# Metabolomic analysis of the endometrium of Large White and Meishan pigs reveals differences in biological processes during late gestation

## TL;DR

This study compares the endometrial metabolism of two pig breeds during late pregnancy to understand differences in piglet survival.

## Contribution

The study provides the first metabolomic analysis of endometrial tissues in two pig breeds with contrasting neonatal survival rates.

## Key findings

- Endometrial metabolism changes during late gestation, with reduced glucogenic amino acids and increased hypoxanthine and succinate.
- Large White sows show decreased glutathione metabolites and increased glutamine and phenylalanine compared to Meishan sows.
- Metabolic differences suggest links to oxidative stress, autophagy, and immune tolerance affecting piglet survival.

## Abstract

In pigs, genetic progress has led to an increase in perinatal mortality, mainly due to reduced piglet maturity. The end of gestation (90-110 days of gestation) plays a decisive role in the acquisition of fetal maturity. The endometrium is crucial for its acquisition as it provides nutrients to the fetus through the placenta. The aim of this study is to describe part of the metabolism of the endometrium in late pregnancy and in relation with neonatal survival. For this purpose, we performed untargeted metabolomic measurements by 1H nuclear magnetic resonance and gas chromatography coupled to a flame-ionization detector on 224 endometrial samples and compared the two days of the end of gestation (D90-D110, term at 114 days) and two maternal breeds with contrasted birth survival: Large White (LW, higher birth mortality) and Meishan (MS, lower birth mortality).

Out of the 191 metabolites available in the ASICS package reference library, 46 metabolites and nine neutral lipids were quantified in the endometrial samples.

Twenty-two metabolites showed a significant differential abundance in the endometrium between 90 and 110 days of gestation. These differences highlighted a decrease in the amount of glucogenic amino acids such as aspartate, glutamate, and glutamine at D110, indicating a depletion of energy resources in the endometrium. As a result of hypoxic catabolism to maintain energy levels, hypoxanthine and succinate accumulated, possibly contributing to the regulation of hypoxia, ROS and modulation of inflammation of the endometrium during late pregnancy.

The study also documented ten endometrial metabolites with a significant differential abundance between LW and MS sows. Glutathione metabolism metabolites showed a decreased abundance in LW, which may contribute to increased oxidative stress. Furthermore, the accumulation of glutamine and phenylalanine may be a possible response to lower amino acid availability in LW, inducing more cellular autophagy and lower maternal immune tolerance in LW endometrium compared to MS.

For the first time, these data provide a metabolic status of the endometrium during late gestation and between two extreme breeds for piglet survival. They reinforce the role of succinate, glutamine, and phenylalanine in influencing piglet survival birth.

The online version contains supplementary material available at 10.1186/s12864-025-12276-4.