Talk:Placenta Development

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Cite this page: Hill, M.A. (2024, May 23) Embryology Placenta Development. Retrieved from


Maternal platelets at the first trimester maternal-placental interface - Small players with great impact on placenta development

Guettler J, Forstner D & Gauster M. (2021). Maternal platelets at the first trimester maternal-placental interface - Small players with great impact on placenta development. Placenta , , . PMID: 34920861 DOI.

DOI: 10.1016/j.placenta.2021.12.009


In human pregnancy, maternal platelet counts decrease with each trimester, reaching a reduction by approximately ten percent at term in uncomplicated cases and recover to the levels of the non-pregnant state a few weeks postpartum. The time when maternal platelets start to occur in the early human placenta most likely coincides with the appearance of loosely cohesive endovascular trophoblast plugs showing capillary-sized channels by mid first trimester. At that time, platelets accumulate in intercellular gaps of anchoring parts of trophoblast columns and start to adhere to the surface of placental villi and the chorionic plate. This is considered as normal process that contributes to placenta development by acting on both the extravillous- and the villous trophoblast compartment. Release of platelet cargo into intercellular gaps of anchoring cell columns may affect partial epithelial-to-mesenchymal transition and invasiveness of extravillous trophoblasts as well as deposition of fibrinoid in the basal plate. Activation of maternal platelets on the villous surface leads to perivillous fibrin-type fibrinoid deposition, contributing to the shaping of the developing placental villi and the intervillous space. In contrast, excess platelet activation at the villous surface leads to deregulation of the endocrine activity, sterile inflammation and local apoptosis of the syncytiotrophoblast. Platelets and their released cargo are adapted to pregnancy, and may be altered in high-risk pregnancies. Identification of different maternal platelet subpopulations, which show differential procoagulant ability and different response to anti-platelet therapy, are promising new future directions in deciphering the role of maternal platelets in human placenta physiology.


FcRn, but not FcγRs, drives maternal-fetal transplacental transport of human IgG antibodies

Transport of IgG antibodies from the maternal to the fetal circulation is a key process for neonatal immunity, as neonates cannot sufficiently generate IgG antibodies to reach protective levels during the first months after birth. In humans and other primates, maternal to fetal transport of IgG antibodies is largely mediated through the placental tissue. FcRn has been previously identified as the major driver of IgG transplacental transport. Here we examine whether other receptors, such as FcγRs, also contribute to the maternal-fetal IgG transfer. By characterizing the Fc domain structure of paired maternal-fetal IgG samples and modeling transplacental IgG transport in genetically engineered mouse strains, we determined that FcRn, but not FcγRs, is the major receptor that mediates transplacental IgG transport.

Historic Embryology - Placenta and Fetal Membranes

Historic: 1883 Embryonic Membranes | 1907 Development Atlas | 1910 Textbook | 1917 Textbook | 1921 Textbook | 1921 Foetal Membranes | 1921 Pig implantation

Internet Archive

Maughs GMB. Placenta praevia. (1879)

by Maughs, G. M. B. (George Madison Brown), 1821-1901, author

Adams F. On the construction of the human placenta : an historical sketch (1858) by Adams, Francis

Ercolani GB. The reproductive process: its histology, physiology, and pathology. Demonstrating the unity of the anatomical type of the placenta in all the Mammalia, and the physiological unity of the nutrition of the fœtus in all the vertebrates. (1884)

In two volumes: one a quarto atlas of illustrations, engraved by Bettini, and reproduced by the heliotype process. Tr. by Henry O. Marcy . by Ercolani, G. B. (Giovanni Battista), 1819-1883; Marcy, Henry O. (Henry Orlando), 1837-1924

Marcy HO. The reproductive process: its histology, physiology, and pathology. Demonstrating the unity of the anatomical type of the placenta in all the Mammalia, and the physiological unity of the nutrition of the fœtus in all the vertebrates. (1884)

In two volumes: one a quarto atlas of illustrations, engraved by Bettini, and reproduced by the heliotype process. Tr. by Henry O. Marcy .. by Ercolani, G. B. (Giovanni Battista), 1819-1883; Marcy, Henry O. (Henry Orlando), 1837-1924, tr

Turner W. Lectures on the comparative anatomy of the placenta(1875) first series : delivered before the Royal college of surgeons of England, June, (1875)


Turco MY & Moffett A. (2019). Development of the human placenta. Development , 146, . PMID: 31776138 DOI.

Development of the human placenta.

Abstract The placenta is essential for normal in utero development in mammals. In humans, defective placental formation underpins common pregnancy disorders such as pre-eclampsia and fetal growth restriction. The great variation in placental types across mammals means that animal models have been of limited use in understanding human placental development. However, new tools for studying human placental development, including 3D organoids, stem cell culture systems and single cell RNA sequencing, have brought new insights into this field. Here, we review the morphological, molecular and functional aspects of human placental formation, with a focus on the defining cell of the placenta - the trophoblast. © 2019. Published by The Company of Biologists Ltd.

