Placentas Of Gestational Ages Research Articles

Association between trimester-specific prenatal air pollution exposure and placental weight of twins

IntroductionThis study investigates the association between maternal exposure to particulate matter (PM10) and nitric dioxide (NO2) during the first, second and third trimester and placental weight and birth weight/placental weight (BW/PW) ratio in twins at birth. MethodsCross-sectional data of 3340 twins from the East Flanders Prospective Twin Survey was used. Air pollutant exposure was estimated via spatial temporal interpolation. Univariable and multivariable mixed model analyses with a random intercept to account for the relatedness of newborns were conducted for twins with separate placentas. Twin pairs with one placental mass were studied with linear and logistic regression. ResultsIn the third trimester, for each 10 μm/m3 increase in PM10 or NO2 placental weight decreased −19.7 g (95%-C.I. −35.1; −4.3) and −17.7 g (95%-C.I. −30.4; −0.5) respectively, in moderate to late preterm twins with separate placentas. Consequently, BW/PW ratio increased with higher air pollution exposure. PM10 exposure in the last week of pregnancy was associated with a higher odds ratio (OR) of 1.20 (95%-C.I. 1.00; 1.44) for a “small for gestational age placenta” (placental weight <10th percentile). Conversely, first trimester air pollutant exposure was associated with lower ORs of 0.55 (95%-C.I. 0.35; 0.88) and 0.60 (95%-C.I. 0.42; 0.84). DiscussionThe association of PM10 and NO2 on placental weight is trimester-specific, differs for twins with one versus two placentas and is most pronounced in moderate to late preterm twins. Longitudinal studies are needed to better understand the relationship between air pollutant exposure and placental weight evolution across different trimesters.

Histopathologic Findings in Large for Gestational Age Placentas and Correlation With CD15 Immunohistochemistry.

The histopathology and CD15 expression in large for gestational age (LGA) placentas is not well-documented. To analyze this, we utilized 2 separate cohorts of placentas from singleton term deliveries. LGA and appropriate for gestational age (AGA) placentas were compared for major histopathologies including acute and chronic inflammation, maternal and fetal vascular malperfusion, delayed villous maturation (DVM), and villous hypervascularity/chorangiosis. We also examined CD15 immunohistochemistry in LGA and AGA placentas. Stained slides were reviewed blinded to the placental weight. Five random 20× fields were scored semi-quantitatively for CD15 staining of villous capillaries on a scale of 0 to 5 (0 = 0%, 1 = 1%-5%, 2 = 5%-25%, 3 = 25%-50%, 4 = 50%-75%, and 5 = >75%). In 1 cohort, 1238 LGA and 7908 AGA placentas were identified. Patients with LGA placentas were significantly more likely to have higher birthweight babies, obesity, hypertensive disorders, pre-gestational, and gestational diabetes. Also, LGA placentas had a higher prevalence of fetal vascular malperfusion, DVM, and villous chorangiosis. In other cohort of 75 LGA placentas and 73 AGA controls, the average score of CD15 staining in villous capillaries was significantly higher amongst LGA placentas. We conclude that LGA placentas have increased expression of CD15 in villous capillary endothelium and higher prevalence of FVM, DVM, and villous chorangiosis than AGA placentas.

Environmental exposure to cadmium impairs fetal growth and placental angiogenesis via GCN-2-mediated mitochondrial stress

