Laura Avagliano

Effects of gestational diabetes on fetal oxygen and glucose levels in vivo

Objective  Fetal hypoxia and acidemia have been reported in pregestational diabetic pregnancies in relation to poor glycaemic control, but it is still uncertain whether this is the case in apparently well‐controlled gestational diabetes.

Autophagy in term normal human placentas

Autophagy is an inducible catabolic process that responds to environment and is essential for cell survival during stress, starvation and hypoxia. Its function in the human placenta it is not yet understood. We collected 14 placentas: 7 at vaginal delivery and 7 at elective caesarean section after uneventful term pregnancies. The presence of autophagy was assessed in different placental areas by immunoblotting, immunohistochemistry and electron microscopy. We found that autophagy is significantly higher in placentas obtained from cesarean section than in those from vaginal delivery. Moreover there is a significant inverse relationship between autophagy and umbilical arterial glucose concentration.

Placental Amino Acids Transport in Intrauterine Growth Restriction

The placenta represents a key organ for fetal growth as it acts as an interface between mother and fetus, regulating the fetal-maternal exchange of nutrients, gases, and waste products. During pregnancy, amino acids represent one of the major nutrients for fetal life, and both maternal and fetal concentrations are significantly different in pregnancies with intrauterine growth restriction when compared to uncomplicated pregnancies. The transport of amino acids across the placenta is a complex process that includes the influx of neutral, anionic, and cationic amino acids across the microvilluos plasma membrane of the syncytiotrophoblast, the passage through the cytoplasm of the trophoblasts, and the transfer outside the trophoblasts across the basal membrane into the fetal circulation. In this paper, we review the transport mechanisms of amino acids across the placenta in normal pregnancies and in pregnancies complicated by intrauterine growth restriction.

Abnormal spiral artery remodelling in the decidual segment during pregnancy: from histology to clinical correlation

Introduction Modification of the spiral arteries with loss of the muscular vascular wall, invaded by the trophoblasts, represents the goal of the physiological vascular adaptation during human implantation. When physiological vascular changes do not occur, an unfavourable evolution of gestation may develop as suggested by uterine biopsies studies. Aims To evaluate the prevalence of the abnormal spiral arteries modification (ASAM) through the routine examination of placentas, to identify maternal predisposing factors and to examine the correlations between the histological lesion and pregnancy outcome. Methods 1534 consecutive singleton pregnancies were retrospectively analysed. An extensive histological and clinical investigation was performed. Results ASAM was present in 5.8% pregnancies. When compared with cases without ASAM, cases with ASAM exhibited a higher prevalence of pre-eclampsia (10% vs 2%), placental abruption (5.5% vs 0.3%), preterm premature rupture of membranes (7% vs 1.3%) and intrauterine fetal death (18% vs 2.2%). Multivariate analysis showed that the maternal body mass index represents the major maternal pregestational factor that can influence the prevalence of ASAM (OR=1.8, 95% CI 1.1 to 3 in cases with BMI>30 kg/m2). Conclusion The abnormal modification of the decidual segment of the spiral arteries is identifiable at the time of the conventional histopathological placental evaluation and is associated with adverse pregnancy outcome. The identification of the cause of the unfavourable evolution of pregnancy is fundamental for parents, both for counselling and for prevention; the identification of ASAM in such pregnancies might provide additional valuable information.

Stillbirth and fetal growth restriction

Objective: To confirm the role of fetal growth restriction (FGR) as a cause of stillbirth, and to compare diagnostic accuracy of customized fetal growth and population-based standards in identifying FGR within a pathological population of early and late stillbirths. Methods: Retrospective study on a cohort of 189 stillbirths occurred in single pregnancy between January 2006 and September 2011. Unexplained stillbirths, defined by Aberdeen-Wigglesworth and ReCoDe classifications, were evaluated on the basis of fetal birthweight with both Tuscany population and Gardosi customized standards. Unexplained stillbirths have been classified as early or late depending on the gestational age of occurrence. Results: Aberdeen-Wigglesworth classification, applied to the 189 cases of stillbirth, left 94 unexplained cases (49.7%), whereas the ReCoDe classification left only 40 (21%). By applying population standards to the 94 unexplained stillbirths we have identified 31 FGRs (33% of sample), while customized standards identified 54 FGRs (57%). Customised standards identified a larger number of FGRs with respect to population standards during the third trimester (i.e. 51% vs. 25% respectively) than in the second trimester (73% vs. 54% respectively) (p = 0.05). Conclusions: Customized standards have a higher diagnostic accuracy in identifying FGRs especially during the third trimester.

Prenatal magnetic resonance imaging of optic nerve head coloboma

Congenital optic nerve head coloboma represents an important cause of childhood visual impairment and blindness; it can be isolated or, more often, it can be associated with several syndromes. Ultrasound has limitations in depicting the posterior aspect of the fetal eye globe, so prenatal information about ocular coloboma are very scarce. The purpose of this paper was to report prenatal magnetic resonance (MR) imaging features of optic nerve head coloboma.