KEYWORDS: Development; Maternal; Placenta; Trophoblast PMID: 31776138 DOI: 10.1242/dev.163428

Associations Between the Features of Gross Placental Morphology and Birthweight

Pediatr Dev Pathol. 2019 May-Jun;22(3):194-204. doi: 10.1177/1093526618789310. Epub 2018 Jul 16.

Freedman AA1, Hogue CJ1, Marsit CJ1,2, Rajakumar A3, Smith AK3, Goldenberg RL4, Dudley DJ5, Saade GR6, Silver RM7, Gibbins KJ7, Stoll BJ8, Bukowski R9, Drews-Botsch C1.

The placenta plays a critical role in regulating fetal growth. Recent studies suggest that there may be sex-specific differences in placental development. The purpose of our study was to evaluate the associations between birthweight and placental morphology in models adjusted for covariates and to assess sex-specific differences in these associations. We analyzed data from the Stillbirth Collaborative Research Network's population-based case-control study conducted between 2006 and 2008, which recruited cases of stillbirth and population-based controls in 5 states. Our analysis was restricted to singleton live births with a placental examination (n = 1229). Characteristics of placental morphology evaluated include thickness, surface area, difference in diameters, shape, and umbilical cord insertion site. We used linear regression to model birthweight as a function of placental morphology and covariates. Surface area had the greatest association with birthweight; a reduction in surface area of 83 cm2, which reflects the interquartile range, is associated with a 260.2-g reduction in birthweight (95% confidence interval, -299.9 to -220.6), after adjustment for other features of placental morphology and covariates. Reduced placental thickness was also associated with lower birthweight. These associations did not differ between males and females. Our results suggest that reduced placental thickness and surface area are independently associated with lower birthweight and that these relationships are not related to sex.

KEYWORDS: birthweight; fetal; neonatal; placenta; placental shape; placental size PMID: 30012074 PMCID: PMC6335186 [Available on 2020-05-01] DOI: 10.1177/1093526618789310

The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4-vessel sampling

FASEB J. 2019 Feb;33(2):2944-2956. doi: 10.1096/fj.201801193R. Epub 2018 Oct 18.

Michelsen TM1,2, Henriksen T2, Reinhold D3, Powell TL4, Jansson T1.

We sought to identify proteins secreted by the human placenta into the maternal and fetal circulations. Blood samples from the maternal radial artery and uterine vein and umbilical artery and vein were obtained during cesarean section in 35 healthy women with term pregnancy. Slow off-rate modified aptamer (SOMA) protein-binding technology was used to quantify 1310 known proteins. The uteroplacental and umbilical venoarterial concentration differences were calculated. Thirty-four proteins were significantly secreted by the placenta into the maternal circulation, including placental growth factor, growth/differentiation factor 15, and matrix metalloproteinase 12. There were 341 proteins significantly secreted by the placenta into the fetal circulation. Only 7 proteins were secreted into both the fetal and maternal circulations, suggesting a distinct directionality in placental protein release. We examined changes across gestation in the proteins found to be significantly secreted by the placenta into the maternal circulation using serial blood samples from healthy women. Among the 34 proteins secreted into the maternal circulation, 8 changed significantly across gestation. The identified profiles of secreted placental proteins will allow us to identify novel minimally invasive biomarkers for human placental function across gestation and discover previously unknown proteins secreted by the human placenta that regulate maternal physiology and fetal development.-Michelsen, T. M., Henriksen, T., Reinhold, D., Powell, T. L., Jansson, T. The human placental proteome secreted into the maternal and fetal circulations in normal pregnancy based on 4-vessel sampling. KEYWORDS: placental physiology; pregnancy proteins; proteomics; trophoblast PMID: 30335547 DOI: 10.1096/fj.201801193R


Sci Rep. 2018 Oct 9;8(1):14997. doi: 10.1038/s41598-018-33387-x. Murine transcription factor Math6 is a regulator of placenta development. Böing M1, Brand-Saberi B2, Napirei M1. Author information Abstract The murine basic helix-loop-helix transcription (bHLH) factor mouse atonal homolog 6 (Math6) is expressed in numerous organs and supposed to be involved in several developmental processes. However, so far neither all aspects nor the molecular mechanisms of Math6 function have been explored exhaustively. To analyze the in vivo function of Math6 in detail, we generated a constitutive knockout (KO) mouse (Math6-/-) and performed an initial histological and molecular biological investigation of its main phenotype. Pregnant Math6-/- females suffer from a disturbed early placental development leading to the death of the majority of embryos independent of the embryonic Math6 genotype. A few placentas and fetuses survive the severe uterine hemorrhagic events at late mid-gestation (E13.5) and subsequently develop regularly. However, these fetuses could not be born due to obstructions within the gravid uterus, which hinder the birth process. Characterization of the endogenous spatiotemporal Math6 expression during placenta development reveals that Math6 is essential for an ordered decidualization and an important regulator of the maternal-fetal endocrine crosstalk regulating endometrial trophoblast invasion and differentiation. The strongly disturbed vascularization observed in the maternal placenta appears as an additional consequence of the altered endocrine status and as the main cause for the general hemorrhagic crisis.

