Disruption of paternal circadian rhythm affects metabolic health in male offspring via nongerm cell factors

Circadian rhythm synchronizes each body function with the environment and regulates physiology. Disruption of normal circadian rhythm alters organismal physiology and increases disease risk.

Recent epidemiological data and studies in model organisms have shown that maternal circadian disruption is important for offspring health and adult phenotypes. Less is known about the role of paternal circadian rhythm for offspring health. Here, we disrupted circadian rhythm in male mice by night-restricted feeding and showed that paternal circadian disruption at conception is important for offspring feeding behavior, metabolic health, and oscillatory transcription.

Mechanistically, our data suggest that the effect of paternal circadian disruption is not transferred to the offspring via the germ cells but initiated by corticosterone-based parental communication at conception and programmed during in utero development through a state of fetal growth restriction. These findings indicate paternal circadian health at conception as a newly identified determinant of offspring phenotypes.

Authors: Maximilian Lassi, Archana Tomar, Gemma Comas-Armangué, Rebekka Vogtmann, Dorieke J. Dijkstra, David Corujo, Raffaele Gerlini, Jonatan Darr, Fabienne Scheid, Jan Rozman, Antonio Aguilar-Pimentel, Omry Koren, Marcus Buschbeck, Helmut Fuchs, Susan Marschall, Valerie Gailus-Durner, Martin Hrabe de Angelis, Torsten Plösch, Alexandra Gellhaus and Raffaele Teperino.

Institutions:

Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany.
German Center for Diabetes Research (DZD) Neuherberg, Germany.
Department of Gynecology and Obstetrics–University Hospital Essen – Essen, Germany.
University of Groningen, University Medical Center Groningen, Department of Obstetrics and Gynecology, Groningen, Netherlands.
Cancer and Leukemia Epigenetics and Biology Program, Josep Carreras Institute for Leukemia Research (IJC) Badalona, Spain.
German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, German Research Center for Environmental Health Neuherberg, Germany.
Czech Centre for Phenogenomics, Institute of Molecular Genetics of the Czech Academy of Sciences, BIOCEV, Prumyslova 595, 252 50, Vestec, Czech Republic.
Azrieli Faculty of Medicine, Bar Ilan University, Safed, Israel.
Program for Predictive and Personalized Medicine of Cancer, Germans Trias i Pujol Research Institute (PMPPC-IGTP), 08916 Badalona, Spain.
Chair of Experimental Genetics, School of Life Science Weihenstephan, Technische Universität München Freising, Germany.

Publication: Science Advances

Date: May 2021

Full paper: https://advances.sciencemag.org/content/7/22/eabg6424.full