Notes: Week 2 Development — Implantation and Fetal Membranes

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• Week 2 of development focuses on implantation and fetal membranes.
• Source: VCOM CaroliNAS campus lecture by Joel Atance, PhD (Sept 16, 2025).

Page 2

• Rule of Twos in Week Two:
  • Embryoblast divides into two layers: the epiblast and the hypoblast.
  • Trophoblast differentiates into two tissues: the cytotrophoblast and the syncytiotrophoblast.
  • Two yolk sacs form: the primary yolk sac followed by the secondary yolk sac.
  • Two new cavities form: the amniotic cavity and the chorionic cavity.
  • The extraembryonic mesoderm splits into two layers that line the chorionic cavity.

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• Topic: Completion of implantation.
• This page serves as a section header for the implantation completion stage.

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• By Day 6, trophoblast at the embryonic pole differentiates into syncytiotrophoblast and cytotrophoblast.
• Mechanisms:
  • Attachment of the blastocyst to the endometrium induces trophoblast cells at the embryonic pole to shed membranes, fuse, and form the syncytiotrophoblast.
  • Other trophoblast cells retain membranes and become the cytotrophoblast.
• Syncytiotrophoblast behavior:
  • Extends finger-like processes that penetrate the endometrium and pull the embryo into the endometrium.
  • Cytotrophoblast secretes enzymes that digest the endometrial extracellular matrix, permitting invasion by syncytiotrophoblast processes.

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• Diagrammatic emphasis on spatial relationships (described in captions):
  • Blastocyst is attaching to the endometrium at the embryonic pole.
  • The syncytiotrophoblast and cytotrophoblast are present; the abembryonic pole is opposite.
  • The blastocyst cavity exists; epiblast and hypoblast line the blastocyst; amniotic cavity formation begins later.
  • Amniotic cavity is forming within the epiblast; Amnion is the membrane surrounding the amniotic cavity (derived from the epiblast).
• Other terms appearing: trophoblastic components, endometrium, endometrial epithelium.

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• By Day 9, the blastocyst is fully implanted and enveloped by the syncytiotrophoblast.
• Coagulation plug forms at the abembryonic pole to seal the entry point, temporarily marking implantation.
• Note: Coagulation plug is an important early marker of implantation site.

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• Amnioblasts (flattened cells) form from the epiblast around the amniotic cavity.
• Epiblast continues to contribute to the amniotic lining.
• A coagulation plug remains at the site of implantation.
• The blastocyst is fully implanted; the blastocyst cavity persists as evidence of implantation.

Page 8

• Section header: Formation of Cavities.
• Cavities develop to create space both inside and outside the embryo.

Page 9

• By roughly one week post-fertilization, the embryo is a bilaminar disk.
• Cavities are necessary to create internal (within) and external (outside) spaces for growth.

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• The amniotic cavity forms within the epiblast on Day 8.
• Process:
  • Fluid collects within the epiblast.
  • Epiblast cells adjacent to the cytotrophoblast become amnioblasts.
  • The amnion is the actual membrane derived from the epiblast that surrounds the amniotic cavity.
• Growth: The amniotic cavity expands and, by Week 8, encloses the entire embryo.

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• Visualization of: Syncytiotrophoblast, Cytotrophoblast, Amniotic cavity forming within the epiblast, Amnioblasts, Epiblast, and the concept of the blastocyst/blastocyst cavity.
• The amniotic cavity grows as amnioblasts line the cavity.

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• Amniotic fluid has multiple mechanical and biochemical functions:
  • Permits free movement of the embryo/fetus, essential for growth (including lung development).
  • Provides a protective cushion.
  • Serves as a hydrostatic wedge aiding dilation of the cervix during labor.
  • Helps control the embryo’s environment (temperature, fluid composition, barrier to infection).
• Amniotic fluid accumulates fetal cells and metabolic by-products, enabling:
  • Detection of developmental abnormalities and/or disease.
  • Harvesting of stem cells for future use (self or relatives).

