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Tmx2 Maintains Mitochondrial Function to Support Preimplantation Embryogenesis.

Shangrong Zhang¹, Qing Liu¹, Siyu Wang¹

¹Anhui Province Key Laboratory of Embryo Development and Reproductive Regulation, Fuyang Normal University, Fuyang, Anhui, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology

|June 11, 2025

Summary

Thioredoxin-related transmembrane protein 2 (TMX2) is crucial for early mouse embryonic development. Its deficiency impairs blastomere proliferation and survival by disrupting mitochondrial function and increasing oxidative stress.

Keywords:

Tmx2 autophagy embryo development mice mitochondrial dysfunction

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Probing for Mitochondrial Complex Activity in Human Embryonic Stem Cells

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Published on: June 17, 2008

Area of Science:

Developmental Biology
Cell Biology
Genetics

Background:

Thioredoxin (TRX)-related transmembrane proteins (TMX) are part of the protein disulfide isomerase (PDI) family.
TMX2 (PDIA12) is poorly characterized but linked to brain development issues via mutations.
Tmx2 mutant embryos show developmental arrest, indicating a role in preimplantation embryogenesis.

Purpose of the Study:

To investigate the essential role of TMX2 in mouse preimplantation embryonic development.
To elucidate the molecular and cellular functions of TMX2 during this critical window.

Main Methods:

Studied TMX2 expression and localization in mouse embryos.
Utilized Tmx2 knockdown to mimic genetic mutations.
Performed EdU incorporation, TUNEL assays, and analyzed cell cycle inhibitor mRNA levels.
Assessed mitochondrial function, oxidative stress, mitophagy, and autophagy.

Main Results:

TMX2 is expressed in early mouse embryos and localizes to mitochondria.
Tmx2 knockdown caused developmental arrest, impaired blastomere proliferation, and increased apoptosis.
Tmx2 deficiency led to disrupted mitochondrial function, elevated oxidative stress, and impaired autophagy/mitophagy.
Increased p21 and p53 mRNA levels were observed in Tmx2-deficient embryos.

Conclusions:

TMX2 is essential for preimplantation embryonic development in mice.
TMX2 regulates mitochondrial integrity and cellular homeostasis.
TMX2 is a key factor in maintaining mitochondrial dynamics and cell survival during early embryogenesis.