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I Cetin

Publications and source records attributed to I Cetin.

At least 19 recordsLinked to original sources
PubMed2006

Placental transport and metabolism in fetal overgrowth -- a workshop report.

Fetal overgrowth in pregnancies complicated by diabetes is the result of an increased substrate availability which stimulates fetal insulin secretion and fetal growth. However, despite strict glycemic control in modern clinical management of the pregnant woman with diabetes, fetal overgrowth remains an important clinical problem. Recent studies in vivo provide evidence for increased delivery of amino acids to the fetus in gestational diabetes (GDM) even when metabolic control is strict. This could be due to that truly normal maternal substrate levels cannot be achieved in diabetic pregnancies and/or caused by altered placental nutrient transport and metabolism. Studies in vitro demonstrate an up-regulation of placental transport systems for certain amino acids in GDM associated with fetal overgrowth. GDM is also characterized by changes in placental gene expression, including up-regulation of inflammatory mediators and Leptin. In type-I diabetes with fetal overgrowth the in vitro activity of placental transporters for both glucose and certain amino acids as well as placental lipoprotein lipase is increased. Furthermore, both clinical observations in type-I diabetic pregnancies and preliminary animal experimental studies suggest that even brief periods of metabolic perturbation early in pregnancy may affect placental growth and transport function for the remainder of pregnancy, thereby contributing to fetal overgrowth. Ultrasound measurements of fetal fat deposits and abdominal circumference as well as 3D ultrasound assessment of placental volume represent non-invasive techniques for in utero diagnosis of fetal and placental overgrowth. It is proposed that these methods represent valuable additions to the clinical management of the diabetic pregnancy. In conclusion, altered placental function may be a mechanism contributing to fetal overgrowth in diabetic pregnancies with apparent optimal metabolic control. It is proposed that detailed information on placental metabolism and transport functions obtained in vitro and in vivo represent a placental phenotype that provides important information and may facilitate diagnosis and improve clinical management of fetal overgrowth.

Amino Acid Transport Systems↗
PubMed2005

Fetal and placental chromosomal mosaicism revealed by QF-PCR in severe IUGR pregnancies.

A number of genetic and environmental factors are taken into account as responsible for intrauterine growth restriction (IUGR); nevertheless, the relevance of genetic alteration in IUGR aetiology remains to be determined. The aim of this study was to investigate using a combined cytogenetic-molecular approach, improved by a new application of QF-PCR method, the presence of mosaic chromosomal changes in fetal/placental samples from 12 pregnancies with unexplained severe IUGR. This multiple approach allowed us to reveal and quantify subtle chromosomal mosaicisms with less than 5% of trisomic cells even in cases in which cytogenetic and FISH analyses failed to reveal them. These are three pregnancies with a mosaic trisomy for chromosomes 7, 2 and 14; the former case presented matUPD7 and was previously described in this journal (Placenta 22 (2001) 813) in association with pre- and postnatal growth restriction. It is intriguing that chromosomes 7, 2 and 14 are known or suspected to harbour imprinted genes, so that an unbalanced gene dosage in a subset of cells during embryonic development could lead to an early impairment of placental function. Our findings indicate that extensive molecular and cytogenetic studies of IUGR fetal and placental tissues are necessary to reveal at least part of the heterogeneous genetic lesions implicated in IUGR phenotypes.

Adult↗
PubMed2004

Adiponectin expression in human fetal tissues during mid- and late gestation.

Adiponectin (ApN), an adipocytokine expressed in adipocytes with antidiabetic and antiatherogenic actions, has been detected in cord blood, suggesting a putative role in intrauterine fetal development. The aim of this study was to confirm the presence of ApN in the fetal circulation and directly investigate ApN expression in fetal tissues. The study showed high ApN levels in umbilical venous blood from fetuses [n = 44; 31.2 +/- 14.1 (sd) mg/liter in umbilical vs. 8.4 +/- 4.0 in maternal circulation (P < 0.0001)] that positively correlated with gestational age. By using RT-PCR, Western blotting, and immunohistochemistry, ApN was detected in several fetal tissues at mid- and late gestation (from 14 to 36 wk) but not in the placenta. ApN was expressed in tissues of mesodermic origin, i.e. brown and white adipocytes, skeletal muscle fibers of diaphragm and iliopsoas, smooth muscle cells of small intestine and arterial walls, perineurium and renal capsule, and tissues of ectodermal origin, i.e. epidermis and ocular lens. The distribution of ApN expression in nonadipose tissues showed a general decline during the progression of gestation. The unexpected pattern of ApN expression in the human fetus may account for the high ApN levels in cord blood and predicts novel roles for ApN during fetal development.

