Abnormal ciliogenesis in decidual stromal cells in recurrent miscarriage

Area of Science:

• Reproductive biology
• Cell biology
• Cilia biology

Background:

• Primary cilia are crucial for cellular signaling and sensing extracellular cues.
• Mutations in DYNC2H1 impacting ciliary biogenesis are linked to recurrent miscarriage (RM).
• The role of primary cilia in the human decidua remains unexplored.

Purpose of the Study:

• To investigate the presence and characteristics of primary cilia in the decidua of patients with unexplained RM.
• To compare primary cilia in decidual stromal cells between RM patients and controls.
• To examine the association between primary cilia, immune cells, and signaling pathways (TGF-β, CREB) in the decidua.

Main Methods:

• Immunohistochemistry was used to analyze primary cilia, extravillous trophoblasts (EVTs), macrophages, uterine Natural Killer (uNK) cells, and decidual stromal cells.
• Quantification of primary cilia number and length in decidual stromal cells.
• Assessment of TGF-β and CREB signaling pathway activation.

Main Results:

• Decidual stromal cell density was higher in RM patients compared to controls.
• A significantly lower percentage of ciliated decidual stromal cells was observed in RM patients.
• Primary cilia length did not differ between groups, but TGF-β signaling (p-Smad2) was diminished in RM patients.

Conclusions:

• Abnormal primary cilia on decidual stromal cells may be a contributing factor to unexplained recurrent miscarriage.
• Inactivation of TGF-β signaling might lead to impaired ciliogenesis in the decidua.
• These findings highlight a potential link between cilia dysfunction and reproductive failure.