Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (534 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
The first of four extra-embryonic membranes to form during embryogenesis. In reptiles and birds, it arises from endoderm and mesoderm to incorporate the egg yolk into the digestive tract for nourishing the embryo. In placental mammals, its nutritional function is vestigial; however, it is the source of intestinal mucosa; blood cells; and germ cells. It is sometimes called the vitelline sac, which should not be confused with the vitelline membrane of the egg.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Sacs, Yolk; Sac, Yolk; Yolk Sacs; Vitelline Sac of Embryo; Embryo Vitelline Sac; Embryo Vitelline Sacs.
Where it fits in the MeSH classification
- Broader topics
- Extraembryonic Membranes; Embryo, Nonmammalian
Related concepts
- Embryogenesis
- Reptiles
- Birds
- Egg Yolk
- Gastrointestinal Tract
- Mammals
- Intestinal Mucosa
- Blood Cells
- Germ Cells
- Vitelline Membrane
Research landscape
PubMed indexes 2,932 records tagged with the MeSH heading “Yolk Sac” (counts retrieved 2026-10-31). 270 of them (9.2%) were published from 2020 onward, and the busiest period so far is through 1999 with 1,465 records.
Reviews account for 224 records (7.6%) and meta-analyses for 2. Randomized controlled trials number 3 (0.1%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 1,465 |
| 2000-2009 | 625 |
| 2010-2019 | 572 |
| 2020 onward | 270 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 224 | 7.6% |
| Meta-analyses | 2 | 0.1% |
| Randomized controlled trials | 3 | 0.1% |
Method: PubMed query "Yolk Sac"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-31.
Reading the evidence in anatomy and physiology
Anatomy describes how body structures are built and physiology describes how they normally work, so most findings here are descriptive or mechanistic rather than evidence about treatment. Much of what is known comes from dissection, imaging, tissue studies and experiments in animals, and measurements in healthy volunteers can differ from those in people with disease or at different ages. Normal ranges vary between individuals and populations. Check whether a result was measured in people or in another species, the age and health of the participants, and the method used.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Yolk sac macrophage progenitors traffic to the embryo during defined stages of development | 2018 | Research article Design not recorded in structured metadata | 254 | cc by PMID 29311541 · DOI · PMC5758709 |
| Origin and function of the yolk sac in primate embryogenesis | 2020 | Review article Design not recorded in structured metadata | 163 | cc by PMID 32724077 · DOI · PMC7387521 |
| Yolk sac cell atlas reveals multiorgan functions during human early development | 2023 | Research article Design not recorded in structured metadata | 93 | cc by PMID 37590359 · DOI · PMC7614978 |
| Eomes directs the formation of spatially and functionally diverse extraembryonic hematovascular tissues | 2025 | Research article Design not recorded in structured metadata | 5 | cc by PMID 40562043 · DOI · PMC7618462 |
Yolk sac macrophage progenitors traffic to the embryo during defined stages of development [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Tissue macrophages in many adult organs originate from yolk sac (YS) progenitors, which invade the developing embryo and persist by means of local self-renewal.
- Closing excerpt
- These findings close an important gap in our understanding of the development of the innate immune system.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (147 words)
Tissue macrophages in many adult organs originate from yolk sac (YS) progenitors, which invade the developing embryo and persist by means of local self-renewal. However, the route and characteristics of YS macrophage trafficking during embryogenesis are incompletely understood. Here we show the early migration dynamics of YS-derived macrophage progenitors in vivo using fate mapping and intravital microscopy. From embryonic day 8.5 (E8.5) CX3CR1+ pre-macrophages are present in the mouse YS where they rapidly proliferate and gain access to the bloodstream to migrate towards the embryo. Trafficking of pre-macrophages and their progenitors from the YS to tissues peaks around E10.5, dramatically decreases towards E12.5 and is no longer evident from E14.5 onwards. Thus, YS progenitors use the vascular system during a restricted time window of embryogenesis to invade the growing fetus. These findings close an important gap in our understanding of the development of the innate immune system.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 29311541 · DOI · PMC5758709
Origin and function of the yolk sac in primate embryogenesis [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Human embryogenesis is hallmarked by two phases of yolk sac development.
- Closing excerpt
- We discuss the intricate relationship between the yolk sac and the primate embryo and highlight the pivotal role of the yolk sac as a multifunctional hub for haematopoiesis, germ cell development and nutritional supply.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (121 words)
Human embryogenesis is hallmarked by two phases of yolk sac development. The primate hypoblast gives rise to a transient primary yolk sac, which is rapidly superseded by a secondary yolk sac during gastrulation. Moreover, primate embryos form extraembryonic mesoderm prior to gastrulation, in contrast to mouse. The function of the primary yolk sac and the origin of extraembryonic mesoderm remain unclear. Here, we hypothesise that the hypoblast-derived primary yolk sac serves as a source for early extraembryonic mesoderm, which is supplemented with mesoderm from the gastrulating embryo. We discuss the intricate relationship between the yolk sac and the primate embryo and highlight the pivotal role of the yolk sac as a multifunctional hub for haematopoiesis, germ cell development and nutritional supply.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 32724077 · DOI · PMC7387521
Yolk sac cell atlas reveals multiorgan functions during human early development [3]
Abstract reading summary — source excerpts
- Opening excerpt
- The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans.
