Talk:Placenta Development

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Cite this page: Hill, M.A. (2020, December 4) Embryology Placenta Development. Retrieved from

Historic Embryology - Placenta and Fetal Membranes

Original Pages

Related Pages: Villi Development | Maternal Decidua | Placental Abnormalities | Stage 13/14 | Stage22 | Placental Histology | [Placental Vascular Beds | Blood | Blood Vessels | Birth | Stem Cells - Cord Blood

Placenta Links: Placenta - Villi Development | Placenta - Maternal Decidua | Placenta - Abnormalities | Placenta - Stage 13/14 | Placenta - Histology | Placenta - Stage22 | Placenta - Vascular Beds

Placental Abnormalities

  • placenta accreta one abnormally adherent to the myometrium, with partial or complete absence of the decidua basalis.
  • battledore placenta one with the umbilical cord inserted at the edge.
  • placenta circumvallata (circumvallate placenta) one encircled with a dense, raised, white nodular ring, the attached membranes being doubled back over the edge of the placenta.
  • placenta fenestrata one that has spots where placental tissue is lacking.
  • placenta increta placenta accreta with penetration of the myometrium.
  • placenta membranacea one that is abnormally thin and spread over an unusually large area of the myometrium.
  • placenta percreta placenta accreta with invasion of the myometrium to the peritoneal covering, sometimes causing rupture of the uterus.
  • placenta previa low implantation of the placenta so that it partially or completely covers the cervical os. Percentages are used to designate the amount of obstruction; e.g., 100 per cent is total placenta previa, and 50 per cent indicates that about half the opening is obstructed. The condition occurs with greater frequency in women who have had multiple pregnancies or are over 35. The exact cause is not known.


Maternal perception of reduced fetal movements is associated with altered placental structure and function

PLoS One. 2012;7(4):e34851. Epub 2012 Apr 16.

Warrander LK, Batra G, Bernatavicius G, Greenwood SL, Dutton P, Jones RL, Sibley CP, Heazell AE. Source School of Biomedicine, Manchester Academic Health Science Centre, University of Manchester, Manchester, United Kingdom.


BACKGROUND: Maternal perception of reduced fetal movement (RFM) is associated with increased risk of stillbirth and fetal growth restriction (FGR). DFM is thought to represent fetal compensation to conserve energy due to insufficient oxygen and nutrient transfer resulting from placental insufficiency. To date there have been no studies of placental structure in cases of DFM. OBJECTIVE: To determine whether maternal perception of reduced fetal movements (RFM) is associated with abnormalities in placental structure and function. DESIGN: Placentas were collected from women with RFM after 28 weeks gestation if delivery occurred within 1 week. Women with normal movements served as a control group. Placentas were weighed and photographs taken. Microscopic structure was evaluated by immunohistochemical staining and image analysis. System A amino acid transporter activity was measured as a marker of placental function. Placentas from all pregnancies with RFM (irrespective of outcome) had greater area with signs of infarction (3.5% vs. 0.6%; p<0.01), a higher density of syncytial knots (p<0.001) and greater proliferation index (p<0.01). Villous vascularity (p<0.001), trophoblast area (p<0.01) and system A activity (p<0.01) were decreased in placentas from RFM compared to controls irrespective of outcome of pregnancy. CONCLUSIONS: This study provides evidence of abnormal placental morphology and function in women with RFM and supports the proposition of a causal association between placental insufficiency and RFM. This suggests that women presenting with RFM require further investigation to identify those with placental insufficiency.

PMID 22523561

IFPA Award in Placentology lecture: molecular regulation of human trophoblast invasion

Placenta. 2012 Feb;33 Suppl:S55-62. Epub 2011 Oct 21.

Knöfler M, Pollheimer J. Source Department of Obstetrics and Fetal-Maternal Medicine, Reproductive Biology Unit, Medical University of Vienna, Waehringer Guertel 18-20, Vienna, Austria.


Invasion of extravillous trophoblast cell types into maternal uterine tissues is essential for successful human placental development and progression of pregnancy. Whereas endovascular trophoblasts migrate into the maternal spiral arteries, interstitial trophoblasts invade the decidual stroma, colonize the vessels from outside and communicate with diverse uterine cell types such as decidual stromal cells, macrophages and uterine NK cells. For example, interstitial trophoblasts expressing polymorphic human leukocyte antigen-C interact with uterine NK cells through binding to their killer immunoglobulin-like receptors which likely plays a role in trophoblast invasion and reproductive success of pregnancy. Both extravillous trophoblast subtypes are critically involved in the vascular transformation of the spiral arteries into dilated conduits ensuring appropriate blood flow into the intervillous space. Failures in this remodeling process are thought to be associated with severe forms of fetal growth restriction, preeclampsia and other pregnancy complications warranting studies on the molecular regulation of extravillous trophoblast differentiation. Moreover, interstitial trophoblast-derived hormones may regulate diverse biological functions in the decidua. In particular, human chorionic gonadotrophin has been shown to promote angiogenesis and to suppress apoptosis of endometrial stromal cells. In return, decidual cells produce a plethora of soluble factors controlling trophoblast invasion in a time- and distance-dependent manner. However, the underlying mechanisms have not been fully elucidated. Here, we will summarize autocrine as well as paracrine factors regulating invasion of extravillous trophoblasts and discuss critical signaling cascades involved. In addition, we will focus on key regulatory transcription factors controlling cell column proliferation and differentiation of the human extravillous trophoblast. Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID 22019198

The discovery of placenta growth factor and its biological activity

Exp Mol Med. 2012 Jan 31;44(1):1-9.

