Refereed journal article or data article (A1)

Inheritable testicular metabolic memory of high-fat diet causes transgenerational sperm defects in mice

List of Authors: Crisostomo L, Jarak I, Rato LP, Raposo JF, Batterham RL, Oliveira PF, Alves MG


Publication year: 2021

Journal: Scientific Reports

Journal name in source: SCIENTIFIC REPORTS

Journal acronym: SCI REP-UK

Volume number: 11

Number of pages: 15

ISSN: 2045-2322



The consumption of energy-dense diets has contributed to an increase in the prevalence of obesity and its comorbidities worldwide. The adoption of unhealthy feeding habits often occurs at early age, prompting the early onset of metabolic disease with unknown consequences for reproductive function later in life. Recently, evidence has emerged regarding the intergenerational and transgenerational effects of high-fat diets (HFD) on sperm parameters and testicular metabolism. Hereby, we study the impact of high-fat feeding male mice (F-0) on the testicular metabolome and function of their sons (F-1) and grandsons (F-2). Testicular content of metabolites related to insulin resistance, cell membrane remodeling, nutritional support and antioxidative stress (leucine, acetate, glycine, glutamine, inosine) were altered in sons and grandsons of mice fed with HFD, comparing to descendants of chow-fed mice. Sperm counts were lower in the grandsons of mice fed with HFD, even if transient. Sperm quality was correlated to testicular metabolite content in all generations. Principal Component Analysis of sperm parameters and testicular metabolites revealed an HFD-related phenotype, especially in the diet-challenged generation and their grandsons. Ancestral HFD, even if transient, causes transgenerational "inherited metabolic memory" in the testicular tissue, characterized by changes in testicular metabolome and function.

Downloadable publication

This is an electronic reprint of the original article.
This reprint may differ from the original in pagination and typographic detail. Please cite the original version.

Last updated on 2022-31-08 at 11:29