# Differential Remodelling of Endometrial Extracellular Matrix in the Non-Pregnant Uterus of Lagostomus maximus as a Potential Mechanism Underlying Embryonic Death

## TL;DR

This study explores how differences in the uterine structure of plains viscachas may explain why some embryos survive while others die during pregnancy.

## Contribution

The study identifies differential extracellular matrix remodelling in the non-pregnant uterus of Lagostomus maximus as a potential mechanism for embryonic death.

## Key findings

- Caudal uterine segments show increased collagen and elastic fibres compared to cranial and middle segments.
- MMP-9 activity is significantly higher in the caudal segment, which may support embryonic survival.
- Endometrial ECM variations along the craniocaudal axis may regulate embryonic survival during gestation.

## Abstract

Embryonic death is an inherent process in the reproductive biology of the plains viscacha (Lagostomus maximus). During this process of embryonic death, embryos implanted in the caudal uterine segments survive, whereas those in the cranial and middle segments do not. Endometrial remodelling plays a key role in embryonic development. In this study, various extracellular matrix molecules (metalloproteinases, their inhibitors, and fibrillar components) were analysed in three uterine segments (cranial, middle, and caudal) of adult viscachas using histology, immunohistochemistry, and zymography. The results revealed greater endometrial remodelling along the craniocaudal axis. This finding may help to explain the phenomenon of embryonic death in this species.

During development, the remodelling of fibrillar components of the uterine extracellular matrix (ECM), mediated by the matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs), plays an essential role in embryonic survival. Previously, we observed that in the plains viscacha (Lagostomus maximus), only caudal implantation sites (IS) contain viable embryos, whereas embryos at cranial and middle IS die and are reabsorbed. The objective of this study was to analyse the distribution and expression of key components of the endometrial ECM, including fibrillar collagens, MMPs 2 and 9, and TIMPs 1 and 2, in three uterine segments (US) of the non-pregnant adult viscachas. In sections from three US, we observed a significant craniocaudal increase in collagen fibres (Van Gieson and Picrosirius red staining) and elastic fibres (Verhoeff-Van Gieson trichrome staining), along with the immunolabelling levels of MMP-2, MMP-9, TIMP-1, and TIMP-2 (immunohistochemistry). Zymography revealed similar gelatinolytic activity of MMP-2 in the three US but higher than the MMP-9 activity. However, MMP-9 activity in the caudal segment was significantly higher than that in the cranial and middle ones. These findings suggest that uterine ECM variations along the craniocaudal axis may contribute to uterine remodelling processes that regulate embryonic survival during gestation.