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• Amniocentesis is typically performed ~4 months into gestation to sample amniotic fluid.
• Contents/uses:
  • Cells and/or metabolites for detecting genetic abnormalities or disease.
  • Potential source of stem cells from amnion for later use.
• Amniotic fluid roles summarized: permits free movement, cushion, environmental control, and involvement in birth wedge.
• Note: The slide also hints at the future development of the amniotic cavity.

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• Hypoblast contributes to the formation of the primary yolk sac (also called primitive yolk sac, primary umbilical vesicle, Heuser’s membrane, or exocoelomic membrane).
• Day 9: Some hypoblast cells migrate along the inside of the cytotrophoblast to help form the primary yolk sac.
• ~Day 10–11: The primary yolk sac gives rise to extraembryonic mesoderm, which lies between the primary yolk sac and the cytotrophoblast.
• ~Day 12: A new space forms within the extraembryonic mesoderm—the chorionic cavity (extraembryonic coelom).

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• The extraembryonic coelom formation continues with:
  • Migrating hypoblast cells give rise to the primary yolk sac.
  • The primary yolk sac gives rise to the extraembryonic mesoderm.
  • The chorionic cavity arises within the extraembryonic mesoderm (originating from the primary yolk sac).
• Key structures: primary yolk sac, chorionic cavity; continued development of yolk sac and mesoderm.

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• The Primary Yolk Sac is replaced by the Secondary (definitive) Yolk Sac:
  • By Day $12$, the primary yolk sac is displaced by a second wave of migrating hypoblast cells, forming the secondary yolk sac; the primary yolk sac degenerates.
• Functions of the secondary yolk sac in humans (first 4 weeks):
  • Transfers nutrients from chorionic cavity to the embryo before placental circulation is established.
  • Week $3$: Primordial germ cells appear in the endodermal lining of the yolk sac wall and migrate to the abdomen.
  • Week $3$: Blood development is initiated in the yolk sac.
  • Week $4$: A portion of yolk sac endoderm is incorporated into the developing midgut.

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• Visual: The primary yolk sac is displaced by the second wave of migrating hypoblast cells; the degenerating primary yolk sac; presence of the secondary yolk sac; chorionic cavity forms.

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• The Definitive (secondary) yolk sac is formed; key components include:
  • Syncytiotrophoblast, Cytotrophoblast, Extraembryonic mesoderm, Connecting stalk, Chorionic cavity, and Villi.
• Function: Storage of nutrients in certain animals; in humans the yolk sac persists briefly but is not primary for nutrient storage.
• The connecting stalk forms the precursor to the umbilical cord.
• Time marker: Days $14-15$.

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• Early embryonic gut and related structures depicted: foregut, hindgut, allantois, genital ridge, heart primordium, yolk sac, and other early germ cell/blood formation structures.
• Week 3–4 developments include:
  • Formation of the primordial heart and circulatory components.
  • Origin points for germ cells and blood cells connected to yolk sac physiology.
• Diagram emphasizes relationships among yolk sac, amniotic cavity, chorion, allantois, and early gut development.

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• Timeline markers for yolk sac involvement:
  • ~Day $21$, $24$, and $28$: The yolk sac is progressively incorporated into the developing embryo to form part of the midgut.

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• The Chorion and chorionic cavity: wall of the chorionic cavity becomes the chorion.
• By ~Day $15$, the embryo, amniotic sac, and secondary yolk sac are suspended within the chorionic cavity by the connecting stalk (which contains extraembryonic mesoderm).
• Once blood vessels develop within the connecting stalk, that stalk will become the umbilical cord.
• The main function of the chorion is to contribute to the placenta.

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• Diagram highlights: chorionic cavity, chorion, secondary yolk sac, syncytiotrophoblast, connecting stalk, cytotrophoblast, extraembryonic mesoderm, trophoblastic lacunae.
• The wall of the blastocyst becomes the chorion.

