Yolk Sac

For medical students2 min readUpdated 2026-10-10

The yolk sac is an extraembryonic membrane formed during early embryogenesis. It develops as the germ layers envelop the yolk (or the corresponding space) and plays a critical role in early hematopoiesis and primordial germ cell formation.

Wall structureComposed of two layers: extraembryonic endoderm and mesoderm.

HematopoiesisBlood cells first form within the mesodermal layer of the yolk sac wall.

Germ cellsServes as the primary site for the formation of primordial germ cell precursors.

MammalsThe yolk sac forms despite the complete absence of actual yolk.

Formation and Histology

The formation of the yolk sac is a process in which the germ layers surround the yolk, enclosing it in a specialized membrane to create a fully functional extraembryonic structure.

Histologically, the wall of this organ always consists strictly of two layers:

Inner layer — represented by extraembryonic endoderm, derived from the hypoblast.
Outer layer — represented by the visceral layer of extraembryonic mesoderm. A key feature of this layer is the active development of blood vessels essential for supporting the embryo's viability.

Topography and Development in Birds

In birds, the yolk itself—the main portion of the ovum that did not participate in cleavage—lies directly inside the sac.

The connection between the organ and the embryonic body undergoes significant changes during embryogenesis:

Initially, the cavity of the yolk sac has a very broad communication with the primitive gut cavity.
Body folds serve as the boundary between them.
As the embryonic body folds and the gut tube closes, this broad connection begins to narrow.
Eventually, the vitelline duct (yolk stalk) is formed—a narrow communicating channel linking the embryonic gut to the yolk sac.

Yolk Sac in Mammals

The main distinguishing feature in mammals is the complete absence of yolk. Nevertheless, the yolk sac still forms: extraembryonic endoderm cells (from the hypoblast) proliferate, simply delimiting a free space within the trophoblast.

At this stage, the spatial arrangement (topography) features a flat embryo, represented by the epiblast, positioned strictly between two vesicles: the amniotic vesicle (located dorsally) and the yolk sac vesicle (located ventrally).

There are two sequential stages of yolk sac formation in mammals:

Primary yolk sac — directly adjacent to the trophoblast, but short-lived and rapidly regresses.
Secondary yolk sac — smaller in volume than the primary one, but functionally significant for subsequent embryogenesis. This organ functions only during early developmental stages before also undergoing regression.

Functions of the Yolk Sac

Despite its provisional nature, the yolk sac performs three vital tasks:

Hematopoietic (blood-forming) function. This is the first site in the body where hematopoiesis begins, localized in the mesoderm of the sac wall.
Generative function. Primordial germ cells are first identified in the wall of the organ. Later, these cells migrate to the embryonic gonad primordia.
Trophic function. Most prominent in birds, where the yolk (along with albumen) serves as the primary source of nutrients and building materials for the growing embryo. In mammals, this function is virtually absent.

Mnemonic

To remember the functions of the yolk sac, use the mnemonic H-G-T: Hematopoiesis, Germ cells (generative), Trophic (nutrition).

Frequently asked questions

By which week of human intrauterine development does the yolk sac completely regress?

The yolk sac undergoes complete regression by the 12th week of pregnancy.

Normally, this organ is clearly visualized on ultrasound at 6 weeks. Before its involution, the yolk sac performs several crucial temporary functions:

Hematopoietic — supplying primary blood cells;
Synthetic — producing alpha-fetoprotein and transferrins;
Excretory, metabolic, and immunoregulatory.

Premature regression of the yolk sac (before the maturation of the fetal liver, spleen, and reticuloendothelial system) is considered a poor prognostic sign, indicating a risk of miscarriage or missed abortion.

Which fetal structure does the vitelline duct eventually incorporate into?

The vitelline duct subsequently becomes part of the connecting stalk (body stalk), which then transforms into the umbilical cord.

The vitelline duct forms as a result of longitudinal and transverse folding of the embryo body when the broad communication between the yolk sac cavity and the primitive gut narrows. Along with the emerging allantois, it becomes enclosed within the connecting stalk. In the fully formed umbilical cord, the vitelline duct undergoes regression, though its vestigial remnants may occasionally be found upon histological examination of the umbilical cord.

From which germ layers is the yolk sac wall formed?

The inner layer is formed from extraembryonic endoderm (a hypoblast derivative), and the outer layer is covered by the visceral layer of extraembryonic mesoderm.

What is the vitelline duct (yolk stalk)?

It is a narrow channel formed as the embryo folds and the gut tube closes. It connects the primitive gut cavity to the yolk sac.

What is the main difference between the mammalian and avian yolk sac?

In mammals, the yolk is completely absent, so the trophic function is practically unexpressed, whereas in birds, it serves as the primary nutritional source.

Go deeper

Migration pathway of primordial germ cells from the yolk sac wall to the gonad primordia
Mechanisms of angiogenesis and initial hematopoiesis in the extraembryonic mesoderm
Formation and role of the amniotic vesicle in the topography of the flat embryo
Regression of the primary yolk sac and formation of the secondary yolk sac in mammals