Human Placentation Research Articles

Fetal sex specific differences in human placentation: A prospective cohort study

IntroductionOur objective was to assess fetal sex specific differences in first trimester placental biomarkers of both physiological and pathological pregnancies and their interaction with environmental influences. This study is embedded in the Generation R Study, a prospective cohort study. MethodsOnly live singleton births were included. Linear regression was performed to assess the effect of sex on first trimester placental biomarkers. Interaction analyses were performed to assess interaction of fetal sex with environmental influences. First trimester soluble fms-like tyrosine kinase (s-Flt1), placental growth factor (PLGF), plasminogen activator inhibitor (PAI-2) and homocysteine levels were assessed. ResultsSignificant fetal sex specific differences in placental biomarkers were observed. S-Flt1, PAI-2 and PLGF log transformated concentrations were 0.08 ng/mL (95% CI 0.05; 0.11), 0.07 ng/mL (95% CI 0.06; 0.09) and 0.04 pg/mL (95% CI 0.01; 0.06) higher in case of female as compared to male placentas. In pregnancies complicated by pre-eclampsia (PE), preterm birth (PTB) or a newborn being small for gestational age (SGA) no fetal sex specific differences were observed. Interaction analyses suggest that concentrations of s-Flt1, PLGF and PAI-2 decrease in male placentas in the case of hyperhomocysteinemia but remain equal in female placentas. DiscussionFetal sex affects early placentation processes with discrepancies regarding pregnancies complicated by PE, PTB or a newborn being SGA. This suggests that other mechanisms causing these complications may dominate the fetal sex effect. The differences concerning homocysteine suggest that fetal sex dependent placental gene–environment interactions exist. ConclusionFetal sex specific differences in placental biomarkers exist.

Wnt-dependent T-cell factor-4 controls human etravillous trophoblast motility.

Formation of migratory extravillous trophoblasts (EVTs) is critical for human placentation and hence embryonic development. However, key regulatory growth factors, hormones, and nuclear proteins controlling the particular differentiation process remain poorly understood. Here, the role of the Wingless (Wnt)-dependent transcription factor T-cell factor-4 (TCF-4) in proliferation and motility was investigated using different trophoblast cell models. Immunofluorescence of first-trimester placental tissues revealed induction of TCF-4 and nuclear recruitment of its coactivator β-catenin in nonproliferating EVTs, whereas membrane-associated β-catenin decreased upon differentiation. In addition, EVTs expressed the TCF-4/β-catenin coactivator Pygopus 2 as well as repressors of the Groucho/transducin-like enhancer of split family. Western blotting revealed Pygopus 2 expression and up-regulation of integrin α1 and nuclear TCF-4 in purified first-trimester cytotrophoblasts (CTBs) differentiating on fibronectin. Concomitantly, elevated TCF-4 mRNA, quantitated by real-time PCR, and increased TCF-dependent luciferase reporter activity were noticed in EVTs of villous explant cultures and differentiated primary CTBs. Gene silencing using specific small interfering RNA decreased TCF-4 transcript and protein levels, TCF-dependent reporter activity as well as basal and Wnt3a-stimulated migration of trophoblastic SGHPL-5 cells and primary CTBs through fibronectin-coated transwells. In contrast, proliferation of SGHPL-5 cells and primary cells, measured by cumulative cell numbers and 5-bromo-2'-deoxy-uridine labeling, respectively, was not affected. Moreover, siRNA-mediated down-regulation of TCF-4 in primary CTBs diminished markers of the differentiated EVT, such as integrin α1 and α5, Snail1, and Notch2. In summary, the data suggest that Wnt/TCF-4-dependent signaling could play a role in EVT differentiation promoting motility and expression of promigratory genes.

