The branching pattern of villous capillaries and structural changes of placental terminal villi in type 1 diabetes mellitus

Maternal diabetes is associated with changes of the placental structure. These changes include great variability of vascularity manifested by strikingly hypovascular as well as hypervascular terminal villi. In this paper, normal placental terminal villi and pathological villi of type 1 diabetic placentas were compared concerning the structure of villous stroma, spatial arrangement of villous capillary bed and quantitative assessment of capillary branching pattern. Formalin fixed and paraffin embedded specimens of 14 normal and 17 Type 1 diabetic term placentas were used for picrosirius staining, vimentin and desmin immunohistochemistry and confocal microscopy. 3D models of villi and villous capillaries were constructed from stacks of confocal optical sections. Hypervascular as well as hypovascular villi of diabetic placenta displayed changed structure of villous stroma, i.e. the collagen envelope around capillaries looked thinner and the network of collagen fibers seemed less dense. The desmin immunocytochemistry has shown that stromal cells of hypervascular as well as hypovascular villi appeared nearly or completely void of desmin filaments. In comparison with normal villi, capillaries of hypovascular villi had a smaller diameter and displayed a markedly wavy course whereas in hypervascular villi numerous capillaries occurred in reduced stroma and often had a large diameter. The quantitative assessment of capillary branching has shown that villous capillaries are more branched in diabetic placentas. It is concluded that type 1 maternal diabetes enhances the surface area of the capillary wall by elongation, enlargement of diameter and higher branching of villous capillaries and disrupts the stromal structure of terminal villi.     

Morphometric investigations of terminal villi of diabetic placentas in relation to the White classification of diabetes mellitus

In this morphometric study, terminal villi of 22 placentas of maternal diabetes mellitus were compared with the results in terminal villi of 22 normal placentas. The results demonstrate that there is a distinct retardation in maturation, statistically significant with bigger cross sectional surfaces of the terminal villi, particularly, when classified in 3000 mu2-steps, the number of the villous vessels and number of epithelial plates. Only slightly decreased in diabetic placentas is the villous vessels cross sectional surface as well as the degree of vascularization. The correlation between the degree of histometric changes and the severity and duration of the disease was separately investigated (classification was done according to White). It could be shown, that the degree of morphologic changes in the terminal villi does not run strictly parallel to the severity and duration of diabetes. The retardation in maturation of the terminal villi increases from White group A to C. In White group D, which is the most severe stage of diabetes mellitus which we investigated, the values of measured parameters are close to the normal placentas. This observation is interpreted as a compensatory reaction of the fetal organ placenta to the reduction in utero placental blood flow in diabetes caused by the diabetic angiopathy.     

Correlation of placental villous immaturity and dysmaturity with clinical control of maternal diabetes]

Strict clinical management of a diabetic mother who is pregnant reduces the risk of neonatal complications. It also reduces the frequency of fetal macrosomia. Diabetic mothers have a heavier placenta than mothers who are not diabetic. Light microscopic placental changes associated with diabetes include villous immaturity and dysmaturity. We have examined the placentas of 27 diabetic mothers whose maternal hemoglobin A1c (HbA1C) levels were measured throughout pregnancy. None of these placentas had a trimmed weight in excess of 600 grams. Eighteen of 27 specimens had immature villi. Four had dysmature villi. Three placentas had fibromuscular sclerosis within the villi. Five had cholangiosis and there was one cholangioma. Villous immaturity was present in 16 of 18 mothers whose HbA1C was more than 5.6% of the total hemoglobin. We found villous immaturity in 2 of 5, within 5.1-5.5% HbA1C. There was no villous immaturity in four cases whose HbA1C was less than 5.0% total hemoglobin. Our findings indicate that maternal hyperglycemia during pregnancy is associated with placental immaturity and dysmaturity.     

