Embryonic period at week 8 - more than 90 % of the 4,500 adult body named structures have appeared by that time. O'Rahilly R. 1979. Early human development and the chief sources of information on staged human embryos. Europ. J. Obstet. Gynec. Reprod. Biol., 9, 273-280. PMID 400868
Human Embryo Collections
- Kyoto Collection (Kyoto University) - begun by Dr. Hideo Nishimura in 1961 and has over 44,000 human embryo specimens.
- 129 embryos with polydactyly in 36,380 human conceptuses obtained through induced abortion during the period from 1962 to 1974. PMID 691840
- Carnegie Collection (Carnegie Institution)
- Central Laboratory for Human Embryology (University of Washington)
- Hamilton-Boyd Collection (Cambridge University)
- Blechschmidt Collection (University of Goettingen)
BMC Med Ethics. 2017 May 30;18(1):38. doi: 10.1186/s12910-017-0198-5. A 14-day limit for bioethics: the debate over human embryo research. Cavaliere G1. Author information Abstract BACKGROUND: This article explores the reasons in favour of revising and extending the current 14-day statutory limit to maintaining human embryos in culture. This limit is enshrined in law in over a dozen countries, including the United Kingdom. In two recently published studies (2016), scientists have shown that embryos can be sustained in vitro for about 13 days after fertilisation. Positive reactions to these results have gone hand in hand with calls for revising the 14-day rule, which only allows embryo research until the 14th day after fertilisation. MAIN TEXT: The article explores the most prominent arguments in favour of and against the extension of the 14-day limit for conducting research on human embryos. It situates these arguments within the history of the 14-day limit. I start by discussing the history of the 14-day limit in the United Kingdom and the reasons behind the decision to opt for a compromise between competing moral views. I then analyse the arguments that those who are generally in favour of embryo research put forward in support of extending the 14-day rule, namely (a) the argument of the beneficence of research and (b) the argument of technical feasibility (further explained in the article). I then show how these two arguments played a role in the recent approval of two novel techniques for the replacement of faulty mitochondrial DNA in the United Kingdom. Despite the popularity and widespread use of these arguments, I argue that they are ultimately problematic and should not be straightforwardly accepted (i.e. accepted without further scrutiny). I end by making a case for respecting value pluralism in the context of embryo research, and I present two reasons in favour of respecting value pluralism: the argument of public trust and the argument of democracy. CONCLUSION: I argue that 14-day limit for embryo research is not a valuable tool despite being a solution of compromise, but rather because of it. The importance of respecting value pluralism (and of respecting different views on embryo research) needs to be considered in any evaluation concerning a potential change to the 14-day rule. KEYWORDS: Beneficence; Compromise; Embryo research; Value pluralism; Warnock report PMID: 28558751 PMCID: PMC5450057 DOI: 10.1186/s12910-017-0198-5
A workflow to process 3D+time microscopy images of developing organisms and reconstruct their cell lineage
Nat Commun. 2016 Feb 25;7:8674. doi: 10.1038/ncomms9674.
Faure E1,2,3, Savy T1,2,3,4, Rizzi B1,3,5, Melani C1,4,5, Stašová O6, Fabrèges D1,3,4, Špir R6, Hammons M1,3,4, Čúnderlík R6, Recher G1,3, Lombardot B1,2,3, Duloquin L1,3, Colin I3, Kollár J6, Desnoulez S3, Affaticati P7, Maury B3, Boyreau A3,4, Nief JY8, Calvat P8, Vernier P7, Frain M3,4, Lutfalla G9, Kergosien Y1,3,4,10, Suret P11, Remešíková M6, Doursat R1,2,3,4, Sarti A5, Mikula K6, Peyriéras N1,3,4, Bourgine P1,2,3,4.
The quantitative and systematic analysis of embryonic cell dynamics from in vivo 3D+time image data sets is a major challenge at the forefront of developmental biology. Despite recent breakthroughs in the microscopy imaging of living systems, producing an accurate cell lineage tree for any developing organism remains a difficult task. We present here the BioEmergences workflow integrating all reconstruction steps from image acquisition and processing to the interactive visualization of reconstructed data. Original mathematical methods and algorithms underlie image filtering, nucleus centre detection, nucleus and membrane segmentation, and cell tracking. They are demonstrated on zebrafish, ascidian and sea urchin embryos with stained nuclei and membranes. Subsequent validation and annotations are carried out using Mov-IT, a custom-made graphical interface. Compared with eight other software tools, our workflow achieved the best lineage score. Delivered in standalone or web service mode, BioEmergences and Mov-IT offer a unique set of tools for in silico experimental embryology.
