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

## TL;DR

This study finds that exposure to Bisphenol B can cause miscarriage by disrupting cellular processes related to migration and migrasome formation.

## Contribution

The study identifies a novel biological mechanism linking Bisphenol B exposure to unexplained miscarriage through migrasome suppression and lnc-HZ04 regulation.

## Key findings

- Higher urinary Bisphenol B levels are associated with suppressed migrasome formation and unexplained miscarriage.
- Bisphenol B exposure upregulates ER and promotes lnc-HZ04 transcription, which suppresses PKCA and migration/invasion.
- Supplementing with Pkca or Tspan4 can counteract Bisphenol B-induced miscarriage in mice.

## Abstract

Unexplained miscarriage (UM) remains challenge due to unclear pathogenesis and biological mechanisms. BPB (Bisphenol B), an extensively used endocrine disrupting chemical, has been widely detected out in human. Migrasomes are newly identified cellular organelles with a large number of unknown functions. However, whether and how BPB exposure may suppress migrasome formation (MF) to induce miscarriage are completely unknown. In this study, it is found that higher urinary BPB levels are associated with the suppressed MF in villous tissues and unexplained miscarriage. It is further confirmed that BPB exposure suppresses MF in the mouse placenta and thus induces miscarriage. Supplement with Pkca or Tspan4, two essential proteins for migration/invasion (MI) and MF, can efficiently treat against BPB‐induced miscarriage. In biological mechanisms, BPB up‐regulates ER levels, enhances its interactions with the lnc‐HZ04 promoter region, and thus promotes ER‐mediated lnc‐HZ04 transcription. Subsequently, lnc‐HZ04 suppresses TCF4‐mediated PKCA transcription and subsequently suppresses MI and MF. Collectively, this study not only identifies BPB as a novel risk factor for unexplained miscarriage, discovers novel pathogenesis and biological mechanisms in BPB‐induced miscarriage, but also provides potential targets for treatment against unexplained miscarriage.

BPB (Bisphenol B) exposure up‐regulates ER (estrogen receptor) levels, enhances its interactions with the lnc‐HZ04 promoter region, and thus promotes ER‐mediated lnc‐HZ04 transcription. Subsequently, lnc‐HZ04 suppresses TCF4 (transcription factor 4)‐mediated PKCA (protein kinase C alpha) transcription and subsequently suppresses migration/invasion and migrasome formation.