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← Theoretical 2

Q71 — Hippo Pathway Signaling in Blastocyst Implantation

Theoretical 2 Real exam question — full text reproduced under IBO's CC BY-NC-SA 4.0 license
Cell Signaling & Communication

One week after fertilization, human embryos implant into the uterus. In order to implant, the embryo needs to develop into a blastocyst (blastoid), a spherical structure covered with cells. Researchers simulated a blastocyst model, using pluripotent stem cells. They also modeled the endometrial layer of the uterus in the dish and blastocyst implantation in the endometrium (Figure 1). They hormonally stimulated endometrial cells, and tested blastocyst attachment (Figure 2). In order to check the effect of the Hippo pathway on blastoid development, researchers tested them under exposure to different concentrations of lysophosphatidic acid (LPA) (a Hippo-pathway inhibitor) (Figure 3). YAP1 is the downstream effector that activates cavitation, after Hippo inhibition, by binding to the TEAD transcription factor. The researchers tested different settings on the appearance of cavitation, an important event in blastocyst formation. They used two different YAP1-overexpressing (OE) blastocysts, overexpressing two different YAP1-mutants: one has a mutation in the TEAD binding site (S94A), while the other is constitutively active (5SA) (Figure 3).

Diagram of blastoid attachment, apposition and invasion into a modeled endometrium, with polar outgrowths forming at the point of contact with the endometrial stroma, alongside a schematic of the endometrial-organoid culture protocol (hormonal stimulation with E2 then EPC+XAV939, followed by an open-face endometrial layer for blastoid transfer and peri-implantation modeling). Figure 1. Diagram of attachment of the blastoid to endometrial cells (left) and the method for producing the endometrial organoids used for in vitro implantation modeling (right).

Two-panel figure. Left: micrographs of blastoids on non-stimulated endometrial cells (no attachment) versus hormonally stimulated endometrial cells (attachment, with polar outgrowths visible), alongside a bar graph showing attachment at roughly 1% for non-stimulated organoids versus roughly 30% for stimulated ones. Right: a bar graph of blastoid yield rising with increasing LPA dose (0–1000 nM), and a bar graph of cavitation per microwell showing high cavitation for wild-type and the constitutively active 5SA YAP1 mutant, but cavitation not significantly different from control for the TEAD-binding-deficient S94A mutant. Figure 2 (left): blastoid attachment to non-stimulated vs. hormonally stimulated endometrial cells. Figure 3 (right): blastoid yield as a function of LPA (Hippo-pathway inhibitor) concentration, and cavitation per microwell for control cells versus cells overexpressing wild-type, 5SA, or S94A YAP1.

Use the information and figures 1-3 to determine whether the following statements are true or false.

A. Blastocysts attach to the hormonally stimulated endometrial cells but not to unstimulated ones. Absence of hormonal stimulation will result in almost inevitable failure of implantation of the blastocyst.
B. Blastocysts develop polar outgrowths when attaching to the endometrium that contribute to the attachment.
C. Hippo pathway activation is crucial for blastoid development.
D. The interaction with TEAD is important for the function of YAP1 in cavitation.
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Question reproduced from IBO 2022, Theoretical Paper 2, licensed under CC BY-NC-SA 4.0 — attributed to the International Biology Olympiad. Open the full exam PDF · Community solutions (unofficial)