# Maternal Separation and Negative Renal Programming, Evidence of Morphofunctional Alterations in Rodent Models: Systematic Review and Meta-Analysis

## TL;DR

This review shows that maternal separation in rodents causes lasting kidney changes, affecting structure, function, and molecular pathways.

## Contribution

The study systematically reviews and meta-analyzes the morphofunctional effects of maternal separation on rodent kidneys.

## Key findings

- Maternal separation increases microvascular density and inflammatory markers in rodent kidneys.
- MS alters ACE1/ACE2 activity and oxidative stress, affecting kidney function.
- Changes in adrenergic receptors and the renin-angiotensin system were observed at the molecular level.

## Abstract

Exposure to stress during early developmental stages correlates with persistent alterations in multiple physiological systems, including the renal system. In rodents, maternal separation (MS) is a widely used experimental model to simulate postnatal adversity. Although this condition affects various renal parameters, a gap persists in knowledge regarding its impact on the functional unit of the kidney and the organization of the parenchyma. Thus, the objective of this systematic review was to analyze the effects of MS on the morphofunctional characteristics of the kidney in rodent models. We developed a protocol a priori following the SYRCLE and PRISMA guidelines and registered it in PROSPERO (CRD420251004703). We searched Web of Science, Scopus, Medline, Embase, BIREME-BVS, and SciELO without language or date restrictions, targeting experimental studies in rodents subjected to MS that evaluated structural, functional, or molecular alterations. Three independent reviewers performed data selection and extraction, and they assessed the risk of bias using the SYRCLE’s RoB tool. We included seven studies that met the eligibility criteria. At the structural level, studies reported cellular infiltrates positive for MPO, CD44, and TLR4, along with increased cortical and medullary microvascular density. Regarding renal function, the included studies described changes in ACE1 and ACE2 activity, oxidative stress, and enzymatic imbalance accompanied by a compensatory antioxidant response. At the molecular level, the studies reported variations in the expression of adrenergic receptors and the renin-angiotensin system. These findings suggest that MS may compromise the organization and functional integrity of the developing kidney, underscoring the need for studies that integrate structural and functional analyses in greater depth.