Publication: Chk1/2 inhibitor AZD7762 blocks the growth of preantral follicles by inducing apoptosis, suppressing proliferation, and interfering with the cell cycle in granulosa cells
Authors
Liu, Xiao Ming ; Chen, Fang ; Zhang, Fan ; Zhao, Jun Zhao
item.page.secondaryauthor
item.page.director
Publisher
Universidad de Murcia. Departamento de Biología Celular e Histología
publication.page.editor
publication.page.department
DOI
https://doi.org/10.14670/HH-18-547
item.page.type
info:eu-repo/semantics/article
Description
Abstract
Background. Checkpoint kinases 1/2
(Chk1/2) have an important role in somatic cell
development and oocyte meiotic maturation. However,
the role of Chk1/2 in folliculogenesis has not been fully
elucidated. The aim of this study was to assess the
effects of Chk1/2 inhibition on ovarian folliculogenesis
and granulosa cell development in mice.
Methods. Preantral follicles (100-120 μm) and
granulosa cells from pre-ovulatory follicles (pre-GCs) of
mice were isolated and cultured with or without Chk1/2
inhibitor AZD7762. Preantral follicles were cultured for
96h. Then, follicle morphology and follicular growth
were assessed every 48h. Granulosa cells were cultured
for 48h with or without AZD7762, after which cell
apoptosis, cell proliferation, and cell cycle analysis were
assessed; meanwhile, the mRNA expression of PCNA
and Bax were measured by real-time RT-PCR, and
PCNA and Bax protein were measured by Western blot.
Results. Compared with control follicles, AZD7762
inhibited growth of preantral follicles (P<0.05).
Furthermore, inhibition of Chk1/2 significantly induced
apoptosis (P<0.05) and inhibited the proliferation of
granulosa cells (P<0.01), arrested cell cycle at S and
G2/M phases, and decreased G1 phase fraction
(P<0.001). Also, the expression of PCNA mRNA and
protein were reduced (P<0.01), while Bax mRNA and
protein were increased (P<0.05) post AZD7762
treatment in granulosa cells.
Conclusions. This study revealed that Chk1 and
Chk2 have a crucial role during preantral follicular
development by regulating the proliferation and
apoptosis of granulosa cells.
publication.page.subject
Citation
item.page.embargo
Ir a Estadísticas
Este ítem está sujeto a una licencia Creative Commons. CC BY 4.0