Adiponectin↗
PubMed2004

Circulating levels of inhibin A, inhibin B and activin A in normal and intrauterine growth restricted (IUGR) fetuses.

OBJECTIVE: To evaluate the relationships between circulating levels of inhibin A, inhibin B and activin A, and sex, gestational age and gonadotropins in normal and pathological fetuses. STUDY DESIGN: The study included 31 normal fetuses and 12 affected with intrauterine growth restriction (IUGR) of gestational age ranging 20-40 weeks. RESULTS: No gender difference in inhibin A and activin A levels were observed. Inhibin B levels were significantly higher in males than in females (P < 0.05). Fetuses with the highest levels of inhibin A and B were found in the IUGR group that also showed activin A levels significantly higher than normal. No correlations were observed between inhibin A, inhibin B, activin A and both gonadotropins. CONCLUSION: Plasma inhibin A, inhibin B and activin A are detectable in both genders during intrauterine life. The different gender pattern of inhibin B suggests that inhibin B may contribute to the assessment of the hypothalamic-pituitary-gonadal set-point at least in males.

Activins↗
PubMed2004

Lack of expression of endometrial prolactin in early implantation failure: a pilot study.

BACKGROUND: Animal models and experimental studies suggest a role for paracrine prolactin (PRL) signalling in decidualization and embryo implantation. We investigated the expression of endometrial prolactin (e-PRL) and prolactin receptor (PRL-R) in the endometrium of women affected by unexplained infertility (UI) and repeated miscarriages (RM). METHODS: Patients (n = 24) were divided into three groups: RM, n = 5; UI, n = 11; controls, n = 8. Endometrial samples were collected at the time of hysteroscopy in the late luteal phase. The presence of transcripts of e-PRL and PRL-R was investigated by qualitative RT-PCR. Pattern and site of expression of e-PRL were studied by immunohistochemistry. RESULTS: PRL-R mRNA was detected in all endometrial samples of the three groups. PRL gene expression was detected in all control samples, only in three of five samples of the RM group and in four of 11 samples of the UI group. RT-PCR results were largely confirmed by immunohistochemistry, study groups showing a defect of expression of e-PRL. CONCLUSIONS: In this pilot study we report a lack of expression of endometrial prolactin during the 'implantation window' in some patients affected by unexplained infertility and repeated miscarriages. These data, in association with those obtained in experimental animals, suggest that the lack of endometrial PRL expression is involved in reproduction failure.

Abortion, Habitual↗
PubMed2004

Flexible treatment of gestational diabetes modulated on ultrasound evaluation of intrauterine growth: a controlled randomized clinical trial.