Cadmium (Cd), a well-known environmental pollutant, can lead to placental insufficiency and fetal growth restriction. However, the underlying mechanism is unknown. The purpose of our study is to explore the effect of Cd on placental angiogenesis and its mechanism using in vitro and in vivo models. Results found that gestational Cd exposure obviously decreased placental weight and impaired placental vascular development in mice. Correspondingly, Cd exposure evidently downregulated the expression of VEGF-A protein (a key indicator of angiogenesis) and progesterone receptor (PR) in placental trophoblasts. Further experiment showed that lentivirus PR overexpression reversed Cd-caused the reduction of VEGF-A level in human placental trophoblasts. In addition, Cd significantly reduced progesterone level, down-regulated the expression of key progesterone synthase (StAR, CYP11A1), and activated mitochondrial stress response and GCN-2/p-eIF2α signaling in placental trophoblasts. Additional experiment showed that GCN-2 siRNA pretreatment markedly alleviated Cd-activated mitochondrial stress response, restored Cd-downregulated the expression of CYP11A1, reversed Cd-reduced the level of progesterone and VEGF-A in human placental trophoblasts. Finally, our case-control study confirmed that impaired placental angiogenesis and reduced progesterone level occurred in all-cause small for gestational age placenta. Taken together, environmental exposure to Cd impairs fetal growth and placental angiogenesis via GCN-2-mediated mitochondrial stress.

Immaturity for gestational age of microvasculature and placental barrier in term placentas with high weight

ObjectiveVillous immaturity for gestational age is a multifactorial developmental deviation associated with unexpected placental insufficiency, fetal hypoxia and term fetal death. In our previous work we have shown that immature CD15+/CD31+/CD34+ endothelial cells were an important indicator of placental villous immaturity and chronic insufficiency. The aim of this study was to perform a comparative analysis of CD15-marked immaturity in the vessel walls between normal and pathological term placentas of clinically and structurally heterogenous groups with normal, low and high weight. Study design165 clinically normal and pathological placentas of gestational age 39–42 with normal weight (25–75 percentile), low weight (<10 percentile) and high weight (>90 percentile) were structurally and immunohistochemically analyzed. Excluded were placentas with a severe form of placental insufficiency associated with intrauterine fetal death, low APGAR-score, genetic and chromosomal diseases or placental inflammations. The distribution patterns of CD15, CD31 and CD34 were assessed separately in the macrovasculature, microvasculature and placental barrier (PB) − associated capillaries. ResultsAll placental groups with normal weight, low weight and high weight include normal, accelerated villous maturation or villous immaturity independent of their weight. However, a significant increase of immature CD15+/CD31+/CD34+ endothelial cells was detected in microvasculature and PB −associated capillaries in high weight-placentas (63.5%/52.2%), compared to those of normal weight (13.8%/8.2%) and low weight (16.1%/17.8%). The distribution of macrovascular immature CD15+/CD31+/CD34+ endothelial cells did not show such marked differences. ConclusionWe have identified the immaturity of microvasculature and PB −associated capillaries with a pathological persistency of immature CD15+/CD31+/CD34+ endothelial cells and a reduction of terminally differentiated CD15-/CD31+/CD34+ endothelial cells in a structurally and clinically heterogeneous group of high weight-placentas. We assume that immaturity of placental vessels are part of prenatal adaptational processes that can be recruited in different emergency situations and may provide potential targets of therapeutic correction of placental growth and chronic insufficiency. We therefore recommend the use of CD15-based immunophenotyping as a method to identify latent unfavorable conditions of fetal development in the intrauterine life and individual risk of disease in the postnatal period.

Pathologic basis of improving the screening utility of 2-dimensional placental morphology ultrasound

ObjectiveTo determine the utility of measuring maximum placental length in the second trimester to predict a small for gestational age placenta by weight at delivery in clinically high-risk women. Study designPlacental dimensions determined by 2-dimensional (2-D) real-time ultrasound at 19–23 weeks' gestation were compared to post-natal placental weights and pathology in 95 high-risk patients with singleton pregnancies. ResultsMaximum placental length <10.0 cm performed poorly (false positive rate 25.5%) for the detection of a small placenta by weight at delivery. Placental pathology examination revealed eccentric cord insertion to be an important explanation for poor screening test result, since this finding was significantly more common in the false negative group (length ≥10.0 cm, weight <10th percentile) compared with the true negative group (length ≥10.0 cm, weight ≥10th percentile) (15/28 vs. 9/38, Fisher's exact test, p = 0.005). ConclusionsPrediction of reduced placental weight by 2-D ultrasound determination of maximum placental length in clinically high-risk pregnancies confounded by the phenomenon of asymmetric chorion regression. Refinement of 2-D ultrasound methods to include orthogonal plane measurements, or replacement by 3-D techniques is predicted to significantly improve the effectiveness of diagnosing small placentas in-utero.