De Falco S. Source Angiogenesis Laboratory and Stem Cell Fate Laboratory Institute of Genetics and Biophysics 'Adriano Buzzati-Traverso' - CNR - Via Pietro Castellino 111, 80131 Napoli, Italy.


Angiogenesis is a complex biological phenomenon crucial for a correct embryonic development and for post-natal growth. In adult life, it is a tightly regulated process confined to the uterus and ovary during the different phases of the menstrual cycle and to the heart and skeletal muscles after prolonged and sustained physical exercise. Conversly, angiogenesis is one of the major pathological changes associated with several complex diseases like cancer, atherosclerosis, arthritis, diabetic retinopathy and age-related macular degeneration. Among the several molecular players involved in angiogenesis, some members of VEGF family, VEGF-A, VEGF-B and placenta growth factor (PlGF), and the related receptors VEGF receptor 1 (VEGFR-1, also known as Flt-1) and VEGF receptor 2 (VEGFR-2, also known as Flk-1 in mice and KDR in human) have a decisive role. In this review, we describe the discovery and molecular characteristics of PlGF, and discuss the biological role of this growth factor in physiological and pathological conditions.

PMID 22228176

Recruitment of 5' Hoxa genes in the allantois is essential for proper extra-embryonic function in placental mammals

Development. 2012 Jan 4. [Epub ahead of print] Scotti M, Kmita M.


The Hox gene family is well known for its functions in establishing morphological diversity along the anterior-posterior axis of developing embryos. In mammals, one of these genes, Hoxa13, is crucial for embryonic survival, as its function is required for the proper expansion of the fetal vasculature in the placenta. Thus, it appears that the developmental strategy specific to placental mammals is linked, at least in part, to the recruitment of Hoxa13 function in developing extra-embryonic tissues. Yet, the mechanism underlying this extra-embryonic recruitment is unknown. Here, we provide evidence that this functional novelty is not exclusive to Hoxa13 but is shared with its neighboring Hoxa11 and Hoxa10 genes. We show that the extra-embryonic function of these three Hoxa genes stems from their specific expression in the allantois, an extra-embryonic hallmark of amniote vertebrates. Interestingly, Hoxa10-13 expression in the allantois is conserved in chick embryos, which are non-placental amniotes, suggesting that the extra-embryonic recruitment of Hoxa10, Hoxa11 and Hoxa13 most likely arose in amniotes, i.e. prior to the emergence of placental mammals. Finally, using a series of targeted recombination and transgenic assays, we provide evidence that the regulatory mechanism underlying Hoxa expression in the allantois is extremely complex and relies on several cis-regulatory sequences.

PMID 22219351


Area of Wharton's jelly as an estimate of the thickness of the umbilical cord and its relationship with estimated fatal weight

Reprod Health. 2011 Nov 4;8:32.

Barbieri C, Cecatti JG, Surita FG, Costa ML, Marussi EF, Costa JV. Source Department of Obstetrics and Gynecology, School of Medical Sciences, Universidade Estadual de Campinas-UNICAMP, Campinas, São Paulo, Brazil. Abstract BACKGROUND: To build a reference curve for the area of Wharton's jelly (WJ) in low-risk pregnancies from 13 to 40 weeks and to assess its relationship with estimated fetal weight (EFW). METHODS: 2,189 low-risk pregnancies had the area of WJ estimated by ultrasound and the 10th, 50th and 90th percentiles calculated using a third-degree polynomial regression procedure. EFW by ultrasound was correlated with the measurement of the area of WJ. RESULTS: The area of WJ increased according to gestational age (R² = 0.64), stabilizing from the 32nd week onwards. There was a significant linear correlation between area of WJ and EFW up to 26 weeks (R = 0.782) and after that 5t remained practically constant (R = 0.047). CONCLUSION: The area of WJ increases according to gestational age, with a trend to stabilize at around 32 weeks of gestation. It is also linearly correlated with EFW only up to 26 weeks of gestation.

PMID 22054163

A transient placental source of serotonin for the fetal forebrain

Nature. 2011 Apr 21;472(7343):347-50.

Bonnin A, Goeden N, Chen K, Wilson ML, King J, Shih JC, Blakely RD, Deneris ES, Levitt P. Source Zilkha Neurogenetic Institute, Keck School of Medicine of USC, Los Angeles, California 90089, USA.


