Mechanism of NPPA/NPR1 signaling promoting ovarian follicle expan-sion in mice
10.3969/j.issn.1000-4718.2025.04.011
- VernacularTitle:NPPA/NPR1信号促进小鼠卵泡扩张的作用机制
- Author:
Jiayu LIU
1
;
Xiao CHEN
;
Xiaoqiong HAO
Author Information
1. 包头医学院生理学教研室,内蒙古 包头 014040;华南理工大学医学院,广东 广州 510006
- Publication Type:Journal Article
- Keywords:
ovarian follicle expansion;
natriuretic peptide receptor 1;
natriuretic peptide A;
mice
- From:
Chinese Journal of Pathophysiology
2025;41(4):714-722
- CountryChina
- Language:Chinese
-
Abstract:
AIM:To explore the role and mechanism of natriuretic peptide A(NPPA)/natriuretic peptide re-ceptor 1(NPR1)signaling in luteinizing hormone(LH)-induced ovarian follicle expansion in mice.METHODS:Three-week-old female mice were injected with pregnant mare serum gonadotropin/equine chorionic gonadotrophin(eCG)48 h before use to stimulate follicle development,or injected with eCG followed by human chorionic gonadotropin(hCG)treat-ment for 4 or 8 h,with 6 mice in each group.Periodic acid-Schiff(PAS)staining in ovarian sections was used to observe the follicular diameter,and qPCR was used to detect the expression of Npr1 mRNA levels in granulosa cells.Wild-type(WT)and Npr1 knockout(Npr1-/-)mice were injected with eCG,or injected with eCG followed by hCG treatment for 4 h.PAS staining was used to observe the follicular diameter,with 6 mice in each group.Superovulation and fertility assays were performed to count the number of ovulated oocytes and pups,with 6 mice in each group subjected to superovulation and 7 mice in each group subjected to fertility assays.The isolated follicles were randomly divided into control,NPPA,LH,LH+NPPA,LH+NPPA+KT5823[protein kinase G(PKG)inhibitor],and LH+NPPA+PPQ-102[cystic fibrosis transmembrane conductance regulator(CFTR)inhibitor]groups,with 20 follicles in each group.In addition,WT and Npr1-/-mice were injected with eCG 48 h or eCG 48 h/hCG 4 h,with 3 mice in each group.In vitro follicle culture and qP-CR were used to explore the effects of PKG and CFTR signalling on NPPA/NPR1-induced follicular expansion.The prolif-eration of granulosa cells in WT and Npr1-/-mice was detected via immunofluorescence staining,with 5 mice in each group.RESULTS:The results revealed that hCG treatment significantly increased the follicle expansion and Npr1 mRNA expression in granulosa cells(P<0.01).The capacity for ovarian follicle expansion,the number of ovulations,and the number of pups per litter were significantly lower in Npr1-/-mice compared with WT mice(P<0.01).In in vitro follicular culture,the addition of PKG inhibitor KT5823 and CFTR inhibitor PPQ-102 significantly inhibited NPPA/NPR1-induced ovarian follicle expansion(P<0.01),and the expression of Pkg mRNA and Cftr mRNA in granulosa cells of Npr1-/-mice was significantly lower than that in WT mice(P<0.01).In addition,the proliferation ability of granulosa cells in Npr1-/-mice was significantly lower than that in WT mice(P<0.01).CONCLUSION:LH promotes mouse ovarian follicle ex-pansion by NPPA/NPR1 signalling-induced PKG and CFTR pathways and granulosa cell proliferation.
