Lidia Hirnle

Urinary Tract Endometriosis

Recently, occurrence of urinary tract endometriosis (UTE) is more frequently diagnosed. According to literature, it refers to approximately 0.3 to even 12% of all women with endometriosis. The pathogenesis of UTE has not been clearly explained so far. The actually proposed hypotheses include embryonic, migration, transplantation, and iatrogenic theory. Most frequently UTE affects bladder, less often ureters and kidneys. One-third of patients remains asymptomatic or exhibits only minor manifestations. In symptomatic patients main complaints include dysuria, urinary urgency, and/or frequency, painful micturition, and burning sensation in the urethra and discomfort in the retropubic area. Treatment of UTE is challenging and can be pharmacological, surgical or can be a combination of both methods. In this paper we present a review of the literature concerning the UTE, its diagnosis and treatment.

Metabolomics of Human Amniotic Fluid and Maternal Plasma during Normal Pregnancy.

Metabolic profiles of amniotic fluid and maternal blood are sources of valuable information about fetus development and can be potentially useful in diagnosis of pregnancy disorders. In this study, we applied 1H NMR-based metabolic profiling to track metabolic changes occurring in amniotic fluid (AF) and plasma (PL) of healthy mothers over the course of pregnancy. AF and PL samples were collected in the 2nd (T2) and 3rd (T3) trimester, prolonged pregnancy (PP) until time of delivery (TD). A multivariate data analysis of both biofluids reviled a metabolic switch-like transition between 2nd and 3rd trimester, which was followed by metabolic stabilization throughout the rest of pregnancy probably reflecting the stabilization of fetal maturation and development. The differences were further tested using univariate statistics at α = 0.001. In plasma the progression from T2 to T3 was related to increasing levels of glycerol, choline and ketone bodies (3-hydroxybutyrate and acetoacetate) while pyruvate concentration was significantly decreased. In amniotic fluid, T2 to T3 transition was associated with decreasing levels of glucose, carnitine, amino acids (valine, leucine, isoleucine, alanine, methionine, tyrosine, and phenylalanine) and increasing levels of creatinine, succinate, pyruvate, choline, N,N-dimethylglycine and urocanate. Lactate to pyruvate ratio was decreased in AF and conversely increased in PL. The results of our study, show that metabolomics profiling can be used to better understand physiological changes of the complex interdependencies of the mother, the placenta and the fetus during pregnancy. In the future, these results might be a useful reference point for analysis of complicated pregnancies.

The expression of fucose isoforms of amniotic and plasma alpha-1-acid glycoprotein derived from 2nd and 3rd trimester normal pregnancies

OBJECTIVES To analyse modifications in AGP fucosylation in relation to different stages of human pregnancy. DESIGN AND METHODS The relative amounts of three fucosyl-glycotopes on AGP were analysed by lectin-ELISA using fucose-specific biotinylated lectins in 169 plasma and 178 amniotic fluid samples from normal pregnancies with gestational ages of 14 to 42 weeks. RESULTS The plasma AGPs of all the pregnant women and amniotic AGPs from the 2nd trimester lacked fucoses. In contrast, in the 3rd trimester the amniotic AGPs were highly decorated by the innermost alpha1,6-fucose as well as alpha1,2- and alpha1,3-fucoses of the outer arms, reaching the highest expression around the perinatal period. At delivery the relative amounts of the alpha1,3- and alpha1,2-AGP isoforms, but not the alpha1,6 isoform, significantly decreased. CONCLUSIONS The highly fucosylated amniotic AGP isoforms could be implicated in regulatory processes to ensure homeostasis during pregnancy and to protect the fetus. They have the potential of becoming laboratory markers in obstetrics to monitor pregnancy.

Cannabinoid Receptor 1 Gene Polymorphisms and Nonalcoholic Fatty Liver Disease in Women with Polycystic Ovary Syndrome and in Healthy Controls

Context. Polycystic ovary syndrome (PCOS) is frequently associated with nonalcoholic fatty liver disease (NAFLD). The endocannabinoid system may play a crucial role in the pathogenesis of NAFLD. Polymorphism of the cannabinoid receptor 1 gene (CNR1) may be responsible for individual susceptibility to obesity and related conditions. Objective. To determine the role of genetic variants of CNR1 in the etiopathology of NAFLD in women with PCOS. Design and Setting. Our department (a tertiary referral center) conducted a cross-sectional, case-controlled study. Subjects. 173 women with PCOS (aged 20–35) and 125 healthy, age- and weight-matched controls were studied. Methods. Hepatic steatosis was assessed by ultrasound evaluation. Single nucleotide polymorphisms of CNR1 (rs806368, rs12720071, rs1049353, rs806381, rs10485170, rs6454674) were genotyped. Results. Frequency of the G allele of rs806381 (P < 0.025) and the GG genotype of rs10485170 (P < 0.03) was significantly higher in women with PCOS and NAFLD than in PCOS women without NAFLD. Frequency of the TT genotype of rs6454674 was higher in PCOS women with NAFLD (not significantly, P = 0.059). In multivariate stepwise regression, allele G of rs806381 was associated with PCOS + NAFLD phenotype. Conclusion. Our preliminary results suggest the potential role of CNR1 polymorphisms in the etiology of NAFLD, especially in PCOS women.