Serotonin (5-hydroxytryptamine or 5-HT) is thought to regulate neurodevelopmental processes through maternal-fetal interactions that have long-term mental health implications. It is thought that beyond fetal 5-HT neurons there are significant maternal contributions to fetal 5-HT during pregnancy but this has not been tested empirically. To examine putative central and peripheral sources of embryonic brain 5-HT, we used Pet1(-/-) (also called Fev) mice in which most dorsal raphe neurons lack 5-HT. We detected previously unknown differences in accumulation of 5-HT between the forebrain and hindbrain during early and late fetal stages, through an exogenous source of 5-HT which is not of maternal origin. Using additional genetic strategies, a new technology for studying placental biology ex vivo and direct manipulation of placental neosynthesis, we investigated the nature of this exogenous source. We uncovered a placental 5-HT synthetic pathway from a maternal tryptophan precursor in both mice and humans. This study reveals a new, direct role for placental metabolic pathways in modulating fetal brain development and indicates that maternal-placental-fetal interactions could underlie the pronounced impact of 5-HT on long-lasting mental health outcomes. Comment in Nature. 2011 Apr 21;472(7343):298-9.

PMID 21512572

Placental Hofbauer cells and complications of pregnancy

Ann N Y Acad Sci. 2011 Mar;1221:103-8. doi: 10.1111/j.1749-6632.2010.05932.x.

Tang Z, Abrahams VM, Mor G, Guller S. Source Department of Obstetrics/Gynecology and Reproductive Sciences, School of Medicine, Yale University, New Haven, Connecticut, USA.


Hofbauer cells (HBCs) are placental macrophages that are present in the villus across gestation. Despite their identification more than 100 years ago, their specific role in placental function remains largely unelucidated. We initially review aspects of their history and biology as well as evidence for putative sites of origin. To gain insight into their potential function, we then describe complications of pregnancy including villitis of unknown etiology (VUE) and histological chorioamnionitis (HCA), in which alterations in numbers, gene expression, or other characteristics of HBCs have been documented to occur. We further review methods for isolation of HBCs and in vitro studies that explore their role in relation to other major cell types in the placenta and examine their actions in cytokine-mediated inflammation. We conclude that HBCs play a key role in placental pathophysiology, and future advances in their isolation and culture would enable mechanistic insight into their villus function. © 2011 New York Academy of Sciences.

PMID 21401637

Review: Placental syncytiotrophoblast membranes--domains, subdomains and microdomains

Placenta. 2011 Mar;32 Suppl 2:S196-202. Epub 2011 Jan 26.

Riquelme G. Source Physiology and Biophysics, ICBM, Faculty of Medicine, University of Chile, Santiago, Chile.


Human placental syncytiotrophoblast (STB) is an epithelium responsible for materno-fetal exchange. Ions play multiple roles in STB, as in other transport epithelia. We have been interested in the character and functional expression of ion channels in STB membrane fractions. Characterization of ion channels and their relationship with different domains, subdomains and microdomains of STB membranes is important to explain the intracellular mechanisms operating in the placental barrier. The aim of this paper is to summarize our work on this subject. We isolated and purified basal membrane (BM) and two fractions from the apical membrane, a classical fraction (MVM) and a light fraction (LMVM). They were used either for reconstitution into giant liposomes or for transplantation into Xenopus oocyte membranes followed by electrophysiological recordings to characterize chloride and cationic channels in STB from term human placenta. In addition, Western blot analysis, using ion channel antibodies, was performed on purified apical and basal membrane fractions. We also reported the presence of two functional microdomains (lipid rafts) in LMVM and MVM, using detergent resistant membranes (DRMs) and cholesterol-sensitive depletion. Moreover we found evidence of cytoskeletal participation in lipid rafts of different composition. Our results contribute to knowledge of the ion channels present in STB membranes and their participation in the physiology of this epithelium in normal and pathological pregnancies. Copyright © 2011 Elsevier Ltd. All rights reserved.

PMID 21272934

Toxicological pathology in the rat placenta

J Toxicol Pathol. 2011 Jun;24(2):95-111. Epub 2011 Jun 30.

Furukawa S, Hayashi S, Usuda K, Abe M, Hagio S, Ogawa I. Source Biological Research Laboratories, Nissan Chemical Industries, Ltd., 1470 Shiraoka, Minamisaitama, Saitama 349-0294, Japan.


The placenta grows rapidly for a short period with high blood flow during pregnancy and has multifaceted functions, such as its barrier function, nutritional transport, drug metabolizing activity and endocrine action. Consequently, the placenta is a highly susceptible target organ for drug- or chemical-induced adverse effects, and many placenta-toxic agents have been reported. However, histopathological examination of the placenta is not generally performed, and the placental toxicity index is only the placental weight change in rat reproductive toxicity studies. The placental cells originate from the trophectoderm of the embryo and the endometrium of the dam, proliferate and differentiate into a variety of tissues with interaction each other according to the development sequence, resulting in formation of a placenta. Therefore, drug- or chemical-induced placental lesions show various histopathological features depending on the toxicants and the exposure period, and the pathogenesis of placental toxicity is complicated. Placental weight assessment appears not to be enough to evaluate placental toxicity, and reproductive toxicity studies should pay more attention to histopathological evaluation of placental tissue. The detailed histopathological approaches to investigation of the pathogenesis of placental toxicity are considered to provide an important tool for understanding the mechanism of teratogenicity and developmental toxicity with embryo lethality, and could benefit reproductive toxicity studies.