PMID 26912388 PMCID: PMC4773431 DOI: 10.1038/ncomms9674
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Imaging of the human embryo with magnetic resonance imaging microscopy and high-resolution transvaginal 3-dimensional sonography: human embryology in the 21st century
Am J Obstet Gynecol. 2011 Jan;204(1):77.e1-16. Epub 2010 Oct 25.
Pooh RK, Shiota K, Kurjak A.
Clinical Research Institute of Fetal Medicine Pooh Maternity Clinic, Osaka, Japan. firstname.lastname@example.org
OBJECTIVE: This article illustrates early human development, demonstrated by magnetic resonance (MR) microscopy and computer graphics on human embryo specimens, and advanced 3-dimensional (3D) sonography in clinical obstetrics. STUDY DESIGN: Fixed human embryo specimens were imaged by MR microscopy coupled with computer graphics technology. Transvaginal 3D sonography was used to examine embryos in ongoing gestations and compare embryological findings. RESULTS: Advances in MR microscopy allowed detailed visualization of embryo specimens. Computational techniques allowed reconstruction of tomographic images to render them as 3D structures. High-resolution transvaginal 3D sonography produced images that demonstrated the neural tube from week 6; brain anatomy and vasculature from week 8; and craniofacial morphology and other structures from week 11. CONCLUSION: MR microscopy is a novel technique that enables nondestructive, high-resolution imaging of embryo specimens. On the other hand, 3D sonoembryology allows detailed anatomical visualization in vivo and is the basis for the assessment of anomalies as well as human development. Copyright © 2011. Published by Mosby, Inc.
Developmental atlas of the early first trimester human embryo
Dev Dyn. 2010 Jun;239(6):1585-95.
Yamada S, Samtani RR, Lee ES, Lockett E, Uwabe C, Shiota K, Anderson SA, Lo CW. Source Laboratory of Developmental Biology, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA. Abstract Rapid advances in medical imaging are facilitating the clinical assessment of first-trimester human embryos at increasingly earlier stages. To obtain data on early human development, we used magnetic resonance (MR) imaging and episcopic fluorescence capture (EFIC) to acquire digital images of human embryos spanning the time of dynamic tissue remodeling and organogenesis (Carnegie stages 13 to 23). These imaging data sets are readily resectioned digitally in arbitrary planes, suitable for rapid high-resolution three-dimensional (3D) observation. Using these imaging datasets, a web-accessible digital Human Embryo Atlas (http://apps.devbio.pitt.edu/humanatlas/ Human Embryo) was created containing serial 2D images of human embryos in three standard histological planes: sagittal, frontal, and transverse. In addition, annotations and 3D reconstructions were generated for visualizing different anatomical structures. Overall, this Human Embryo Atlas is a unique resource that provides morphologic data of human developmental anatomy that can accelerate basic research investigations into developmental mechanisms that underlie human congenital anomalies.
Structural anomalies in early embryonic death: a 3-dimensional pictorial essay
J Ultrasound Med. 2010 Mar;29(3):445-53. Bromley B, Shipp TD, Benacerraf BR.
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA. email@example.com Abstract OBJECTIVE: The purpose of this pictorial essay was to determine whether 3-dimensional (3D) surface rendering of a dead first-trimester embryo can provide any information for the loss. METHODS: Three-dimensional surface rendering was performed on a collection of dead first-trimester embryos with crown-rump lengths between 12 and 27 mm. These were compared with 2-dimensional (2D) images of the same embryos and with 2D images and 3D surface renderings of normally developing embryos. RESULTS: Surface rendering of dead embryos showed a variety of abnormalities in the contour and limb formation. CONCLUSIONS: The use of 3D sonography may provide insight into the etiology of first-trimester embryonic death.
Further observations on the empty "amnion sign"
J Clin Ultrasound. 2010 Mar-Apr;38(3):113-7. Yegul NT, Filly RA.