Methadone Metabolism by Early Gestational Age Placentas

The objective of this study was to identify the enzyme that metabolizes methadone in preterm placentas. Microsomal fractions were obtained from preterm (17 to 34 weeks) placentas (36 total; 12 per each gestational age group) and their activity in metabolizing methadone to 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) was determined. The enzyme catalyzing the reaction was identified by using chemical inhibitors selective for various cytochrome P450 isozymes and monoclonal antibodies raised against them. The metabolism of methadone by microsomes revealed saturation kinetics. Methadone was N-demethylated to EDDP by aromatase. The affinity of methadone to aromatase (apparent Km) did not change with gestation, but the activity of the enzyme (Vmax) increased and varied widely between individual placentas. Aromatase/CYP19 is the placental enzyme metabolizing methadone during pregnancy. The variability in enzyme activity among individuals should be reflected by the concentration of methadone in the fetal circulation and might be one of the factors affecting the incidence and intensity of neonatal abstinence syndrome.

Culture of syncytiotrophoblast for the study of human placental transfer. Part II: Production, culture and use of syncytiotrophoblast

The conditions necessary for producing syncytical syncytiotrophoblast are examined. Tissue disaggregation conditions, culture media composition, different extracellular matrices and the influence of placental gestational age are all assessed. The importance of evaluating the biochemical and functional differentiational state of the cells is also stressed. Evidence is summarized that syncytiotrophoblast in culture is morphologically and ultrastructurally very similar to syncytiotrophoblast in vivo, and what is so far known biochemically is largely consistent with what is known in vivo. Studies published to date on microvillous membrane uptake and release and relationships with intracellular metabolism using syncytiotrophoblast in conventional culture are outlined from the point of view of the advantages and potential of this model. The present state of development of the two-sided model is assessed, mentioning factors to be considered such as the supporting membrane to be used, accounting for passive diffusion and paracellular leak components of transport and dealing with quantitative effects in kinetic studies of the presence of the supporting membrane. It is concluded that satisfactory methods are now in place for preparing pure villous syncytial syncytiotrophoblast in culture from cytotrophoblast derived from term (but not early) placentae, suitable for studying microvillous membrane transport and relationships with intracellular metabolism. Cytotrophoblast from early gestational age placenta may require different conditions to form true syncytiotrophoblast. A two-sided model for studies of overall transfer, basal transport and basal control mechanisms is now available and possibly with some development should be a good model for such investigations.

Gestational changes in nitric oxide synthase activity in the rat placenta.

To assess the importance of nitric oxide (NO) generated in the placenta on pregnancy, nitric oxide synthase (NOS) activities were measured in the rat placentas of different gestational ages. NOS activity was determined by [3H] L-arginine to [3H]-citrulline conversion assay on rat placenta of day 5, 10, 15 and 21 of gestation. NOS activity distributed both in the soluble and particulate fractions. Inhibition of NOS activity by L-arginine analogs confirmed the substrate specificity. The requirement of calcium/calmodulin for the maximal activity indicated that the rat placenta NOS was of a constitutive calcium/calmodulin dependent isoform. The activities in both fractions were higher in the earlier gestational age placentas, decreasing with progression of gestation, and the lowest in the term placentas. Although NOS activity was detected in the placenta throughout gestation, it was highest in the early gestational age placenta, suggesting a possible significant role of NO in early gestation.

Alterations of human placental epidermal growth factor receptor in intrauterine growth retardation.