The FOS Transcription Factor Family Differentially Controls Trophoblast Migration and Invasion

Extravillous trophoblast invasion is a fundamental component of human placentation. Invading trophoblast cells promote blood flow to the conceptus by actively remodeling the uterine vasculature. The extent of trophoblast invasion is tightly regulated; aberrant invasion is linked with several obstetrical complications. However, the transcriptional networks responsible for controlling the extent of trophoblast invasion are not well defined. Previous studies have identified high levels of FOS (FOS, FOSB, FOS-like (FOSL) 1, and FOSL2) proteins in extravillous trophoblast cells. These proteins form part of the activating protein-1 (AP-1) transcription factor complex and are implicated in regulating gene networks controlling cellular invasion in diverse biological systems. Therefore, we hypothesized that FOS family proteins play a role in regulating trophoblast invasion. We assessed expression of FOS family proteins in trophoblast cell lines and human placentae at different gestational ages. FOS, FOSB, and FOSL1 proteins were robustly increased in trophoblast cells subject to wound-based migration assays as well as Matrigel-based invasion assays. FOS knockdown resulted in cessation of proliferation and an induction of migration and invasion concomitant with robust expression of matrix metalloproteinase (MMP) 1, MMP3, and MMP10. Conversely, FOSL1 knockdown abrogated trophoblast migration and invasion and inhibited the production of MMP1, MMP3, and MMP10. In human placenta, FOS was expressed in proximal anchoring villi in conjunction with phospho-ERK. FOSL1 was temporally expressed only in the distal-most extravillous trophoblast cells, which represent a migratory cell population. Therefore, FOS and FOSL1 exert opposing effects on trophoblast invasion.

The Lin28/Let-7 System in Early Human Embryonic Tissue and Ectopic Pregnancy

Our objective was to determine the expression of the elements of the Lin28/Let-7 system, and related microRNAs (miRNAs), in early stages of human placentation and ectopic pregnancy, as a means to assess the potential role of this molecular hub in the pathogenesis of ectopic gestation. Seventeen patients suffering from tubal ectopic pregnancy (cases) and forty-three women with normal on-going gestation that desired voluntary termination of pregnancy (VTOP; controls) were recruited for the study. Embryonic tissues were subjected to RNA extraction and quantitative PCR analyses for LIN28B, Let-7a, miR-132, miR-145 and mir-323-3p were performed. Our results demonstrate that the expression of LIN28B mRNA was barely detectable in embryonic tissue from early stages of gestation and sharply increased thereafter to plateau between gestational weeks 7–9. In contrast, expression levels of Let-7, mir-132 and mir-145 were high in embryonic tissue from early gestations (≤6-weeks) and abruptly declined thereafter, especially for Let-7. Opposite trends were detected for mir-323-3p. Embryonic expression of LIN28B mRNA was higher in early stages (≤6-weeks) of ectopic pregnancy than in normal gestation. In contrast, Let-7a expression was significantly lower in early ectopic pregnancies, while miR-132 and miR-145 levels were not altered. Expression of mir-323-3p was also suppressed in ectopic embryonic tissue. We are the first to document reciprocal changes in the expression profiles of the gene encoding the RNA-binding protein, LIN28B, and the related miRNAs, Let-7a, mir-132 and mir-145, in early stages of human placentation. This finding suggests the potential involvement of LIN28B/Let-7 (de)regulated pathways in the pathophysiology of ectopic pregnancy in humans.

Exploring the world of human development and reproduction.

Susan Fisher has spent her career studying human development, proteomics, and the intersection between the two. When she began studying human placentation, there had been extensive descriptive studies of this fascinating organ that intertwines with the mother's vasculature during pregnancy. Susan can be credited with numerous major findings on the mechanisms that regulate placental cytotrophoblast invasion. These include the discovery that cytotrophoblasts undergo vascular mimicry to insert themselves into uterine arteries, the finding that oxygen tension greatly effects placentation, and identifying how these responses go awry in pregnancy complications such as preeclamsia. Other important work has focused on the effect of post-translational modifications such as glycosylation on bacterial adhesion and reproduction. Susan has also forayed into the world of proteomics to identify cancer biomarkers. Because her work is truly groundbreaking, many of these findings inspire research in other laboratories around the world resulting in numerous follow up papers. Likewise, her mentoring and support inspires young scientists to go on and make their own important discoveries. In this interview, Susan shares what drove her science, how she continued to do important research while balancing other aspects of life, and provides insights for the next generation.

