# Estradiol Alleviates Elevated Temperature-Induced Damage in Yak Oviductal Epithelial Cells by Maintaining Endoplasmic Reticulum Calcium Homeostasis

## TL;DR

Estradiol helps protect yak oviduct cells from heat damage by maintaining calcium balance in the endoplasmic reticulum.

## Contribution

E2's role in maintaining ER-Ca2+ homeostasis to alleviate heat-induced damage in yak oviduct cells is newly identified.

## Key findings

- E2 reduced apoptosis and restored OVGP1 protein levels in heat-stressed YOECs.
- E2 preserved ER-Ca2+ distribution similar to normal temperature conditions.
- SERCA and IP3R3 fluorescence intensity in E2-treated cells did not fully recover to normal levels.

## Abstract

The oviduct is an organ involved in multiple reproductive processes and responsible for providing nutrients and a microenvironment. Under hyperthermic conditions, the composition and levels of secretory proteins in oviduct epithelial cells undergo alterations, accompanied by a significant increase in the number of apoptotic cells. A series of changes can lead to phenomena such as abnormal early embryonic development and spontaneous abortion. Therefore, identifying the mechanisms that alleviate damage to oviduct epithelial cells under elevated temperature provides a foundation for maintaining normal reproductive processes. Intriguingly, E2 modulates cellular defense mechanisms by sustaining endoplasmic reticulum Ca2+ homeostasis. This discovery establishes a theoretical foundation for understanding strategies to address hyperthermia-induced reproductive impairments.

Background: The oviduct is an organ that participates in multiple critical reproductive processes and provides essential nutritional support while maintaining a specialized microenvironment. It is particularly vulnerable to damage following heat stress-induced hyperthermia. Therefore, mitigating heat-induced damage to oviduct epithelial cells while preserving their physiological integrity under hyperthermia represents a critical therapeutic goal. Objective: This study aims to simulate the cellular damage state in yak oviduct epithelial cells (YOECs) under thermal challenge by increasing the incubation temperature of cultured cells, while observing changes in cellular injury upon supplementation with 17β-estradiol (E2), in order to explore the underlying cellular regulatory mechanisms involved. Results: After 48 h of exposure to 41 °C, YOECs exhibited elevated HSP70 and HSP90 protein expression levels, reduced OVGP1 protein expression, and increased apoptotic cells. Compared to the 41 °C group, the E2 + 41 °C group displayed decreased HSP70 protein levels, increased OVGP1 protein expression, and reduced apoptotic cell numbers. Additionally, changes in endoplasmic reticulum calcium ion (ER-Ca2+) distribution and fluorescence intensity variations in ER-Ca2+ regulatory proteins SERCA and IP3R3 were analyzed in the 37 °C, 41 °C, and E2 + 41 °C groups. The ER-Ca2+ distribution pattern in the E2 + 41 °C group remained similar to that of the 37 °C group. However, the fluorescence intensity levels of SERCA and IP3R3 proteins in the E2 + 41 °C group did not recover to levels comparable to the 37 °C group. Conclusion: These findings suggest that E2 may mitigate thermal challenge-induced cellular damage in YOECs by maintaining ER-Ca2+ homeostasis, thereby preserving cellular functionality under elevated temperatures.