# SGK1 Is Upregulated in Retained Placenta and Mediates Estradiol Effects in Bovine Endometrial Cells

## TL;DR

SGK1 is linked to retained placenta in cows and mediates estradiol effects on cell survival and junctions.

## Contribution

SGK1 is newly identified as a mediator of estradiol effects and a potential biomarker for retained placenta in dairy cows.

## Key findings

- SGK1 is upregulated in retained placenta and correlates with suppressed apoptosis and increased tight junction proteins.
- Estradiol upregulates SGK1, and its knockdown abolishes estradiol effects on cell migration and junctional proteins.
- SGK1 is proposed as a critical mediator of estradiol signaling in bovine endometrial cells.

## Abstract

What are the main findings?
SGK1 is upregulated in retained placenta of dairy cows and correlates with suppressed apoptosis, increased tight junction proteins, and enhanced epithelial marker expression.Estradiol upregulates SGK1 in bovine endometrial epithelial cells, and knockdown of this kinase abolishes estradiol effects on apoptosis, junctional protein expression, and cell migration.

SGK1 is upregulated in retained placenta of dairy cows and correlates with suppressed apoptosis, increased tight junction proteins, and enhanced epithelial marker expression.

Estradiol upregulates SGK1 in bovine endometrial epithelial cells, and knockdown of this kinase abolishes estradiol effects on apoptosis, junctional protein expression, and cell migration.

What are the implications of the main findings?
The findings propose a new mechanistic hypothesis: sustained estradiol–SGK1 signaling may excessively stabilize the fetomaternal interface, contributing to retained placenta.SGK1 is a candidate tissue biomarker for retained placenta, providing a foundation for future validation and translational studies.

The findings propose a new mechanistic hypothesis: sustained estradiol–SGK1 signaling may excessively stabilize the fetomaternal interface, contributing to retained placenta.

SGK1 is a candidate tissue biomarker for retained placenta, providing a foundation for future validation and translational studies.

Retained placenta (RP) is a significant postpartum complication in dairy cows. Although abnormal estradiol (E2) levels are implicated, the underlying cellular mechanisms remain poorly defined. Through RNA-seq analysis of postpartum blood from cows with or without RP, we identified Serum and Glucocorticoid-regulated Kinase 1 (SGK1) as a differentially expressed gene candidate. Analysis of fetal cotyledonary tissues revealed that SGK1 expression was significantly elevated in these tissues, concomitant with markers of suppressed apoptosis, increased levels of tight junction proteins, and an inhibited epithelial–mesenchymal transition (EMT) phenotype. To explore a potential mechanistic link between E2 and these cellular alterations, we investigated the E2-SGK1 axis in bovine endometrial epithelial cells in vitro. E2 treatment upregulated SGK1 expression, reduced apoptosis, increased tight junction protein levels, and suppressed EMT. Conversely, SGK1 knockdown induced apoptosis, disrupted tight junctions, and impaired EMT. Notably, E2 could not rescue the apoptosis and EMT alterations in SGK1-knockdown cells, indicating that SGK1 is a critical mediator of these E2 effects in this cellular model. Based on these initial correlative findings in tissues, combined with the subsequent mechanistic experiments in cells, we propose a novel model whereby dysregulation of the E2- SGK1 axis could contribute to RP pathogenesis by stabilizing the placental interface. Our findings provide the first experimental evidence linking SGK1 to RP and establish a foundation for future in vivo validation.