SNAT2 expression and regulation in human growth-restricted placentas

Background:Amino acid placental delivery is reduced in human intrauterine growth–restricted (IUGR) fetuses, and the activity of placental amino transporters has been consistently shown to be decreased in in vitro studies. We hypothesized lower placental expression and localization of sodium-coupled neutral amino acid transporter 2 (SNAT2 (also known as SLC38A2)), altered levels of intron-1 methylation, and altered distribution of single-nucleotide polymorphisms in human IUGR vs. normal pregnancies.Methods:We studied 88 IUGR and 84 control placentas from singleton pregnancies at elective caesarean section. SNAT2 expression was investigated by real-time PCR and immunohistochemistry. Intron-1 methylation levels were analyzed by pyrosequencing, and single-nucleotide polymorphism distribution was analyzed by allelic discrimination.Results:mRNA levels were significantly decreased in IUGR placentas with reduced umbilical blood flows. Syncytiotrophoblast immunostaining was lower in IUGR placentas than in control placentas. Methylation levels were steadily low in both IUGR and control placentas. SNP genotype and allele frequencies did not differ between the two groups.Conclusion:This is the first study investigating SNAT2 expression and regulation mechanisms in human IUGR placentas. We confirm previous results obtained in rats and cell cultures that support the fundamental role of SNAT2 in fetal growth and well-being, as well as a possible role of oxygen levels in regulating SNAT2 expression, indicating the relevance of hypoxia in IUGR.

Thrombosis of the umbilical vessels revisited. An observational study of 317 consecutive autopsies at a single institution

Thrombosis of the umbilical vessels has been associated with conditions like fetal death, cerebral palsy, and severe fetal distress, which are common causes for litigation in todays obstetrics practice. Although different anatomical conditions of the umbilical cord as well as maternal or fetal pathologies are considered risk factors, the etiology of thrombosis of the umbilical vessels is still obscure in many cases that pathologists handle. We diagnosed 32 cases of umbilical vessel thrombosis in a series of 317 consecutive autopsies of spontaneous intrauterine fetal death selected from a file of 914 fetal and neonatal autopsies. All cases were singleton pregnancies without chromosomal abnormalities or structural malformations. Our data confirm the heterogeneous etiology and pathogenesis of umbilical vessel thrombosis and highlight a much higher incidence of this lesion than what has been previously reported. In addition, they point out the correlation between thrombosis of the umbilical vessels and specific histologic placental patterns that, in turn, might help explain the etiology and pathogenesis of thrombosis of the umbilical vessels.

Prolactin and proinflammatory cytokine expression at the fetomaternal interface in first trimester miscarriage

OBJECTIVE To investigate the expression of prolactin (PRL), PRL-receptor (PRL-R), and the TH1 cytokines interleukin-2 (IL-2), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) at the maternofetal interface. DESIGN Case-control study. SETTING University hospital unit of gynecology and obstetrics and research laboratories. PATIENT(S) Women undergoing suction curettage for spontaneous miscarriage (study group) and voluntary termination of pregnancy (control group) in the first trimester. INTERVENTION(S) Samples of decidua and villi collected and histologically examined at the time of suction curettage. MAIN OUTCOME MEASURE(S) Evaluation of all villous samples for karyotype with only euploid cases included; detection of transcripts of PRL, PRL-R, TNF-α, IFN-γ, and IL-2 by qualitative reverse-transcriptase-polymerase chain reaction (RT-PCR); investigation of pattern and site of expression by immunohistochemistry. RESULT(S) In both groups, PRL-R and IFN-γ were broadly expressed. The expression of PRL was impaired or absent in the villi of the study group compared with controls. Expression of TNF-α was reduced, although not statistically significantly, in both decidual and villous samples of the study group. Immunohistochemical analysis showed the lack of IL-2 expression in decidual specimens of the control group versus the full expression shown in the study group. CONCLUSION(S) Our results highlight the correspondence between PRL expression and vital pregnancy and the involvement of the TH1 cytokines with different specific roles at the implantation site. Prolactin and IL-2 may reciprocally influence expression.

Expression of carbohydrate-antigen sialyl-Lewis a on colon cancer cells promotes xenograft growth and angiogenesis in nude mice.

We investigated the role of carbohydrate antigen sialyl-Lewis a (sLea), an E-selectin ligand and epitope of tumor marker CA19.9, in the development of xenografts in nude mice. To this end, animals were inoculated with the human colon cancer cell line HCT-15, expressing no Lewis antigens, or with a clone expressing sLea (HCT-15-T5). The size of HCT-15-T5 xenografts appeared larger than those of HCT-15 and their average weight was over twice bigger. In both xenografts the mitotic index was found elevated, as determined by Ki-67 assay, and no apoptosis was detected in the tumor cells by both caspase 8 or TUNEL assays. Some apoptotic signals were instead detected in the vessels. Conversely, microvessel density, determined through CD-31 immunohistochemistry, was found 3.2-folds bigger in HCT-15-T5 xenografts (p<0.012). Only the membranes of HCT-15-T5 cells grown as xenografts reacted intensively with the anti CA19.9 antibody 1116-NS-19-9 by immunofluorescence, but not by immunohistochemistry. Unknown structures were instead stained by such technique in both xenografts, as were in mouse tissues not expressing the antigen and in human colon adenocarcinoma. We conclude that expression of sLea on the surface of colon cancer cells improves xenograft growth and is associated with enhanced angiogenesis, while immunohistochemistry with 1116-NS-19-9 antibody appears not suitable to determine CA19.9 expression.