The Role of Placental Hormones in Mediating Maternal Adaptations to Support Pregnancy and Lactation.

During pregnancy, the mother must adapt her body systems to support nutrient and oxygen supply for growth of the baby in utero and during the subsequent lactation. These include changes in the cardiovascular, pulmonary, immune and metabolic systems of the mother. Failure to appropriately adjust maternal physiology to the pregnant state may result in pregnancy complications, including gestational diabetes and abnormal birth weight, which can further lead to a range of medically significant complications for the mother and baby. The placenta, which forms the functional interface separating the maternal and fetal circulations, is important for mediating adaptations in maternal physiology. It secretes a plethora of hormones into the maternal circulation which modulate her physiology and transfers the oxygen and nutrients available to the fetus for growth. Among these placental hormones, the prolactin-growth hormone family, steroids and neuropeptides play critical roles in driving maternal physiological adaptations during pregnancy. This review examines the changes that occur in maternal physiology in response to pregnancy and the significance of placental hormone production in mediating such changes

Advanced maternal age compromises fetal growth and induces sex-specific changes in placental phenotype in rats

Funder: TN is supported by an EU Marie Skłodowska-Curie Fellowship (PlaEndo/703160).Funder: SD is supported as a Canada Research Chair in Maternal and Perinatal Cardiovascular Health. The animal work was funded by grants to SD from the Canadian Institutes of Health Research (CIHR: MOP 133675, FS 154313) and the Women and Children’s Health Research Institute (WCHRI) through the generosity of the Stollery Children’s Hospital Foundation and supporters of the Lois Hole Hospital for WomenAbstract: Advanced maternal age is associated with an increased risk of pregnancy complications. It programmes sex-specific cardiovascular dysfunction in rat offspring, however the intrauterine mechanisms involved remain unknown. This study in the rat assessed the impact of advanced maternal age on placental phenotype in relation to the growth of female and male fetuses. We show that relative to young (3–4 months) dams, advanced maternal age (9.5–10 months) compromises growth of both female and male fetuses but affects the placental phenotype sex-specifically. In placentas from aged versus young dams, the size of the placental transport and endocrine zones were increased and expression of Igf2 (+41%) and placental lactogen (Prl3b1: +59%) genes were upregulated in female, but not male fetuses. Placental abundance of IGF2 protein also decreased in the placenta of males only (−95%). Moreover, in placentas from aged versus young dams, glucocorticoid metabolism (11β-hsd2: +63% and 11β-hsd1: −33%) was higher in females, but lower in males (11β-hsd2: −50% and 11β-hsd1: unaltered). There was however, no change in the placental abundance of 11β-HSD2 protein in aged versus young dams regardless of fetal sex. Levels of oxidative stress in the placenta were increased in female and male fetuses (+57% and +90%, respectively) and apoptosis increased specifically in the placenta of males from aged rat dams (+700%). Thus, advanced maternal age alters placental phenotype in a sex-specific fashion. These sexually-divergent changes may play a role in determining health outcomes of female and male offspring of aged mothers

Author Correction: Advanced maternal age compromises fetal growth and induces sex-specific changes in placental phenotype in rats.

An amendment to this paper has been published and can be accessed via a link at the top of the paper

Placental secretome characterization identifies candidates for pregnancy complications.

Alterations in maternal physiological adaptation during pregnancy lead to complications, including abnormal birthweight and gestational diabetes. Maternal adaptations are driven by placental hormones, although the full identity of these is lacking. This study unbiasedly characterized the secretory output of mouse placental endocrine cells and examined whether these data could identify placental hormones important for determining pregnancy outcome in humans. Secretome and cell peptidome analyses were performed on cultured primary trophoblast and fluorescence-activated sorted endocrine trophoblasts from mice and a placental secretome map was generated. Proteins secreted from the placenta were detectable in the circulation of mice and showed a higher relative abundance in pregnancy. Bioinformatic analyses showed that placental secretome proteins are involved in metabolic, immune and growth modulation, are largely expressed by human placenta and several are dysregulated in pregnancy complications. Moreover, proof-of-concept studies found that secreted placental proteins (sFLT1/MIF and ANGPT2/MIF ratios) were increased in women prior to diagnosis of gestational diabetes. Thus, placental secretome analysis could lead to the identification of new placental biomarkers of pregnancy complications

Diet-induced maternal obesity impacts feto-placental growth and induces sex-specific alterations in placental morphology, mitochondrial bioenergetics, dynamics, lipid metabolism and oxidative stress in mice.