PMID: 30301918 PMCID: PMC6177472 DOI: 10.1038/s41598-018-33387-x

Development of the Human Placenta and Fetal Heart: Synergic or Independent?

Front Physiol. 2018 Apr 12;9:373. doi: 10.3389/fphys.2018.00373. eCollection 2018.

Burton GJ1, Jauniaux E2. Author information Abstract The placenta is the largest fetal organ, and toward the end of pregnancy the umbilical circulation receives at least 40% of the biventricular cardiac output. It is not surprising, therefore, that there are likely to be close haemodynamic links between the development of the placenta and the fetal heart. Development of the placenta is precocious, and in advance of that of the fetus. The placenta undergoes considerable remodeling at the end of the first trimester of pregnancy, and its vasculature is capable of adapting to environmental conditions and to variations in the blood supply received from the mother. There are two components to the placental membranes to consider, the secondary yolk sac and the chorioallantoic placenta. The yolk sac is the first of the extraembryonic membranes to be vascularized, and condensations in the mesenchyme at ~17 days post-conception (p.c.) give rise to endothelial and erythroid precursors. A network of blood vessels is established ~24 days p.c., with the vitelline vein draining through the region of the developing liver into the sinus venosus. Gestational sacs of early pregnancy failures often display aberrant development of the yolk sac, which is likely to be secondary to abnormal fetal development. Vasculogenesis occurs in the villous mesenchyme of the chorioallantoic placenta at a similarly early stage. Nucleated erythrocytes occupy the lumens of the placental capillaries and end-diastolic flow is absent in the umbilical arterial circulation throughout most of the first trimester, indicating a high resistance to blood flow. Resistance begins to fall in the umbilico-placental circulation around 12-14 weeks. During normal early pregnancy the placental capillary network is plastic, and considerable remodeling occurs in response to the local oxygen concentration, and in particular to oxidative stress. In pregnancies complicated by preeclampsia and/or fetal growth restriction, utero-placental malperfusion induces smooth muscle cells surrounding the placental arteries to dedifferentiate and adopt a proliferative phenotype. This change is associated with increased umbilical resistance measured by Doppler ultrasound, and is likely to exert a major effect on the developing heart through the afterload. Thus, both the umbilical and maternal placental circulations may impact on development of the heart. KEYWORDS: congenital heart disease; fetal heart; placenta; pregnancy; umbilical circulation; vascular resistance PMID: 29706899 PMCID: PMC5906582 DOI: 10.3389/fphys.2018.00373

Species Placental Forms and Types
Order Species Placental Form   Maternal-fetal Interface   Maternal-fetal Membrane  
Primates Ape, Human Discoid Villi Haemochorial
Rhesus Bidiscoid Villi Haemochorial
Tupaia Bidiscoid Labyrinth Endotheliochorial
Galago Diffuse Folded Epitheliochorial
pig Diffuse Folded Epitheliochorial
sheep Cotyledonary Villi Epithelio- & Syndesmo-chorial
Cow, ?goat Cotyledonary Villi Epitheliochorial
guinea pig Discoid Labyrinth Haemomonochorial
rat, mouse Discoid Labyrinth Haemotrichorial
Beaver Discoid Labyrinth Hemodichorial
Lagomorpha rabbit Discoid Labyrinth Haemochorial
Carnivora dog, cat Zonary Labyrinth Endotheliochorial
Perissodactyla   horse Diffuse, spec. Villi, "cups" Epitheliochorial
Cetacea Whale, dolphin   Diffuse Villi Epitheliochorial
Sirenia Manatee Zonary Labyrinth Haemochorial
Chiroptera bat Discoid Labyrinth Endotheliochorial Occas. Hemochorial
Insectivora Europ. Mole
 Discoid Labyrinth Haemochorial
Scalopus Diffuse Labyrinth Haemochorial
  Table based upon Comparative Placentation    Links: placenta

Based upon

Sex differences in umbilical artery Doppler indices: a longitudinal study

Widnes C, Flo K, Wilsgaard T, Kiserud T & Acharya G. (2018). Sex differences in umbilical artery Doppler indices: a longitudinal study. Biol Sex Differ , 9, 16. PMID: 29669590 DOI.

