Impact of contraception and IVF hormones on metabolic, endocrine, and inflammatory status

Assisted reproductive technologies (ART) represent commonly utilized management strategies for infertility with multifactorial causes (including genetically predisposed diseases). Amongst ART, in vitro fertilization (IVF) is the most popular. IVF treatment may predispose the mother to increased risks and complications during pregnancy, and there may be adverse fetal outcomes. Hormonal therapies, including oral contraceptives, may impair glucose and lipid metabolism, and promote insulin resistance and inflammation. IVF treatment involves administration of reproductive hormones, similar in composition but in much higher doses than those used for oral contraception. The provision of IVF reproductive hormones to mice associates with glucose intolerance. In addition, the physiological and hormonal changes of pregnancy can trigger an inflammatory response, and metabolic and endocrine changes. There is controversy regarding the potential effects of IVF hormonal therapies in the promotion of diabetogenic and inflammatory states, additional to those that occur during pregnancy, and which may therefore predispose women with IVF-conceived pregnancies to adverse obstetric outcomes compared with women with spontaneously conceived pregnancies. This review summarizes the limited published evidence regarding the effect of IVF-based fertility therapies on glucose homeostasis, insulin resistance, cardio-metabolic profile, and markers of inflammation

Effects of IVF therapies on metabolic, endocrine and inflammatory status in IVF-conceived pregnancy

Rationale In vitro fertilization (IVF) is a common treatment for infertility. In mice, IVF is associated with development of glucose intolerance. However, human data are limited regarding the metabolic, endocrine and inflammatory effects of IVF therapy in IVF‐conceived pregnancies. Objective To explore effects of IVF therapies on metabolic, endocrine and inflammatory parameters in IVF‐conceived pregnancy. Methodology Twelve‐week prospective observational study of adult normoglycaemic women, BMI 18.5‐38 kg/m2 and ≤ 39 years awaiting IVF therapy. Fasting blood samples were collected at baseline and 12 weeks, and serum analysed for reproductive hormones, glucose, lipids, insulin sensitivity, thyroid status, adiponectin inflammatory marker and lipopolysaccharide‐binding protein (LBP). Results Two hundred and seventy‐five women were analysed: 158 IVF‐conceived pregnant women and 117 with failed IVF. Compared with baseline, nonpregnant women had significant (P < .001) increases in 12‐week glucose (86.04‐87.62 mg/dL), insulin (8.72‐9.37 µIU/mL), HOMA‐IR (1.9‐2.1), T‐Chol (169.5‐174.9 mg/dL), TG (71.0‐83.7 mg/dL) and HDL‐C (52.0‐54.11 mg/dL) levels. At 12 weeks, pregnant women also had (P < .001) increases in T‐Chol (177.5‐199.5 mg/dL), TG (73.5‐126.78 mg/dL) and HDL‐C (55.3‐65.1 mg/dL), while a significant reduction in glucose (86.15‐82.19 mg/dL), HbA1c (5.3‐5.08%) and TSH (1.71‐1.36 µIU/mL) levels from baseline. Adiponectin and LBP levels remained the same in either group. Conclusion In vitro fertilization hormonal therapy impairs glucose and insulin levels; these effects are masked in early pregnancy. Changes in lipid profile occur following IVF therapies regardless of pregnancy outcome. Neither adiponectin nor LBP is affected by IVF therapies and during early IVF‐conceived pregnancy

ESKIMO1 Disruption in Arabidopsis Alters Vascular Tissue and Impairs Water Transport

Water economy in agricultural practices is an issue that is being addressed through studies aimed at understanding both plant water-use efficiency (WUE), i.e. biomass produced per water consumed, and responses to water shortage. In the model species Arabidopsis thaliana, the ESKIMO1 (ESK1) gene has been described as involved in freezing, cold and salt tolerance as well as in water economy: esk1 mutants have very low evapo-transpiration rates and high water-use efficiency. In order to establish ESK1 function, detailed characterization of esk1 mutants has been carried out. The stress hormone ABA (abscisic acid) was present at high levels in esk1 compared to wild type, nevertheless, the weak water loss of esk1 was independent of stomata closure through ABA biosynthesis, as combining mutant in this pathway with esk1 led to additive phenotypes. Measurement of root hydraulic conductivity suggests that the esk1 vegetative apparatus suffers water deficit due to a defect in water transport. ESK1 promoter-driven reporter gene expression was observed in xylem and fibers, the vascular tissue responsible for the transport of water and mineral nutrients from the soil to the shoots, via the roots. Moreover, in cross sections of hypocotyls, roots and stems, esk1 xylem vessels were collapsed. Finally, using Fourier-Transform Infrared (FTIR) spectroscopy, severe chemical modifications of xylem cell wall composition were highlighted in the esk1 mutants. Taken together our findings show that ESK1 is necessary for the production of functional xylem vessels, through its implication in the laying down of secondary cell wall components

Comparative transcriptomics of drought responses in Populus: a meta-analysis of genome-wide expression profiling in mature leaves and root apices across two genotypes