The Risk of Placenta Accreta Following Primary Elective Caesarean Delivery

The rate of abnormal human placentation has risen dramatically, with an increased risk of placenta accreta in older women, women with placenta previa in the present pregnancy, and those with a previous cesarean delivery (CD). This case-control study was performed to determine the association between placenta accreta in a pregnancy complicated by placenta previa and the type of primary CD. Parturients with placenta accreta and placenta previa from 1993 to 2008 were included. Data analysis examined the effects of delivery mode for the primary CD on the development of placenta accreta or its variants in a pregnancy complicated by placenta previa. The primary outcome was the influence of the indication for the primary CD (elective without labor or emergency after some labor) on the subsequent risk of developing placenta accreta. Secondary outcomes were the risk of placenta accreta considering parity, gravidity, uterine surgery before the primary CD, and vaginal delivery before and after the primary CD. Criteria for controls included placenta previa, delivery during the study period, and a history of 1 or more CDs. Statistical analysis was performed using SPSS version 18 for Windows and Logxact 8.1. All tests were 2 sided, and P < 0.05 indicated statistical significance. From 82,667 live births, 88 cases of placenta accreta were identified. The final cohort included 65 women with placenta accreta or variants matched with 101 controls; 67% of cases and 38% of controls delivered at less than 37 weeks’ gestation. Thirty-seven cases (56.9%) had placenta accreta, 15 (23.1%) had placenta increta, and 13 (20.0%) had placenta percreta. Cases and controls differed neither in maternal age, gravidity, or parity nor in other demographic or socioeconomic factors (all P > 0.05). A primary elective CD was performed in 46.2% of the cases and 18.6% of controls (P < 0.001). For women with primary emergency CD, significant differences were noted between cases and controls neither in cervical dilatation or length of labor in the primary labor nor in gestational age or presentation when the primary CD occurred without labor. Compared with women in whom the primary CD occurred after some labor, women whose primary CD occurred without labor were significantly more likely to develop placenta accreta (adjusted odds ratio [aOR], 3.00; 95% confidence interval [CI], 1.47–6.12; P = 0.025). Gravidity (aOR, 0.79; 95% CI, 0.61–1.03, P = 0.063), parity (aOR, 1.12; 95% CI, 0.75–1.66; P = 0.588), previous vaginal delivery (aOR, 0.85; 95% CI, 0.60–1.21; P = 0.364), and previous uterine surgery (aOR, 1.06; 95% CI, 0.53–2.15; P = 0.866) were not associated with placenta accreta with coexisting placenta previa. Women who undergo a primary CD without labor are 3 times more likely to develop placenta accreta in a subsequent pregnancy complicated by placenta previa than women whose primary CD occurred after labor onset. Clinicians should be aware of this risk when counseling women for whom CD is an option. They should consider limiting the availability of elective CD as a choice to women in whom the alternatives of labor with vaginal delivery or the possibility of an emergency CD pose an unacceptable risk to her and the fetus’s well-being.

The chrondroitin sulfate proteoglycan (CSPG4) regulates human trophoblast function

IntroductionTrophoblast growth and invasion of the uterine endometrium are critical events during placentation and are tightly regulated by locally produced factors. Abnormal placentation can result in early miscarriage or preeclampsia and intrauterine growth restriction, leading to impaired fetal and/or maternal health. Chondroitin sulfate proteoglycan 4 (CSPG4) is involved in cancer cell migration and invasion, processes which are critical during placentation but unlike in cancer, trophoblast invasion is highly regulated. CSPG4 expression and function in trophoblast is unknown. We determined CSPG4 expression in human first trimester placenta and implantation sites, and investigated whether CSPG4 influenced proliferation, migration and invasion of a human extravillous trophoblast (EVT) cell line (HTR8/SVneo cells) as a model for extravillous trophoblast (EVT). Methods and resultsImmunoreactive CSPG4 localized to EVT cells in the trophoblast shell, subpopulations of interstitial EVT cells within the decidua and cytotrophoblast cells in placental villi. In HTR8/SVneo cells, siRNA knockdown of CSPG4 stimulated proliferation and decreased migration/invasion. In primary first trimester placental villi explants two cytokines, interleukin 11 (IL11) and leukemia inhibitory factor (LIF) with known roles in trophoblast function, stimulated CSPG4 mRNA expression and immunoreactive protein in the cyotrophoblast. Discussion and conclusionThis is the first demonstration of the production and function of CSPG4 in human placentation. These data suggest that locally produced CSPG4 stimulates human EVT migration and invasion and suggests that IL11 and LIF regulate villous cytotrophoblast differentiation towards the invasive phenotype at least in part via CSPG4.