Widnes C1,2, Flo K3,4, Wilsgaard T5, Kiserud T6,7, Acharya G3,4,8. Author information

Abstract BACKGROUND: Sexual dimorphism in placental size and function has been described. Whether this influences the clinically important umbilical artery (UA) waveform remains controversial, although a few cross-sectional studies have shown sex differences in UA pulsatility index (PI). Therefore, we tested whether fetal sex influences the UA Doppler indices during the entire second half of pregnancy and aimed to establish sex-specific reference ranges for UA Doppler indices if needed. METHODS: Our main objective was to investigate gestational age-associated changes in UA Doppler indices during the second half of pregnancy and compare the values between male and female fetuses. This was a prospective longitudinal study in women with singleton low-risk pregnancies during 19-40 weeks of gestation. UA Doppler indices were serially obtained at a 4-weekly interval from a free loop of the umbilical cord using color-directed pulsed-wave Doppler ultrasonography. Sex-specific reference intervals were calculated for the fetal heart rate (HR), UA PI, resistance index (RI), and systolic/diastolic ratio (S/D) using multilevel modeling. RESULTS: Complete data from 294 pregnancies (a total of 1261 observations from 152 male and 142 female fetuses) were available for statistical analysis, and sex-specific reference ranges for the UA Doppler indices and fetal HR were established for the last half of pregnancy. UA Doppler indices were significantly associated with gestational age (P < 0.0001) and fetal HR (P < 0.0001). Female fetuses had 2-8% higher values for UA Doppler indices than male fetuses during gestational weeks 20+0-36+6 (P < 0.05), but not later. Female fetuses had higher HR from gestational week 26+0 until term (P < 0.05). CONCLUSIONS: We have determined gestational age-dependent sex differences in UA Doppler indices and fetal HR during the second half of pregnancy, and correspondingly established new sex-specific reference ranges intended for refining diagnostics and monitoring individual pregnancies. KEYWORDS: Fetal Doppler; Obstetric ultrasound; Placental blood flow; Reference ranges; Sex differences; Umbilical artery PMID: 29669590 PMCID: PMC5907403 DOI: 10.1186/s13293-018-0174-x

S100P enhances the motility and invasion of human trophoblast cell lines

Sci Rep. 2018 Jul 31;8(1):11488. doi: 10.1038/s41598-018-29852-2.

Tabrizi MEA1, Lancaster TL1, Ismail TM2, Georgiadou A3, Ganguly A4, Mistry JJ1, Wang K3, Rudland PS2, Ahmad S3, Gross SR5.


S100P has been shown to be a marker for carcinogenesis where its expression in solid tumours correlates with metastasis and a poor patient prognosis. This protein's role in any physiological process is, however, unknown. Here we first show that S100P is expressed both in trophoblasts in vivo as well as in some corresponding cell lines in culture. We demonstrate that S100P is predominantly expressed during the early stage of placental formation with its highest expression levels occurring during the first trimester of gestation, particularly in the invading columns and anchoring villi. Using gain or loss of function studies through overexpression or knockdown of S100P expression respectively, our work shows that S100P stimulates both cell motility and cellular invasion in different trophoblastic and first trimester EVT cell lines. Interestingly, cell invasion was seen to be more dramatically affected than cell migration. Our results suggest that S100P may be acting as an important regulator of trophoblast invasion during placentation. This finding sheds new light on a hitherto uncharacterized molecular mechanism which may, in turn, lead to the identification of novel targets that may explain why significant numbers of confirmed human pregnancies suffer complications through poor placental implantation. PMID: 30065265 PMCID: PMC6068119 DOI: 10.1038/s41598-018-29852-2


A comparative study of five physiological key parameters between four different human trophoblast-derived cell lines

Sci Rep. 2017 Jul 19;7(1):5892. doi: 10.1038/s41598-017-06364-z.

Rothbauer M1, Patel N2, Gondola H3, Siwetz M4, Huppertz B4, Ertl P3.


The human placenta plays a crucial role as the interface between mother and fetus. It represents a unique tissue that undergoes morphological as well as functional changes on the cellular and tissue level throughout pregnancy. To better understand how the placenta works, a variety of techniques has been developed to re-create this complex physiological barrier in vitro. However, due to the low availability of freshly isolated primary cells, choriocarcinoma cell lines remain the usual suspects as in vitro models for placental research. Here, we present a comparative study on the functional aspects of the choriocarcinoma cell lines BeWo, JAR and Jeg-3, as well as the first trimester trophoblast cell line ACH-3P as placental in vitro barrier models for endocrine and transport studies. Functional assays including tight junction immunostaining, sodium fluorescein retardation, trans epithelial resistance, glucose transport, hormone secretion as well as size-dependent polystyrene nanoparticle transport were performed using the four cell types to evaluate key functional parameters of each cell line to act a relevant in vitro placental barrier model.