Page 23

• The Amniotic Cavity Persists While Other Cavities Obliterate:
  • The amniotic cavity is the last embryonic cavity to persist; the yolk sac and chorionic cavity are transient.
  • From conception to about Week $8$, the membranes are pushed outward as the embryo grows; by Week $6$ the chorionic cavity and uterine cavity are largely obliterated.
  • By end of the 2nd month, the amnion and chorion (laeve) fuse to form the avascular amniochorionic membrane, obliterating the chorionic cavity.
  • The amniochorionic membrane ruptures during labor (the breaking of water).
  • By end of the 3rd month, the uterine cavity is obliterated due to fusion of chorion with the uterine wall.

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• Week Day timeline (highlights):
  • Day $1$ to Day $6$: Trophoblast differentiates into cytotrophoblast and syncytiotrophoblast; implantation begins; embryonic disc becomes bilaminar; blastocyst cavity present.
  • Day $7$ to Day $9$: Amniotic cavity forms; syncytiotrophoblast expands; implantation continues.
  • Day $9$ to Day $11$: Cells migrate from hypoblast to form primary yolk sac; lacunae form within syncytiotrophoblast; implantation complete; syncytiotrophoblast surrounds embryo.
  • Day $11$ to Day $12$: Yolk sac forms; extraembryonic mesoderm forms and splits to create the chorionic cavity; trophoblastic lacunae anastomose with maternal sinusoids; chorionic cavity is about to develop.

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• A–D frames illustrate progressively complex organization around Day $13–24$:
  • A: Early trophoblast arrangement at embryonic pole with developing yolk sac and chorion components.
  • B: Amniotic and yolk sac relationships; formation of the allantoenteric diverticulum and amniotic duct; connecting stalk forming; chorion and chorionic cavity appear.
  • C: Early villous stems forming; foregut and hindgut regions begin; head fold shapes begin.
  • D: Extraembryonic coelom and tail fold features; placental area (chorion frondosum) appears with villous stems and connecting stalk features.
• Overall takeaway: progressive compartmentalization of the chorionic cavity, amnion, yolk sacs, and connecting stalk leads to early placental development.

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• Week 6 to Week 8 developments:
  • By Week 6, the chorionic cavity and amniotic cavity are both present, with the amniotic cavity enlarging relative to the chorionic cavity.
  • By Week 8, the amniotic cavity is larger, and the chorionic cavity is nearly obliterated.
  • The connecting stalk remains as the precursor to the umbilical cord.

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• End of the 2nd month to end of the 3rd month:
  • The uterine cavity becomes obliterated as the amniochorion fuses with the decidua (parietalis;
  • The fused amnion and chorion laeve (amniochorionic membrane) ruptures during labor, creating the “breaking of water.”
  • By the end of the 3rd month, the chorionic cavity is fully obliterated.

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• Section header: Placent al Circulation.
• Focus on how maternal and fetal systems exchange nutrients, gases, and wastes via the placenta.

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• Conceptus nutrition progresses through three overlapping sources:
  • Early nutrition from uterine milk produced by uterus and fallopian tubes (glycogen-rich secretions).
  • Decidual reaction: stroma of the endometrium accumulates glycogen, proteins, and lipids; trophoblastic nutrition from digested decidual cells by the invading syncytiotrophoblast provides nutrients to the embryo.
  • Placental circulation becomes established as a vascular organ for exchange of gases, nutrients, and wastes between mother and fetus; diffusion is the initial mechanism, later replaced by perfusion via placental circulation.

Page 30

• Summary illustration of embryonic nutrition over time:
  • Embryo nourished by uterine milk, then by uterine milk plus trophoblastic nutrition, and finally by placenta as the circulatory exchange becomes established (~Day 7–Day 14 and beyond).
• Key timeline note: diffusion suffices in early weeks; a circulatory system must develop for sustained growth.

Page 31

• The placenta forms from maternal decidua basalis and fetal chorion frondosum:
  • Decidua basalis is the maternal component of the placenta.
  • In early weeks, villi cover the entire surface of the chorion.
  • As pregnancy progresses, villi on the embryonic pole proliferate to form the chorion frondosum (the fetal part of the placenta).
  • The remaining chorionic villi degenerate and become the chorion laeve (smooth).

