Absence of CDK12 in oocyte leads to female infertility

J 2025

Absence of CDK12 in oocyte leads to female infertility

JANSOVA, Denisa; Veronika SEDMIKOVA; Fatima J BERRO; Daria ALESHKINA; Michal DVORAN et al.

Základní údaje

Originální název

Absence of CDK12 in oocyte leads to female infertility

Autoři

JANSOVA, Denisa; Veronika SEDMIKOVA; Fatima J BERRO; Daria ALESHKINA; Michal DVORAN; Michal KUBELKA; Jitka REZACOVA; Jana RUTAROVA; Jiří KOHOUTEK a Andrej SUSOR

Vydání

Cell Death and Disease, Springer Nature, 2025, 2041-4889

Další údaje

Jazyk

angličtina

Typ výsledku

Článek v odborném periodiku

Obor

10608 Biochemistry and molecular biology

Stát vydavatele

Velká Británie a Severní Irsko

Utajení

není předmětem státního či obchodního tajemství

Odkazy

URL

Impakt faktor

Impact factor: 9.600 v roce 2024

Označené pro přenos do RIV

Ano

Organizační jednotka

Přírodovědecká fakulta

DOI

https://doi.org/10.1038/s41419-025-07536-w

UT WoS

001455374000004

EID Scopus

2-s2.0-105001134423

Klíčová slova anglicky

Infertility; Oogenesis

Štítky

14314010, rivok

Příznaky

Mezinárodní význam, Recenzováno

Změněno: 27. 6. 2025 08:16, Mgr. Marie Novosadová Šípková, DiS.

Anotace

V originále

Transcriptional activity and gene expression are critical for the development of mature, meiotically competent oocytes. Our study demonstrates that the absence of cyclin-dependent kinase 12 (CDK12) in oocytes leads to complete female sterility, as fully developed oocytes capable of completing meiosis I are absent from the ovaries. Mechanistically, CDK12 regulates RNA polymerase II activity in growing oocytes and ensures the maintenance of the physiological maternal transcriptome, which is essential for protein synthesis that drives further oocyte growth. Notably, CDK12-deficient growing oocytes exhibit a 71% reduction in transcriptional activity. Furthermore, impaired oocyte development disrupts folliculogenesis, leading to premature ovarian failure without terminal follicle maturation or ovulation. In conclusion, our findings identify CDK12 as a key master regulator of the oocyte transcriptional program and gene expression, indispensable for oocyte growth and female fertility.A schematic illustrating the effects of loss of CDK12 in mammalian oocytes on the regulation of transcription by polymerase II and the concomitant effects on translation. This disruption leads to an aberrant transcriptome and translatome, resulting in the absence of fully mature oocytes and ultimately female sterility.

Návaznosti

LX22NPO5102, projekt VaV

Název: Národní ústav pro výzkum rakoviny (Akronym: NÚVR)

Investor: Ministerstvo školství, mládeže a tělovýchovy ČR, Národní ústav pro výzkum rakoviny, 5.1 EXCELES

90236, velká výzkumná infrastruktura

Název: CCP III

Přiložené soubory

2505818.pdf

Citovat

JANSOVA, Denisa; Veronika SEDMIKOVA; Fatima J BERRO; Daria ALESHKINA; Michal DVORAN; Michal KUBELKA; Jitka REZACOVA; Jana RUTAROVA; Jiří KOHOUTEK a Andrej SUSOR. Absence of CDK12 in oocyte leads to female infertility. Cell Death and Disease. Springer Nature, 2025, roč. 16, č. 1, s. 213-225. ISSN 2041-4889. Dostupné z: https://doi.org/10.1038/s41419-025-07536-w.

@article{2505818,
   author = {Jansova, Denisa and Sedmikova, Veronika and Berro, Fatima J and Aleshkina, Daria and Dvoran, Michal and Kubelka, Michal and Rezacova, Jitka and Rutarova, Jana and Kohoutek, Jiří and Susor, Andrej},
   article_number = {1},
   doi = {https://doi.org/10.1038/s41419-025-07536-w},
   keywords = {Infertility; Oogenesis},
   language = {eng},
   issn = {2041-4889},
   journal = {Cell Death and Disease},
   title = {Absence of CDK12 in oocyte leads to female infertility},
   url = {https://doi.org/10.1038/s41419-025-07536-w},
   volume = {16},
   year = {2025}
}

TY  - JOUR
ID  - 2505818
AU  - Jansova, Denisa - Sedmikova, Veronika - Berro, Fatima J - Aleshkina, Daria - Dvoran, Michal - Kubelka, Michal - Rezacova, Jitka - Rutarova, Jana - Kohoutek, Jiří - Susor, Andrej
PY  - 2025
TI  - Absence of CDK12 in oocyte leads to female infertility
JF  - Cell Death and Disease
VL  - 16
IS  - 1
SP  - 213
EP  - 213
PB  - Springer Nature
SN  - 20414889
KW  - Infertility
KW  - Oogenesis
UR  - https://doi.org/10.1038/s41419-025-07536-w
N2  - Transcriptional activity and gene expression are critical for the development of mature, meiotically competent oocytes. Our study demonstrates that the absence of cyclin-dependent kinase 12 (CDK12) in oocytes leads to complete female sterility, as fully developed oocytes capable of completing meiosis I are absent from the ovaries. Mechanistically, CDK12 regulates RNA polymerase II activity in growing oocytes and ensures the maintenance of the physiological maternal transcriptome, which is essential for protein synthesis that drives further oocyte growth. Notably, CDK12-deficient growing oocytes exhibit a 71% reduction in transcriptional activity. Furthermore, impaired oocyte development disrupts folliculogenesis, leading to premature ovarian failure without terminal follicle maturation or ovulation. In conclusion, our findings identify CDK12 as a key master regulator of the oocyte transcriptional program and gene expression, indispensable for oocyte growth and female fertility.A schematic illustrating the effects of loss of CDK12 in mammalian oocytes on the regulation of transcription by polymerase II and the concomitant effects on translation. This disruption leads to an aberrant transcriptome and translatome, resulting in the absence of fully mature oocytes and ultimately female sterility.
ER  -

JANSOVA, Denisa; Veronika SEDMIKOVA; Fatima J BERRO; Daria ALESHKINA; Michal DVORAN; Michal KUBELKA; Jitka REZACOVA; Jana RUTAROVA; Jiří KOHOUTEK a Andrej SUSOR. Absence of CDK12 in oocyte leads to female infertility. \textit{Cell Death and Disease}. Springer Nature, 2025, roč.~16, č.~1, s.~213-225. ISSN~2041-4889. Dostupné z: https://doi.org/10.1038/s41419-025-07536-w.

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