PMID 22272049

Fig. 10. Placental comparison between the rat and human

Evolution and development of fetal membranes and placentation in amniote vertebrates

Respir Physiol Neurobiol. 2011 Aug 31;178(1):39-50. Epub 2011 Apr 4.

Ferner K, Mess A. Source Department of Research, Museum für Naturkunde Leibniz Institute for Research on Evolution and Biodiversity at the Humboldt University Berlin, Berlin, Germany. Abstract We review aspects of fetal membrane evolution and patterns of placentation within amniotes, the most successful land vertebrates. Special reference is given to embryonic gas supply. The evolution of fetal membranes is a prerequisite for reproduction independent from aquatic environments. Starting from a basically similar repertoire of fetal membranes - the amnion, chorion, allantois and yolk sac, which form the cleidoic egg - different structural solutions for embryonic development have evolved. In oviparous amniotes the chorioallantoic membrane is the major site for the exchange of respiratory gases between fetus and outer environment. The richly vascularised yolk sac and allantois in concert with the chorion play an important role in the evolution of placentation in various viviparous amniotes. Highly complex placentas have evolved independently among squamate sauropsids and in marsupial and placental mammals. In conclusion, there seems to be a natural force to improve gas exchange processes in intrauterine environments by reducing the barrier between the blood systems and optimising the exchange areas. Copyright © 2011 Elsevier B.V. All rights reserved.

PMID 21470579

miR-16 and miR-21 Expression in the Placenta Is Associated with Fetal Growth

Maccani MA, Padbury JF, Marsit CJ.

PLoS One. 2011;6(6):e21210. Epub 2011 Jun 15.

Source Department of Pathology and Laboratory Medicine, Brown University, Providence, Rhode Island, United States of America.


BACKGROUND: Novel research has suggested that altered miRNA expression in the placenta is associated with adverse pregnancy outcomes and with potentially harmful xenobiotic exposures. We hypothesized that aberrant expression of miRNA in the placenta is associated with fetal growth, a measurable phenotype resulting from a number of intrauterine factors, and one which is significantly predictive of later life outcomes. METHODOLOGY/PRINCIPAL FINDINGS: We analyzed 107 primary, term, human placentas for expression of 6 miRNA reported to be expressed in the placenta and to regulate cell growth and development pathways: miR-16, miR-21, miR-93, miR-135b, miR-146a, and miR-182. The expression of miR-16 and miR-21 was markedly reduced in infants with the lowest birthweights (p<0.05). Logistic regression models suggested that low expression of miR-16 in the placenta predicts an over 4-fold increased odds of small for gestational age (SGA) status (p = 0.009, 95% CI = 1.42, 12.05). Moreover, having both low miR-16 and low miR-21 expression in the placenta predicts a greater increase in odds for SGA than having just low miR-16 or miR-21 expression (p<0.02), suggesting an additive effect of both of these miRNA. CONCLUSIONS/SIGNIFICANCE: Our study is one of the first to investigate placental miRNA expression profiles associated with birthweight and SGA status. Future research on miRNA whose expression is associated with in utero exposures and markers of fetal growth is essential for better understanding the epigenetic mechanisms underlying the developmental origins of health and disease.

PMID: 21698265


Placental surface shape, function, and effects of maternal and fetal vascular pathology

Placenta. 2010 Oct 6. [Epub ahead of print]

Salafia CM, Yampolsky M, Misra DP, Shlakhter O, Haas D, Eucker B, Thorp J.

Placental Analytics, LLC, 93 Colonial Avenue, Larchmont, NY 10538, USA; Department of Obstetrics and Gynecology and Pediatrics, New York Methodist Hospital, Brooklyn, NY, USA. Abstract

GOAL: In clinical practice, variability of placental surface shape is common. We measure the average placental shape in a birth cohort and the effect deviations from the average have on placental functional efficiency. We test whether altered placental shape improves the specificity of histopathology diagnoses of maternal uteroplacental and fetoplacental vascular pathology for clinical outcomes.

MATERIALS AND METHODS: 1225 Placentas from a prospective cohort had chorionic plate digital photographs with perimeters marked at 1-2 cm intervals. After exclusions of pre-term (n = 202) and velamentous cord insertion (n = 44), 979 (95.7%) placentas were analyzed. Median shape and mean perimeter were estimated. The relationship of fetal and placental weight was used as an index of placental efficiency termed "β". The principal placental histopathology diagnoses of maternal uteroplacental and fetoplacental vascular pathologies were coded by review of individual lesion scores. Acute fetal inflammation was scored as a "negative control" pathology not expected to affect shape. ANOVA with Bonferroni tests for subgroup comparisons were used.