PMID: 28724925 PMCID: PMC5517571 DOI: 10.1038/s41598-017-06364-z


The endocrine function of human placenta: an overview

Reprod Biomed Online. 2016 Jan;32(1):14-43. doi: 10.1016/j.rbmo.2015.10.005. Epub 2015 Oct 27.

Costa MA1.


During pregnancy, several tightly coordinated and regulated processes take place to enable proper fetal development and gestational success. The formation and development of the placenta is one of these critical pregnancy events. This organ plays essential roles during gestation, including fetal nourishment, support and protection, gas exchange and production of several hormones and other mediators. Placental hormones are mainly secreted by the syncytiotrophoblast, in a highly and tightly regulated way. These hormones are important for pregnancy establishment and maintenance, exerting autocrine and paracrine effects that regulate decidualization, placental development, angiogenesis, endometrial receptivity, embryo implantation, immunotolerance and fetal development. In addition, because they are released into maternal circulation, the profile of their blood levels throughout pregnancy has been the target of intense research towards finding potential robust and reliable biomarkers to predict and diagnose pregnancy-associated complications. In fact, altered levels of these hormones have been associated with some pathologies, such as chromosomal anomalies or pre-eclampsia. This review proposes to revise and update the main pregnancy-related hormones, addressing their major characteristics, molecular targets, function throughout pregnancy, regulators of their expression and their potential clinical interest. Copyright © 2015 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

KEYWORDS: placental hormones, peptide hormones, pregnancy, steroid hormones, syncytiotrophoblast PMID 26615903 DOI: 10.1016/j.rbmo.2015.10.005


Influence of maternal anemia during pregnancy on placenta and newborns

Med Arch. 2014 Jun;68(3):184-7. doi: 10.5455/medarh.2014.68.184-187. Epub 2014 May 31.

Lelic M1, Bogdanovic G2, Ramic S1, Brkicevic E3.


INTRODUCTION: Sideropenic anemia is a common pregnancy disorder. Depending on severity, maternal anemia can significantly influence morphometric characteristic of placental tissue, pregnancy course and outcome. OBJECTIVES: to estimate if maternal anemia a) results with significant placental changes; b) influence on newborn weight, length and vitality. PATIENTS MATERIAL AND METHODS: Research included 100 women and their newborns, 50 anemic, and 50 women in the control group. Sixty placentas were collected, placental mass and volume was determined, and blood vessels of terminal villi were stereologically analyzed. Newborns mass and body length, and Apgar scores within 1 and 5 minutes after delivery were recorded. THE RESULTS: Placentas of anemic pregnant women showed significant increase of terminal villi blood vessels (224,18 vs. 197,00 cm(3); p<0,0001), but total placental mass and volume did not differ significantly. Anemic mothers' newborns were significantly shorter (51,76 vs. 55,54 cm; p<0,0001), smaller body mass (3048,00 vs. 3615,60 g; p<0,0001) and delivered one week early (38,2 vs. 39,2 GW; p<0,0001), but not significantly poorer vitality (p>0,05) comparing with the control group. CONCLUSION: Sideropenic anemia increase placental maturity, that could be a possible cause of earlier spontaneous delivery among anemic women. The anemic mothers' newborns are shorter and lower body mass, but not poorer vitality index. KEYWORDS: Newborns; Pregnancy anemia; Terminal villi blood vessels

PMID 25568530

United we stand not dividing: the syncytiotrophoblast and cell senescence

Placenta. 2014 Jun;35(6):341-4. doi: 10.1016/j.placenta.2014.03.012. Epub 2014 Mar 22.

Goldman-Wohl D1, Yagel S2.


The multinucleate syncytiotrophoblast of the human placenta is responsible for transport functions between maternal and fetal blood supplies and is a major site of protein synthesis and steroid production. It is formed by cell fusion of the underlying cytotrophoblast cells. The nuclei of the multinucleate syncytiotrophoblast are non-mitotic yet the mechanism of cell cycle arrest in the syncytiotrophoblast is not known. The recent publication by the group of Krizhanovsky (2013), demonstrates that cell fusion induces cell senescence. The work reported the exciting finding that term placenta syncytiotrophoblast displays markers associated with cellular senescence. Cellular senescence is perhaps best known as a component of aging, a response to stress and an important factor in preventing tumor cell growth. The aforementioned study suggests myriad avenues of investigation in placental biology with intriguing possibilities to furthering our understanding of placental development and aging, health of pregnancy and placental pathologies having their origin in placental stress. Copyright © 2014 Elsevier Ltd. All rights reserved. KEYWORDS: Aging; Cell fusion; Cell senescence; Syncytiotrophoblast