Subcutaneous injection of orally tolerated proteins in the mother disturbs embryo implantation in mice

Subcutaneous injection of orally tolerated proteins in the mother disturbs embryo implantation in mice

Comparative placentation in the spiny rat Thrichomys laurentinus (Rodentia, Hystricognathi, Echimyidae)

Comparative placentation in the spiny rat Thrichomys laurentinus (Rodentia, Hystricognathi, Echimyidae)

Metabolic response of syncytiotrophoblast mitochondria to maternal obesity

Metabolic response of syncytiotrophoblast mitochondria to maternal obesity

Development and morphology of the inverted yolk sac in the guinea pig (Cavia porcellus)

Although the guinea pig is an important animal model for human placentation, aspects of fetal nutrition are not fully understood, especially in regard to the yolk sac that is regarded to be essential for early development of the embryo. We investigated differentiation by means of histology, histochemistry, immunohistochemistry, and transmission electron microscopy. Data suggest that the guinea pig's yolk sac was not sufficiently developed to facilitate substantial fetal nutrition in early pregnancy. On Day 12, it was a flat, inverted, but avascular structure. This was followed by differentiation to form the typical, highly villous and vascularized condition of advanced gestation. Finally, the yolk sac degenerated toward term. We suggest that the guinea pig and other caviomorphs rely predominantly on hemotrophic nutrition via the placenta even in very early pregnancy. In contrast to the general pattern of mammals, histiotrophic nutrition via yolk sac routes seems to be most essential during mid-gestation.

BMPR2 is required for postimplantation uterine function and pregnancy maintenance

Abnormalities in cell-cell communication and growth factor signaling pathways can lead to defects in maternal-fetal interactions during pregnancy, including immunologic rejection of the fetal/placental unit. In this study, we discovered that bone morphogenetic protein receptor type 2 (BMPR2) is essential for postimplantation physiology and fertility. Despite normal implantation and early placental/fetal development, deletion of Bmpr2 in the uterine deciduae of mice triggered midgestation abnormalities in decidualization that resulted in abnormal vascular development, trophoblast defects, and a deficiency of uterine natural killer cells. Absence of BMPR2 signaling in the uterine decidua consequently suppressed IL-15, VEGF, angiopoietin, and corin signaling. Disruption of these pathways collectively lead to placental abruption, fetal demise, and female sterility, thereby placing BMPR2 at a central point in the regulation of several physiologic signaling pathways and events at the maternal-fetal interface. Since trophoblast invasion and uterine vascular modification are implicated in normal placentation and fetal growth in humans, our findings suggest that abnormalities in uterine BMPR2-mediated signaling pathways can have catastrophic consequences in women for the maintenance of pregnancy.

Circulating matrix metalloproteinase MMP-9 and MMP-2/TIMP-2 complex are associated with spontaneous early pregnancy failure

BackgroundTrophoblast cell (CTB) invasion into the maternal endometrium plays a crucial role during human embryo implantation and placentation. This invasion is facilitated by the activity of matrix metalloproteinases, which are regulated by tissue inhibitors of MMPs (TIMPs).MethodsThis study compares the serum levels of MMP-9, MMP-2/TIMP-2 complex, TIMP-1 and TIMP-2 in 129 patients with ongoing pregnancy (n = 40) or spontaneous early pregnancy failure (n = 89).ResultsMMP-9 was markedly (p < 0.0001) elevated in missed abortions, as was MMP-2/TIMP-2 complex (p < 0.0005). However, the serum levels of TIMP-1 and TIMP-2 were markedly elevated (p < 0.0001) in ongoing pregnancies.ConclusionsHuman placentation is mediated by fetal trophoblastic cells that invade the maternal uterine endometrium. Trophoblast invasion requires a precisely regulated secretion of specific proteolytic enzymes able to degrade the endometrial basement membrane and extracellular matrix. The elevated levels of MMP-9 and MMP-2/TIMP-2 complex may play a role in spontaneous termination of pregnancy.