RESULTS: The mean placental chorionic shape at term was round with a radius estimated at 9.1 cm. Increased variability of the placental shape was associated with lower placental functional efficiency. After stratifying on placental shape, the presence of either maternal uteroplacental or fetoplacental vascular pathology was significantly associated with lower placental efficiency only when shape was abnormal.

CONCLUSIONS: Quantifying abnormality of placental shape is a meaningful clinical tool. Abnormal shapes are associated with reduced placental efficiency. We hypothesize that such shapes reflect deformations of placental vascular architecture, and that an abnormal placental shape serves as a marker of maternal uteroplacental and/or fetoplacental vascular pathology of sufficiently long standing to impact placental (and by extension, potentially fetal) development. Copyright © 2010 Elsevier Ltd. All rights reserved.

PMID: 2093328


Understanding placental nutrient transfer--why bother? New biomarkers of fatal growth

J Physiol. 2009 Jul 15;587(Pt 14):3431-40. Epub 2009 May 5.

Sibley CP. Source Maternal and Fetal Health Research Centre, Research School of Clinical and Laboratory Sciences, University of Manchester, Research Floor, St Mary's Hospital, Manchester M13 OJH, UK.


The placenta, in general and the physiology of maternofetal nutrient transfer is under-researched compared to other organs with epithelial transport function, as evidenced, for example, by publication numbers. This report provides reasons why more researchers should become involved in this topic. First, the syncytiotrophoblast, the transporting epithelium of the placenta, though having many basic cell physiology properties similar to those of other transporting epithelia, has several properties which are markedly different. Better information on these might help fundamental understanding of how epithelia in general function as well as improving knowledge of how the syncytiotrophoblast operates. Second, the synctiotrophoblast has a key role in controlling fetal growth, not only by transporting nutrients and waste products of metabolism but also because it increasingly appears to be one site, perhaps even the dominant site, in which integration of, sometimes conflicting, signals between mother and fetus takes place. Finally, better understanding of placental nutrient transfer and especially of how it is regulated by maternal and fetal signals could provide better information on the placental phenotype in fetal growth disorders--information which might contribute to providing better biomarkers which the obstetrician could use to improve early diagnosis of these disorders.

PMID 19417095

Figure 1 Electron micrograph showing the key features of the exchange barrier in the human placenta (Image kindly provided by Dr Carolyn Jones).

Special Issue - The Intra-uterine Environment and Placentation

July 2009 Volume 215, Issue 1 Pages 1–90



The architecture of first trimester chorionic villous vascularization: a confocal laser scanning microscopical study

Hum Reprod. 2007 Aug;22(8):2254-60. Epub 2007 Jun 1.

Lisman BA, van den Hoff MJ, Boer K, Bleker OP, van Groningen K, Exalto N.

Department of Obstetrics and Gynaecology, Academic Medical Centre, University of Amsterdam, PO Box 22700, 1100 DE Amsterdam, The Netherlands. Abstract BACKGROUND: The aim of this study was to investigate normal chorionic villous vascularization using CD31 immunofluorescence and confocal laser scanning microscopy (CLSM) to elucidate the spatial arrangement in terms of connections between vessels and cords and their branching patterns compared to deficient chorionic villous vascularization in complicated pregnancies.

METHODS: A descriptive morphologic study using CLSM after CD31 immunofluorescence staining of placental biopsies from normal pregnancies (n = 20), complete hydatidiform molar pregnancies (CHMs; n = 3) and empty sacs (n = 3), with a well documented gestational age (GA).

RESULTS: In this three-dimensional study, first trimester chorionic villi were occupied by a complex network of mainly cords with redundant connections as early as 5(+5) weeks GA. With increasing GA cords transform into vessels. From about 9 weeks GA onwards, vascular development is characterized by the presence of two large vessels located centrally and surrounded by and connected to a capillary network. In first trimester CHM and empty sacs, we observed a primitive network of mainly cords.

CONCLUSIONS: This first visualization of the spatio-temporal patterns of blood vessel formation in placental villi is characterized by the development of the vasculosyncytial membrane from a complex network of cords and can be regarded as the placental development before it becomes functional at the end of organogenesis.

PMID 17545656

Timing below - gestational age (LMP)

  • 3- 4 weeks (5 and 6 weeks GA) - a complex network of cords and vessels with redundant connections in chorionic villi is seen. This network comprises mainly cords, already connected together. All vessels and cords are connected to each other without any interruptions. The chorionic villus is completely dominated by a network of vascular elements. Vessels and cords are located centrally as well as peripherally and as a consequence contact the overlying trophoblastic layer (Fig. 1A and B). The luminal diameter of the vessels ranges between 10 and 15 µm (Table 1).