Department of Radiology, University of California, San Francisco, L374, 505 Parnassus Avenue, San Francisco, CA 94143-0628, USA. Abstract OBJECTIVE: To assess the positive predictive value of the empty "amnion sign" (visualization of an amnion without concomitant visualization of an embryo) for the diagnosis of early pregnancy failure. METHODS: Retrospective study of 882 1st trimester sonographic examinations with abnormal findings among women who were threatening to abort. Eight hundred six met the inclusion criteria. RESULTS: In the study cohort 286 (35.5%) had no identifiable embryo and 71 of those without an identifiable embryo had a visible amnion (24.8%). The breakdown of the mean sac diameter of the study cohort was as follows: those measuring less than 16 mm (n = 16); those measuring 16-20 mm (n = 20); those measuring 21 mm or more (n = 35). Sixty-eight of the 71 patients had adequate follow-up. Pregnancy failure was confirmed in all 68 patients (positive predictive value = 100%). CONCLUSIONS: The data from this study indicate that visualization of an amnion without concomitant visualization of an embryo (the empty "amnion sign") confirms pregnancy failure regardless of the mean sac diameter and with a sufficiently high positive predictive value to make a definitive diagnosis. Copyright 2010 Wiley Periodicals, Inc.
Developmental Stages in Human Embryos: Revised and New Measurements
O'Rahilly R, Müller F. Cells Tissues Organs. 2010 Feb 26. Epub ahead of print PMID: 20185898
The yolk stalk sign: evidence of death in small embryos without heartbeats
J Ultrasound Med. 2010 Feb;29(2):237-41. Filly MR, Callen PW, Yegul NT, Filly RA.
Department of Radiology and Biomedical Imaging, University of California, 505 Parnassus Ave, San Francisco, CA 94143-0628 USA. firstname.lastname@example.org Abstract OBJECTIVE: The purpose of this study was to assess the positive predictive value for confirming early embryonic death in the clinical sonographic scenario wherein an embryo is identified without a visible heartbeat; the embryonic crown-rump length (CRL) is 5 mm or less; and the embryo is not immediately adjacent to the yolk sac. METHODS: A retrospective study of 882 first-trimester sonograms was performed among women who had an intrauterine pregnancy of uncertain viability based on 1 or more sonographic findings (eg, no visible heartbeat in an embryo with a CRL of < or =5 mm). Eight hundred six cases met the inclusion criteria. RESULTS: Among the cohort of 806 cases, 520 (64.5%) had an identifiable embryo. One hundred fifty-nine of these embryos had no demonstrable heartbeat and a CRL of 5 mm or less. The CRLs of these embryos ranged from 1.7 to 5.4 mm. This cohort's sonograms were reviewed to determine whether there was a separation between the embryo and yolk sac. Twenty-one cases were discovered. Recall that as a retrospective study, no specific effort was made to show this finding. Thus, a computation of the sensitivity of this finding would result in an underestimate of indeterminate magnitude. All of these cases were subsequently proven to be failed pregnancies. CONCLUSIONS: The positive predictive value of the "yolk stalk sign" in determining early pregnancy failure for an embryo with a CRL of 5 mm or less and no visible heartbeat was 100% in this cohort.
Variability in human embryonic development and its implications for the susceptibility to environmental teratogenesis
Birth Defects Res A Clin Mol Teratol. 2009 Aug;85(8):661-6.
Department of Anatomy and Developmental Biology and Congenital Anomaly Research Center, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, Japan. email@example.com
Abstract Considerable variability is observed in the size and developmental stage among human embryos at a given gestational age, suggesting that prenatal development does not proceed at the same speed in every embryo. Such variability in embryonic development seems to occur in many (probably all) animal species, and is probably a normal "biologic" phenomenon to some extent. In the case of humans, some other factors (e.g., maternal memory bias, difficulty in assessing the timing of ovulation and fertilization) make it more difficult to assess the developmental stage of embryos in utero. Such facts related to human embryonic development should be taken into account when the teratogenic risk of a human embryo is considered.
(c) 2009 Wiley-Liss, Inc.