Lectin-based analysis of fucose and sialic acid expressions on human amniotic IgA during normal pregnancy

The sugar moiety of IgA is known to provide a link between the innate and adaptive immune systems. Terminally located glycotopes on IgA are potential ligands engaged in the interactions which may modulate the biological activities of IgA. In the present work the expressions of Maackia amurensis (MAA), Sambucus nigra (SNA), Lens culinaris (LCA), Tetragonolobus purpureus (LTA), and Ulex europaeus (UEA) reactive glycotopes on maternal plasma and amniotic IgA were evaluated in relation to the progression of a normal human pregnancy, from the 2nd trimester, throughout the 3rd trimester, perinatal period, post-date pregnancy and delivery, by lectin-IgA-ELISA, using specific biotinylated lectins. The amniotic and maternal plasma IgA concentrations and a degree of SNA and LCA reactivity of maternal plasma IgA were almost unaltered during the normal pregnancy. The amniotic IgA from the 2nd trimester was decorated by MAA-, SNA-reactive and LCA-, LTA-, and UEA-reactive glycotopes. At the turn of the 2nd and 3rd trimesters the expression of MAA-, SNA-, LTA-, and UEA-reactive glycotopes, except for LCA-reactive, increased and remained almost at unaltered levels throughout the perinatal period and delivery. However, in the post-date pregnancy the expression of LCA-, LTA-, and UEA-reactive and SNA-reactive glycotopes were significantly higher. The unique fucosylated and sialylated glycovariants of amniotic IgA associated with the progression of the normal pregnancy may illustrate a general importance of carbohydrate-lectin receptor interactions in the control and modulation of biological events to ensuring homeostasis during pregnancy, protection and well-being of fetus.

Classic PCOS phenotype is not associated with deficiency of endogenous vitamin D and VDR gene polymorphisms rs731236 (TaqI), rs7975232 (ApaI), rs1544410 (BsmI), rs10735810 (FokI): a case–control study of lower Silesian women

Abstract Context: The role of endogenous vitamin D and vitamin D receptor (VDR) gene polymorphism in polycystic ovary syndrome (PCOS) is still controversial. Objective: The objective of this study was to investigate for the first time in women with “classic” PCOS phenotype and healthy controls the role of the serum endogenous vitamin D level and VDR gene polymorphisms in PCOS etiology. Design: Ninety-two women with “classic” PCOS phenotype and 85 controls from lower Silesia with comparable body mass index (BMI) were studied. In all women the waist circumference, android/gynoid fat deposit, parameters of lipid and glucose metabolism, testosterone, free androgen index, sex hormone binding globulin (SHBG) and vitamin D were evaluated. Also, VDR gene polymorphisms rs731236, rs7975232, rs1544410 and rs10735810 were assessed. Results: Serum vitamin D levels in both groups were comparable. Also high, comparable frequencies of hypovitaminosis and vitamin D deficiency in both groups were observed. Women with “classic” PCOS phenotype had statistically significantly higher values of all measured parameters, except serum SHBG and high-density lipoprotein (HDL)-cholesterol, which were lower. The frequency of VDR genotype polymorphism was also comparable in both groups. Conclusions: For the first time, we show that endogenous vitamin D deficiency and VDR polymorphisms are not associated with homogeneous “classic” PCOS phenotype.

Terminal glycotope expression on milk fibronectin differs from plasma fibronectin and changes over lactation

OBJECTIVES Fibronectin (FN) is a multifunctional glycoprotein appearing in various glycovariants with potential biological activities. Using lectins we analyzed the expression of terminal glycotopes on human milk fibronectin over lactation and compared it with that of the mothers plasma. DESIGN AND METHODS FN concentration and relative amounts of its fucosylated and sialylated glycovariants as well as O-glycans were analyzed in early colostrum, colostrum, transitional and mature milk samples of 132 healthy mothers by lectin-FN-ELISA using α2,3- and α2,6-sialic acid, α1,2-, α1,3-, and α1,6-fucose, and sialyl-T, asialyl-T and Tn antigen specific biotinylated Maackia amurensis, Sambucus nigra, Ulex europaeus, Tetragonolobus purpureus, Lens culinaris, Artocarpus integrifolia, Arachis hypogaea, and Vicia villosa lectins, respectively. RESULTS FN concentration was almost unchanged during human milk maturation and was about 150 times lower than in plasma of lactating mothers. Milk FN elicited significantly higher expression of sialylated glycotopes including sialyl-T antigen than plasma FN, and contained fucose-linked glycans, as well as T and Tn antigens absent in plasma FN. With milk maturation the expression of α2,6-sialylated, sialyl-T, α1,6- and α1,2-fucosylated epitopes decreased in transitional milk compared with colostrum, whereas that of asialyl-T antigen increased. The expression levels of α2,3-sialyl- and α1,3-fucosyl-glycotopes and Tn antigen on FN were low and did not change over lactation. CONCLUSION The expression of terminal sugars on milk FN is different from that of plasma FN of the lactating mother and is associated with milk maturation. The analysis of degree of milk sialylation and fucosylation should be considered during control of biochemical quality of milk collected in milk banks.