<p>Abstract</p> <p>Background</p> <p>Comparative genomics has emerged as a promising means of unravelling the molecular networks underlying complex traits such as drought tolerance. Here we assess the genotype-dependent component of the drought-induced transcriptome response in two poplar genotypes differing in drought tolerance. Drought-induced responses were analysed in leaves and root apices and were compared with available transcriptome data from other <it>Populus </it>species.</p> <p>Results</p> <p>Using a multi-species designed microarray, a genomic DNA-based selection of probesets provided an unambiguous between-genotype comparison. Analyses of functional group enrichment enabled the extraction of processes physiologically relevant to drought response. The drought-driven changes in gene expression occurring in root apices were consistent across treatments and genotypes. For mature leaves, the transcriptome response varied weakly but in accordance with the duration of water deficit. A differential clustering algorithm revealed similar and divergent gene co-expression patterns among the two genotypes. Since moderate stress levels induced similar physiological responses in both genotypes, the genotype-dependent transcriptional responses could be considered as intrinsic divergences in genome functioning. Our meta-analysis detected several candidate genes and processes that are differentially regulated in root and leaf, potentially under developmental control, and preferentially involved in early and long-term responses to drought.</p> <p>Conclusions</p> <p>In poplar, the well-known drought-induced activation of sensing and signalling cascades was specific to the early response in leaves but was found to be general in root apices. Comparing our results to what is known in arabidopsis, we found that transcriptional remodelling included signalling and a response to energy deficit in roots in parallel with transcriptional indices of hampered assimilation in leaves, particularly in the drought-sensitive poplar genotype.</p

Different reprogramming propensities in plants and mammals: Are small variations in the core network wirings responsible?

Although the plant and animal kingdoms were separated more than 1,6 billion years ago, multicellular development is for both guided by similar transcriptional, epigenetic and posttranscriptional machinery. One may ask to what extent there are similarities and differences in the gene regulation circuits and their dynamics when it comes to important processes like stem cell regulation. The key players in mouse embryonic stem cells governing pluripotency versus differentiation are Oct4, Sox2 and Nanog. Correspondingly, the WUSCHEL and CLAVATA3 genes represent a core in the Shoot Apical Meristem regulation for plants. In addition, both systems have designated genes that turn on differentiation. There is very little molecular homology between mammals and plants for these core regulators. Here, we focus on functional homologies by performing a comparison between the circuitry connecting these players in plants and animals and find striking similarities, suggesting that comparable regulatory logics have been evolved for stem cell regulation in both kingdoms. From in silico simulations we find similar differentiation dynamics. Further when in the differentiated state, the cells are capable of regaining the stem cell state. We find that the propensity for this is higher for plants as compared to mammalians. Our investigation suggests that, despite similarity in core regulatory networks, the dynamics of these can contribute to plant cells being more plastic than mammalian cells, i.e. capable to reorganize from single differentiated cells to whole plants-reprogramming. The presence of an incoherent feed-forward loop in the mammalian core circuitry could be the origin of the different reprogramming behaviour.This work was supported Swedish Research Council, grant VR 621-2013-4547 to CP; the Swedish Foundation for Strategic Research, grant A3 04 159p to CP; the Gatsby Charitable Foundation (GB), grant GAT3395-PR4 to HJ and the Swedish Research Council, grant VR 621- 2013-4632 to HJ

Prevention of atelectasis formation during the induction of general anesthesia in morbidly obese patients