PMID: 19606457 http://www.ncbi.nlm.nih.gov/pubmed/19606457
Measurement of embryo volume at 7-10 weeks' gestation by 3D-sonography
Rolo LC, Nardozza LM, Araujo Júnior E, Nowak PM, Bortoletti Filho J, Moron AF. J Obstet Gynaecol. 2009 Apr;29(3):188-91.
- Alternative stagings http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2693928&tool=pmcentrez
Morphometric study on the characteristic external features of normal and abnormal human embryos
Congenit Anom (Kyoto). 2008 Mar;48(1):18-28.
Otani H, Udagawa J, Lundh T, Hatta T, Hashimoto R, Matsumoto A, Satow F.
Department of Developmental Biology, Faculty of Medicine, Shimane University, Izumo, Japan. firstname.lastname@example.org Abstract The embryonic period is characterized by organogenesis and accompanying dynamic changes in external features. The measurement of human embryos has been limited to whole body dimensions, such as crown-rump length. More detailed measurements would add quantitative information about these characteristic events and provide a better understanding of normal and abnormal embryonic development. In the present study, we defined axes, landmarks, and measurements for human embryos, and measured 250 externally normal human embryos at Carnegie stages 14-23 (6.5-29.3 mm in crown-rump length, approximately 5-8 weeks of estimated ovulation age) that were fixed in Bouin's solution and preserved in 10% formalin solution. The axes, landmarks, and measurements defined for human embryos are corresponding to those in human and primate fetuses. The whole body, head, face, and extremities were measured using a scale attached to a dissecting microscope. Axial length, head height plus ear-shoulder length plus trunk height, was designated as a new measurement of the whole body, which is comparable with crown-rump length. Approximate standards of these measurements were obtained. The ratios of some measurements to trunk height and between the different parts were also obtained, and several different developmental patterns were recognized. The reproducibility of each measurement was evaluated by measuring 50 specimens three times each at intervals of one or two months. As a pilot study for the application of the proposed measurements, 84 human embryos with external anomalies, including holoprosencephaly, anomalies of extremities, and pharyngeal arch anomalies, were measured using the same method, and a few tendencies characteristic to holoprosencephaly were noticed.
Fetal cardiac activity at 4 weeks after in vitro fertilization predicts successful completion of the first trimester of pregnancy
Fertil Steril. 2008 Nov;90(5):1711-5. Epub 2007 Dec 3. Seungdamrong A, Purohit M, McCulloh DH, Howland RD, Colon JM, McGovern PG.
Department of Obstetrics, Gynecology, and Women's Health, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey 07101-1709, USA. Abstract OBJECTIVE: To determine the predictive value of fetal cardiac activity (FCA), measured at 6 weeks' gestation, on first-trimester pregnancy success after IVF. DESIGN: Retrospective cohort study. SETTING: University-based reproductive endocrinology and infertility practice. PATIENT(S): One hundred thirty-nine women, without a history of recurrent miscarriage, who were undergoing fresh IVF cycles from August 1, 2004 to February 28, 2005. INTERVENTION(S): Transvaginal ultrasound. MAIN OUTCOME MEASURE(S): First-trimester pregnancy success. RESULT(S): Ninety-three percent (51/53) of gestational sacs with FCA completed the first trimester (positive predictive value of 93%). Eighty-seven percent (13/15) of sacs without FCA failed in the first trimester (negative predictive value of 87%). In singletons, the positive and negative predictive value of FCA on first-trimester success was 100%. All twin pregnancies (n = 11) successfully completed the first trimester. CONCLUSION(S): This analysis, which was performed strictly in an IVF population with no history of recurrent pregnancy loss, demonstrates that positive FCA at 6 weeks' gestation is an excellent predictor of first-trimester pregnancy outcome.
Embryonic staging using a 3D virtual reality system
Hum Reprod. 2008 Jul;23(7):1479-84. Epub 2008 Feb 21.
