STUDY QUESTIONHow does a maternal diabetic hyperadiponectineamia affect signal transduction and lipid metabolism in rabbit preimplantation blastocysts?SUMMARY ANSWERIn a diabetic pregnancy increased levels of adiponectin led to a switch in embryonic metabolism towards a fatty acid-dependent energy metabolism, mainly affecting genes that are responsible for fatty acid uptake and turnover.WHAT IS KNOWN ALREADYAlthough studies in cell culture experiments have shown that adiponectin is able to regulate lipid metabolism via 5′-AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα), data on the effects of adiponectin on embryonic lipid metabolism are not available. In a diabetic pregnancy in rabbits, maternal adiponectin levels are elevated fourfold and are accompanied by an increase in intracellular lipid droplets in blastocysts, implying consequences for the embryonic hormonal and metabolic environment.STUDY DESIGN, SIZE, DURATIONRabbit blastocysts were cultured in vitro with adiponectin (1 μg/ml) and with the specific AMPK-inhibitor Compound C for 15 min, 1 h and 4 h (N ≥ 3 independent experiments: for RNA analysis, n ≥ 4 blastocysts per treatment group; for protein analysis three blastocysts pooled per sample and three samples used per experiment). Adiponectin signalling was verified in blastocysts grown in vivo from diabetic rabbits with a hyperadiponectinaemia (N ≥ 3 independent experiments, n ≥ 4 samples per treatment group, eight blastocysts pooled per sample).PARTICIPANTS/MATERIALS, SETTING, METHODSIn these blastocysts, expression of molecules involved in adiponectin signalling [adaptor protein 1 (APPL1), AMPK, acetyl-CoA carboxylase (ACC), p38 mitogen-activated protein kinases (p38 MAPK)], lipid metabolism [PPARα, cluster of differentiation 36 (CD36), fatty acid transport protein 4 (FATP4), fatty acid binding protein (FABP4), carnitine palmityl transferase 1 (CPT1), hormone-senstive lipase (HSL), lipoprotein lipase (LPL)] and members of the insulin/insulin-like growth factor (IGF)-system [IGF1, IGF2, insulin receptor (InsR), IGF1 receptor (IGF1R)] were analyzed by quantitative RT-PCR and western blot. Analyses were performed in both models, i.e. adiponectin stimulated blastocysts (in vitro) and in blastocysts grown in vivo under increased adiponectin levels caused by a maternal diabetes mellitus.MAIN RESULTS AND THE ROLE OF CHANCEIn both in vitro and in vivo models adiponectin increased AMPK and ACC phosphorylation, followed by an activation of the transcription factor PPARα, and CPT1, the key enzyme of β-oxidation (all P < 0.05 versus control). Moreover, mRNA levels of the fatty acid transporters CD36, FATP4 and FABP4, and HSL were upregulated by adiponectin/AMPK signalling (all P < 0.05 versus control). Under diabetic developmental conditions the amount of p38 MAPK was upregulated (P < 0.01 versus non-diabetic), which was not observed in blastocysts cultured in vitro with adiponectin, indicating that the elevated p38 MAPK was not related to adiponectin. However,...

In a diabetic pregnancy, an altered maternal metabolism led to increased formation of reactive α‐dicarbonyls such as glyoxal (GO) and methylglyoxal (MGO) in the reproductive organs and embryos. The enzyme glyoxalase (GLO) 1 detoxifies reactive α‐dicarbonyls thus protecting cells against malfunction or modifications of proteins by advanced glycated end products (AGEs). The aim of this study was to analyse the influence of a maternal insulin‐dependent diabetes mellitus (IDD) on GLO1 expression and activity in preimplantation embryos in vivo and human trophoblast cells (Ac‐1M88) in vitro. Maternal diabetes was induced in female rabbits by alloxan before conception and maintained during the preimplantation period. GLO1 expression and activity were investigated in 6‐day‐old blastocysts from healthy and diabetic rabbits. Furthermore, blastocysts and human trophoblast cells were exposed in vitro to hyperglycaemia, GO and MGO and analysed for GLO1 expression and activity. During gastrulation, GLO1 was expressed in all compartments of the rabbit blastocyst. Maternal diabetes decreased embryonic GLO1 protein amount by approx. 30 per cent whereas the enzymatic activity remained unchanged, indicating that the specific GLO1 activity increases along with metabolic changes. In in vitro cultured embryos, neither hyperglycaemia nor MGO and GO had an effect on GLO1 protein amount. In human trophoblast cells, a stimulating effect on the GLO1 expression was shown in the highest GO concentration, only. Our data show that maternal diabetes mellitus affects the specific activity of GLO1, indicating that GLO1 was post‐translationally modified due to changes in metabolic processes in the preimplantation embryos.