Résumé: La formation des atélectasies durant l'induction de l'anesthésie générale est plus importante chez le patient obèse morbide. Nous avons démontré dans des travaux de recherche antérieurs que l'utilisation de la PEEP (Pression Positive en Fin d'Expiration) durant l'induction de l'anesthésie prévient la formation d'atélectasies chez des patients non obèses. Par conséquent, nous voulions étudier l'efficacité de la pression positive en fin d'expiration chez le patient obèse morbide dans la prévention de la formation d'atélectasies. Nous avons fait une étude de 23 patients obèses morbides (BMI &gt; 35 kg / m2) dans 2 groupes. Dans le groupe utilisant la pression positive en fin d'expiration, les patients respiraient 100% d'oxygène pendant 5 minutes par l'intermédiaire d'un masque facial type CPAP avec une pression de 10 cm H20. Après l'induction de l'anesthésie, nous avons ventilé les patients au masque facial avec une PEEP de 10 cm H20. Dans le groupe de contrôle, nous avons procédé au même type d'induction sans utiliser la pression positive en fin d'expiration. La surface de poumon atélectatique a été évaluée par tomographie (CT scann). L'étude des échanges gazeux se faisait à 2 reprises, à partir de gazométries réalisées juste avant l'induction de l'anesthésie puis juste après l'intubation. Après l'induction de l'anesthésie et l'intubation, les patients du groupe de contrôle présentaient une quantité d'atélectasies plus importante que les patients du groupe où la PEEP avait été utilisée (10.4% + 4.8% dans le groupe de contrôle versus 1.3% dans le groupe utilisant la pression positive en fin d'expiration p &lt; 0.001). Après l'intubation, en présence d'une fraction inspirée en oxygène à 100%, la Pa02 était significativement supérieure dans le groupe ayant utilisé la pression positive en fin d'expiration en comparaison avec le groupe de contrôle (respectivement 457 ± 130 mmHg versus 315 ± 100 mmHg). Nous avons conclu que chez le patient obèse morbide, le recours à la pression positive en fin d'expiration lors de l'induction de l'anesthésie permet de prévenir largement la formation d'atélectasies et s'accompagne d'une meilleure oxygénation. Abstract: Atelectasis caused by general anesthesia is increased in morbidly obese patients. We have shown that application of positive end-expiratory pressure (PEEP) during the induction of anesthesia prevents atelectasis formation in nonobese patients. We therefore studied the efficacy of PEEP in morbidly obese patients to prevent atelectasis. Twenty-three adult morbidly obese patients (b ody mass index &gt;35 kg/m2) were randomly assigned to one of two groups. In the PEEP group, patients breathed 100% oxygen (5 min) with a continuous positive airway pressure of 10 cm H20 and, after the induction, mechanical ventilation via a face mask with a PEEP of 10 cm H2O. In the control group, the same induction was applied but without continuous positive airway pressure or PEEP. Atelectasis, determined by computed tomography, and blood gas analysis were measured twice: before the induction and directly after intubation. After endotracheal intubation, patients of the control group showed an increase in the amount of atelectasis, which was much larger than in the PEEP group (10.4% -± 4.8% in control group versus 1.7% ± 1.3% in PEEP group; P &lt;0.001). After in.tubation with a fraction of inspired oxygen of 1.0, Pao, was significantly higher in the PEEP group compared with the control group (457 ±- 130 mm Hg versus 315 ± 100 mm Hg, respectively; P = 0.035) We conclude that in morbidly obese patients, atelectasis formation is largely prevented by PEEP applied during the anesthetic induction and is associated with a better oxygenation

Early predictors of gestational diabetes mellitus in IVF-conceived pregnancies

Objective Gestational diabetes mellitus (GDM) associates with adverse maternal and foetal outcomes. The aim of our study was to identify early and reliable GDM predictors, which will enable implementation of preventive and management measures. Methodology 28-week prospective cohort of IVF-conceived pregnant women (≤39years, BMI 18.5-38kg/m2) without known history of diabetes mellitus. Fasting blood samples were analysed at baseline (pre-IVF) and 12-week gestation for reproductive hormones, glucose, serum insulin, lipids, thyroid function, adiponectin and LBP. At 28 weeks, 75-gram OGTT was used to screen for GDM. Results For the pregnant group overall at baseline, 22% had a BMI≥30kg/m2, 45% with PCOS, 16% with HbA1c of 5.7–6.1% and 14% with a past history of GDM. At 28-week gestation (n=158): 34 women developed GDM and 124 did not. Significant baseline predictors of GDM onset included: greater BMI (29.0 vs. 25.8kg/m2), older age (34 vs. 32years) and higher levels of FSH/LH ratio (1.2 vs. 1.0), HbA1C (5.5 vs. 5.2%), insulin (10.6 vs. 7.1μIU/mL), HOMA-IR (2.2 vs. 1.7), T-Chol (199 vs. 171mg/dL) and LDL-C (123 vs. 105mg/dL), and lower TG levels (74 vs. 76mg/dL). Significant 12-week GDM predictors included: greater maternal weight gain (delta: 3.4 vs. 1.5kg) and higher levels of insulin (11.3 vs. 7.6μIU/mL), TG (178 vs. 120mg/dL) and HOMA-IR (2.3 vs. 1.5). 12-week BMI is a predictor of GDM following adjustment for PCOS status and maternal age. Conclusion While preconception maternal BMI, age and FSH/LH ratio are predictors for subsequent development of GDM, early IVF-conceived gestational weight gain predicted best GDM onset

Use of Artificial Cell Microcapsule Containing Thalidomide for Treating TNBS-induced Crohn's Disease in Mice

In this study, we examined the in-vivo characteristics of a novel microencapsulated thalidomide formulation in a murine model of experimental Crohn's disease. Crohn's disease was induced with a single intra-colonic injection of 120 mg/kg of bodyweight of 2,5,6-trinitrobenzene sulfonic acid (TNBS) dissolved in 30% ethanol in Balb/c mice. Level of tumor necrosis factor alpha (TNF-), interleukin one beta (IL-1), interleukin 6 (IL-6) and nitric oxide (NO) were measured in tissue homogenate. Moreover, myeloperoxidase (MPO) activity was determined to assess the extent of neutrophil infiltration. Dose response study showed that treating the mice with microencapsulated thalidomide (100 mg/kg of bodyweight) for two weeks significantly decreased the degree of intestinal inflammation related to Crohn’s disease. Higher and lower doses (0, 25, 50 and 200 mg/kg of bodyweight) did not exhibit comparable effects. The present study validates the success of alginate-poly-L-lysine-alginate (APA) microcapsules containing thalidomide in reducing colonic inflammation, and proposes a potential remedy for Crohn’s disease