We studied human placental microvillous EGF receptor (EGFR) and its relationship with maternal and placental features in 14 cases of intrauterine growth retardation. Placental EGFR phosphorylation was significantly decreased or absent in 12 cases of small for gestational age neonates, as shown by SDS-PAGE, autoradiography, and scanning analysis. Specific [125I]EGF binding and Scatchard plots of the binding data showed a decreased number of EGFR in 6 of the 12 cases, with a mean maximal binding capacity of 1.09 +/- 0.32 pmol/mg for high affinity sites (mean control value = 2.30 +/- 0.23 pmol/mg). Most of the hypertensive women and smokers belonged to this subgroup. In three of the remaining six cases of small gestational age placentas with low EGFR phosphorylation, there was no maternal pathology or significant parenchymatous placental lesions. Five showed a 175-kD EGFR species when probed by [125I]EGF cross-linking and Western blotting with RK2 and C-Term, two polyclonal anti-EGFR antibodies, suggesting abnormal transduction of the EGF-induced signal. The sixth placenta yielded a single 145-kD EGFR band consistent with an abnormal EGFR structure; Western blot analysis showed no immunoreactive band. In conclusion, maternal and placental pathologies in intrauterine growth retardation are associated with various alterations of placental EGFR, pointing out the importance of EGFR ligands in the regulatory pathway of placental and fetal growth.

Localization of alpha-interferon in the human feto-placental unit.

The distribution of alpha-interferon in human placental tissue was investigated by immunocytochemical study of paraffin wax-embedded tissue sections using a sheep alpha-interferon antiserum. Fifty-eight placentas of gestational ages from 8 to 40 weeks were examined. alpha-Interferon was present in the syncytiotrophoblast of the chorionic villi of all placentas and was also in macrophages in 28 cases. The appearances suggest production of interferon in human placental trophoblast and, in view of its diverse biological effects, support the concept of a role for alpha-interferon in the complex series of events required for successful gestation.

Fetal microcirculation of abnormal human placenta I. Scanning electron microscopy of placental vascular casts from small for gestational age fetus

The latex injection-corrosion cast technique coupled with scanning electron microscopy was applied to the study of small for gestational age placentas. The main ultrastructural changes observed in the fetal vasculature of small for gestational age placentas were less branching of arteries and veins, capillaries with variable diameters, and many capillary bud projections; also numerous “H”-shaped anastomoses were present in the capillary network. The corrosion/cast technique approach enabled us to visualize the three-dimensional distribution of arteries, veins, and capillary network as well as the ultrastructural alterations among the various-sized vessels in the abnormal placenta. Light microscopic examination of these placentas revealed numerous syncytial knots and fibrinoid deposits pressing on arteriolar and capillary vessels at different locations. We suggest that the numerous capillary buds and anastomoses are characteristics of neovascularization and may be a compensatory phenomenon of the capillary network. This information could shed new light on alterations of physiologic functions of the pathologic placenta.

Fetal microcirculation of abnormal human placenta II. Scanning electron microscopy of placental vascular casts from fetus with severe erythroblastosis fetalis

The latex injection—corrosion cast technique coupled with scanning electron microscopy was applied to the study of severe Rh sensitization of the placenta. The main observed ultrastructural changes in fetal vasculature in this type of placenta were very similar to those of the small for gestational age placenta; large-sized vessels exhibited less branching than those of the normal placenta, and the capillary network showed numerous vascular buds and “H”-shaped anastomoses. In addition, in Rh-sensitized placentas, the capillary network was remarkably sparse, and the cast also revealed smooth-surfaced veins with distinct U shapes undulating through the placental stroma. These U-shaped veins may be the result of umbilical flow impedance with subsequent umbilical venous hypertension, which stretches the veins into undulating form.

Effect of length of gestation on maternal cellular immunity to human trophoblast antigens

Maternal lymphocyte reactivity to human trophoblast antigens was studied in placentas of gestational ages 8 to 14 weeks and 32 to 34 weeks, respectively. Significant trophoblast lysis became apparent after 24 hours' incubation in the latter case compared with a time lag of 72 hours in the terminated gestations. Maternal cellular immunity, therefore, was not detected during the first 3½ months of pregnancy, but was detectable by the time of parturition. The possible significance is discussed with respect to the antigenic stimulus and survival of the fetal allograft.