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The human yolk sac (hYS) is essential for embryo nutrient biosynthesis/transport and development. However, there lacks a comprehensive study of hYS nutrient-gene interactions. Here we performed a secondary analysis of hYS transcript profiles (n = 9 samples) to identify nutrient-sensitive hYS genes and regulatory networks, including those that associate with adverse perinatal phenotypes with embryonic origins. Overall, 14.8% highly expressed hYS genes are nutrient-sensitive; the most common nutrient cofactors for hYS genes are metals and B vitamins. Functional analysis of highly expressed hYS genes reveals that nutrient-sensitive hYS genes are more likely to be involved in metabolic functions than hYS genes that are not nutrient-sensitive. Through nutrient-sensitive gene network analysis, we find that four nutrient-sensitive transcription regulators in the hYS (with zinc and/or magnesium cofactors) are predicted to collectively regulate 30.9% of highly expressed hYS genes. Lastly, we identify 117 nutrient-sensitive hYS genes that associate with an adverse perinatal outcome with embryonic origins. Among these, the greatest number of nutrient-sensitive hYS genes are linked to congenital heart defects (n = 54 genes), followed by microcephaly (n = 37). Collectively, our study characterises nutrient-sensitive hYS functions and improves understanding of the ways in which nutrient-gene interactions in the hYS may influence both typical and pathological development. [ABSTRACT FROM AUTHOR]

Abstract The human yolk sac (hYS) is essential for embryo nutrient biosynthesis/transport and development. However, there lacks a comprehensive study of hYS nutrient-gene interactions. Here we performed a secondary analysis of hYS transcript profiles (n = 9 samples) to identify nutrient-sensitive hYS genes and regulatory networks, including those that associate with adverse perinatal phenotypes with embryonic origins. Overall, 14.8% highly expressed hYS genes are nutrient-sensitive; the most common nutrient cofactors for hYS genes are metals and B vitamins. Functional analysis of highly expressed hYS genes reveals that nutrient-sensitive hYS genes are more likely to be involved in metabolic functions than hYS genes that are not nutrient-sensitive. Through nutrient-sensitive gene network analysis, we find that four nutrient-sensitive transcription regulators in the hYS (with zinc and/or magnesium cofactors) are predicted to collectively regulate 30.9% of highly expressed hYS genes. Lastly, we identify 117 nutrient-sensitive hYS genes that associate with an adverse perinatal outcome with embryonic origins. Among these, the greatest number of nutrient-sensitive hYS genes are linked to congenital heart defects (n = 54 genes), followed by microcephaly (n = 37). Collectively, our study characterises nutrient-sensitive hYS functions and improves understanding of the ways in which nutrient-gene interactions in the hYS may influence both typical and pathological development.

The yolk sac (YS) is the oldest of the extraembryonic membranes in vertebrates. Considered a transitory structure in the human species, the importance of the YS for a successful pregnancy is often overlooked. Due to the general inaccessibility of healthy human YS tissue for research, the use of experimental animal models is of great value. In order to better understand whether the mouse could be used as a translational model for the study of the human YS under normal and pathological conditions, this review comprehensively describes key developmental aspects of the human and mouse YS, detailing their development and function. YS major similarities in both species comprise the following: (1) histological composition (both being composed of endoderm, mesoderm, and mesothelium layers); (2) endoderm endocytosis, synthesis, secretion, and transport capabilities; and (3) mesoderm onset of haematopoiesis and angiogenesis. Examples of main dissimilarities include (1) persistence across pregnancy (i.e. early pregnancy in humans vs term pregnancy in mice); (2) the existence of a secondary YS in humans; (3) the presence of proliferative primordial germ cells (PGCs) in the human versus their absence in mice; and (4) eversion of histological layers in the mouse. Although these differences should be considered when interpreting data from mouse-based studies, the overall morphofunctional similarities in the YS between these species indicate that the mouse can be potentially used as a translational model for the study of the human YS. [ABSTRACT FROM AUTHOR]

Structure of the mesothelial cells of the human yolk sac was examined with light and transmission electron microscopy as well as quantitative morphometry methods. In 6-8 week of the embryonic development epithelial cells demonstrate absorptive activity confirmed by numerous microvilli on the apical cell pole, pinocytic vesicles and extended intercell space. By 11-12 week of embryogenesis the epithelial cells function along with some morphometric parameters tend to decrease. The mesothelial cells of human yolk sac might transfer matters from exocoelomic cavity to embryonic blood vessels. Gradual decrease of exocoelomic cavity size is accompanied by involution in its epithelium structure.