  • 5-6 weeks (7 and 8 weeks GA) - chorionic villi are dominated by a capillary network consisting of vessels and cords. The capillary network contains more vessels than cords. At the tip of the chorionic villus, regular small branched off (mesenchymal) chorionic villi are observed containing a conglomeration of CD31 positive cells (Fig. 2). The luminal diameter of the vessels, ranging between 10 and 26 µm, has increased compared with the earlier stage.
  • 7-8 weeks (9 and 10 weeks GA) - chorionic villi are characterized by the presence of two large vessels located centrally and surrounded by and connected to a capillary network at the periphery of the villus. The capillary network contains mainly vessels with a lumen that are in tight contact with the overlying trophoblastic layer (Fig. 3A and B). From this GA onwards, we observed villous projections containing blindly ending capillary sprouts arising from the underlying capillary network. The luminal diameter of the two centrally located vessels varies between 60 and 75 µm, whereas the vessels of the capillary network range between 26 and 34 µm (Table 1).
  • 9-10 weeks (11 and 12 weeks GA) - immature intermediate villi are characterized by the presence of two large vessels surrounded by a capillary network. Within the network, cords are infrequently present. Blindly ending capillary sprouts branching off the capillary network are present (Fig. 4). The centrally located large vessels range between 70 and 90 µm in diameter and are wider than the vessels between 9 and 10 weeks GA. However, the diameter of the vessels of the capillary network is similar to the previous stage


The subplacenta of the red-rumped agouti (Dasyprocta leporina L)

Reprod Biol Endocrinol. 2006 Jun 1;4:31.

Rodrigues RF, Carter AM, Ambrosio CE, dos Santos TC, Miglino MA. Source Department of Surgery, School of Veterinary Medicine, University of Sao Paulo, Sao Paulo, Brazil.


BACKGROUND: Hystricognath rodents have a lobed placenta, comprising labyrinthine exchange areas and interlobular trophoblast. These correspond to the labyrinthine and spongy zones of other rodent placentae. Beneath them, however, is a structure unique to hystricognath rodents called the subplacenta. We here describe the subplacenta of the red-rumped agouti and examine the possible functional correlates of this structure. METHODS: Placentae were collected from early in midgestation to near term of pregnancy and examined by standard histological techniques, immunohistochemistry and transmission electron microscopy. In addition, to study the microvasculature of the subplacenta, vessel casts were inspected by scanning electron microscopy. RESULTS: In the subplacenta, lamellae of connective tissue support a layer of mononuclear cytotrophoblast cells. Beneath this is found syncytiotrophoblast. Clusters of multinuclear giant cells occur in the transition zone between the subplacenta and decidua. There are prominent intercellular spaces between the cytotrophoblast cells. The basal membrane of these cells is often close to fetal blood vessels. The syncytiotrophoblast surrounds an extensive system of lacunae. Microvilli project into these lacunae from the plasma membrane of the syncytiotrophoblast. The syncytial cytoplasm contains electron-dense granules. This is probably the amylase-resistant PAS-positive material identified by histochemistry. The subplacenta is supplied entirely from the fetal circulation. Within it the vessels pursue a tortuous course with sinusoidal dilatations and constrictions. CONCLUSION: The functions that have been attributed to the subplacenta include hormone production. Our findings are consistent with this interpretation, but suggest that hormone secretion is directed towards the fetal circulation rather than the maternal tissues.

PMID 16740154

Good placental histology images


Vasculogenesis, angiogenesis and the molecular organisation of endothelial junctions in the early human placenta

J Vasc Res. 2002 May-Jun;39(3):246-59.

Leach L, Babawale MO, Anderson M, Lammiman M. Source School of Biomedical Sciences, Faculty of Medicine and Health Sciences, University of Nottingham, Queens Medical Centre, UK.


Vasculogenesis and angiogenesis are regulated by the capacity of endothelial cells to adhere to each other and form new tubes. The presence and role of junctional adhesion molecules during physiological vasculogenesis is unknown. Using ultrastructural and immunocytochemical approaches, we compared the junctional phenotype of developing vessels of the first-trimester human placenta with vessels in the last trimester; the latter include newly formed terminal capillaries and the quiescent vascular bed. First-trimester placental vessels contained the adherens junctional molecules, vascular endothelial cadherin and alpha- and beta-catenin but lacked plakoglobin, the component of fully differentiated adherens junctions. Furthermore, these vessels did not contain the transmembrane tight junctional molecules occludin and claudin-1 and -2. This profile reflects the phenotype of terminal capillaries but differs from large vessels of the full-term placenta. Electron microscopic studies revealed that endothelial tight junctions are present in the first-trimester placenta. Thus, occludin and claudin-1 appear to play no part in the formation of endothelial tight junctions, but are a later requirement. In the early placenta, the predominant growth factor appears to be vascular endothelial growth factor (VEGF), whilst at term, angiopoietin-1 was present in large vessels, with intense angiopoietin-2 immunofluorescence (and VEGF) located in terminal villous capillaries. Thus, endothelial junctions in the human placenta possess two distinct molecular phenotypes, i.e. stable or dynamic, dependent on maturity and plasticity. These distinct phenotypes may be influenced by the angiopoietins/VEGF present in the placenta. Copyright 2002 S. Karger AG, Basel

PMID 12097823


Dynamics of immunoglobulins at the feto-maternal interface

Rev Reprod. 1999 May;4(2):81-9.