OBJECTIVES: In order to prevent abnormalities of fetal growth still characterizing pregnancies complicated by Gestational Diabetes (GDM), in the present study we evaluated a therapeutic strategy for GDM based on ultrasound (US) measurement of fetal insulin-sensitive tissues. METHODS: All GDM women diagnosed before 28th week immediately started diet and self-monitoring of blood glucose; after 2 weeks they were randomized to conventional (C) or modified (M) management. In C the glycemic target (GT) was fixed at 90 fasting/120 post-prandial mg/dl; in M GT varied, according to US measurement of the Abdominal Circumference (AC) centile performed every 2 weeks: 80/100 if AC > or =75th, 100/140 if AC<75th. Therapy was tailored to mean fasting (FG) and postprandial glycemia (PPG). RESULTS: Globally, 229 women completed the study, 78 in C, 151 in M. Use of insulin was 16.7% in C, 30.4% in M (total groups), significantly more frequent in M than in C (59.7% vs 15.4%) when considering only women with AC > or =75th c. Mean metabolic data were similar in the 2 groups, but in M a tightly-optimized subgroup, resulting from the lowering of GT due to AC > or =75th, coexisted with a less-controlled one, whose higher GT was justified by AC<75th. Pregnancy outcome was better in M, with lower (p<0.05*) rate of LGA* (7.9% vs 17.9%), SGA (6.0% vs 9.0%) and Macrosomia* (3.3% vs 11.5%). CONCLUSIONS: Our data show the value of a flexible US-based approach to the treatment of GDM. This model does not necessarily involve a generalized aggressive treatment, allowing to concentrate therapeutical efforts on a small subgroup of women showing indirect US evidence of fetal hyperinsulinization. Such a selective approach allowed to obtain a near-normalization of fetal growth, with clear advantages on global pregnancy outcome.

Adult↗
PubMed2004

Relationship between plasma fatty acid profile and antioxidant vitamins during normal pregnancy.

OBJECTIVE: To study the changes of plasma fatty acids and lipophilic vitamins during normal pregnancy. DESIGN: Plasma fatty acid profile and the concentration of carotenoids, tocopherols and retinol were measured in healthy women at the first and third trimesters of pregnancy, at delivery, and in cord blood plasma. RESULTS: Maternal plasma cholesterol and triglycerides increased from the first to the third trimester of gestation, while free fatty acids progressively increased from the first trimester through the third trimester to delivery, suggesting an enhanced lipolytic activity. Plasma levels of alpha- and gamma-tocopherols, lycopene and beta-carotene also progressively increased with gestation, but values in cord blood plasma were lower than in mothers at delivery. Retinol levels declined with gestational time and values in cord blood plasma were even lower. The proportion of total saturated fatty acids increased with gestation, and it further increased in cord blood plasma. Total n-9 fatty acids remained stable throughout pregnancy, and slightly declined in cord blood plasma, the change mainly corresponding to oleic acid. Total n-6 fatty acids declined with gestation and further decreased in cord blood plasma, and a similar trend was found for linoleic acid. However, arachidonic acid declined in women at the third trimester and at delivery as compared to the first trimester, but was enhanced in cord blood plasma. The proportion of total n-3 fatty acids remained stable throughout pregnancy at the expense of decreased alpha-linolenic acid at delivery but enhanced eicosapentaenoic acid, with small changes in docosahexaenoic acid. The proportion of these n-3 fatty acids was similar in cord blood plasma and maternal plasma at delivery. CONCLUSIONS: Owing to the different placental transfer mechanisms and fetal capability to metabolize some of the transferred fatty acids and lipophilic vitamins, the fetus preserves the essential compounds to assure their appropriate availability to sustain its normal development and to protect itself from the oxidative stress of extrauterine life. SPONSORSHIP: The studies reported herein have been carried out with financial support from the Commission of the European Communities, specific RTD programme 'Quality of Life and Management of Living Resources', QLK1-2001-00138 'Influence of Dietary Fatty Acids on the Pathophysiology of Intrauterine Foetal Growth and Neonatal Development' (PeriLip). It does not necessarily reflect its views and in no way anticipates the Commission's future policy in this area.

Adult↗
PubMed2004

Plasma amino acid concentrations throughout normal pregnancy and early stages of intrauterine growth restricted pregnancy.

OBJECTIVES: Assessment of maternal plasma amino acids during normal gestation and in early stages of intrauterine growth restriction (IUGR). STUDY DESIGN: Plasma amino acid concentrations were measured in: (1) non-pregnant women (n=7); (2) normal pregnant women in the first (n=13), second (n=17) and third (n=12) trimester; and (3) pregnant women in the first trimester with later development of IUGR (n=8). Amino acid levels were quantified by electrochemical detection in a reversed-phase high-performance liquid chromatography (HPLC) system. RESULTS: The levels of most essential and non-essential amino acids changed markedly in the first trimester during normal pregnancy and thereafter remained almost constant. In the first trimester of IUGR, a number of both essential and non-essential amino acids were significantly different from those observed in normal pregnancies, with values more similar to those observed in non-pregnant women. CONCLUSIONS: Levels of most maternal amino acids decrease and some increase during early gestation reflecting a metabolic adaptation that occurs in normal pregnancies. Pregnancies that later develop IUGR show a lack of these adaptations for a significant number of both essential and non-essential amino acids, suggesting a lack of adaptation.

