The hormone leptin, which is thought to be primarily produced by adipose tissue, is a polypeptide that was initially characterized by its ability to regulate food intake and energy metabolism. Leptin appears to signal the status of body energy stores to the brain, resulting in the regulation of food intake and whole-body energy expenditure. Subsequently, it was recognized as a cytokine with a wide range of peripheral actions and is involved in the regulation of a number of physiological systems including reproduction. In the fed state, leptin circulates in the plasma in proportion to body adiposity in all species studied to date. However other factors such as sex, age, body mass index (BMI), sex steroids and pregnancy may also affect leptin levels in plasma. In pregnant mice and humans, the placenta is also a major site of leptin expression. Leptin circulates in biological fluids both as free protein and in a form that is bound to the soluble isoform of its receptor or other binding proteins such as one of the immunoglobulin superfamily members Siglec-6 (OBBP1). Although the actions of leptin in the control of reproductive function are thought to be exerted mainly via the hypothalamicpituitary-gonadal axis, there have also been reports of local direct effects of leptin at the peripheral level, however, these data appear contradictory. Therefore, there is a need to summarize the current status of research outcomes and analyze the possible reasons for differing results and thus provide researchers with new insight in designing experiments to investigate leptin effect on reproduction. Most importantly, our recent experimental data suggesting that reproductive performance is improved by decreasing concentrations of peripheral leptin was unexpected and cannot be explained by hypotheses drawn from the experiments of excessive exogenous leptin administration to normal animals or ob/ob mice., M. Herrid, S. K. A. Palanisamy, U. A. Ciller, R. Fan, P. Moens, N. A. Smart, J. R. McFarlane., and Obsahuje bibliografii
We measured plasma concentrations, adipose tissue and placental mRNA expression of hepatokines fetuin A, fetuin B and fibroblast growth factor 21 (FGF21) in 12 healthy pregnant women (P group), 12 pregnant women with gestational diabetes (GDM) and 10 healthy non-pregnant women (N group) to explore their potential role in the etiopathogenesis of GDM. GDM and P group had comparable BMI, C-reactive protein (CRP) and glycated hemoglobin levels while IL-10 and TNF-α levels were higher in GDM group. Fetuin A and fetuin B levels were higher in pregnancy as compared to N group and decreased after delivery with no apparent influence of GDM. In contrast, the pattern of changes of circulating FGF21 levels differed between GDM and P group. Fetuin A concentrations positively correlated with CRP, TNF-α mRNA expression in adipose tissue and IL-6 mRNA expression in placenta. Fetuin B positively correlated with CRP. FGF21 levels correlated positively with IFN-γ mRNA in adipose tissue and inversely with IL-8 mRNA in the placenta. Taken together, fetuin A and fetuin B levels were increased during pregnancy regardless of the presence of GDM. In contrast, FGF21 patterns differed between healthy pregnant women and GDM patients suggesting a possible role of this hepatokine in the etiopathogenesis of GDM., P. Šimják, A. Cinkajzlová, K. Anderlová, J. Kloučková, H. Kratochvílová, Z. Lacinová, P. Kaválková, H. Krejčí, M. Mráz, A. Pařízek, M. Kršek, M. Haluzík., and Obsahuje bibliografii
Smoking during pregnancy presents health risks for both the mother and her child. In this study we followed changes in the production of steroid hormones in pregnant smokers. We focused on changes in steroidogenesis in the blood of mothers in their 37th week of pregnancy and in mixed cord blood from their newborns. The study included 88 healthy women with physiological pregnancies (17 active smokers and 71 nonsmokers). We separately analyzed hormonal changes associated with smoking according to the sex of newborns. In women with male fetuses, we found higher levels of serum cortisone, dehydroepiandrosterone (DHEA), 7α-OH-DHEA, 17-OH pregnenolone, testosterone, and androstenedione in smokers at the 37th week compared to non-smokers. In women with female fetuses, we found lower serum levels of 7β-OH-DHEA and higher androstenedione in smokers at the 37th week. We found significantly higher levels of testosterone in newborn males of smokers and higher levels of 7α-OH-DHEA in female newborns of smokers. Smoking during pregnancy induces changes in the production of steroids in both the mother and her child. These changes are different for different fetal sexes, with more pronounced changes in mothers carrying male newborns as well as in the newborn males themselves., K. Adamcová, L. Kolátorová, T. Chlupáčová, M. Šimková, H. Jandíková, A. Pařízek, L. Stárka, M. Dušková., and Obsahuje bibliografii
