NINJ1 triggers extravillous trophoblast cell dysfunction through blocking the STAT3 signaling pathway

Area of Science:

• Reproductive Biology
• Cell Biology
• Pathology

Background:

• Trophoblast dysfunction is a key factor in early pregnancy complications like recurrent spontaneous abortion (RSA).
• Elevated nerve injury-induced protein 1 (NINJ1) RNA levels have been observed in the villi tissues of RSA patients.

Purpose of the Study:

• To investigate the role of NINJ1 in trophoblast behavior and its impact on pregnancy loss.
• To elucidate the underlying molecular mechanisms by which NINJ1 influences trophoblast function and spontaneous abortion (SA).

Main Methods:

• NINJ1 expression was analyzed in villi tissues from RSA patients and controls.
• Loss-of-function (NINJ1 knockdown) and gain-of-function (NINJ1 overexpression) experiments were conducted using the HTR-8/SVneo trophoblast cell line.
• In vivo studies involved inducing SA in a mouse model and administering NINJ1 inhibition via adenovirus vectors.

Main Results:

• NINJ1 expression (mRNA and protein) was significantly higher in RSA patients' villi tissues.
• NINJ1 knockdown enhanced trophoblast proliferation, migration, and invasion, while reducing apoptosis and promoting angiogenesis.
• NINJ1 inhibition attenuated pregnancy loss in vivo and was linked to STAT3 pathway activation.

Conclusions:

• NINJ1 plays a critical role in the pathogenesis of spontaneous abortion (SA).
• NINJ1 contributes to trophoblast cell dysfunction by inhibiting the STAT3 signaling pathway.
• Targeting NINJ1 presents a potential therapeutic strategy for preventing pregnancy loss.