Adaptation, Physiological↗
PubMed2003

Fetal development after assisted reproduction--a review.

Despite the success of assisted reproduction technologies (ART) in allowing conception in couples with infertility problems, a growing body of evidence points to implication of ART on fetal birth weight alterations, fetal malformations, chromosomal aneuploidies and syndromes related to genomic imprinting modifications. Different causes can be accounted for to explain the increased risk of fetal defects. Pregnancies generated by ART differ from spontaneously achieved pregnancies in that gametes and embryos are cultured in vitro, more than one conceptus is transferred into the uterine cavity, and the time of transfer is different to what occurs in normal conditions. Epigenetic reprogramming of gene expression has been advocated in relation to the gamete and embryo manipulation, with a significant role of genomic imprinting in determining changes in fetal growth. Moreover, the maternal environment, with the ovarian hyperstimulation of the beginning of pregnancy, could alter the maternal response to the early phases of trophoblast invasion. There are suggestions that placental weights and placental/fetal weight ratios are increased in these pregnancies resembling the model of maternal undernutrition in the early phases of pregnancy. Therefore concern has also arisen around the possible long term and transgenerational effects of assisted reproduction procedures and studies should be carried out to evaluate these possibilities.

Adult↗
PubMed2003

Foetal and placental weights in relation to maternal characteristics in gestational diabetes.

An increased placental weight has been reported in pregnancies complicated with gestational diabetes (GDM). We have analysed foetal (F) and placental weight (P) and foetal length in 143 consecutive normal (N) and 132 GDM pregnancies in relation to type of treatment and to a number of maternal variables. All N pregnancies had a negative oral glucose challenge test at 24-28 weeks. GDM was diagnosed at 28-32 weeks by a 100-gm, 3-h oral glucose tolerance test (OGTT). Treatment was diet (D: n=82) or diet plus insulin (D+I: n=50) according to self-monitoring of blood glucose. A significant difference was observed between N and GDM pregnancies for maternal age (N=30.6+/-5.38 years; GDM=33.2+/-4.53 years; P< 0.001), pre-pregnancy weight (N=58.2+/-8.0 kg; GDM=63.0+/-12.9 kg; P< 0.001) and BMI (N= 21.9+/-2.63; GDM=24.4+/-4.71;P< 0.001). Foetal weight became significantly higher in the GDM group (N=3274.2+/-296.0 g; GDM=3287.1+/-474.1g; P< 0.05) once correction was made for the significant difference in gestational age between the two groups (N=39.4+/-1.17 weeks; GDM=38.8+/-1.39 weeks; P< 0.001). Significantly higher placental weights (N=561.87+/-91.0 g; GDM=592.2+/-115.8 g;P< 0.01) and significantly lower F/P weight ratios were found in GDM pregnancies (N=5.96+/-1.02; GDM=5.69+/-1.13; P< 0.05). In GDM pregnancies a significantly negative correlation was found between the OGTT response and weights of foetus and placentae at delivery, suggesting that both foetal and placental growth are affected by maternal insulin resistance.

Adult↗
PubMed2003

Advanced tubal pregnancy associated with severe fetal growth restriction: a case report.

A case is described of advanced tubal pregnancy associated with severe fetal growth restriction delivered at 27 weeks. The placenta was implanted on the salpinx and on the uterotubal angle. Progressing tubal pregnancy and its placental histological characteristics could be a model of placental dysfunction typically associated with intrauterine growth restriction.

Adult↗
PubMed2002

Cationic amino acid transporter activity in the syncytiotrophoblast microvillous plasma membrane and oxygenation of the uteroplacental unit.

