Zhonghua Yu Fang Yi Xue Za Zhi
Department of Gynecology Endocrine & Reproductive Center,Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, National Clinical Research Center for Obstetric & Gynecologic Diseases Department of Obstetrics and Gynecology, Beijing 100730, China.
Published: February 2024
This study explores the effects and possible mechanisms of nuclear factor E2 related factor 2 (NRF2) on ovarian granulosa cells, providing a scientific basis to prevent premature ovarian failure. An ovarian cell injury model was constructed by treating human ovarian granulosa cell (KGN cell) with 4-Vinylcyclohexene dioxide (VCD). Firstly, KGN cells were treated with different concentrations of VCD, and cell counting kit 8 (CCK-8) was used to detect ovarian cell proliferation. After determining IC by CCK8, the levels of estradiol and progesterone in the cell supernatant were detected using enzyme-linked immunosorbent assay (ELISA), reactive oxygen species (ROS) assay kit was used to detect the content of ROS in ovarian cells, real-time fluorescence quantitative polymerase chain reaction (qRT PCR) was used to detect the mRNA expression level of NRF2, and Western blot was used to detect the protein expression level of NRF2. Further, NRF2 silence (siNRF2) and overexpression (NRF2-OE) cell models were constructed through lentivirus transfection, and the effects of regulating NRF2 on VCD treated cell models were investigated by detecting hormone levels, oxidative stress indicators (ROS, SOD, GSH-Px), and autophagy (LC3B level). The results showed that VCD intervention inhibited the proliferation of ovarian granulosa cells in a time-dependent and dose-dependent manner (>100, <0.05), with an IC of 1.2 mmol/L at 24 hours. After VCD treatment, the level of estradiol in the cell supernatant decreased from (56.32±10.18) ng/ml to (24.59±8.75) ng/ml (=5.78, <0.05). Progesterone decreased from (50.25±7.03) ng/ml to (25.13±6.67) ng/ml (=6.54, <0.05). After VCD treatment, the SOD of cells decreased from (44.47±7.71) ng/ml to (30.92±4.97) ng/ml (=3.61, <0.05). GSH-Px decreased from (68.51±10.17) ng/ml to (35.19±6.59) ng/ml (=5.73, <0.05). Simultaneously accompanied by an increase in autophagy and a decrease in NRF2. This study successfully constructed KGN cell models that silenced NRF2 and overexpressed NRF2. Subsequently, this study treated each group of cells with VCD and found that the cell proliferation activity of the siNRF2 group was significantly reduced (=8.37, <0.05), while NRF2-OE could reverse the cell activity damage caused by VCD (=3.37, <0.05). The siNRF2 group had the lowest level of estradiol (=5.78, <0.05), while NRF2-OE could reverse the decrease in cellular estradiol levels caused by VCD (=5.58, <0.05). The siNRF2 group had the lowest progesterone levels (=3.02, <0.05), while NRF2-OE could reverse the decrease in cellular progesterone levels caused by VCD (=2.41, <0.05). The ROS level in the siNRF2 group was the highest (=2.86, <0.05), NRF2-OE could reverse the increase in ROS caused by VCD (=3.14, <0.05), the SOD enzyme content in the siNRF2 group was the lowest (=2.98, <0.05), and NRF2-OE could reverse the decrease in SOD enzyme content caused by VCD (=4.72, <0.05). The GSH-Px enzyme content in the siNRF2 group was the lowest (=3.67, <0.05), and NRF2-OE could reverse the decrease in antioxidant enzyme content caused by VCD (=2.71, <0.05). The LC3B level was highest in the siNRF2 group (=2.45, <0.05), and NRF2-OE was able to reverse the LC3B elevation caused by VCD (=9.64, <0.05). In conclusion, NRF2 inhibits ROS induced autophagy, thereby playing a role in reducing ovarian granulosa cell damage, which may be a potential target for premature ovarian failure.
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http://dx.doi.org/10.3760/cma.j.cn112150-20230905-00159 | DOI Listing |
Am J Obstet Gynecol
January 2025
Women's Health, Aabenraa, University Hospital of Southern Denmark; Institute of Regional Health Research, University of South Denmark.
Background: Sex cord-stromal cell tumors (SCST) are rare tumors of the ovary. Some of the SCSTs secrete hormone originating from the sex or stromal cell of the ovaries. Previous studies have indicated an increased risk of breast and endometrial cancers.
View Article and Find Full Text PDFPurpose: To investigate the effects of C-type natriuretic peptide (CNP) on human granulosa cell growth and elucidate its regulatory mechanisms.
Methods: A human non-luteinizing granulosa cell line (HGrC) developed from small antral follicles was used to assess the impact of CNP on cell proliferation and estrogen synthesis. cGMP production via the guanylate cyclase domain of the CNP receptor, natriuretic peptide receptor 2 (NPR2), was confirmed.
Adv Biol (Weinh)
January 2025
Department of Life, Health and Environmental Sciences, University of L'Aquila, L'Aquila, 67100, Italy.
Polycystic ovary syndrome is one of the most common endocrine disorders in women of reproductive age, characterized by functional and structural alterations of the female reproductive organs. Due to the unknown underlying molecular mechanisms, in vivo murine models and in vitro human cellular models are developed to study the syndrome. These models are used to analyze various aspects of the pathology by replicating the conditions of the syndrome.
View Article and Find Full Text PDFCurr Med Chem
January 2025
Center of Reproductive Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450000, China.
Background: Metabolic Syndrome (MS) is a cluster of conditions that significantly increase the risk of infertility in women. Granulosa cells are crucial for ovarian folliculogenesis and fertility. Understanding molecular alterations in these cells can provide insights into MS-associated infertility.
View Article and Find Full Text PDFComb Chem High Throughput Screen
January 2025
Hospital of Chengdu University of Traditional Chinese Medicine, No. 39 Shierqiao Road, Jinniu District, Chengdu, Sichuan, 610072, P.R. China.
Objective: This study aimed to investigate the possible mechanism through which acupuncture protects ovaries with Poor Ovarian Response (POR) in rats based on microRNA (miRNA).
Methods: Thirty-six SPF SD female non-pregnant rats aged 8 weeks were randomly divided into the blank group, model group, and acupuncture group, with 12 rats in each group. According to the group, the rats were given gavage of Tripterygium wilfordii polyglycosides suspension for 14 days to establish the model of POR, and then the rats were treated with acupuncture for 2 weeks, once a day, for 20 minutes.
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