Funder: Department of Physiology, Development and Neuroscience Seed FundingFunder: Isaac Newton Trust Research GrantFunder: Medical Research Council PhD StipendFunder: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior FellowshipAIM: The current study investigated the impact of maternal obesity on placental phenotype in relation to fetal growth and sex. METHODS: Female C57BL6/J mice were fed either a diet high in fat and sugar or a standard chow diet, for 6 weeks prior to, and during, pregnancy. At day 19 of gestation, placental morphology and mitochondrial respiration and dynamics were assessed using high-resolution respirometry, stereology, and molecular analyses. RESULTS: Diet-induced maternal obesity increased the rate of small for gestational age fetuses in both sexes, and increased blood glucose concentrations in offspring. Placental weight, surface area, and maternal blood spaces were decreased in both sexes, with reductions in placental trophoblast volume, oxygen diffusing capacity, and an increased barrier to transfer in males only. Despite these morphological changes, placental mitochondrial respiration was unaffected by maternal obesity, although the influence of fetal sex on placental respiratory capacity varied between dietary groups. Moreover, in males, but not females, maternal obesity increased mitochondrial complexes (II and ATP synthase) and fission protein DRP1 abundance. It also reduced phosphorylated AMPK and capacity for lipid synthesis, while increasing indices of oxidative stress, specifically in males. In females only, placental mitochondrial biogenesis and capacity for lipid synthesis, were both enhanced. The abundance of uncoupling protein-2 was decreased by maternal obesity in both fetal sexes. CONCLUSION: Maternal obesity exerts sex-dependent changes in placental phenotype in association with alterations in fetal growth and substrate supply. These findings may inform the design of personalized lifestyle interventions or therapies for obese pregnant women

Placental secretome characterization identifies candidates for pregnancy complications

Abstract: Alterations in maternal physiological adaptation during pregnancy lead to complications, including abnormal birthweight and gestational diabetes. Maternal adaptations are driven by placental hormones, although the full identity of these is lacking. This study unbiasedly characterized the secretory output of mouse placental endocrine cells and examined whether these data could identify placental hormones important for determining pregnancy outcome in humans. Secretome and cell peptidome analyses were performed on cultured primary trophoblast and fluorescence-activated sorted endocrine trophoblasts from mice and a placental secretome map was generated. Proteins secreted from the placenta were detectable in the circulation of mice and showed a higher relative abundance in pregnancy. Bioinformatic analyses showed that placental secretome proteins are involved in metabolic, immune and growth modulation, are largely expressed by human placenta and several are dysregulated in pregnancy complications. Moreover, proof-of-concept studies found that secreted placental proteins (sFLT1/MIF and ANGPT2/MIF ratios) were increased in women prior to diagnosis of gestational diabetes. Thus, placental secretome analysis could lead to the identification of new placental biomarkers of pregnancy complications

Selected Qualitative Parameters of Honey Bee Colonies from Třeboň Area

The topic of this thesis is "Selected qualitative indicators of honey in Třeboň area. The goal was to make exploration of facts of the topic and then to compare chosen qualitative indicators of honey that were gained out of twenty colonies of bees within the Třeboň area. The research part was based on analysis of 40 samples of honey gained from local bee keepers, basic legislative physical-chemical parameters were specified that is water content, titration acidity and proof of honey violation by starch syrup, starch sugar and malt extract. Within the researched samples of honey, no sample was violated in terms of water content according to Public notice nr. 76/2003, the regulation was fulfilled in all 40 samples. Water content parameter was not fulfilled in 5 samples according to standards of Quality norm ČSV 1/1999 Český med. Acidity parameter, proof of honey violation by starch syrup, starch sugar and malt extract parameter was fulfilled in all 40 samples according to standards of Quality norm ČSV 1/1999 Český med

Exploring the causes and consequences of maternal metabolic maladaptations during pregnancy: Lessons from animal models.

Pregnancy is a remarkable physiological state, during which the metabolic system of the mother adapts to ensure that nutrients are made available for transfer to the fetus for growth and development. Adaptations of maternal metabolism during pregnancy are influenced by the metabolic and nutritional status of the mother and the production of endocrine factors by the placenta that exert metabolic effects. Insufficient or inappropriate adaptations in maternal metabolism during pregnancy may lead to pregnancy complications with important short- and long-term effects for both the health of the child and mother. This is very evident in gestational diabetes, which is marked by greater glucose intolerance and insulin resistance above that expected of a normal pregnancy. Gestational diabetes is associated with increased fetal weight and/or increased adiposity, higher instrumented delivery rates and greater risks for both mother and child of developing type 2 diabetes in the long-term. However, despite the negative health impacts of such metabolic imbalances during pregnancy, the precise mechanisms responsible for orchestrating these changes remain largely unknown. The present review describes the dynamic pregnancy-specific changes that occur in the metabolic system of the mother during pregnancy. It also discusses findings using surgical, pharmacological, genetic and dietary methods in experimental animals that highlight the role of pathways in maternal tissues that lead to metabolic dysfunction, with a particular focus on gestational diabetes. Finally, it summarises the work largely employing gene targeting and hormone administration in rodents that have illuminated the involvement of placental endocrine function in driving maternal metabolic adaptations. While current animal models may not fully replicate what is observed in humans, these have been instrumental in showing that there is a dynamic interplay between changes in maternal metabolic physiology and the placental production of endocrine factors that govern the availability of nutrients to the growing fetus. However, more work is required to specifically identify the placenta-driven changes in maternal metabolic physiology that ensure the appropriate level of insulin production and action during pregnancy. In doing so, these studies may pave the way to understanding the development of pregnancy complications like gestational diabetes, as well as further our understanding of type-2 diabetes and the control of metabolic physiology more broadly