The purpose of this study was to determine whether there is any relationship between the activity of cationic amino acid transporters in the microvillous plasma membrane (MVM) of the syncytiotrophoblast and the oxygenation of the uteroplacental unit. Oxygenation data were obtained at the time of caesarean section from the uterine veins, the maternal radial artery and the umbilical vessels of 7 normal (AGA) and 13 intrauterine growth restricted (IUGR) pregnancies. Microvillous plasma membranes were isolated from the same placentas and the activity of the system y(+) and y(+)L cationic amino acid transporters determined by measuring (3)H- l -arginine uptake in the presence and absence of l -glutamine. In IUGR pregnancies uterine venous Po(2) was significantly higher (AGA=44.7+/-8.0 mmHg; IUGR=57.2+/-2.3 mmHg, P< 0.05) and umbilical venous Po(2) was significantly lower (AGA=33.4+/-3.0 mmHg; IUGR=25.1+/-2.0 mmHg, P< 0.05) than in AGA pregnancies. System y(+)L activity, but not system y(+) activity, was inversely correlated with uterine venous Po(2) (P< 0.01; r(2)=0.4) in AGA and IUGR pregnancies. In IUGR pregnancies without associated maternal pre-eclampsia, y(+)L activity, but not y(+) activity, was also directly related to the umbilical O(2) content difference (P< 0.01; r(2)=0.9). A significant negative correlation was found between system y(+) and the umbilical O(2) content difference in AGA pregnancies (P< 0.01; r(2)=0.9). Our data are consistent with the hypothesis that in IUGR fetuses uterine oxygenation is not reduced and can be increased. The inverse correlation between system y(+)L activity and uterine venous Po(2) and the correlations with umbilical venous-arterial O(2) content difference suggest a relationship between cationic amino acid transporter activity and oxygen tension in the uteroplacental unit.

Adult↗
PubMed2002

Intrauterine growth of normal thyroid.

In this study we describe fetal thyroid growth during gestation and establish normal reference values using a simple linear ultrasound measurement of the thyroid. A total of 1180 normal singleton pregnancies, with no known risk factors for thyroid disorders, were enrolled from 12 to 39 weeks of gestation. The thyroid antero-posterior diameter was measured on a transverse axial plane through the fetal neck. The best fit regression was a power equation: thyroid diameter = 0.2412 weeks(1.0278) (r(2) = 0.55). The percentiles smoothed curves were calculated for each week. In conclusion, the results of the present study support previous findings that the fetal thyroid grows between 12 and 39 weeks of gestation with a steepest increase during the second trimester, that is when the fetal thyroid becomes functionally active. The normal ranges of this simple index of thyroid growth can be useful both as screening and for the clinical evaluation of pregnant patients with thyroid disorders.

Female↗
PubMed2001

Mutations in the thrombomodulin and endothelial protein C receptor genes in women with late fetal loss.

Late fetal loss can be associated with placental insufficiency and coagulation defects. Thrombomodulin (TM) and the endothelial protein C receptor (EPCR) are glycoprotein receptors expressed mainly on the endothelial surface of blood vessels and also in the placenta; they both play a key physiological role in the protein C anticoagulant pathway. Defects in these proteins might play an important role in the pathogenesis of late fetal loss. We performed a case-control study in 95 women with unexplained late fetal loss (> 20 weeks), to elucidate whether TM or EPCR gene mutations were associated with an increased risk for this complication of pregnancy. The control group comprised 236 women who gave birth to at least one healthy baby and had no history of late fetal death or obstetrical complications. The entire TM and EPCR genes, including the promoter region, were screened. In total, five mutations were identified in the TM gene in 95 patients and three in 236 control subjects, and two mutations were identified in the EPCR gene in 95 patients and one in 236 control subjects. The relative risk for late fetal loss when having a mutation in the TM or EPCR gene was estimated by an odds ratio of 4.0 (95% CI 1.1-14.9). In conclusion, identified mutations in the TM and EPCR genes of women with unexplained fetal loss are more prevalent compared with women with no obstetrical complications.

Abortion, Habitual↗