PMID 24709558

Probability distributions for measures of placental shape and morphology

Physiol Meas. 2014 Feb 20;35(3):483-500. [Epub ahead of print]

Gill JS1, Woods MP, Salafia CM, Vvedensky DD. Author information


Birthweight at delivery is a standard cumulative measure of placental growth, but is a crude summary of other placental characteristics, such as, e.g., the chorionic plate size, and the shape and position of the umbilical cord insertion. Distributions of such measures across a cohort reveal information about the developmental history of the chorionic plate which is unavailable from an analysis based solely on the mean and standard deviation. Various measures were determined from digitized images of chorionic plates obtained from the pregnancy, infection, and nutrition study, a prospective cohort study of preterm birth in central North Carolina between 2002 and 2004. Centroids (geometric centers) and umbilical cord insertions were taken directly from the images. Chorionic plate outlines were obtained from an interpolation based on a Fourier series, while eccentricity (of the best-fit ellipse), skewness, and kurtosis were determined from the method of moments. Histograms of each variable were compared against the normal, lognormal, and Lévy distributions. Only a single measure (eccentricity) followed a normal distribution. All others followed lognormal or 'heavy-tailed' distributions for moderate to extreme deviations from the mean, where the relative likelihood far exceeded those of a normal distribution. PMID 24557061

Maternal Factors Associated with Fetal Growth and Birthweight Are Independent Determinants of Placental Weight and Exhibit Differential Effects by Fetal Sex


Cell fusion induced by ERVWE1 or measles virus causes cellular senescence

Genes Dev. 2013 Nov 1;27(21):2356-66. doi: 10.1101/gad.227512.113.

Chuprin A1, Gal H, Biron-Shental T, Biran A, Amiel A, Rozenblatt S, Krizhanovsky V.


Cellular senescence limits proliferation of potentially detrimental cells, preventing tumorigenesis and restricting tissue damage. However, the function of senescence in nonpathological conditions is unknown. We found that the human placental syncytiotrophoblast exhibited the phenotype and expressed molecular markers of cellular senescence. During embryonic development, ERVWE1-mediated cell fusion results in formation of the syncytiotrophoblast, which serves as the maternal/fetal interface at the placenta. Expression of ERVWE1 caused cell fusion in normal and cancer cells, leading to formation of hyperploid syncytia exhibiting features of cellular senescence. Infection by the measles virus, which leads to cell fusion, also induced cellular senescence in normal and cancer cells. The fused cells activated the main molecular pathways of senescence, the p53- and p16-pRb-dependent pathways; the senescence-associated secretory phenotype; and immune surveillance-related proteins. Thus, fusion-induced senescence might be needed for proper syncytiotrophoblast function during embryonic development, and reuse of this senescence program later in life protects against pathological expression of endogenous fusogens and fusogenic viral infections. KEYWORDS: ERVWE1; cell fusion; cellular senescence; p53; pRb; placenta

Comment in Cell fusion induced senescence. [Aging (Albany NY). 2014]

PMID 24186980

Paternal age, placental weight and placental to birthweight ratio: a population-based study of 590,835 pregnancies

Hum Reprod. 2013 Nov;28(11):3126-33. doi: 10.1093/humrep/det299. Epub 2013 Jul 19.