Villous histomorphometry and placental bed biopsy investigation in Type I diabetic pregnancies

Insulin-dependent diabetes mellitus (Type I) is associated with disregulation of the glucose and oxygen metabolic pathways during pregnancy, both of which affect placental villous development. Term complete placentas and placental bed biopsies, between 37 and 40 weeks, from 12 singleton pregnancies complicated by Type I diabetes were collected following delivery by elective Caesarean section. The controls consisted of 10 term placentas from uncomplicated pregnancies delivered by elective Caesarean section. Villous morphology was investigated using unbiased histomorphometric techniques, in relation to the degree of transformation of the spiral arteries and the presence of fetal macrosomia. A significant increase in fetal and placental weights, placental volume, volumes of the intervillous space and the trophoblast was found in the diabetic group compared to the controls. A significant reduction in the villous membrane specific diffusing capacity was observed between the diabetic and control groups (1.32 vs 1.72 cm3 min(-1)mmHg(-1)kg(-1), P=0.032). A significant increase in the volume of the intermediate and terminal villi, the surface area of the villi and of the fetal capillaries, and the harmonic thickness of the villous membrane was found in the macrosomic subgroup compared to the controls. There were no differences between the hypertensive subgroup with histological evidence of partial transformation of the spiral arteries and the controls. These data indicate that placental development in insulin-dependent diabetic pregnancies is affected differentially when pregnancies complicated by fetal macrosomia are separated from those complicated by maternal hypertensive disorders with partial transformation of the spiral arteries. The reduction in the specific diffusing capacity of the villous membrane may contribute to the fetal hypoxia and increased fetal and neonatal morbidity associated with diabetes.     

Apoptosis in placentas from human T-lymphotropic virus type I-seropositive pregnant women: a possible defense mechanism against transmission from mother to fetus.

OBJECTIVE: The mechanism by which the placenta serves as the barrier against mother-to-fetus transmission of microorganisms remains to be elucidated. Programmed cell death, apoptosis, is considered a cellular defense mechanism against infection. The hypothesis of this study is that apoptosis of human T-lymphotropic virus type I (HTLV-I)-infected placental villous cells is involved in the defense mechanism against mother-to-fetus transmission of HTLV-I. METHODS: Apoptosis was compared in term placentas from eight HTLV-I-seropositive pregnant women and eight HTLV-I-seronegative pregnant women by the terminal deoxynucleotidyl transferase-mediated deoxyuridine nick end-labeling method. In addition, an in vitro cocultivation with an HTLV-I-infected lymphocyte cell line (MT-2 cells) was performed to examine whether placental villous cells were infected with HTLV-I and apoptosis was induced. RESULTS: The incidence of apoptosis-positive cells (nuclei) in placentas from the HTLV-I-seropositive pregnant women was higher than in the HTLV-I-seronegative pregnant women (P < .02). Cocultivation with MT-2 cells showed that trophoblast cells were able to be infected with HTLV-I and that apoptosis was induced in the placental villous cells. CONCLUSION: HTLV-I infection induces apoptosis in the placenta. We speculate that apoptosis may be involved in the defense mechanism of the placenta against mother-to-fetus transmission of HTLV-I.     

Comparison of placental findings in type 1 and type 2 diabetic pregnancies

IntroductionThe aim of this study is to compare placental pathology and related clinical parameters between gravidas with type 1 and type 2 pregestational diabetes.MethodsThis is a retrospective cohort study of women with singleton gestations and pregestational diabetes who delivered at Women and Infants Hospital from 2003 to 2011. Pathology reports, maternal and neonatal outcomes were extracted and compared between the two groups.ResultsIn our cohort, 293 pregnancies were studied, including 117 with type 1 diabetes and 176 with type 2 diabetes. Women with type 1 diabetes had worse glycemic control during pregnancy, as characterized by higher HbA1c values and average fasting and postprandial blood sugars. More infants from the type 1 group were admitted to Neonatal ICU. Pregestational diabetes led to small for gestational age (SGA) placentas in nearly 20% pregnancies and large for gestational age (LGA) placentas in 30% of cases. Both groups shared similar incidences of preeclampsia and significant placental pathology related to uteroplacental (maternal) and fetal circulatory disorders; however, maternal decidual vasculopathy and placentas with insufficiency (fetal-to-placental weight ratio < 10th %tile) were more commonly found in placentas from women with type 2 diabetes.DiscussionBoth types of pregestational diabetes have significant impact on placental growth and development. The comparison between the two groups suggests different pathogenetic mechanisms and may be helpful for better management of diabetic pregnancy.     

