Sex-specific programming of the gastric and duodenal mitochondrial biogenesis by early-life stress

Abstract

Background: Early-life stress (ELS) is a significant risk factor for the development of numerous metabolic and physiological disorders later in life.

Objective: This study aims to investigate the effects of early-life stress on mitochondrial biogenesis, thermogenesis-related genes, and developmental signalling pathways in the stomach and duodenum of offspring.

Methods: This study consists of three groups: the first is the control group, and the second and third groups were randomly exposed to unpredictable maternal separation (MS) for three hours a day on postnatal days (PND) 1-14. The third group was exposed to unpredictable maternal stress (MSUS) in addition to MS. Mice were sacrificed at PND35. Total RNA was extracted from the tissues (corpus region of the stomach and the start zone of the duodenum) via the phenol‒chloroform technique. The expression levels of miR-34c-5p, Notch1, Prdm16, Ppargc1a, and Ucp1 were measured via Rotor-Gene Q.

Results: Although the expression of miR-34c-5p remained unchanged between the groups, the mRNA expression of genes associated with mitochondrial biogenesis and thermogenesis increased significantly with increasing stress in females. In males, the expression also increased significantly in the MS but returned to control levels in the MSUS.

Conclusions: ELS can stimulate Ucp1-mediated thermogenesis in gastrointestinal tissues by promoting mitochondrial biogenesis, which is driven by Prdm16 and mediated by Ppargc1a. ELS might initiate mitochondrial biogenesis to accommodate the growing energy demands of the digestive system. However, increased stress alters mitochondrial biogenesis and thermogenesis-related gene expression in a sex-specific manner.

Keywords: Chronic stress; Intestine; MSU; MitBio; miR-34c.