Human placental trophoblast invasion and differentiation: a particular focus on Wnt signaling

Wingless ligands, a family of secreted proteins, are critically involved in organ development and tissue homeostasis by ensuring balanced rates of stem cell proliferation, cell death and differentiation. Wnt signaling components also play crucial roles in murine placental development controlling trophoblast lineage determination, chorioallantoic fusion and placental branching morphogenesis. However, the role of the pathway in human placentation, trophoblast development and differentiation is only partly understood. Here, we summarize our present knowledge about Wnt signaling in the human placenta and discuss its potential role in physiological and aberrant trophoblast invasion, gestational diseases and choriocarcinoma formation. Differentiation of proliferative first trimester cytotrophoblasts into invasive extravillous trophoblasts is associated with nuclear recruitment of β -catenin and induction of Wnt-dependent T-cell factor 4 suggesting that canonical Wnt signaling could be important for the formation and function of extravillous trophoblasts. Indeed, activation of the pathway was shown to promote trophoblast invasion in different in vitro trophoblast model systems as well as trophoblast cell fusion. Methylation-mediated silencing of inhibitors of Wnt signaling provided evidence for epigenetic activation of the pathway in placental tissues and choriocarcinoma cells. Similarly, abundant nuclear expression of β -catenin in invasive trophoblasts of complete hydatidiform moles suggested a role for hyper-activated Wnt signaling. In contrast, upregulation of Wnt inhibitors was noticed in placentae of women with preeclampsia, a disease characterized by shallow trophoblast invasion and incomplete spiral artery remodeling. Moreover, changes in Wnt signaling have been observed upon cytomegalovirus infection and in recurrent abortions. In summary, the current literature suggests a critical role of Wnt signaling in physiological and abnormal trophoblast function.

Human pluripotent stem cells as alternative models to study trophoblast development

OPINION article Front. Physiol., 17 December 2013Sec. Craniofacial Biology and Dental Research https://doi.org/10.3389/fphys.2013.00374

Uterus transplantation in the human: a complex surgical, medical and ethical challenge

As discussed in the current issue of this journal, uterine transplant- ation in the human is becoming a real possibility, and a range of re- search and ethical criteria have been proposed to regulate its introduction (Del Priore et al., 2012). However, the need to ensure a normal pregnancy outcome will become a major clinical challenge for several reasons. First, the vascular anastomoses of the transplanted uterus will be severely tested during pregnancy. The uterus is indeed not a steady-state organ, such as the liver or kidney, but an organ re- quiring exceptional vascular plasticity to accommodate a growing fetus. During gestation, blood supply to the uterus increases from 45 to 750 ml/min, representing 25% of the cardiac output at term. Furthermore, deep placentation in humans involves transform- ation of a relative small number of spiral arteries into large vessels that provide 90% of uterine blood flow to the intervillous space of the placenta by midpregnancy. Without high-quality vascular anasto- moses that can accommodate such a dramatic increase in blood flow in a short space of time, fatal placental ischemia during pregnancy may be unavoidable. Achieving an adequate level of vascular plasticity in the transplanted uterus remains a major challenge. Autotransplantation in the porcine model using a microvascular anastomotic technique failed because of

Evolution of Placental Function in Mammals: The Molecular Basis of Gas and Nutrient Transfer, Hormone Secretion, and Immune Responses

Placenta has a wide range of functions. Some are supported by novel genes that have evolved following gene duplication events while others require acquisition of gene expression by the trophoblast. Although not expressed in the placenta, high-affinity fetal hemoglobins play a key role in placental gas exchange. They evolved following duplications within the beta-globin gene family with convergent evolution occurring in ruminants and primates. In primates there was also an interesting rearrangement of a cassette of genes in relation to an upstream locus control region. Substrate transfer from mother to fetus is maintained by expression of classic sugar and amino acid transporters at the trophoblast microvillous and basal membranes. In contrast, placental peptide hormones have arisen largely by gene duplication, yielding for example chorionic gonadotropins from the luteinizing hormone gene and placental lactogens from the growth hormone and prolactin genes. There has been a remarkable degree of convergent evolution with placental lactogens emerging separately in the ruminant, rodent, and primate lineages and chorionic gonadotropins evolving separately in equids and higher primates. Finally, coevolution in the primate lineage of killer immunoglobulin-like receptors and human leukocyte antigens can be linked to the deep invasion of the uterus by trophoblast that is a characteristic feature of human placentation.