The microcirculation, like all physiological systems undergoes modifications during the course of pregnancy. These changes aid the adaption to the new anatomical and physiological environment of pregnancy and ensure adequate oxygen supply to the fetus. Even though the microcirculation is believed to be involved in major pregnancy related pathologies, it remains poorly understood. The availability of safe and non-interventional technologies enabling scientists to study the intact microcirculation of the pregnant patient will hopefully expand our understanding. In this article we review the physiological changes occurring in the microcirculation during pregnancy and the role of the microcirculation in gestational related pathologies. We will also describe the available techniques for the measurement and evaluation of the microcirculation. Lastly we will highlight the possible fields in which these techniques could be utilized to help provide a clearer view of the microcirculation in the pregnant woman., I. Abdo, R. B. George, M. Farrag, V. Cerny, C. Lehmann., and Obsahuje bibliografii
Endocrine disruptors (EDs) are known to have harmful effects on the human endocrine system; special effort is actually given to the exposure during pregnancy. Humans are usually exposed to a mixture of EDs, which may potentiate or antagonize each other, and the combined effect may be difficult to estimate. The main phthalate monoesters monoethyl-, mono-n -butyl-, monoisobutyl-, monobenzyl-, mono-(2-ethylhexyl)-, mono-(2- ethyl-5-hydroxyhexyl)- and mono-(2-ethyl-5-oxohexyl) phthalate were determined in 18 maternal (37th week of pregnancy) and cord plasma samples using liquid chromatography-tandem mass spectrometry. Previously determined levels of selected bisphenols, parabens and steroids were also considered in this study. In cord blood, there were significantly higher mono-n-butyl phthalate levels than in maternal blood (p=0.043). The results of multiple regression models showed that maternal plasma phthalates were negatively associated with cord plasma androstenedione, testosterone and dehydroepiandrosterone and positively associated with estradiol and estriol. For estriol, a cumulative association was also observed for Σbisphenols. To the best of our knowledge, this is the first pilot study evaluating the effect of prenatal exposure by multiple EDs on newborn steroidogenesis. Our results confirmed phthalate accumulation in the fetal area and disruption of fetal steroidogenesis. This preliminary study highlights the negative impacts of in utero EDs exposure on fetal steroidogenesis., L. Kolatorova, J. Vitku, A. Vavrous, R. Hampl, K. Adamcova, M. Simkova, A. Parizek, L. Starka, M. Duskova., and Obsahuje bibliografii
In modern societies, living organisms are exposed daily to multiform pollution from industrial chemical products. Some of these substances have been shown to affect the endocrine system, and have been termed endocrine disruptors (EDs). Bisphenol A (BPA), which can leach from plastics, and parabens, used in cosmetic products, are among the most well-studied. Prenatal development is a vulnerable phase of human life, and disruptions during this period may have lifelong consequences. Since EDs are known to cross the placental barrier and BPA may accumulate in the fetus, "BPA-free" products have been introduced to the market. However, such products often contain alternative bisphenols (e.g. BPS, BPF) that have not yet been extensively examined or regulated. Moreover, alternative bisphenols often occur together with BPA. The human organism is thus exposed to a mixture of EDs, some of which can have additive or synergic effects. Recent findings have also shown that paraben exposure can alter bisphenol pharmacokinetics. Taking into account the widespread occurrence of various EDs and the potential multiplicity of their effects, doses of EDs currently considered safe may not actually be as safe as they appear, especially during pregnancy., L. Kolatorova, M. Duskova, J. Vitku, L. Starka., and Obsahuje bibliografii
a1_Antiphospholipid antibodies (APAs) are characterized as a heterogeneous population of autoantibodies directed against different target antigens, predominantly anionic phospholipids or phospholipid-containing structures. The presence of APAs has been strongly associated with a variety of clinical disorders including adverse pregnancy complications such as spontaneous abortions, pregnancy-induced hypertension, preeclampsia and intrauterine growth retardation. The purpose of this study was to compare the prevalence of anticardiolipin antibodies (ACAs), which are routinely examined, with APAs directed against phosphatidylserine (APS), phosphatidylinositol (API), phosphatidylethanolamine (APE) and phosphatidylcholine (APC) in the sera of pregnant women. We examined 410 serum samples of pregnant women hospitalized in the department for pathological pregnancies. They underwent prenatal biochemical screening of fetal congenital abnormalities in the first and the second trimester of gravidity. Anticardiolipin IgG and IgM were measured using commercial ELISA kits (ImmuLisaTM Anti-Cardiolipin Antibody), whereas APS, APE, API and APC were determined by our modified ELISA kit. Among 410 pregnant women we found 21 patients (5.1 %) positive for ACA IgG (>20 GPL) and 30 patients (7.3 %) positive for ACA IgM (>10 MPL). It was found that 7.8 % of