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Human Cell

, Volume 32, Issue 3, pp 285–296 | Cite as

PGC-1α protects against oxidized low-density lipoprotein and luteinizing hormone-induced granulosa cells injury through ROS-p38 pathway

  • Ying Liu
  • Jianjun ZhaiEmail author
  • Jing Chen
  • Xiaomin Wang
  • Tingru Wen
Research Article
  • 77 Downloads

Abstract

Obese women with polycystic ovary syndrome (PCOS) often suffer from ovulation failure, which may be driven by granulosa cells (GCs) injury caused by increased levels of circulating oxidized low-density lipoprotein (ox-LDL) and luteinizing hormone (LH). PGC-1α may play an important role in this pathophysiological processes. However, the effect and the potential mechanism of PGC-1α on GCs injury evoked by obese PCOS is fully unclear. To investigate the protective effect and the potential mechanism of PGC-1α on GCs injury evoked by ox-LDL + LH stimulation. Patients with PCOS and women of normal reproductive age who undergoing egg retrievals and consenting for this research were collected. Those women were divided into normal-weight non-PCOS group, obese non-PCOS group, normal-weight PCOS group and obese PCOS group according to the body mass index (BMI) and PCOS diagnosis. Follicular fluid was collected and primary GCs were isolated. The levels of LH and ox-LDL in follicular fluid in the four groups were measured. And, the expressions of PGC-1α, cell apoptosis and ROS generation in primary GCs in the four groups were evaluated. After GCs from women of normal reproductive age at normal-weight pre-treated with adenovirus encoding PGC-1α (Ad-PGC-1α) prior to ox-LDL + LH treatment in vitro, the cell viability, apoptosis, apoptosis-related proteins expressions and ROS generation were evaluated by CCK-8 assay, AnnexinV/PI double staining, Western blot and H2DCF-DA staining, respectively. The expression of PGC-1α was significantly decreased, whereas the cell apoptosis and ROS generation were significantly increased in GCs of PCOS group, especially obese PCOS group. Our data also revealed that over-expression of PGC-1α in GCs from women of normal reproductive age at normal-weight markedly inhibited cell injury, ROS generation and p38 activation, accompanied by increased Bcl-2 expression, decreased Bax and cleaved caspase-3 expressions induced by ox-LDL + LH stimulation. Ox-LDL + LH-induced cell apoptosis was abrogated by attenuation of ROS generation or p38 activation. Attenuation of ROS generation reversed ox-LDL + LH-induced p38 activation, however, p38 inhibitors had an effect on ROS generation. Our findings suggested that PGC-1α protected against ox-LDL + LH-induced GCs injury through inhibiting cell apoptosis. And, the mechanism may be related to the inhibition of ROS-initiated p38 pathway. Our data indicated that PGC-1α may be a potential therapeutic target for obese PCOS.

Keywords

Polycystic ovary syndrome PGC-1α Oxidized low-density lipoprotein Granulosa cell Apoptosis ROS p38 

Notes

Author contributions

YL carried out the study, data statistics and drafted the manuscript; JZ supervised the study and the data statistics; JC participated in study design and the data statistics; XW and TW participated in scientific discussion of the data.

Compliance with ethical standards

Conflict of interest

The authors have declared that no competing interests exist.

Ethics approval

All the subjects undergoing egg retrievals and consenting for this research, and all the clinical data were collected with the consent of the subjects and their family members and signed the relevant informed consent. Moreover, the experimental design was approved by the Committee for Ethics of Beijing Tongren Hospital.

Informed consent

This study is approved by all authors for publication.

Availability of data and supporting materials

All data are included in this published article.

Supplementary material

13577_2019_252_MOESM1_ESM.doc (1020 kb)
Supplementary material 1 (DOC 1012 kb)

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Copyright information

© Japan Human Cell Society and Springer Japan KK, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Gynaecology and ObstetricsEmergency General HospitalBeijingChina
  2. 2.Department of Gynaecology and Obstetrics, Beijing Tongren HospitalCapital Medical UniversityBeijingChina
  3. 3.Department of Blood TransfusionDingzhou City HospitalDingzhouChina
  4. 4.Department of Gynaecology and ObstetricsTangshan People’s HospitalTangshanChina
  5. 5.Department of Gynaecology and ObstetricsBeijing United Family HospitalBeijingChina

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