- Closing excerpt
- The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (117 words)
The extraembryonic yolk sac (YS) ensures delivery of nutritional support and oxygen to the developing embryo but remains ill-defined in humans. We therefore assembled a comprehensive multiomic reference of the human YS from 3 to 8 postconception weeks by integrating single-cell protein and gene expression data. Beyond its recognized role as a site of hematopoiesis, we highlight roles in metabolism, coagulation, vascular development, and hematopoietic regulation. We reconstructed the emergence and decline of YS hematopoietic stem and progenitor cells from hemogenic endothelium and revealed a YS-specific accelerated route to macrophage production that seeds developing organs. The multiorgan functions of the YS are superseded as intraembryonic organs develop, effecting a multifaceted relay of vital functions as pregnancy proceeds.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 37590359 · DOI · PMC7614978
Eomes directs the formation of spatially and functionally diverse extraembryonic hematovascular tissues [4]
Abstract reading summary — source excerpts
- Opening excerpt
- During mouse gastrulation, extraembryonic mesoderm (ExEM) contributes to the extraembryonic yolk sac (YS) and allantois, both of which are essential for successful gestation.
- Closing excerpt
- Our study highlights previously unrecognized functional and mechanistic diversity in ExEM diversification and endothelial development and introduces a tractable EB model to dissect the signaling pathways and transcriptional networks driving the formation of key extraembryonic tissues.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (149 words)
During mouse gastrulation, extraembryonic mesoderm (ExEM) contributes to the extraembryonic yolk sac (YS) and allantois, both of which are essential for successful gestation. Although the genetic networks coordinating intra-embryonic mesodermal subtype specification are well studied, ExEM diversification remains poorly understood. Here, we identify that embryoid body (EB) in vitro differentiation generates distinct lineages of mesodermal cells, matching YS and allantois development. Combining in vitro and in vivo mouse models, we discover that Eomesodermin (Eomes) controls the formation of YS-fated ExEM but is dispensable for allantois formation. Furthermore, simultaneous disruption of Eomes and T impedes the specification of any YS or allantois mesoderm, indicating compensatory roles for T during allantois formation upon Eomes depletion. Our study highlights previously unrecognized functional and mechanistic diversity in ExEM diversification and endothelial development and introduces a tractable EB model to dissect the signaling pathways and transcriptional networks driving the formation of key extraembryonic tissues.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 40562043 · DOI · PMC7618462
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article Fetal monocytes and the origins of tissue-resident macrophages [5]
- Research article Yolk-sac hematopoiesis: the first blood cells of mouse and man [6]
- Research article Development, morphology, and function of the yolk-sac placenta of laboratory rodents [7]
- Research article Blood island formation: longstanding observations and modern interpretations [8]
- Research article Maternal cholesterol in fetal development: transport of cholesterol from the maternal to the fetal circulation [9]
- Research article Hematopoiesis in the yolk sac: more than meets the eye [10]
References
- Stremmel C, Schuchert R, Wagner F, Thaler R, Weinberger T, Pick R, et al.. Yolk sac macrophage progenitors traffic to the embryo during defined stages of development. . 2018. PMID 29311541 · DOI · PMC5758709
- Ross C, Boroviak TE. Origin and function of the yolk sac in primate embryogenesis. . 2020. PMID 32724077 · DOI · PMC7387521
- Goh I, Botting RA, Rose A, Webb S, Engelbert J, Gitton Y, et al.. Yolk sac cell atlas reveals multiorgan functions during human early development. . 2023. PMID 37590359 · DOI · PMC7614978
- Theeuwes B, Harland LTG, Bisia AM, Costello I, Ton MN, Lohoff T, et al.. Eomes directs the formation of spatially and functionally diverse extraembryonic hematovascular tissues. . 2025. PMID 40562043 · DOI · PMC7618462
- Hoeffel G, Ginhoux F. Fetal monocytes and the origins of tissue-resident macrophages. Cell Immunol. 2018. PMID 29475558 · DOI
- Palis J, Yoder MC. Yolk-sac hematopoiesis: the first blood cells of mouse and man. Exp Hematol. 2001. PMID 11495698 · DOI
- Jollie WP. Development, morphology, and function of the yolk-sac placenta of laboratory rodents. Teratology. 1990. PMID 2187257 · DOI
- Ferkowicz MJ, Yoder MC. Blood island formation: longstanding observations and modern interpretations. Exp Hematol. 2005. PMID 16140152 · DOI
- Woollett LA. Maternal cholesterol in fetal development: transport of cholesterol from the maternal to the fetal circulation. Am J Clin Nutr. 2005. PMID 16332646 · DOI
- McGrath KE, Palis J. Hematopoiesis in the yolk sac: more than meets the eye. Exp Hematol. 2005. PMID 16140150 · DOI
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-31.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.