Saji F, Samejima Y, Kamiura S, Koyama M. Source Department of Gynecology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Japan. Abstract Transplacental transport of maternal immunoglobulin G (IgG) to the developing fetus is extremely important in the protection of the newborn from infection. Although the exact mechanisms of the selective and active transfer of IgG across the placental barrier are not fully understood, receptors for the Fc part of IgG (FcgammaRs) in the placenta are believed to play a key role. Several known Fc receptors, FcgammaRI, FcgammaRII, FcgammaRIII and FcRn (neonatal FcR), demonstrate heterogeneous expression patterns in placenta. Immunohistochemical analysis shows the expression of FcgammaRI on Hofbauer cells in stromal tissue, FcbetaRII on Hofbauer cells and fetal blood endothelium, FcgammaRIII on Hofbauer cells and trophoblasts, and FcRn on syncytiotrophoblasts and endothelial cells. Recent studies provide evidence for important associations among these receptors and transcytosis of IgG, as well as scavenger mechanisms for clearing immune complexes in the placenta during pregnancy.

PMID 10357095


Examination of the placenta

Am Fam Physician. 1998 Mar 1;57(5):1045-54.

Yetter JF 3rd. Source Department of Family Practice, Madigan Army Medical Center, Fort Lewis, Wash, USA.


A one-minute examination of the placenta performed in the delivery room provides information that may be important to the care of both mother and infant. The findings of this assessment should be documented in the delivery records. During the examination, the size, shape, consistency and completeness of the placenta should be determined, and the presence of accessory lobes, placental infarcts, hemorrhage, tumors and nodules should be noted. The umbilical cord should be assessed for length, insertion, number of vessels, thromboses, knots and the presence of Wharton's jelly. The color, luster and odor of the fetal membranes should be evaluated, and the membranes should be examined for the presence of large (velamentous) vessels. Tissue may be retained because of abnormal lobation of the placenta or because of placenta accreta, placenta increta or placenta percreta. Numerous common and uncommon findings of the placenta, umbilical cord and membranes are associated with abnormal fetal development and perinatal morbidity. The placenta should be submitted for pathologic evaluation if an abnormality is detected or certain indications are present. PMID 9518951


Fetal vasculogenesis and angiogenesis in human placental villi

Acta Anat (Basel). 1989;136(3):190-203.

Demir R, Kaufmann P, Castellucci M, Erbengi T, Kotowski A.

Department of Histology and Embryology, Faculty of Medicine, Akdeniz University, Antalya, Turkey. Abstract Placental villi of 5 exactly defined early human specimens ranging from day 21 post conception (p.c.) until day 42 p.c. and from an additional 43 specimens from about 5 to 40 weeks menstrual age have been analyzed ultrastructurally with regard to fetal vasculogenesis and angiogenesis. The following results were obtained: The first cells differentiating at day 21 p.c., probably originating from mesenchymal precursors, are macrophage-like cells. At almost the same time, mesenchymal cells transform into haemangioblastic cell cords which are the forerunners of the capillary endothelium and haematopoietic stem cells. A third cell population related to the fetal circulatory system and derived from the mesenchymal cells are presumptive pericytes. Capillary formation takes place by the aggregation of haemangioblastic cells which are attached to each other by intercellular junctions. The lumen is formed by the dehiscence of the intercellular clefts. A capillary basal lamina cannot be detected earlier than in the last trimester. In this last period of gestation, fetal villous angiogenesis takes place by the proliferation of the existing endothelium and pericytes rather than via haemangioblastic cells.

Vascularization of the placenta takes place around day 21 post conception (p.c.) endothelial progenitor cells appear as cords right beneath the trophoblastic layer. which are called angiogenic cell cords (ACC).

  • These cells proliferate, differentiate and migrate to form main vascular patterns and form primitive vascular tubes (VT), which demonstrate a primitive lumen formation.

PMID 2481376

Placenta Issue

Vol. 54 Nos. 2/3 (2010)

Anthropometry of fetal vasculature in the chorionic plate

Gordon Z, Elad D, Almog R, Hazan Y, Jaffa AJ, Eytan O. J Anat. 2007 Dec;211(6):698-706. Epub 2007 Oct 30. PMID: 17973911

A photomicrograph of the human endometrium on the fourth day of menstruation showing an eroded spiral artery (arrowed) projecting freely into the uterine lumen. b) A photomicrograph of spiral arteries in a rhesus monkey during the phase of ovulation injected with India ink in gelatin. The arrow marks the endometrial–myometrial boundary, and a marked constriction (asterisked) can be seen in the spiral artery in the junctional zone just below. c) Reconstruction from serial sections of a converted spiral artery passing through the myometrium (M) and endometrium (E) before opening into the intervillous space through the basal plate of a term placenta. The widest dimension of the opening is given as 2.4 mm. Reproduced from Refs. [83], [15] and [16] respectively with permission of the Carnegie Institute of Washington.