Strøm-Roum EM1, Haavaldsen C, Tanbo TG, Eskild A. Author information


STUDY QUESTION: Is the age of the father associated with placental weight or the ratio of placental weight to birthweight? SUMMARY ANSWER: Placental weight and placental to birthweight ratio increased according to increasing paternal age, also after adjustment for maternal age. WHAT IS KNOWN ALREADY: High paternal age and also high placental to birthweight ratio have been associated with adverse pregnancy outcome. STUDY DESIGN, SIZE AND DURATION: We performed a population-based study and included all singleton births after 22 weeks of gestation in the Medical Birth Registry of Norway (n = 590,835) during the years 1999-2009. PARTICIPANTS/MATERIALS, SETTING, METHODS: We compared mean placental weight and placental to birthweight ratio between paternal age groups. The association of paternal age with placental weight was estimated by linear regression analyses, and adjustments were made for maternal age, birthweight, parity, offspring sex, gestational age at birth, maternal smoking, pre-eclampsia, maternal diabetes mellitus and pregnancy after assisted reproductive technology (ART). MAIN RESULTS AND THE ROLE OF CHANCE: In pregnancies with fathers aged 20-24 years old, the mean placental weight was 656.2 g [standard deviation (SD) 142.8], whereas it was 677.8 g (SD 160.0) in pregnancies with fathers aged 50 years or older (P < 0.001). The mean offspring birthweight in pregnancies with fathers aged 20-24 year old was 3465.0 g (SD 583.8), and it was 3498.9 g (SD 621.8) when the father was 50 years or older (P < 0.001). The placental to birthweight ratio in the corresponding paternal age groups were 0.191 (SD 0.039) and 0.196 (SD 0.044) (P < 0.001). In multivariable linear regression analysis the placentas in pregnancies fathered by a man of 50 years or older were estimated to weigh 13.99 g [95% confidence interval (CI) 10.88-17.10] more than in pregnancies with a 20-24-year-old father (P < 0.001) after adjustment for maternal age, birthweight, parity, offspring sex, gestational age at birth, maternal smoking, pre-eclampsia, maternal diabetes mellitus and pregnancy after ART. LIMITATIONS, REASONS FOR CAUTION: Paternal age explains only a small proportion of the total variation in placental weight. WIDER IMPLICATIONS OF THE FINDINGS: Our findings may increase the understanding of the father's role in human pregnancy. STUDY FUNDING/ COMPETING INTEREST(S): Norwegian Resource Centre for Women's Health, Norway. No conflict of interest. TRIAL REGISTRATION NUMBER: N/A. KEYWORDS: birthweight, paternal age, placenta, population study, pregnancy

PMID 23873147

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.

Male Placenta - seahorses

  • family Syngnathidae - seahorses and pipefishes
  • sole vertebrate group where the embryonic development occurs within a special pouch (brood pouch) in males (Herald, 1959)
  • pouch is similar to the placental function in mammals - provides aeration, protection, osmoregulation and nutrition to the embryo or offspring
    • after the females deposits eggs during mating (Linton and Soloff, 1964; Berglund et al., 1986; Partridge et al., 2007; Ripley, 2009).
  • pouch acts like the mammalian uterus - embryos embedded within depressions of the interior lining (Carcupino et al., 1997; Foster and Vincent, 2004).

PMID 23213429


Human placentation from nidation to 5 weeks of gestation. Part I: What do we know about formative placental development following implantation?

Placenta. 2012 May;33(5):327-34. doi: 10.1016/j.placenta.2012.01.020. Epub 2012 Feb 26.

James JL, Carter AM, Chamley LW.


The implantation of the blastocyst and early development of the placenta are crucial for the success of implantation and pregnancy. However, the formative stages of human placental development are largely unknown because of their existence in a 'black box' where access to samples is extremely limited for ethical reasons. In this review we discuss our current knowledge of early placental formation from the time of implantation at 3 weeks of gestation to approximately 5-6 weeks of gestation, encompassing both the significant anatomical findings derived from the unique specimens obtained in the mid-20th century and the renewed study of this period over the past 10 years as novel models of implantation have been developed. Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID 22374510

Human placentation from nidation to 5 weeks of gestation. Part II: Tools to model the crucial first days

Placenta. 2012 May;33(5):335-42. doi: 10.1016/j.placenta.2012.01.019. Epub 2012 Feb 25.

James JL, Carter AM, Chamley LW.


Human pregnancy is unusual with respect to monthly spontaneous decidualisation as well as the degree of placental invasion and interaction with the decidualised endometrial stroma. This review covers in vivo animal models and in vitro cell culture models that have been used to study the earliest stages of human implantation and placentation from nidation to 5 weeks of gestation. The field has expanded rapidly in recent years due to the generation of human embryonic stem cell lines and the ability of some scientists to culture human blastocysts. These models have enabled researchers to begin to elucidate the interactions involved in human blastocyst apposition, adhesion and implantation. However, we still understand very little about the differentiation processes involved in the formation of the placenta. Continued improvements to current models, including the potential isolation of a human trophoblast stem cell, will significantly enhance our ability to define the molecular and structural events occurring during human implantation and early placental development. Copyright © 2012 Elsevier Ltd. All rights reserved.

PMID 22365889

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', 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

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 fetal 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


Aspects of human fetoplacental vasculogenesis and angiogenesis. I. Molecular regulation

Placenta. 2004 Feb-Mar;25(2-3):103-13.

Charnock-Jones DS, Kaufmann P, Mayhew TM. Source Departments of Pathology and Obstetrics & Gynaecology, The Rosie Hospital, University of Cambridge, UK.