Verwoerd-Dikkeboom CM, Koning AH, van der Spek PJ, Exalto N, Steegers EA. Source Department of Obstetrics and Gynaecology, Division of Obstetrics and Prenatal Medicine, PO Box 2040, Erasmus MC, University Medical Centre Rotterdam, 3000 CA Rotterdam, The Netherlands. email@example.com
BACKGROUND: The aim of this study was to demonstrate that Carnegie Stages could be assigned to embryos visualized with a 3D virtual reality system. METHODS: We analysed 48 3D ultrasound scans of 19 IVF/ICSI pregnancies at 7-10 weeks' gestation. These datasets were visualized as 3D 'holograms' in the BARCO I-Space virtual reality system. Embryos were staged according to external morphological features (i.e. mainly limb development). After staging, the crown rump length (CRL) was measured. Stage and CRL were compared with gestational age based on the date of oocyte retrieval and with the classical data on embryology from the Carnegie Collection. RESULTS: Embryonic staging was relatively easy because the I-Space allows depth perception, which helps in the estimation of size and position. The presumed stages corresponded well with the measured CRL. However, in 28 out of 48 cases, the stages seemed to have been reached earlier than previously described for the Carnegie Collection. CONCLUSIONS: The I-Space, tentatively named Virtual Embryoscopy, is a promising non-invasive tool for early pregnancy evaluation. Combining embryonic growth with embryonic development opens a new area to study the relationship between embryonic growth, development and morphology, as well as second and third trimester pregnancy complications.
PMID 18296447 http://humrep.oxfordjournals.org/content/23/7/1479.long
Three-dimensional sonographic volumetry of the gestational sac and the amniotic sac in the first trimester
Odeh M, Hirsh Y, Degani S, Grinin V, Ofir E, Bornstein J. J Ultrasound Med. 2008 Mar;27(3):373-8.
Human embryo: a biological definition
Hum Reprod. 2007 Apr;22(4):905-11. Epub 2006 Dec 18.
Findlay JK, Gear ML, Illingworth PJ, Junk SM, Kay G, Mackerras AH, Pope A, Rothenfluh HS, Wilton L.
National Health and Medical Research Council, Canberra, Australia.
Abstract This paper defines a human embryo from a biological standpoint that takes into account emerging technologies in reproductive science. The paper does not consider legal, moral, religious or social views. As the definition of a human embryo must reflect the multifactorial processes of development, an approach has been adopted which combines recognition of observed events with potential for further development. This acknowledges that fertilization and development are not static processes, and as such embryo status can only be defined by observation of specific markers. The following biological definition of 'human embryo' is proposed. A human embryo is a discrete entity that has arisen from either: the first mitotic division when fertilization of a human oocyte by a human sperm is complete or any other process that initiates organized development of a biological entity with a human nuclear genome or altered human nuclear genome that has the potential to develop up to, or beyond, the stage at which the primitive streak appears, and has not yet reached 8 weeks of development since the first mitotic division.
PMID: 17178746 http://www.ncbi.nlm.nih.gov/pubmed/17178746
A history of normal plates, tables and stages in vertebrate embryology
Int J Dev Biol. 2007;51(1):1-26.
Department of History and Philosophy of Science, University of Cambridge, UK. firstname.lastname@example.org Abstract Developmental biology is today unimaginable without the normal stages that define standard divisions of development. This history of normal stages, and the related normal plates and normal tables, shows how these standards have shaped and been shaped by disciplinary change in vertebrate embryology. The article highlights the Normal Plates of the Development of the Vertebrates edited by the German anatomist Franz Keibel (16 volumes, 1897-1938). These were a major response to problems in the relations between ontogeny and phylogeny that amounted in practical terms to a crisis in staging embryos, not just between, but (for some) also within species. Keibel's design adapted a plate by Wilhelm His and tables by Albert Oppel in order to go beyond the already controversial comparative plates of the Darwinist propagandist Ernst Haeckel. The project responded to local pressures, including intense concern with individual variation, but recruited internationally and mapped an embryological empire. Though theoretically inconclusive, the plates became standard laboratory tools and forged a network within which the Institut International d'Embryologie (today the International Society of Developmental Biologists) was founded in 1911. After World War I, experimentalists, led by Ross Harrison and Viktor Hamburger, and human embryologists, especially George Streeter at the Carnegie Department of Embryology, transformed Keibel's complex, bulky tomes to suit their own contrasting demands. In developmental biology after World War II, normal stages-reduced to a few journal pages-helped domesticate model organisms. Staging systems had emerged from discussions that questioned the very possibility of assigning an embryo to a stage. The historical issues resonate today as developmental biologists work to improve and extend stage series, to make results from different laboratories easier to compare and to take individual variation into account.