Lactation Stage-Related Expression of Sialylated and Fucosylated Glycotopes of Human Milk α-1-Acid Glycoprotein

BACKGROUND Because terminal sugars of α-1-acid glycoprotein (AGP) are reported to be involved in anti-inflammatory and immunomodulatory processes, their expressions might have an influence on the proper function of immune system of newborns. Here, relative amounts of sialylated and fucosylated glycotopes on human milk AGP over normal lactation were investigated. MATERIALS AND METHODS AGP concentration and relative amounts of its sialylated and fucosylated glycovariants were analyzed in early colostrum, colostrum, and transitional and mature milk samples of 127 healthy mothers by lectin-AGP enzyme-linked immunosorbent assay using α2,3- and α2,6-sialic acid and α1,2-, α1,3-, and α1,6-fucose specific biotinylated Maackia amurensis, Sambucus nigra, Ulex europaeus, Tetragonolobus purpureus, and Lens culinaris lectins, respectively. RESULTS AGP concentration in human milk was about 30 times lower than in plasma of lactating mothers and decreased gradually over lactation. Milk AGP showed significantly higher expression of sialylated and fucosylated glycotopes in comparison with those of plasma AGP. Milk AGP glycovariants containing α2,6-sialylated and α1,6- and α1,2-fucosylated glycotopes showed the highest relative amounts in early colostrums. With progression of lactation, the expressions of glycotopes α1,2-fucosylated decreased starting from Day 4 and those of α2,6-sialylated and α1,6-fucosylated from Day 8 of lactation, whereas the level of α2,3-sialyl-glycotope was almost constant over 45 days of lactation. In contrast, the expression of α1,3-linked fucose on AGP was low in colostrums and significantly higher in transitional and mature milk. CONCLUSIONS The relative amounts of sialylated and fucosylated glycovariants of human hindmilk AGP significantly varied between Days 2 and 45 of normal lactation.

Selected CNR1 polymorphisms and hyperandrogenemia as well as fat mass and fat distribution in women with polycystic ovary syndrome.

Abstract The endocannabinoid system is postulated to play an important role in the etiology of obesity, insulin resistance, fat distribution and metabolic disorders. Insulin resistance associated with abdominal obesity plays a leading role in the etiology of hyperandrogenism and other clinical features of the polycystic ovary syndrome (PCOS). A total of 174 women 16–38 years old, diagnosed with PCOS according to the Rotterdam criteria are recruited. Control group consisted of 125 healthy women 18–45 years old. Medical history, physical examination, anthropometric parameters and metabolic parameters were carried out. Six CNR1 gene polymorphisms were diagnosed. We observed a significantly three times higher risk of GG genotype in the polymorphism rs12720071 in women with PCOS versus the control group (p = 0.0344, OR = 3.01). A similar, significant 8-fold higher risk (p = 0.0176, OR = 8.81) was demonstrated for genotype CC polymorphism rs806368 associated with PCOS. We observed a 3.6-fold increased risk of hyperandrogenemia (free androgen index – FAI > 7) in patients with GG genotype in the rs12720071 polymorphism and AA genotype in the polymorphism rs1049353 (OR = 2.7). Our study may indicate a role of the endocannabinoid system in the occurrence of a specific hyperandrogenemia phenotype of PCOS. Chinese abstract 内源性大麻素系统被假定在肥胖、胰岛素抵抗、脂肪分布和代谢紊乱的病原学方面起重要作用。与腹型肥胖相关的胰岛素抵抗在多囊卵巢综合征（polycystic ovary syndrome，PCOS）雄激素增多症和其他临床特点的病因学上起主要作用。我们招募了174名16-38岁经鹿特丹诊断标准诊断的PCOS患者。对照组为125名18-45岁健康女性。我们对受试者采集病史，进行体格检查，收集人体测量参数和代谢指标。大麻素受体1（cannabinoid receptor 1，CNR1）基因多态性有六种。我们观察到PCOS患者在rs12720071位点多态性的GG基因型风险比对照组高出三倍（p=0.0344, OR=3.01）；类似的，PCOS患者在rs806368位点多态性的CC基因型风险比对照组高8倍（p=0.0176, OR=8.81）。我们也观察到rs12720071位点多态性的GG基因型和rs1049353位点多态性的AA基因型患者的高雄激素血症（free androgen index – FAI>7）风险增加了3.6倍（OR=2.7）。我们的研究可能表明内源性大麻素系统对PCOS一种特定的高雄激素血症表型的发生起作用。

Degree of sialylation and fucosylation of plasma and amniotic immunoglobulin G changes progressively during normal pregnancy

Terminal‐located glycotopes on immunoglobulin G (IgG) are potential ligands engaged in the interactions that may modulate the biological activities of IgG. The expressions of sialic acid and fucose residues on amniotic IgG were evaluated here in relation to the progression of normal human pregnancy.