Immunology of placentation in eutherian mammals

The human placenta is a hematopoietic organ during the embryonic and fetal periods of development

"We studied the potential role of the human placenta as a hematopoietic organ during embryonic and fetal development. Placental samples contained two cell populations-CD34(++)CD45(low) and CD34(+)CD45(low)-that were found in chorionic villi and in the chorioamniotic membrane. CD34(++)CD45(low) cells express many cell surface antigens found on multipotent primitive hematopoietic progenitors and hematopoietic stem cells. CD34(++)CD45(low) cells contained colony-forming units culture (CFU-C) with myeloid and erythroid potential in clonogenic in vitro assays, and they generated CD56(+) natural killer cells and CD19(+)CD20(+)sIgM(+) B cells in polyclonal liquid cultures. CD34(+)CD45(low) cells mostly comprised erythroid- and myeloid-committed progenitors, while CD34(-) cells lacked CFU-C. The placenta-derived precursors were fetal in origin, as demonstrated by FISH using repeat-sequence chromosome-specific probes for X and Y. The number of CD34(++)CD45(low) cells increased with gestational age, but their density (cells per gram of tissue) peaked at 5-8 wk, decreasing more than sevenfold at the onset of the fetal phase (9 wk of gestation). In addition to multipotent progenitors, the placenta contained myeloid- and erythroid-committed progenitors indicative of active in situ hematopoiesis. These data suggest that the human placenta is an important hematopoietic organ, raising the possibility of banking placental hematopoietic stem cells along with cord blood for transplantation."

De novo synthesis of estrogen in pregnant uterus is critical for stromal decidualization and angiogenesis. Das A, Mantena SR, Kannan A, Evans DB, Bagchi MK, Bagchi IC. Proc Natl Acad Sci U S A. 2009 Jul 28;106(30):12542-7. Epub 2009 Jul 20. Erratum in: Proc Natl Acad Sci U S A. 2009 Sep 15;106(37):16003. PMID: 19620711 | PNAS

  • Implantation is initiated when the embryo attaches to the uterine luminal epithelium during early pregnancy.
  • Following this event, uterine stromal cells undergo steroid hormone-dependent transformation into morphologically and functionally distinct decidual cells in a unique process known as decidualization.
  • An angiogenic network is also formed in the uterine stromal bed, critically supporting the early development of the embryo.
  • ovarian progesterone as a key regulator of decidualization is well established
  • these studies in mice - identified the decidual uterus as a novel site of estrogen biosynthesis and uncovered estrogen-regulated maternal signaling pathways that critically control uterine differentiation and angiogenesis during early pregnancy.

Classification of human placental stem villi: review of structural and functional aspects

Microsc Res Tech. 1997 Jul 1-15;38(1-2):29-41.

Demir R, Kosanke G, Kohnen G, Kertschanska S, Kaufmann P.

Department of Histology and Embryology, Medical Faculty, Akdeniz University, Antalya, Turkey. Abstract The stem villi of the human placenta represent the central branches of the villous trees. They are characterized by a condensed fibrous stroma in which the fetal arteries and veins as well as the arterioles and venules are embedded. Functionally they are accepted as the mechanically supporting structures of the villous trees, and they are supposed to control fetal blood flow to the maternofetal exchange area, which is located in the peripheral villi. To obtain further insights into the functions of the stem villi, the recent literature has been reviewed, and some immunohistochemical, ultrastructural, and reconstruction studies have been added. These new studies were aimed at identifying immunohistochemically different subtypes of stem villi, their branching patterns, the distribution of macrophages, the stromal proliferation patterns, and the differentiation of extravascular stromal cells. Our findings demonstrate that the stem villi and their precursors, the immature intermediate villi, can selectively be identified by anti-gamma-smooth muscle (sm) actin staining. Furthermore, the existence of three different subtypes of stem villi is shown; these differ regarding the presence and distribution of gamma-sm actin-positive cells. These cells were immunohistochemically and ultrastructurally identified as smooth muscle cells and myofibroblasts. Increasingly complex coexpression patterns of cytoskeletal proteins reflect a clearly defined differentiation gradient of extravascular stromal cells, which covers the whole range of an undifferentiated germinative layer beneath the trophoblast to highly differentiated myofibroblasts surrounding the medias of the stem vessels. Possible functions of the extravascular contractile system include the regulation of villous turgor and the control of intervillous blood flow impedance.

PMID 9260835

Placenta Measurements

Morphometric indices at term of placental composition, villous capillarization and the mean cross-sectional areas of peripheral villi and capillaries.

Variable Unit Placenta (mean, n = 15)
Intervillous space mL 213
Stem villi mL 71.4
Peripheral villi mL 326
Trophoblast mL 95.5
Stroma mL 184
Fetal capillaries mL 46.9
Non-parenchyma mL 41.5
Peripheral villi km 89.2
Fetal capillaries km 310
TS area villi µm2 3700
TS area capillary µm2 150
Capillaries mL mL-1 0.147
Length ratio km km-1 3.6

Data: (Table 2. based on Mayhew et al. (2008) PMID 18328557