PMID: 17183461 http://www.ncbi.nlm.nih.gov/pubmed/17183461
Structural and functional early human development assessed by three-dimensional and four-dimensional sonography
Fertil Steril. 2005 Nov;84(5):1285-99.
Kurjak A, Pooh RK, Merce LT, Carrera JM, Salihagic-Kadic A, Andonotopo W.
Department of Obstetrics and Gynecology, Medical School, University of Zagreb, Sveti Duh Hospital, Zagreb, Croatia. email@example.com Abstract OBJECTIVE: To summarize the role of three-dimensional and four-dimensional ultrasound in the assessment of early human development.
DESIGN: Review of literature.
SETTING: Ultrasound research center and obstetrics and gynecology department in a tertiary care facility.
RESULT(S): The introduction of high-frequency transvaginal tranducers has resulted in remarkable progress in ultrasonographic visualization of early embryos and fetuses and the development of sonoembryology. Furthermore, recent introduction of three-dimensional and four-dimensional ultrasounds combined with the transvaginal approach has produced more objective and accurate information on embryonal and early fetal development. For the first time parallel analyses of structural and functional parameters in the first 12 weeks of gestation become possible.
CONCLUSION(S): The anatomy and physiology of placental and embryonic development is a field where medicine exerts its greatest impact on early pregnancy at present time, and it opens fascinating aspects of embryonic differentiation. Clinical assessment of those stages of growth rely heavily on three-dimensional and four-dimensional sonography, one of the most promising forms of noninvasive diagnostics today and embryological phenomenon, once matters for textbooks are now routinely recorded with outstanding clarity.
Segmentation in staged human embryos: the occipitocervical region revisited
J Anat. 2003 Sep;203(3):297-315.
Müller F, O'Rahilly R.
School of Medicine, University of California, Davis, California, USA.
Abstract The first seven somites, the rhombomeres, and the pharyngeal arches were reassessed in 145 serially sectioned human embryos of stages 9-23, 22 of which were controlled by precise graphic reconstructions. Segmentation begins in the neuromeres, somites and aortic arches at stage 9. The following new observations are presented. (1) The first somite in the human, unlike that of the chick, is neither reduced in size nor different in structure, and it possesses sclerotome, somitocoel and dermatomyotome. (2) Somites 1-4, unlike those of the chick, are related to rhombomere 8 (rather than 7 and 8) and are caudal to pharyngeal arch 4 (rather than in line with 3 and 4). (3) Occipital segment 4 resembles a developing vertebra more than do segments 1-3. (4) The development of the basioccipital resembles that of the first two cervical vertebrae in that medial and lateral components arise in a manner that differs from that in the rest of the vertebral column. (5) The two groups of somites, occipital 1-4 and cervical 5-7, each form a median skeletal mass. (6) An 'S-shaped head/trunk interface', described for the chick and unjustifiably for the mouse, was not found because it is not compatible with the topographical development of the otic primordium and somite 1, between which neural crest migrates without hindrance in mammals. (7) Occipital segmentation and related features are documented by photomicrographs and graphic interpretations for the first time in the human. It is confirmed that the first somite, unlike that of the chick, is separated from the otic primordium by a distance, although the otic anlage undergoes a relative shift caudally. The important, although frequently neglected, distinction between lateral and medial components is emphasized. Laterally, sclerotomes 3 and 4 delineate the hypoglossal foramen, 4 gives rise to the exoccipital and participates in the occipital condyle, 5 forms the posterior arch of the atlas and 6 provides the neural arch of the axis, which is greater in height than the arches of the other cervical vertebrae. Medially, the perinotochord and migrated sclerotomic cells give rise to the basioccipital as well as to the vertebral centra, including the tripartite column of the axis. Registration between (1) the somites and (2) the occipital and cervical medial segments becomes interrupted by the special development of the axis, the three components of which come to occupy the height of only 2 1/2 segments.
PMID: 14529047 http://www.ncbi.nlm.nih.gov/pubmed/14529047
Nutrition of the human fetus during the first trimester--a review
Placenta. 2001 Apr;22 Suppl A:S70-7.