O103 EFFICACY OF HUMAN PLACENTAL EXTRACT AND LYCOPENE IN CLEARING INFLAMMATORY CERVICAL SMEARS

International Journal of Gynecology & ObstetricsVolume 119, Issue S3 p. S296-S297 Free communication (oral) presentations O103 EFFICACY OF HUMAN PLACENTAL EXTRACT AND LYCOPENE IN CLEARING INFLAMMATORY CERVICAL SMEARS N. Bhatla, N. BhatlaSearch for more papers by this authorS. Shree, S. ShreeSearch for more papers by this authorS.R. Mathur, S.R. MathurSearch for more papers by this authorA. Kriplani, A. KriplaniSearch for more papers by this authorN. Agarwal, N. AgarwalSearch for more papers by this authorS. Vashist, S. VashistSearch for more papers by this authorV. Sreenivas, V. SreenivasSearch for more papers by this author N. Bhatla, N. BhatlaSearch for more papers by this authorS. Shree, S. ShreeSearch for more papers by this authorS.R. Mathur, S.R. MathurSearch for more papers by this authorA. Kriplani, A. KriplaniSearch for more papers by this authorN. Agarwal, N. AgarwalSearch for more papers by this authorS. Vashist, S. VashistSearch for more papers by this authorV. Sreenivas, V. SreenivasSearch for more papers by this author First published: 22 October 2012 https://doi.org/10.1016/S0020-7292(12)60533-5AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume119, IssueS3Abstracts of XX FIGO World Congress of Gynecology and ObstetricsOctober 2012Pages S296-S297 RelatedInformation

Cytomegalovirus Impairs Cytotrophoblast-Induced Lymphangiogenesis and Vascular Remodeling in an in Vivo Human Placentation Model

We investigated human cytomegalovirus pathogenesis by comparing infection with the low-passage, endotheliotropic strain VR1814 and the attenuated laboratory strain AD169 in human placental villi as explants in vitro and xenografts transplanted into kidney capsules of SCID mice (ie, mice with severe combined immunodeficiency). In this in vivo human placentation model, human cytotrophoblasts invade the renal parenchyma, remodel resident arteries, and induce a robust lymphangiogenic response. VR1814 replicated in villous and cell column cytotrophoblasts and reduced formation of anchoring villi in vitro. In xenografts, infected cytotrophoblasts had a severely diminished capacity to invade and remodel resident arteries. Infiltrating lymphatic endothelial cells proliferated, aggregated, and failed to form lymphatic vessels. In contrast, AD169 grew poorly in cytotrophoblasts in explants, and anchoring villi formed normally in vitro. Likewise, viral replication was impaired in xenografts, and cytotrophoblasts retained invasive capacity, but some partially remodeled blood vessels incorporated lymphatic endothelial cells and were permeable to blood. The expression of both vascular endothelial growth factor (VEGF)-C and basic fibroblast growth factor increased in VR1814-infected explants, whereas VEGF-A and soluble VEGF receptor-3 increased in those infected with AD169. Our results suggest that viral replication and paracrine factors could undermine vascular remodeling and cytotrophoblast-induced lymphangiogenesis, contributing to bleeding, hypoxia, and edema in pregnancies complicated by congenital human cytomegalovirus infection.

The fetomaternal interface in the placenta of three species of armadillos (Eutheria, Xenarthra, Dasypodidae)

BackgroundPlacental characters vary among Xenarthra, one of four supraordinal clades of Eutheria. Armadillos are known for villous, haemochorial placentas similar to humans. Only the nine-banded armadillo has been well studied so far.MethodsPlacentas of three species of armadillos were investigated by means of histology, immunohistochemistry including proliferation marker, and transmission and scanning electron microscopy.ResultsThe gross anatomy differed: Euphractus sexcinctus and Chaetophractus villosus had extended, zonary placentas, whereas Chaetophractus vellerosus had a disk. All taxa had complex villous areas within the maternal blood sinuses of the endometrium. Immunohistochemistry indicated the validity of former interpretations that the endothelium of the sinuses was largely intact. Tips of the villi and the columns entering the maternal tissue possessed trophoblast cell clusters with proliferation activity. Elsewhere, the feto-maternal barrier was syncytial haemochorial with fetal vessels near the surface.ConclusionsDifferences among armadillos occurred in regard to the extension of the placenta, whereas the fine structure was similar. Parallels to the human suggest that armadillos are likely to be useful animal models for human placentation.