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• End of 2nd month to End of 3rd month placenta anatomy:
  • Amnion remains present.
  • Decidua basalis + chorion frondosum persist as the fetal component of the placenta at the placental pole.
  • Villi are present in the placental region (chorion frondosum) but other portions become smooth (chorion laeve).

Page 33

• Uteroplacental circulation begins to develop early in Week 2:
  • For the first ~two weeks, the embryo exchanges gases, nutrients, and wastes by simple diffusion due to a single-cell-thick epiblast and hypoblast.
  • The embryo’s growth necessitates:
  • Development of its own circulation (begins in Week 3).
  • Connection to maternal circulation (begins early in Week 2).
  • Placental circulation refers to the exchange system between maternal and fetal blood in the placenta; this occurs via diffusion and proximity without significant mixing.

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• The two circulatory systems connect via the placenta:
  • Initially, exchange is by diffusion across a thin barrier between maternal and fetal compartments.
  • Later, the fetal circulation becomes independent and connected to maternal circulation.
• Diagrammatic cues: spiral arteries, chorionic cavity, placental membrane, and developing uteroplacental interface.

Page 35

• Trophoblastic lacunae develop and fill with maternal blood around Day ~9:
  • Syncytiotrophoblast lacunae fill with maternal blood as spiral arteries expand to form sinusoids.
  • From Days 11–13, finger-like extensions of the syncytiotrophoblast with a cytotrophoblast core invade the lacunae; these outgrowths are the primary chorionic stem villi.

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• Chorionic villous maturation and placental vascularization:
  • By Day ~Day 16, extraembryonic mesoderm adjacent to the cytotrophoblast penetrates the core of the primary stem villi, forming secondary (chorionic) stem villi.
  • By Week 3, chorionic blood vessels develop within the mesoderm of the secondary stem villi, creating tertiary (chorionic) stem villi.
  • The blood vessels of the tertiary stem villi connect to embryonic blood vessels, establishing a functional placental circulation as sinusoids are linked to embryonic vasculature via chorionic vessels.

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• Placental membrane (placental barrier) details:
  • Four layers separate maternal and embryonic blood:
    1) Endothelial lining of chorionic capillaries
    2) Connective tissue in the villus core
    3) Cytotrophoblast
    4) Syncytiotrophoblast
  • The placental membrane regulates nutrient delivery and waste removal and protects the fetus from potentially harmful substances, though it is not an absolute barrier.
  • Small numbers of embryonic blood cells may cross defects in the membrane.

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• Cross-sectional and schematic views of the placenta:
  • Visuals show amniotic cavity, chorion, chorionic cavity, syncytiotrophoblast, cytotrophoblast, maternal capillaries, trophoblastic lacunae.
  • Emphasizes the barrier and exchange interface between fetal and maternal blood.

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• Section through a tertiary villus ( Placental exchange area )
• Emphasizes structural components of the placental exchange, including maternal blood in the intervillous spaces and fetal blood in capillaries of the chorionic villi.

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• Placental circulation mechanics:
  • Fetal blood reaches the placenta via a pair of umbilical arteries that branch into fetal capillary networks in the tertiary villi.
  • Maternal blood enters the intervillous spaces via spiral arteries.
  • Exchange occurs across the placental barrier via diffusion; fetal blood returns to the embryo via the single umbilical vein.
  • The placental barrier normally prevents mixing of maternal and fetal blood; however, many substances can cross.

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• Schematic pairing:
  • Maternal blood in intervillous spaces (left) vs. fetal blood in villous capillaries (right).
  • Placental interface shows chorion frondosum as fetal interface.

Page 42

• Bleeding at implantation site can be confused with menses:
  • By Day $13$, the coagulation plug in the endometrium has usually healed.
  • Bleeding may occur due to increased blood flow into trophoblastic lacunar spaces near the implantation site.
  • Because this bleeding can resemble menstrual bleeding, it can lead to errors in dating pregnancy.

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• Additional note:
  • Around Day $13$, the coagulation plug may still bleed partially as maternal blood begins to fill trophoblastic lacunae, which can be mistaken for normal menstrual bleeding.
  • Emphasizes diagnostic caution in early pregnancy dating.