Decreased vascularization and cell proliferation in placentas of intrauterine growth-restricted fetuses with abnormal umbilical artery flow velocity waveforms

OBJECTIVE: The purpose of this study was to compare the morphologic features of placentas in severe intrauterine fetal growth restriction with abnormal umbilical artery blood flow velocity waveforms and normal gestation. STUDY DESIGN: Immunohistochemical methods were used to evaluate cell proliferation, vascular density, and alpha-smooth muscle actin expression by stromal cells in a group of 9 age-matched intrauterine growth-restricted and control placentas at 25 to 41 weeks of gestation. RESULTS: Fewer MIB1-positive nuclei were observed in both trophoblast and stromal cell populations in intrauterine growth restriction, which indicates fewer cells in cycle. Furthermore, a greatly reduced vascular density was observed, along with higher levels of alpha-smooth muscle actin expression in stromal cells. CONCLUSION: Intrauterine growth-restricted placentas show reduced cell proliferation in both trophoblast and stromal cell compartments. Peripheral villous vascularization is highly reduced.     

Relative amount of telomeric sequences in terminal villi does not differ between normal term placentas and placentas from patients with well-controlled type 1 diabetes mellitus

We applied qPCR to compare relative telomere length in terminal villi microdissected from term control placentas and placentas of patients suffering from type 1 diabetes. Significant differences were not found in the relative T/S ratios between placental groups or between the diabetic placentas affected and those not affected with chorangiosis. We hypothesize that there is no relationship between decreased placental proliferative ability in maternal diabetes type 1 and telomere shortening.     

妊娠中晚期乙型肝炎表面抗原阳性妇女胎盘感染的研究

目的 探讨乙型肝炎表面抗原（ＨＢｓＡｇ）阳性妇女妊娠中晚期胎盘各层细胞的乙型肝炎病毒感染状况。方法 收集太原市传染病医院妇产科ＨＢｓＡｇ阳性产妇胎盘１６７例（其中足月分娩胎盘１５８例,中期引产胎盘９例）,用免疫组织化学ＡＢＣ染色法检测胎盘蜕膜细胞、滋养层细胞、绒毛间质细胞和绒毛毛细血管内皮细胞ＨＢｓＡｇ和乙型肝炎核心抗原（ＨＢｃＡｇ）。结果 （１）足月分娩胎盘蜕膜细胞、滋养层细胞、绒毛间质细胞和绒毛毛细血管内皮细胞均感染乙型肝炎病毒,以胞浆分布为主,局灶性分布多见。从蜕膜细胞、滋养层细胞、盈盘间质细胞至绒毛毛细血管内皮细胞,乙型肝炎病毒感染率呈下降趋势,总感染率分别为６６．４６％（１０５／１５８）、５８．２３％（９２／１５８）、２７．２２％（４３／１５８）和１２．６６％（２０／１５８）。（２）中期引产胎盘有１例     

Moderate maternal nutrient restriction, but not glucocorticoid administration, leads to placental morphological changes in the baboon (Papio sp.)

The aims of the present study were to describe the ontogeny of spatial relationships between placental components in baboons and to investigate alterations in these indices following (1) moderate maternal nutrient restriction and (2) administration of glucocorticoids to pregnant baboons. We investigated the effects of glucocorticoids since they have been shown to play a role in the altered fetal growth that accompanies maternal nutrient restriction. Glucocorticoids are also given to pregnant women who threaten premature labor to accelerate fetal lung maturation. A third aim was to compare our findings to those in similar conditions in human pregnancy. Volumetric placental development in the baboon was similar to that in the human, although growth of fetal capillaries was slower over the second half of gestation in baboon than in human placentas. Intervillous space (IVS) and villous star volumes were halved at the end of gestation compared to the middle of gestation, as described in the human placenta. When mothers were fed 70% of feed eaten by controls fed ad libitum, placental volumetric structure was unchanged at mid-gestation but was altered by the end of gestation when placental weight, but not fetal weight or length, was decreased. At the end of gestation villous volume and surface area, capillary surface area, and the villous isomorphic coefficient were all decreased, In contrast, IVS hydraulic diameter was increased. All parameters were similar in pregnancies with male and female fetuses, with the exception of fetal capillary volume, which was unchanged in pooled samples and those from male fetuses, but decreased in pregnancies with female fetuses. Glucocorticoid administration during the second half of gestation did not produce any changes in the measured indices of placental composition. In summary, these changes in placental structure, associated with maternal nutrient restriction, would all act to decrease placental transport of nutrients. The influence of MNR on villous capillarization depends on fetal gender.     

Pathologic features of the placenta in women with severe pregnancy complications and thrombophilia.

