TY - JOUR
T1 - Inheritable testicular metabolic memory of high-fat diet causes transgenerational sperm defects in mice
AU - Crisóstomo, Luís
AU - Jarak, Ivana
AU - Rato, Luís P.
AU - Raposo, João F.
AU - Batterham, Rachel L.
AU - Oliveira, Pedro F.
AU - Alves, Marco G.
N1 - Funding Information:
This work was supported by the Portuguese Foundation for Science and Technology: L. Crisóstomo (SFRH/ BD/128584/2017), M.G. Alves (IFCT2015 and PTDC/MEC-AND/28691/2017), P.F. Oliveira (IFCT2015), UMIB (UIDB/00215/2020 and UIDP/00215/2020) and QOPNA (UID/QUI/00062/2019) co-funded by FEDER funds (POCI/COMPETE 2020); by the Portuguese Society of Diabetology: L. Crisóstomo and M.G. Alves (“Nuno Castel-Branco” research grant and Group of Fundamental and Translational Research); and by the European Foundation for the Study of Diabetes: L. Crisóstomo (Albert Renold Travel Grant). NMR data was collected at the UC-NMR facility which is supported in part by FEDER—European Regional Development Fund through the COMPETE Programme (Operational Programme for Competitiveness) and by National Funds through FCT— Fundação para a Ciência e a Tecnologia (Portuguese Foundation for Science and Technology) through grants REEQ/481/QUI/2006, RECI/QEQ-QFI/0168/2012, CENTRO-07-CT62-FEDER-002012, and Rede Nacional de Ressonância Magnética Nuclear (RNRMN). We thank Prof. Pedro N. Oliveira (University of Porto, Portugal) and Matthieu Bourgery (University of Turku, Finland) for their advice in Statistical Analysis.
Publisher Copyright:
© 2021, The Author(s).
Copyright:
Copyright 2021 Elsevier B.V., All rights reserved.
PY - 2021/5/3
Y1 - 2021/5/3
N2 - 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 (F0) on the testicular metabolome and function of their sons (F1) and grandsons (F2). 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.
AB - 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 (F0) on the testicular metabolome and function of their sons (F1) and grandsons (F2). 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.
UR - http://www.scopus.com/inward/record.url?scp=85105152676&partnerID=8YFLogxK
U2 - 10.1038/s41598-021-88981-3
DO - 10.1038/s41598-021-88981-3
M3 - Article
C2 - 33941835
AN - SCOPUS:85105152676
SN - 2045-2322
VL - 11
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 9444
ER -