pregnant women had at least one high-titer APA IgG and 9.8 % high-titer APA IgM. One third of ACA IgG or IgM positive sera contained polyspecific autoantibodies reactive to at least two various phospholipids. In the group of IgG ACA positive women, 28.6 % patients were positive for APS, 28.6 % were positive or moderately positive for API, 23.8 % for APC and 19 % for APE. In the group of IgM ACA positive women, 33.3 % were also positive for APS, 26.7 % for APE, 26.7 % for API and 23.3 % for APC were present., a2_IgG and IgM ACA negative patients exhibited a significantly lower incidence of other APA than the group of ACA positive pregnant women. It still remains to clarify if the routine examination of APA reacting with other anionic and zwitterionic antigens other than cardiolipin would improve the probability of identifying women liable to adverse pregnancy complications., L. Fialová, L. Mikulíková, I. Matouš-Malbohan, O. Benešová, A. Zwinger., and Obsahuje bibliografii
This review focuses on current knowledge of leptin biology and the role of leptin in various physiological and pathophysiological states. Leptin is involved in the regulation of body weight. Serum leptin can probably be considered as one of the best biological markers reflecting total body fat in both animals and humans. Obesity in man is accompanied by increased circulating leptin concentrations. Gender differences clearly exist. Leptin is not only correlated to a series of endocrine parameters such as insulin, glucocorticoids, thyroid hormones, testosterone, but it also seems to be involved in mediating some endocrine mechanisms (onset of puberty, insulin secretion) and diseases (obesity, polycystic ovary syndrome). It has also been suggested that leptin can act as a growth factor in the fetus and the neonate., R. Janečková., and Obsahuje bibliografii
Intrahepatic cholestasis of pregnancy (ICP) is a disorder of liver function, commonly occurring in the third trimester but sometimes also as soon as the end of the second trimester of pregnancy. Symptoms of this disorder include pruritus, plus abnormal values of bile acids and hepatic transaminases. After birth, symptoms disappear and liver function returns to normal. Though ICP is relatively non-complicated and often symptomatically mild from the point-of-view of the mother, it presents a serious risk to the fetus, making this disease the subject of great interest. The etiology and pathogenesis of ICP is multifactorial and as yet not fully elucidated. Hormonal factors likely play a significant role, along with genetic as well as exogenous factors. Here we summarize the knowledge of changes in steroid hormones and their role in the development of intrahepatic cholestasis of pregnancy. In addition, we consider the role of exogenous factors as possible triggers of steroid hormone changes, the relationship between metabolic steroids and bile acids, as well as the combination of these factors in the development of ICP in predisposed pregnant women., A. Pařízek, M. Dušková, L. Vítek, M. Šrámková, M. Hill, K. Adamcová, P. Šimják, A. Černý, Z. Kordová, H. Vráblíková, B. Boudová, M. Koucký, K. Malíčková, L. Stárka., and Obsahuje bibliografii
Thyroid nodules are a very frequent pathology among common population. Despite the vast majority of them are of benign origin, the incidence of thyroid cancer is currently rather rising. Although there are several risk factors of thyroid cancer and several clinical, ultrasound, biochemical and molecular diagnostic markers, the exact mechanisms of thyroid oncogenesis and the linkage between thyroid nodule ultrasound appearance and its biological character remain unclear. While ionizing radiation is the only one well-known risk factor for thyroid cancer, the significance of some others remains unclear. The aim of our review was to discuss some not completely known pathophysiological mechanisms involved in thyroid oncogenesis as hypothyroidism, mutations of genes regulating cell proliferation, thyroid autoimmunity and pregnancy and to describe pathophysiological background of some ultrasound markers of thyroid cancer (size, echogenicity, vascularization, calcifications and stiffness). Better knowledge in this field is crucial for development of novel diagnostic techniques and therapeutic approaches. For exampl e, the analysis of BRAF, RAS and other mutations in cytological samples may help to distinction between follicular thyroid carcinoma and follicular thyroid adenoma and may signific antly decrease the number of unnecessary surgery among patients with thyroid nodules. Alternatively, the different malign cells growth, angiogenesis, destructions of thyroid follicles, reparative changes, growth retardation, fibrosis and increased interstitial fluid pressure implicate the typical ultrasound appearance of papillary thyroid cancer (hypoechogenicity, irregular vascularization, microcalcifications, stiffness) which is essential to catch the suspicious nodules on the basis of their ultrasound appearance among large amount of benign nodules., J. Krátký, H. Vítková, J. Bartáková, Z. Telička, M. Antošová, Z. Límanová, J. Jiskra., and Obsahuje bibliografii