OBJECTIVE: To compare placental pathology between women with and without thrombophilia who had severe preeclampsia, intrauterine growth retardation, severe abruptio placentae, or stillbirth. METHODS: After delivery, 68 women with singleton pregnancies with one of the above complications were evaluated for an inherited thrombophilia: factor V Leiden, methylenetetrahydrofolate reductase and prothrombin gene mutation, and deficiencies of protein S, protein C, and antithrombin III. Thirty-two women were thrombophilic (group A), and 36 women were not (group B). There was no difference in maternal age, parity, and type of pregnancy complication. A single pathologist examined each placenta. RESULTS: The gestational age at delivery, birth weight, and placental weight were significantly lower in group A. Three parameters showed significant differences between the groups: thrombophilic women had a higher number of villous infarcts (P <.01), more multiple infarcts (P <.05), and a higher incidence of placentas with fibrinoid necrosis of decidual vessels (P <.05). CONCLUSION: Placentas of women with severe complications and thrombophilia have an increased rate of vascular lesions.     

Expression of vascular endothelial growth factor in third-trimester placentas is not increased in growth-restricted fetuses

OBJECTIVE: Vascular endothelial growth factor (VEGF) is considered the growth factor that stimulates vasculogenesis and angiogenesis. Recent studies have demonstrated its role in regulating placental growth and invasion. Its expression can be upregulated by hypoxia. Intrauterine growth restriction (IUGR) is thought to be associated with inadequate placental perfusion, which might result from a failure in the development of the villous vascular network. Our present study was undertaken to examine the relationship between VEGF expression and IUGR in pregnancies with preserved umbilical artery end-diastolic flow. METHODS: VEGF Expression was determined by immunohistochemical analysis of placentas from 17 pregnancies with normal infant birth weight and 17 pregnancies complicated by IUGR. RESULTS: We found no significant differences in the expression of VEGF in villous syncytiotrophoblasts and intermediate trophoblasts in maternal decidua between IUGR and normal pregnancies. However, in both groups there was a strong correlation in the expression of VEGF with villous syncytiotrophoblasts and intermediate trophoblasts. In normal and IUGR pregnancies the infants' Apgar scores at birth were significantly correlated with VEGF staining in both syncytiotrophoblasts and intermediate trophoblasts (P < .05). A strong correlation also was found between cord hematocrit and VEGF staining in villous syncytiotrophoblasts (P < .05), but VEGF staining in intermediate trophoblasts was not correlated with cord hemoglobin or hematocrit. CONCLUSIONS: Our results suggest that VEGF acts in an autocrine and paracrine fashion in both normal and IUGR placentas, and its expression can have an effect on the well being of the infant at birth.     

正常妊娠及妊高征孕妇胎盘组织中细胞凋亡及增殖基因表达的研究

目的 :探讨正常妊娠及妊高征 (PIH)孕妇胎盘组织bcl - 2、bax及ki6 7基因的表达及其相互关系。方法 :采用免疫组化方法测定正常早、中、晚期妊娠 30例及轻、中、重度PIH 36例的胎盘组织bcl - 2、bax及ki6 7的表达。结果 :(1)bcl - 2表达主要定位在绒毛的合体滋养层细胞 (S -cells) ,而bax在S -cells和细胞滋养层细胞 (C -cells)均呈阳性 ,在绒毛间质中bax也呈阳性表达 ,但强度低于滋养层细胞。ki6 7定位于C -cells;(2 )bcl - 2在晚期妊娠组的阳性率低于早、中期妊娠组 (P <0 .0 5 )。ki6 7在正常早、中、晚期妊娠组 ,对照组与PIH组 ,轻、中、重度PIH组之间均有显著性差异 (P <0 .0 1) ;(3)bcl - 2和bax表达及与ki6 7的表达无相关性 (P >0 .0 5 )。结论 :bcl - 2及bax在高水平上达到平衡 ,在胎盘组织中并不起介导细胞凋亡的主导作用 ,而且二者的表达不影响细胞的增殖     

Does fetal gender affect cytotrophoblast cell activity in the human term placenta? Correlation with maternal hCG levels