Patterns of fetoplacental angiogenesis vary during gestation and in association with certain pregnancy pathologies. In a set of three linked reviews, we provide a survey of current knowledge about the molecular regulation, cellular players, qualitative and quantitative morphological features of the vascularization of human placental villi. Here, an account is given of the role played by hypoxia-inducible factor in mediating the effects of oxygen on production of growth factor ligands and receptors which regulate angiogenesis and vessel maturation. However, it should be noted that, for the human placenta early in gestation, the normal (i.e. physiological) partial pressure of O(2)is low but this does not mean that the tissue is hypoxic. Thus, the mechanisms of regulating angiogenic growth factor production may differ at this time in comparison to those found later in gestation or in other tissues or organs. The vasculature in the placenta is plastic and changes markedly as gestation progresses. This is controlled by the complex interplay between physical factors and chemical factors including oxygen, growth factors and growth inhibitors. The companion reviews describe morphological features of normal and pathological development of the human placenta in the context of the factors discussed here. PMID 14972443

Aspects of human fetoplacental vasculogenesis and angiogenesis. II. Changes during normal pregnancy

Placenta. 2004 Feb-Mar;25(2-3):114-26.

Kaufmann P, Mayhew TM, Charnock-Jones DS. Source Department of Anatomy II, University Hospital, RWTH-Aachen, Germany.


In this second review, we describe the main morphological events which accompany the development of the fetoplacental vascular system throughout normal human pregnancy and summarize findings on the expression of angiogenic growth factors and their receptors. Fetoplacental vasculogenesis starts at day 21 after conception by formation of haemangioblastic cords. In the following phase of branching angiogenesis (day 32 to week 25 post conception), haemangioblastic cords develop into a richly branched villous capillary bed with low fetoplacental blood flow impedance. This period is characterized by high placental levels of VEGF but moderate PlGF expression. In week 15, large centrally located villi show regression of peripheral capillary nets. In parallel, some remaining central capillaries acquire a tunica media and transform into arteries and veins. Beginning at about week 25 in the newly formed peripheral villi, angiogenesis switches from branching to non-branching and this period is accompanied by a steep drop in VEGF and a slower decline in PlGF expression. As a consequence of this switch, long poorly branched capillary loops are formed in the periphery of the fetoplacental vascular trees. These increase fetoplacental impedance but blood flow still increases due to rising fetal blood pressure. The possible interactions between (a). the biphasic development of intraplacental oxygen tensions, (b). changes in VEGF and PlGF levels and (c). developing vascular geometry are discussed. Special attention is given to the obvious discrepancy between sudden elevation of intervillous oxygen tensions which is not coincident with the appearance of angiogenic growth factor peaks and the switch from branching to non-branching angiogenesis. Finally, we deal with methods of quantifying aspects of angiogenesis in the villous vascular system and summarize the main findings during uncomplicated human pregnancy.

PMID 14972444

Aspects of human fetoplacental vasculogenesis and angiogenesis. III. Changes in complicated pregnancies

Placenta. 2004 Feb-Mar;25(2-3):127-39. Mayhew TM, Charnock-Jones DS, Kaufmann P. Source Centre for Integrated Systems Biology and Medicine, School of Biomedical Sciences, E Floor, Queen's Medical Centre, University of Nottingham, Nottingham NG7 2UH, UK.


Patterns of fetoplacental angiogenesis vary not only during the course of a normal pregnancy but also in certain pregnancy pathologies. Here, we review some of the molecular and morphological events which occur in complicated pregnancies. The pregnancy complications are chosen in an attempt to represent the possible different origins (preplacental, uteroplacental, postplacental) of fetal hypoxia. Molecular events focus on reported changes in hypoxia-inducible factors, angiopoietins and the vascular endothelial, basic fibroblast and placenta growth factors and their receptors. Morphological changes focus on patterns of angiogenesis (branching and non-branching) and a consistent set of morphometric descriptors (covering measures of total capillary growth, villous capillarization and capillary size and shape in transverse section). Apart from some uncertainties due to lack of information, or failure to resolve fully the effects of intrauterine growth restriction and pre-eclampsia, alterations in the angiogenic growth factors and morphologies of capillaries and villi in different complicated pregnancies seem to conform reasonably well to those predicted by the fetal hypoxia paradigm. However, it is clear that future studies on the effects of different origins of fetal hypoxia should exercise more care in the choice and interpretation of relevant descriptors and take more account of the parallel effects of possible confounders. In addition, rather than comparing uncomplicated and complicated pregnancies only at term, more information about molecular and morphological events that occur throughout gestation would be extremely valuable. This includes further studies on changes in growth factor receptors, the less-well-documented angiogenic factors (e.g. angiogenin, angiostatin, endostatin) and the associations between endothelial cells and pericytes. A more integrated approach involving also parallel analysis of the effects of erythropoietin and other potential vasoactive factors on the behaviour and morphology of fetal vessels would be beneficial.


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

PMID 19073167

"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

Placenta Crossing



  • erythropoietin (EPO) "Since EPO does not cross the placenta and is not stored, fetal plasma and amniotic fluid levels indicate EPO synthesis and elimination." PMID 18776724

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

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