Bisphenol B Exposure Induces Miscarriage by Suppressing Migration/Invasion and Migrasome Formation

Area of Science:

• Reproductive Biology
• Endocrinology
• Cell Biology

Background:

• Unexplained miscarriage (UM) pathogenesis is poorly understood.
• Bisphenol B (BPB) is an endocrine-disrupting chemical found in humans.
• Migrasomes are newly identified organelles with largely unknown functions.

Purpose of the Study:

• To investigate the association between BPB exposure and unexplained miscarriage.
• To explore the role of BPB in suppressing migrasome formation (MF).
• To elucidate the underlying biological mechanisms of BPB-induced miscarriage.

Main Methods:

• Association study of urinary BPB levels with MF in villous tissues.
• In vivo studies using mouse models to assess BPB effects on placental MF and miscarriage.
• Investigating the molecular pathway involving ER, lnc-HZ04, and PKCA.

Main Results:

• Higher urinary BPB levels correlate with suppressed MF and UM.
• BPB exposure in mice suppresses placental MF and induces miscarriage.
• Pkca or Tspan4 supplementation mitigates BPB-induced miscarriage.
• BPB up-regulates ER, promoting lnc-HZ04 transcription, which suppresses PKCA, impacting migration/invasion (MI) and MF.

Conclusions:

• BPB is identified as a novel risk factor for unexplained miscarriage.
• A new pathogenic pathway for BPB-induced miscarriage involving ER-mediated lnc-HZ04 and PKCA suppression is discovered.
• Pkca and Tspan4 represent potential therapeutic targets for BPB-induced miscarriage.