Mitochondrial Unfolded Protein Response Gene Clpp Is Required for Oocyte Function and Female Fertility

Author:

Ergun Yagmur12,Imamoglu Aysegul Gizem1,Cozzolino Mauro134ORCID,Demirkiran Cem1ORCID,Basar Murat15ORCID,Garg Akanksha16,Yildirim Raziye Melike1ORCID,Seli Emre157

Affiliation:

1. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale School of Medicine, New Haven, CT 06510, USA

2. IVIRMA Global Research Alliance, IVIRMA New Jersey, Marlton, NJ 07920, USA

3. IVIRMA Global Research Alliance, IVI Roma, 00169 Rome, Italy

4. IVIRMA Global Research Alliance, IVI Foundation, Instituto de Investigación Sanitaria La Fe (IIS La Fe), 46026 Valencia, Spain

5. Department of Obstetrics, Gynecology, and Reproductive Sciences, Yale Fertility Center, Orange, CT 06477, USA

6. Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2BX, UK

7. IVIRMA Global Research Alliance, IVIRMA New Jersey, Basking Ridge, NJ 07920, USA

Abstract

Mitochondrial unfolded protein stress response (mtUPR) plays a critical role in regulating cellular and metabolic stress response and helps maintain protein homeostasis. Caseinolytic peptidase P (CLPP) is one of the key regulators of mtUPR and promotes unfolded protein degradation. Previous studies demonstrated that global deletion of Clpp resulted in female infertility, whereas no impairment was found in the mouse model with targeted deletion of Clpp in cumulus/granulosa cells. These results suggest the need to delineate the function of Clpp in oocytes. In this study, we aimed to further explore the role of mtUPR in female reproductive competence and senescence using a mouse model. Oocyte-specific targeted deletion of Clpp in mice resulted in female subfertility associated with metabolic and functional abnormalities in oocytes, thus highlighting the importance of CLPP-mediated protein homeostasis in oocyte competence and reproductive function.

Funder

Foundation for Embryonic Competence to E.S

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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