Paternally expressed gene 3 (Pw1/Peg3) promotes sexual dimorphism in metabolism and behavior

Karo Tanaka; Vanessa Besson; Manon Rivagorda; Franck Oury; Giovanna Marazzi; David A Sassoon

doi:10.1371/journal.pgen.1010003

Paternally expressed gene 3 (Pw1/Peg3) promotes sexual dimorphism in metabolism and behavior

PLoS Genet. 2022 Jan 13;18(1):e1010003. doi: 10.1371/journal.pgen.1010003. eCollection 2022 Jan.

Authors

Karo Tanaka¹, Vanessa Besson¹, Manon Rivagorda², Franck Oury², Giovanna Marazzi¹, David A Sassoon¹

Affiliations

¹ Stem Cells and Regenerative Medicine, Institute of Cardiometabolism and Nutrition (ICAN), INSERM U1166, University of Pierre and Marie Curie Paris VI, Paris, France.
² Hormonal Regulation of Brain Development and Functions, INSERM U1151, Institut Necker Enfants Malades, Paris, France.

Abstract

The paternally expressed gene 3 (Pw1/Peg3) is a mammalian-specific parentally imprinted gene expressed in stem/progenitor cells of the brain and endocrine tissues. Here, we compared phenotypic characteristics in Pw1/Peg3 deficient male and female mice. Our findings indicate that Pw1/Peg3 is a key player for the determination of sexual dimorphism in metabolism and behavior. Mice carrying a paternally inherited Pw1/Peg3 mutant allele manifested postnatal deficits in GH/IGF dependent growth before weaning, sex steroid dependent masculinization during puberty, and insulin dependent fat accumulation in adulthood. As a result, Pw1/Peg3 deficient mice develop a sex-dependent global shift of body metabolism towards accelerated adiposity, diabetic-like insulin resistance, and fatty liver. Furthermore, Pw1/Peg3 deficient males displayed reduced social dominance and competitiveness concomitant with alterations in the vasopressinergic architecture in the brain. This study demonstrates that Pw1/Peg3 provides an epigenetic context that promotes male-specific characteristics through sex steroid pathways during postnatal development.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adiposity
Animals
Body Size
Female
Gene Expression Regulation, Developmental
Gene Knockout Techniques
Genomic Imprinting
Insulin-Like Growth Factor I / metabolism*
Intercellular Signaling Peptides and Proteins / metabolism*
Kruppel-Like Transcription Factors / genetics*
Kruppel-Like Transcription Factors / metabolism
Male
Mice
Paternal Inheritance
Phenotype
Sex Characteristics

Substances

Intercellular Signaling Peptides and Proteins
Kruppel-Like Transcription Factors
Peg3 protein, mouse
insulin-like growth factor-1, mouse
Insulin-Like Growth Factor I

Grants and funding

This work was supported by the French Ministry of Research Chaire d'Excellence and the European Community Seventh Framework Program projects ENDOSTEM (Activation of vasculature associated stem cells and muscle stem cells for the repair and maintenance of muscle tissue-agreement number 241440) and support from the Agence Nationale de la Recherche (Laboratoire d'Excellence Revive, Investissement d'Avenir; ANR-10-LABX-73) and Carmaa (RHU-ANR). We also thank Inserm and the University of Paris (VI) Sorbonne for institutional support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.