BACKGROUND: Pregnant women with female fetuses have higher maternal serum human chorionic gonadotropin (hCG) levels than pregnant women with male fetuses. Ki-67, a cell proliferation and activity marker, is confined mostly in the nuclei of villous cytotrophoblasts of the human placenta. In this study, we examined the effect of fetal gender on the cytotrophoblast cell activity in human term placenta, with special regard to maternal serum and cord blood hCG levels. METHODS: Thirty-four uncomplicated, singleton, term pregnancies (17 male and 17 female fetuses) were recruited in the study. hCG was measured in maternal peripheral serum and umbilical cord blood. Placental samples were collected in each patient during the cesarean section. Cytotrophoblast cell activity was measured by using immunohistochemistry for Ki-67 antigen. Ki-67 staining index values of the cytotrophoblasts were compared between the female and male placentas. RESULTS: Maternal serum and cord blood hCG levels were higher in pregnant women with female fetuses than in those carrying male fetuses. There was no sex difference in Ki-67 immunostaining rates of the cytotrophoblast cells. There was no correlation between maternal serum and cord blood hCG levels and Ki-67 staining index values of the cytotrophoblast cells. CONCLUSIONS: The difference in maternal serum and cord blood hCG levels in correlation with the fetal gender is not associated with cytotrophoblast cell activity in the human term placenta. The gender of the fetus does not seem to affect the regulation of cytotrophoblast cell proliferation.     

Running throughout pregnancy: effect on placental villous vascular volume and cell proliferation

Many studies have documented that placental development is altered by a variety of environmental factors which alter placental bed blood flow and/or oxygen delivery. One of these is sustained weight-bearing exercise. The purpose of this investigation was to examine the effects of running throughout pregnancy on villous vascular development and cell proliferation by testing the null hypothesis that continuing a regular running regimen throughout pregnancy has no effect on villous vascular volume or cell proliferation at term. Accordingly, placentae of 11 healthy runners with uncomplicated pregnancies were matched by placental weight, maternal diet and birth weight with those of 11 healthy controls and examined using systematic random sampling and point counting of placental tissues stained immunohistochemically with either an endothelial (CD 31, PECAM-1, endoCam) or a proliferative (Ki-67, MIB-1) marker. The placentae of the runners had greater villous vascular volumes in both absolute (77 +/- 20 cm(3) versus 47 +/- 18 cm(3), p < 0.02) and relative (% of total villous volume: 29 +/- 5% versus 20 +/- 6%, p < 0.003) terms. Likewise, they had a greater proliferation index (45 +/- 14 mitoses/1000 nuclei versus 29 +/- 10 mitoses/1000 nuclei, p < 0.008). We conclude that continuing to run regularly throughout pregnancy increases both absolute and relative villous vascular volume and cell proliferation at term. We also speculate that this exercise effect may have clinical value in cases at risk for anomalous feto-placental growth as increased villous vascular volume should improve feto-placental growth by enhancing placental transfer of oxygen and diffusible substrate.     

Maternal obesity and its effect on placental cell turnover

Abstract

Background: Maternal obesity is a frequent obstetric risk factor, linked with short- and long-term consequences for mother and child, including foetal overgrowth, growth restriction and stillbirth. The mechanisms underlying these pathologies remain unknown but likely involve the placenta.

Aims: To study placental cell turnover in relation to maternal body mass index (BMI).

Methods: Term placental villous tissue was randomly sampled from 24 pregnancies, with a range of maternal BMI of 19.5–49.6. Immunohistochemistry was performed for human chorionic gonadotropin, Ki67 and M30 and image analysis used to calculate syncytiotrophoblast area and proliferative and apoptotic indices. Results were compared categorically between women of BMI 18.5–24.9 (normal), BMI 30.0–39.9 (obese classes 1and 2) and BMI 40+ (obese class 3) and continuously against BMI; p?<?0.05 by the Kruskal–Wallis test or linear regression was considered statistically significant.

Results: Increased maternal BMI was associated with categorical (normal versus obese class 3 and obese classes 1 and 2 versus obese class 3, both p?<?0.05) and continuous (r²?=?0.24, p?=?0.016) reductions in the proliferative index and a continuous reduction (r²?=?0.17, p?=?0.047) in the apoptotic index.

Discussion: Maternal obesity is associated with a dose-dependent reduction in placental villous proliferation and apoptosis which may increase susceptibility to adverse pregnancy outcomes.     

