FABP4 mediates endoplasmic reticulum stress and autophagy to regulate endometrial epithelial cell function during early sheep gestation

Dynamic changes in the endometrium are crucial for establishing early pregnancy in ruminants. Blastocyst elongation and implantation require hormones and nutrients to be secreted from the maternal endometrium. The fatty acid-binding protein FABP4 is a widely expressed fatty acid transport protein that promotes cell proliferation, migration, and invasion and is involved in conceptus implantation. However, the mechanism underlying the functional regulation of endometrial epithelial cells (EECs) by FABP4 during ovine peri-implantation remains unclear. We simulated hormonal changes in vitro in sheep EECs (SEECs) during the peri-implantation period and found that it elevated FABP4 expression. FABP4 inhibition significantly reduced cell migration, endoplasmic reticulum stress, and autophagy, suggesting that FABP4 regulates endometrial function in sheep. Moreover, the FABP4 inhibitor BMS309403 counteracted hormone-mediated functional changes in SEECs, and an endoplasmic reticulum stress activator and autophagy inhibitor reversed the abnormal secretion of prostaglandins induced by FABP4 inhibition. These results suggest that FABP4 affects ovine endometrial function during early gestation by regulating endoplasmic reticulum stress and autophagy in SEECs.

 

Comments:

The provided passage describes a study conducted on sheep endometrial cells (SEECs) to understand the role of fatty acid-binding protein FABP4 in regulating endometrial function during early pregnancy in ruminants, specifically in sheep. Here's a breakdown of the key findings and implications of the study:

### Key Findings:

1. **Importance of Endometrial Changes:** Dynamic changes in the endometrium are crucial for early pregnancy in ruminants. These changes involve the secretion of hormones and nutrients from the maternal endometrium, facilitating blastocyst elongation and implantation.

2. **Role of FABP4:** FABP4, a fatty acid transport protein, is widely expressed and plays a significant role in cell proliferation, migration, and invasion. In this study, it was found that FABP4 is involved in conceptus implantation.

3. **In Vitro Simulation:** The study simulated hormonal changes in vitro using sheep endometrial cells (SEECs) during the peri-implantation period. This simulation led to an elevation in FABP4 expression.

4. **Functional Impact:** Inhibiting FABP4 had several effects on SEECs:
   - **Reduced Cell Migration:** FABP4 inhibition significantly reduced cell migration, a crucial process during implantation.
   - **Endoplasmic Reticulum Stress:** FABP4 inhibition led to endoplasmic reticulum stress in SEECs.
   - **Autophagy:** FABP4 inhibition also affected autophagy, another cellular process important for various biological functions.

5. **Counteracting FABP4 Inhibition:** The study used a specific FABP4 inhibitor (BMS309403) and found that it counteracted hormone-mediated functional changes in SEECs. Additionally, an endoplasmic reticulum stress activator and autophagy inhibitor were used to reverse the abnormal secretion of prostaglandins induced by FABP4 inhibition.

### Implications:

1. **Regulation of Endometrial Function:** FABP4 plays a significant role in regulating endometrial function in sheep. By influencing processes like cell migration, endoplasmic reticulum stress, and autophagy, FABP4 affects the crucial early stages of pregnancy, including blastocyst elongation and implantation.

2. **Therapeutic Potential:** The study suggests that targeting FABP4 could have therapeutic potential in managing or enhancing fertility in ruminants. By understanding the molecular mechanisms involved in early pregnancy, researchers might develop interventions to aid fertility in livestock.

3. **Contribution to Reproductive Biology:** This research contributes to the broader field of reproductive biology, enhancing our understanding of the intricate processes involved in early pregnancy. Insights gained from studies like these can also have implications for human fertility research.

In summary, this study sheds light on the specific role of FABP4 in regulating endometrial function during early gestation in sheep, providing valuable information for both animal science and reproductive biology.

Related Products

Cat.No.	Product Name	Information
S6622	BMS309403	BMS309403 is a small-molecule FABP4 inhibitor with nM affinity (Kd=4 nM for FABP4) and >100-fold selectivity against FABP5 as well as the heart isoform FABP3.

Related Targets

FABP