Aims To establish a diagnostic immunohistochemical panel for various histotypes of yolk sac (primitive endodermal) tumours ( YSTs) by comparison with the human yolk sac ( HYS) immunophenotype. Methods and results Twenty-five YSTs showing either classical patterns ( CPs) of histology (microcystic/reticular, n = 14; polyvesicular, n = 1; and hepatoid, n = 1) or somatic glandular patterns ( SGPs; n = 9) were analysed for expression of α-fetoprotein ( AFP), glypican-3 ( GPC3), villin, hepatocyte paraffin-1 ( Hep Par-1), CDX2, SALL4 and LIN28. AFP expression was constantly heterogeneous in CPs but tended to be focal/absent in SGPs. GPC3 was diffuse in CPs but heterogeneous (seven cases) or focal/absent (two cases) in SGPs. HepPar-1 expression was focal in all but three cases (diffuse in one CP-hepatoid and two SGPs). CDX2 positivity was focal in CPs but heterogeneous (seven cases) or diffuse (two cases) in SGPs. Villin, SALL4 and LIN28 were diffusely positive in nearly all cases. Conclusions CPs reproduce the immunophenotype of HYS and early endoderm with variable expression of both AFP and markers of early gut or hepatic differentiation. SGPs with intestinal differentiation often have incomplete immunophenotypes. A differential diagnosis panel, including both markers of pluripotentiality ( SALL4 and/or LIN28) and endoderm ( AFP, GPC3 and villin), is proposed. It identifies overlapping multidifferentiation of primitive and somatic immunophenotypes, supporting the recently proposed term of primitive endodermal tumours. [ABSTRACT FROM AUTHOR]

Nogales FF, Preda O & Nicolae A (2012) Histopathology 60, 1023-1033 Yolk sac tumours revisited. A review of their many faces and names We review the current knowledge on human yolk sac tumours (YSTs) 50 years after their initial description. Their complex nomenclature and histogenesis stress the fact that they are not a discrete entity, but represent a multifaceted group of neoplasms, for which the term primitive endodermal tumours would be more appropriate, accounting for their capacity to differentiate into various extraembryonal and somatic cell types. Different histological patterns of human YSTs correlate with the developmental potential of primitive endoderm and mesenchyme, but they are also similar to some murine experimental tumours. Exceptionally, YSTs replicate the tubular structures of the human yolk sac and allantois. Endodermal somatic differentiation reproduces pulmonary, intestinal and hepatic tissues and are identical with some, embryonal-type endodermal, gastric and lung carcinomas, which are indistinguishable from YSTs. YSTs may show an overgrowth of their mesenchymal (sarcomatous) and epithelial components (such as mucinous carcinoma or carcinoid) and also be a source of haematological malignancies. YSTs associated with non-germ cell tumours probably originate from malignant pluripotent somatic stem cells. Only AFP and glypican-3 are characteristic immunohistochemical markers. Pluripotent antibodies (SALL4, Lin28, IMP-3) help in differential diagnoses, while some differentiation markers (CDX2, TTF-1, HepPar1) facilitate recognition of unusual variants of YSTs. [ABSTRACT FROM AUTHOR]

Organogenesis occurs during the first 8 weeks of human embryonic development; in consequence, early human growth and development take place before and in the absence of fully developed internal organs. During this period, normal development depends on several factors, but two are imperative: nutrition and a functional transport system for the distribution of nutrients and for waste disposal. The yolk sac (YS), a highly differentiated adnexal organ, is known to accomplish this fundamental task during early pregnancy. In this review, we summarize our contribution to the understanding of early human embryology, focusing interest on analysis of the morphofunctional link that is established between the human embryo and the YS during the embryonic period. Embryos were collected from the gestational sac after salpingectomies performed on patients with singleton pregnancies occurring in the fallopian tube. Samples of YS were taken from 20 human embryos at Carnegie stages ranging from 12 to 20. The age of the embryo was estimated from data of the patient's last menstrual history and confirmed from crown-rump length measurements and morphological characteristics of the specimen. The samples were fixed in 3% glutaraldehyde and then postfixed in 2% osmium tetroxide and prepared for light, transmission, and scanning electron microscopy according to conventional techniques. The samples were examined with a Philips 301 EM and an S-4000 Hitachi field emission SEM. The yolk stalk, and the YS wall with its corresponding endodermal, mesenchymal, and mesothelial layers, were analyzed. In accordance with their morphological features, the endodermal cells are equipped with organelles to fulfill several functions that are expressed in absorption from the vitelline cavity via microvilli present into the outer cell surface, in secretion to the extracellular space, and in the synthesis of numerous proteins which are transported by the bloodstream to the embryo. The mesothelial surface is provided with cell-surface differentiation that promotes a protective coat to prevent damage from compression or friction of the YS wall against the amnios, umbilical cord, and chorionic cavity wall during growth. The mesenchyme is the main site for blood vessel formation and gives rise to a network that provides the embryo with nutrients and a means of waste disposal. A critical analysis of the role of the endodermal vesicle in the production of fluid that is accumulated in the YS, and of the role that the vitelline duct play in the exchange function between the YS and intestinal tract, is presented. We have demonstrated that the vitelline duct is not functional after week 5 because of the closure of its lumen. This finding is discussed with reference to the biological meaning of the vitelline duct and its functional period of activity, and its possible role in the physiology of exchange during the embryonic period is assessed. [ABSTRACT FROM AUTHOR]