Maternal Undernutrition During Late Pregnancy Impairs Fetal Renal Development and Induces Apoptotic Pathway Activation in the Sheep Model.

Abstract

This study investigated the effects of maternal nutritional restriction during late pregnancy on fetal kidney development in sheep. Eighteen Mongolian ewes with singleton fetuses were allocated to three groups at 90&#x2009;days of gestation: restricted group 1 (RG1, 0.18&#x2009;MJ ME&#x2009;&#xb7;&#x2009;kg BW&#x2009;&#xb7;&#x2009;day, n&#x2009;=&#x2009;6), restricted group 2 (RG2, 0.33&#x2009;MJ ME&#x2009;&#xb7;&#x2009;kg BW&#x2009;&#xb7;&#x2009;day, n&#x2009;=&#x2009;6), and a control group (CG, ad&#xa0;libitum, 0.67&#x2009;MJ ME&#x2009;&#xb7;&#x2009;kg BW&#x2009;&#xb7;&#x2009;day, n&#x2009;=&#x2009;6). Fetal kidney samples were collected on Day 140 of pregnancy. The results indicated that maternal nutritional restriction significantly decreased fetal kidney weight (p&#x2009;<&#x2009;0.05) and total DNA content (p&#x2009;<&#x2009;0.01). Masson staining showed an increase in total collagen fibers and a decrease in collagen I levels (p&#x2009;<&#x2009;0.01). In the apoptotic pathway, nutritional restriction up-regulated the expression of proapoptotic protein p53 and Bax (p&#x2009;<&#x2009;0.01) and activated Caspase-3 (p&#x2009;<&#x2009;0.05) and cytochrome C (p&#x2009;<&#x2009;0.01). It is suggested that maternal nutritional restriction in late pregnancy may impair normal fetal kidney development by interfering with extracellular matrix metabolic balance and activating p53-mediated mitochondrial apoptosis pathway. This provides important evidence for understanding the molecular mechanism of maternal undernutrition-related kidney development programming, improving ruminant reproductive efficiency, and exploring the developmental origin of human-related diseases.