# Relative Expression of Peptidylarginine Deiminase 2 and Sex Steroid Receptors in XX and XY Mouse Placenta

**Authors:** Amanda Wewer, Autumn Bennitt, Emily Hinners, Morgan Helmich, Nathan Schnepp, Sean Pitcher, Agata M. Parsons, Gerrit J. Bouma

PMC · DOI: 10.3390/ijms262110523 · International Journal of Molecular Sciences · 2025-10-29

## TL;DR

This study finds that male (XY) mouse placentas have higher levels of PAD2 and AR compared to female (XX) placentas, suggesting a potential role in sex-specific placental function.

## Contribution

The study is the first to demonstrate sex differences in PAD2 and AR levels in mouse placentas.

## Key findings

- AR and PAD2 levels were significantly higher in XY compared to XX placentas.
- This is the first study to show sex differences in PAD2 and AR in the placenta.

## Abstract

Although female (XX) and male (XY) placentas generally function the same, it is evident that there are sex-specific postnatal health outcomes following placental dysfunction and pregnancy complications. Although the underlying causes for these sex differences are unclear, it is postulated that differences in XX and XY placental function are involved due to sex chromosomes and/or sex steroids. Studies in breast and prostate cancer cells demonstrated a role for the citrullination enzyme peptidylarginine deiminase 2 (PAD2) in post-translational regulation of estrogen (ESR) and androgen receptor (AR) signaling. The goal of this study is to determine if PAD2 is present in mouse placentas and if XX versus XY differences exist in the relative level of PAD2. Fetuses and placentas were collected from three pregnant mice (C57BL6) at 14 days of gestation. Total RNA and protein were isolated from XX and XY placentas, and relative mRNA and protein were analyzed by real-time PCR and Western blot. AR and PAD2 levels were significantly higher in XY than in XX placentas. This study is the first to demonstrate XX and XY differences in PAD2 and AR in the placenta. It suggests a role for PAD2 regulation of androgen receptor signaling in the XY placenta.

## Linked entities

- **Genes:** PADI2 (peptidyl arginine deiminase 2) [NCBI Gene 11240], AR (androgen receptor) [NCBI Gene 367], ESR1 (estrogen receptor 1) [NCBI Gene 2099]
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Ar (androgen receptor) [NCBI Gene 11835] {aka Tfm}
- **Diseases:** placental dysfunction (MESH:D010922), breast and prostate cancer (MESH:D001943), pregnancy complications (MESH:D011248)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

2 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12607503/full.md

## References

32 references — full list in the complete paper: https://tomesphere.com/paper/PMC12607503/full.md

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Source: https://tomesphere.com/paper/PMC12607503