Distinct effects of short- and long-term type 1 diabetes to the placental extracellular matrix and fetal development in mice

PurposeWe have previously shown that the development of complications in the early pregnant decidua and myometrium in mice correlates with diabetes progression. In the current study, we investigated the influence of diabetes progression on the placental extracellular matrix (ECM) and on fetal development at the end of pregnancy.MethodsAlloxan-induced type 1 diabetic female mice were bred either 30–50 days after diabetes induction (D) or 90-110D. Fetal and placental weights were registered at the 19th day of pregnancy together with analysis of gene expression, deposition and turnover of the placental ECM.ResultsThe short-term diabetic group (30-50D) showed elevated embryonic losses and underweight fetuses (89%) with normal weight placentas. In contrast, the long-term group (90-110D) had increased malformations/fetal deaths and underweight fetuses (42%) and heavy placentas (50%). Normal-weight fetuses from the long-term group had placentas with either regular weight and fetal/placental weight ratio or increased weight and low fetal/placental weight ratio. Furthermore, the placentas of the short-term group showed alterations in the synthesis and deposition of collagen types I and V and in the activity of MMP2 whereas placentas of the 90-110D group presented alterations in collagen type III and V and MMP9.ConclusionsDiabetes progression promoted distinct outcomes in pregnancy. Modifications of both synthesis and turnover of ECM occurred even before changes of placental weight were detected. Adjustment of fetal/placental weight ratio or placental enlargement restored normal growth in part of the fetuses from the long-term group.     

Altered perlecan expression in placental development and gestational diabetes mellitus

The proteoglycan perlecan is involved in cell signaling, regulation of growth factor activity, and maintenance of basement membranes. This study aims to investigate the expression of perlecan during placental development and whether hyperglycemia of gestational diabetes mellitus induces the alteration of perlecan expression in placenta. Immunohistochemistry, immunoprecipitation/sodium dodecyl sulfate-polyacrylamide gel electrophoresis, and quantitative real-time PCR were carried out to study the placental perlecan expression at different trimesters of pregnancies and in gestational diabetes mellitus. The perlecan protein was mainly immunolocalized in the trophoblast and vessel basement membranes with some staining in the villous stroma of placental villus. Perlecan was also found to co-localize with laminin and collagen IV in the basement membranes of placenta. The protein and mRNA levels of placental perlecan were significantly decreased as the gestational age increased. However, a significant increase in perlecan expression was observed in the third trimester placentas with gestational diabetes mellitus compared to the gestational age-matched controls. Furthermore, trophoblast cells cultured in a high glucose (30 mM) medium and a high osmotic pressure medium (5.6 mM glucose and 24.4 mM mannitol) showed increased perlecan expression compared to cells cultured in the low glucose (5.6 mM) regular medium. These alterations of perlecan expression may be associated with the structural changes of placenta during maturation. The metabolic effect of high glucose and high osmotic pressure of gestational diabetes mellitus may contribute to the increased perlecan expression of diabetic placentas.     

Fibroblast growth factor-10 and fibroblast growth factor receptors 1-4: expression and peptide localization in human decidua and placenta

The development of the chorionic villous tree into a complex and organized ramified tubular network can be termed branching morphogenesis. Studying the molecular mechanisms involved in this process may contribute to the understanding of pregnancy complications such as preeclampsia. We hypothesized that fibroblast growth factor-10 (FGF-10) and fibroblast growth factor receptors 1-4 (FGFR 1-4) are expressed in human decidual and placental tissues. We analyzed the expression of FGF-10 and FGFRs 1-4 in 1st, 2nd and 3rd trimester placentas, as well as in decidua. RT-PCR and immunohistochemistry were employed to study mRNA and protein expression. FGF-10 was expressed by decidual cells and by cytotrophoblasts of the cytotrophoblast columns during all three trimesters. FGFR 1-4 were expressed in the placenta but not in the decidua. Placental expression of FGFRs was temporally regulated: In 1st trimester placentas, FGFR 1-4 were expressed by Hofbauer cells, FGFR-1 and FGFR-4 were expressed in cytotrophoblast columns, and the latter was also expressed by syncytiotrophoblasts. Similar expression was seen in 2nd trimester placentas with additional expression of FGFR-1 in blood vessel walls. The expression of FGFR-1 and FGFR-4 in the 3rd trimester was comparable to that seen in the 2nd trimester. The expression of FGF-10, FGFR-1 and FGFR-4 in the maternal-fetal interphase suggests their role in decidual-trophoblast interaction. The abundance of FGFR expression in Hofbauer cells implies that mesenchymal-trophoblast interaction is important for regulation of villous development.