Burton GJ, Hempstock J, Jauniaux E. Source Department of Anatomy, University of Cambridge, UK. firstname.lastname@example.org
In all mammalian species nutrition of the conceptus is initially histiotrophic, with the trophectoderm phagocytosing first oviductal and then uterine secretions. Following implantation and establishment of the chorioallantoic placenta there is a transition to haemotrophic nutrition, with exchange between the maternal and fetal circulations. It has long been assumed that the transition occurs soon after implantation in the human, due to the invasive nature of this process. However, the recent realization that the maternal circulation to the placenta is not fully established until the end of the first trimester casts doubt on the validity of this assumption. There is new evidence that the uterine glands discharge secretions into the intervillous space until at least 8 weeks of pregnancy, and that these are taken up by the syncytiotrophoblast. Also, during early pregnancy selected maternal proteins accumulate within the fluid of the coelomic cavity, from which they may be transported to the fetus by the secondary yolk sac. Histiotrophic nutrition may be advantageous to the fetus during the first trimester as it provides nutrients under a low oxygen concentration, so reducing the risk of free radical mediated damage during the sensitive period of organogenesis. Once this is complete, and fetal oxygen requirements rise, there is a transition to haemotrophic nutrition at the start of the second trimester, when the maternal placental circulation is fully established.
Copyright 2001 IFPA and Harcourt Publishers Ltd.
Human post-implantation embryo collection: medical and surgical techniques
Early Hum Dev. 1998 Jul 10;51(3):213-21.
Bullen PJ, Robson SC, Strachan T.
Department of Fetal Medicine, University of Newcastle upon Tyne, Royal Victoria Infirmary, UK. Abstract Knowledge of the genetic control of early human development is limited with most information being extrapolated from studies in animal models. There is compelling evidence that undertaking gene expression studies in human embryos can be expected to dramatically enhance our understanding of embryonic formation and malformation. Such studies require the systematic and coordinated collection, storage and study of human embryos. We have successfully collected intact embryos from cases undergoing termination of pregnancy (TOP). Embryonic material was collected from 62% of attempts using a technique of surgical aspiration carried out under ultrasound guidance. Collection rates were lower after medical termination of pregnancy (41%) although the proportion of undisrupted embryos was identical with the two methods (26%). Surgical aspiration provided intact embryos between Carnegie stages (CS) 16-22 while earlier developmental stages were collected from medical terminations. Our collection of over 60 intact specimens, spanning Carnegie stages 10 to 22 (about 21 to 53 days of development) covers a huge window of critical developmental events and hence represents an exciting and valuable research resource.
Morphological and molecular characteristics of living human fetuses between Carnegie stages 7 and 23: developmental stages in the post-implantation embryo
Hum Reprod Update. 1997 Jan-Feb;3(1):3-23.
Harkness LM, Baird DT.
Department of Obstetrics and Gynaecology, University of Edinburgh, UK. Abstract Determination of embryonic age groups or stages has been based on the Carnegie Institute collection started in 1887. Improved technology has enabled the building of a new collection of embryos of < 9 weeks gestation; these were then used to compare with the original Carnegie collection. The results suggest that in providing definitive stages that are rigidly bound by developmental events, limitations are placed on categorizing the embryo. Allocation of embryos to a specific stage can assist in identifying post-ovulatory age but overlaps between stages could lead to classification into an incorrect stage.
Early (34-56 days from last menstrual period) ultrasonographic measurements in normal pregnancies
Hum Reprod. 1996 Aug;11(8):1771-4.
Coulam CB, Britten S, Soenksen DM.
Genetics & IVF Institute, Fairfax, VA 22031, USA. Abstract To assess early embryonic growth and development, 361 pregnancies were studied from 34 to 56 days from last menstrual period. All pregnancies had a subsequent successful outcome. Transvaginal ultrasonography was performed using an Acuson 128 x P/10 with a 5-7.5 MHz probe. Gestational sac diameter, embryonic pole length and embryonic heart rates were measured. Embryonic heart rates were determined by M-mode. Gestational sac diameter, embryonic pole length and embryonic heart rate increased linearly relative to gestational age and to each other. Regression equations comparing gestational sac diameter and embryonic pole length as well as comparing embryonic heart rate with gestational sac diameter and embryonic pole length were constructed. To be normal, gestations that have (i) sac diameter of 20 mm and 30 mm should contain at least a 2 mm and 5 mm embryo with embryonic heart rates of at least 75 and 100 beats per min, respectively, and (ii) embryos measuring 2 mm, 5 mm, 10 mm and 15 mm should display embryonic heart rates of at least 75, 100, 120 and 130 beats per minute respectively.
