in the female reproductive tracts, and it acts on cannabinoid receptors expressed on the cell surface of the embryo to regulate the preimplantation embryo development and implantation in mice. This review presents genetic, molecular, physiological and pharmacological evidence that the levels of uterine anandamide and blastocyst CB1 cannabinoid receptors are coordinately regulated to synchronize preimplantation development and uterine receptivity for implantation in mice.     

Desynapsis and spontaneous trisomy in jute (Corchorus olitorius L.)

Summary Cytological studies in desynaptic plants, isolated at the F₆ generation of an intervarietal cross of Corchorus olitorius L., have shown variable numbers of bivalents and univalents in the PMC's at metaphase I, resulting in irregular distribution of chromosomes at anaphase I. The progenies of the desynaptic plants consisted of 9.24 percent of all possible primary trisomies except trisomie 6. The desynaptic condition is controlled by a pair of simple recessive genes.     

Production of a Recombinant Peptide (Lasioglossin LL ΙΙΙ) and Assessment of Antibacterial and Antioxidant Activity

International Journal of Peptide Research and Therapeutics - The use of antimicrobial peptides (AMPs) as biopreservative to replace chemical preservatives has become of interest among consumers....     

Gradual Rewarming with Gradual Increase in Pressure during Machine Perfusion after Cold Static Preservation Reduces Kidney Ischemia Reperfusion Injury

In this study we evaluated whether gradual rewarming after the period of cold ischemia would improve organ quality in an Isolated Perfused Kidney Model. Left rat kidneys were statically cold stored in University of Wisconsin solution for 24 hours at 4°C. After cold storage kidneys were rewarmed in one of three ways: perfusion at body temperature (38°C), or rewarmed gradually from 10°C to 38°C with stabilization at 10°C for 30 min and rewarmed gradually from 10°C to 38°C with stabilization at 25°C for 30 min. In the gradual rewarming groups the pressure was increased stepwise to 40 mmHg at 10°C and 70 mmHg at 25°C to counteract for vasodilatation leading to low perfusate flows. Renal function parameters and injury biomarkers were measured in perfusate and urine samples. Increases in injury biomarkers such as aspartate transaminase and lactate dehydrogenase in the perfusate were lower in the gradual rewarming groups versus the control group. Sodium re-absorption was improved in the gradual rewarming groups and reached significance in the 25°C group after ninety minutes of perfusion. HSP-70, ICAM-1, VCAM-1 mRNA expressions were decreased in the 10°C and 25°C groups. Based on the data kidneys that underwent gradual rewarming suffered less renal parenchymal, tubular injury and showed better endothelial preservation. Renal function improved in the gradual rewarming groups versus the control group.     

Alkaline Phosphatase Protects Lipopolysaccharide-Induced Early Pregnancy Defects in Mice

Excessive cytokine inflammatory response due to chronic or superphysiological level of microbial infection during pregnancy leads to pregnancy complications such as early pregnancy defects/loss and preterm birth. Bacterial toxin lipopolysaccharide (LPS), long recognized as a potent proinflammatory mediator, has been identified as a risk factor for pregnancy complications. Alkaline phosphatase (AP) isozymes have been shown to detoxify LPS by dephosphorylation. In this study, we examined the role of alkaline phosphatase (AP) in mitigating LPS-induced early pregnancy complications in mice. We found that 1) the uterus prior to implantation and implantation sites following embryo implantation produce LPS recognition and dephosphorylation molecules TLR4 and tissue non-specific AP (TNAP) isozyme, respectively; 2) uterine TNAP isozyme dephosphorylates LPS at its sites of production; 3) while LPS administration following embryo implantation elicits proinflammatory cytokine mRNA levels at the embryo implantation sites (EISs) and causes early pregnancy loss, dephosphorylated LPS neither triggers proinflammatory cytokine mRNA levels at the EISs nor induces pregnancy complications; 4) AP isozyme supplementation to accelerate LPS detoxification attenuates LPS-induced pregnancy complications following embryo implantation. These findings suggest that a LPS dephosphorylation strategy using AP isozyme may have a unique therapeutic potential to mitigate LPS- or Gram-negative bacteria-induced pregnancy complications in at-risk women.     

Integration of life cycle assessment,artificial neural networks,and metaheuristic optimization algorithms for optimization of tomato-based cropping systems in Iran

Purpose

The main purpose of this study was to evaluate the use of an integrated life cycle assessment (LCA), artificial neural network, and metaheuristic optimization model to improve the sustainability of tomato-based cropping systems in Iran. The model outputs the combination of input usage in a tomato cropping system, which leads to the highest economic output and the least environmental impact.

Methods

The LCA inventory was created using data from 114 open-field tomato farms in the Alborz Province of Iran during one growing period in 2015. Among all management components, the main focus was on irrigation management systems. The optimization problem was designed by integrating three indicators: carbon footprint (CF), benefit-cost ratio (BCR), and energy use efficiency (EUE) as the objective of field tomato production. The functional unit was 1 kg of tomato aligned with the system boundary of the cradle to market life cycle. Three artificial neural networks (ANNs) were applied to model relationships between the inputs and three indices (CF, BCR, and EUE) as the objective functions. Multi-objective genetic algorithm (MOGA) and multi-objective particle swarm optimization (MOPSO) were used to minimize the CF and maximize the BCR and EUE indicators. The abovementioned aims have been pursued by developing codes in MATLAB software.

Results and discussion

CF, BCR, and EUE were calculated to be 0.26 kg CO_2?eq (kg tomato)^?1, 1.8, and 0.5, respectively. MOGA results envisage the possibility of an increase of 86% and 50% in the EUE and BCR and a 43% reduction in the CF of tomato production systems. Moreover, EUE and BCR increased by 83% and 49%, and CF was reduced by 39% from the optimum results obtained from the MOPSO algorithm. It was revealed that in order to optimize field tomato production with the target objectives of this study, a large additional use for irrigation pipes, plastic, and machinery in comparison to current situation is required, while a large reduction of biocide, chemical fertilizer, and electricity consumption is indispensable.

Conclusions

According to the results of our study, it was concluded that the optimal solutions require a modernization of irrigation systems and a decrease in the consumption of chemical fertilizers and pesticides. The implementation of management options for such solutions is discussed.