"Meiosis arrester" C-natriuretic peptide directly stimulates oocyte mtDNA accumulation and is implicated in aging-associated oocyte mtDNA loss

© 2023 Federation of American Societies for Experimental Biology..

C-natriuretic peptide (CNP) is the central regulator of oocyte meiosis progression, thus coordinating synchronization of oocyte nuclear-cytoplasmic maturation. However, whether CNP can independently regulate cytoplasmic maturation has been long overlooked. Mitochondrial DNA (mtDNA) accumulation is the hallmark event of cytoplasmic maturation, but the mechanism underlying oocyte mtDNA replication remains largely elusive. Herein, we report that CNP can directly stimulate oocyte mtDNA replication at GV stage, and deficiency of follicular CNP may contribute largely to lower mtDNA copy number in in vitro matured oocytes. The mechanistic study showed that cAMP-PKA-CREB1 signaling cascade underlies the regulatory role of CNP in stimulating mtDNA replication and upregulating related genes. Of interest, we also report that CNP-NPR2 signaling is inhibited in aging follicles, and this inhibition is implicated in lower mtDNA copy number in oocytes from aging females. Together, our study provides the first direct functional link between follicular CNP and oocyte mtDNA replication, and identifies its involvement in aging-associated mtDNA loss in oocytes. These findings, not only update the current knowledge of the functions of CNP in coordinating oocyte maturation but also present a promising strategy for improving in vitro fertilization outcomes of aging females.

Medienart:

E-Artikel

Erscheinungsjahr:

2023

Erschienen:

2023

Enthalten in:

Zur Gesamtaufnahme - volume:37

Enthalten in:

FASEB journal : official publication of the Federation of American Societies for Experimental Biology - 37(2023), 12 vom: 01. Dez., Seite e23295

Sprache:

Englisch

Beteiligte Personen:

Tang, Yawen [VerfasserIn]
Cui, Jian [VerfasserIn]
Wang, Xiaodong [VerfasserIn]
Yang, Qianying [VerfasserIn]
Yue, Yuan [VerfasserIn]
Gao, Chunxiao [VerfasserIn]
Wang, Yue [VerfasserIn]
Wang, Wenjing [VerfasserIn]
Zhang, Shuai [VerfasserIn]
Tian, Jianhui [VerfasserIn]
Xi, Guangyin [VerfasserIn]
An, Lei [VerfasserIn]

Links:

Volltext

Themen:

127869-51-6
Aging
C-natriuretic peptide (CNP)
CAMP-PKA-CREB1 signaling cascade
DNA, Mitochondrial
Journal Article
Mitochondrial DNA (mtDNA) replication
Natriuretic Peptide, C-Type
Natriuretic Peptides
Oocyte cytoplasmic maturation
Research Support, Non-U.S. Gov't
Vasodilator Agents

Anmerkungen:

Date Completed 27.11.2023

Date Revised 02.02.2024

published: Print

Citation Status MEDLINE

doi:

10.1096/fj.202300886R

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM36476239X