PMID: 8921130 [PubMed - indexed for MEDLINE]
Embryonic death in early pregnancy: a new look at the first trimester
Obstet Gynecol. 1994 Aug;84(2):294-7. Goldstein SR.
Department of Obstetrics and Gynecology, New York University School of Medicine, New York. Abstract OBJECTIVE: To examine the frequency of pregnancy loss following successful development of anatomical embryonic landmarks identified with endovaginal ultrasound. METHODS: Two hundred thirty-two women with positive urinary pregnancy tests and no antecedent history of vaginal bleeding had endovaginal sonography performed at the initial visit and at subsequent visits as indicated clinically. The presence of anatomical and embryonic structures (gestational sac, yolk sac, embryo) and cardiac activity was recorded. Patients were followed until delivery unless sonographic evidence of nonviability was seen or spontaneous loss occurred. RESULTS: Twenty-seven losses occurred during the embryonic period, four losses occurred in the fetal period, and there were 201 live births. If a gestational sac developed, subsequent loss of viability in the embryonic period occurred in 11.5%; loss rates were 8.5% with a yolk sac, 7.2% for an embryo up to 5 mm, 3.3% for an embryo of 6-10 mm, and 0.5% for an embryo larger than 10 mm. No pregnancies were lost between 8.5 and 14 menstrual weeks. The fetal loss rate after 14 weeks was 2.0%. CONCLUSIONS: The rate of early pregnancy loss decreases successively with gestational age and is virtually complete by the end of the embryonic period (70 days after onset of the last menstrual period). Subsequent pregnancy losses in the fetal period occur between 14 and 20 weeks. This pattern of early pregnancy death suggests a period of embryonic loss distinct from one of fetal loss. Based on these data, the physiologic significance of the traditional boundary of the first trimester as an appropriate dividing time line for early pregnancy may be questioned.
PMID: 8041550 [PubMed - indexed for MEDLINE]
Embryonic length and cerebral landmarks in staged human embryos
Anat Rec. 1984 Jun;209(2):265-71.
O'Rahilly R, Müller F.
Abstract The greatest length (GL) and the crown-rump (C-R) length were compared in 43 staged human embryos. It was found that point C, which overlies the middle of the midbrain, was sometimes difficult to locate and that point R is not precise. These disadvantages render the C-R measurement unsatisfactory. At 4 weeks (stage 13) the GL comes to exceed the C-R and continues to do so until about 7 weeks (stages 17-19). The maximum difference is approximately 1.5 mm. Thereafter, the two lengths are basically equal and coincide from about stages 18 and 19 onward. In a series of 100 embryos of stages 19-23, female embryos at stages 21 and 22 were found to be shorter (by a mean of 1 mm) than male embryos, but not at stages 19, 20, and 23. The greatest length, which is independent of fixed points, is much simpler to measure than the C-R length, and it is recommended that it be used instead. It is pointed out that Streeter had already made that substitution. The greatest length has the further advantage of being a practicable measurement from two postovulatory weeks (stage 6) throughout the remainder of the embryonic and also in the fetal period. The lower limbs are excluded from measurement.
Comparative development of the nervous, respiratory, and cardiovascular systems
Environ Health Perspect. 1976 Dec;18:55-60.
Abstract The timing of some key embryological events is given for man, rat, chick, and certain other animals. Such times, however, are approximations, and variations occur among members of the same strain and even among members of the same litter. Some differences in developmental patterns are indicated.
PMID: 829490 Environ Health Perspect. 1976 Dec;18:55-60. Comparative development of the nervous, respiratory, and cardiovascular systems. Monie IW.
Abstract The timing of some key embryological events is given for man, rat, chick, and certain other animals. Such times, however, are approximations, and variations occur among members of the same strain and even among members of the same litter. Some differences in developmental patterns are indicated.
PMID: 829490 http://www.ncbi.nlm.nih.gov/pubmed/829490