Metabolic disorders of the mother adversely affect early embryo development, causing changes in maternal metabolism and consequent alterations in the embryo environment in the uterus. The goal of this study was to analyse the biochemical profiles of embryonic fluids and blood plasma of rabbits with and without insulin-dependent diabetes mellitus (DT1), to identify metabolic changes associated with maternal diabetes mellitus in early pregnancy. Insulin-dependent diabetes was induced by alloxan treatment in female rabbits 10 days before mating. On day 6 post-coitum, plasma and blastocoel fluid (BF) were analysed by ultrahigh performance liquid chromatography-tandem mass spectroscopy (UPLC-MS/MS) (Metabolon Inc. Durham, NC, USA). Metabolic datasets comprised a total of 284 and 597 compounds of known identity in BF and plasma, respectively. Diabetes mellitus had profound effects on maternal and embryonic metabolic profiles, with almost half of the metabolites changed. As predicted, we observed an increase in glucose and a decrease in 1,5-anhydroglucitol in diabetic plasma samples. In plasma, fructose, mannose, and sorbitol were elevated in the diabetic group, which may be a way of dealing with excess glucose. In BF, metabolites of the pentose metabolism were especially increased, indicating the need for ribose-based compounds relevant to DNA and RNA metabolism at this very early stage of embryo development. Other changes were more consistent between BF and plasma. Both displayed elevated acylcarnitines, body3-hydroxybutyrate, and multiple compounds within the branched chain amino acid metabolism pathway, suggesting that lipid beta-oxidation is occurring at elevated levels in the diabetic group. This study demonstrates that maternal and embryonic metabolism are closely related. Maternal diabetes mellitus profoundly alters the metabolic profile of the preimplantation embryo with changes in all subclasses of metabolites.

During the first days of development the preimplantation embryo is supplied with nutrients from the surrounding milieu. Maternal diabetes mellitus affects the uterine microenvironment, leading to a metabolic adaptation processes in the embryo. We analysed embryonic fatty acid (FA) profiles and expression of processing genes in rabbit blastocysts, separately in embryoblasts and trophoblasts, to determine the potential consequences of maternal diabetes mellitus on intracellular FA metabolism. Insulin-dependent diabetes was induced by alloxan in female rabbits. On day 6 post coitum, FA profiles in blastocysts (embryoblast, trophoblast and blastocoel fluid) and maternal blood were analysed by gas chromatography. The expression levels of molecules involved in FA elongation (fatty acid elongases, ELOVLs) and desaturation (fatty acid desaturases, FADSs) were measured in embryoblast and trophoblast. Maternal diabetes mellitus influenced the FA profile in maternal plasma and blastocysts. Independent from metabolic changes, rabbit blastocysts contained a higher level of saturated fatty acids (SFAs) and a lower level of polyunsaturated fatty acids (PUFAs) compared to the FA profile of the maternal plasma. Furthermore, the FA profile was altered in the embryoblast and trophoblast, differently. While SFAs (palmitic and stearic acid) were elevated in embryoblast of diabetic rabbits, PUFAs, such as docosahexaenoic acid, were decreased. In contrast, in the trophoblast, lower levels of SFAs and higher levels of oleic acid were observed. Embryoblast and trophoblast specific alterations in gene expression were found for ELOVLs and FADSs, key enzymes for FA elongation and desaturation. In conclusion, maternal diabetes mellitus alters embryonic FA metabolism differently in embryoblast and trophoblast, indicating a lineage-specific metabolic adaptive response.

Although social isolation (SI) has shown to impede health and well-being, there is little knowledge about regional factors affecting SI. While urban life may hinder close contact with neighbors, advance in public transportation can make contact with friends and relatives easier. This study examined how the two aspects of urbanization affect SI among older adults when ADL declines. Data came from the National Survey of Japanese Elderly, a nationwide longitudinal study of Japanese older adults aged 60 and older. We analyzed 3132 respondents who lived in 192 municipalities (regions) and responded to 2-5 waves' interviews between 1996 and 2012, through hierarchical generalized linear models (threelevel model). SI was defined as having less contact than once a week with anyone outside the household. Regional level explanatory variables were "close-knit neighborhood" represented as median number of neighbors with whom one has close contact among respondents in the region, and availability of public transportation assessed by interviewers. Key individual time-varying or baseline attributes included gender, age, ADL/IADL, family/financial status, and number of close neighbors. Results showed that living in regions with close-knit neighborhood lowered probability of SI even after controlling for the individual characteristics, while availability of public transportation did not. Functional decline increased the probability of SI, but this negative impact was buffered by living in regions with higher availability of public transportation. Our findings indicate that urbanization does not necessarily promote SI, and that various resources are required to prevent SI according to phases of functional decline in later life. Recently South Koreans over the age of 65 committed suicide at a highest rate among the OECD countries. Therefore, there is a growing interest in early detection of depressive symptoms and other mental health problems in community settings. In order to analyze the factors influencing the competency of care providers regarding mental health issues, 324 family caregivers and 291 service providers working in facilities for elderly were surveyed using a structured questionnaire in 2016 in three cities in Korea. The average score for understanding mental health of older people was 3.29(5-point scale). Service providers had slightly higher score than the family caregivers. Family members were more reluctant than service providers towards seeking professional help for mental issues. However, service providers had more negative perception about current mental health service delivery system. Implications for improving the accessibility to early detection and prevention of mental health problems are discussed. Older adults comprise 7% of the Mongolian population and it is projected that they will account for 25% by 2050. Health care for older adults was greatly impacted by Mongolia's transition from a centrally planned to a free market economy. In 1998, the government established universal health insurance centralize...