High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by <i>L-PRLR</i> and <i>S-PRLR</i>
High prolactin (PRL) concentration has been shown to induce the apoptosis of ovine ovarian granulosa cells (GCs), but the underlying mechanisms are unclear. This study aimed to investigate the mechanism of apoptosis induced by high PRL concentration in GCs. Trial 1: The optimal concentration of glut...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-09-01
|
| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/24/19/14407 |
| _version_ | 1797575821437698048 |
|---|---|
| author | Ruochen Yang Chunhui Duan Shuo Zhang Yunxia Guo Xinyu Shan Meijing Chen Sicong Yue Yingjie Zhang Yueqin Liu |
| author_facet | Ruochen Yang Chunhui Duan Shuo Zhang Yunxia Guo Xinyu Shan Meijing Chen Sicong Yue Yingjie Zhang Yueqin Liu |
| author_sort | Ruochen Yang |
| collection | DOAJ |
| description | High prolactin (PRL) concentration has been shown to induce the apoptosis of ovine ovarian granulosa cells (GCs), but the underlying mechanisms are unclear. This study aimed to investigate the mechanism of apoptosis induced by high PRL concentration in GCs. Trial 1: The optimal concentration of glutathion was determined according to the detected cell proliferation. The results showed that the optimal glutathione concentration was 5 μmol/mL. Trial 2: 500 ng/mL PRL was chosen as the high PRL concentration. The GCs were treated with 0 ng/mL PRL (C group), 500 ng/mL PRL (P group) or 500 ng/mL PRL, and 5 μmol/mL glutathione (P-GSH group). The results indicated that the mitochondrial respiratory chain complex (MRCC) I–V, ATP production, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and thioredoxin peroxidase (TPx) in the C group were higher than those in the P group (<i>p</i> < 0.05), while they were lower than those in the P-GSH group (<i>p</i> < 0.05). Compared to the C group, the P group exhibited elevated levels of reactive oxygen species (ROS) and apoptosis (<i>p</i> < 0.05) and increased expression of ATG7 and ATG5 (<i>p</i> < 0.05). However, MRCC I–V, ATP, SOD, A-TOC, TPx, ROS, and apoptosis were decreased after the addition of glutathione (<i>p</i> < 0.05). The knockdown of either <i>L-PRLR</i> or <i>S-PRLR</i> in P group GCs resulted in a significant reduction (<i>p</i> < 0.05) in MRCC I–V, ATP, T-AOC, SOD and TPx, while the overexpression of either receptor showed an opposite trend (<i>p</i> < 0.05). Our findings suggest that high PRL concentrations induce apoptotic cell death in ovine ovarian GCs by downregulating <i>L-PRLR</i> and <i>S-PRLR</i>, activating oxidative stress and autophagic pathways. |
| first_indexed | 2024-03-10T21:44:44Z |
| format | Article |
| id | doaj.art-738e826b90ac426698e305db349668ed |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:44:44Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-738e826b90ac426698e305db349668ed2023-11-19T14:26:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-09-0124191440710.3390/ijms241914407High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by <i>L-PRLR</i> and <i>S-PRLR</i>Ruochen Yang0Chunhui Duan1Shuo Zhang2Yunxia Guo3Xinyu Shan4Meijing Chen5Sicong Yue6Yingjie Zhang7Yueqin Liu8College of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaCollege of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaCollege of Animal Science and Technology, China Agricultural University, Beijing 100089, ChinaCollege of Life Sciences, Hebei Agricultural University, Baoding 071000, ChinaCollege of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaCollege of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaCollege of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaCollege of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaCollege of Animal Science and Technology, Hebei Agricultural University, Baoding 071000, ChinaHigh prolactin (PRL) concentration has been shown to induce the apoptosis of ovine ovarian granulosa cells (GCs), but the underlying mechanisms are unclear. This study aimed to investigate the mechanism of apoptosis induced by high PRL concentration in GCs. Trial 1: The optimal concentration of glutathion was determined according to the detected cell proliferation. The results showed that the optimal glutathione concentration was 5 μmol/mL. Trial 2: 500 ng/mL PRL was chosen as the high PRL concentration. The GCs were treated with 0 ng/mL PRL (C group), 500 ng/mL PRL (P group) or 500 ng/mL PRL, and 5 μmol/mL glutathione (P-GSH group). The results indicated that the mitochondrial respiratory chain complex (MRCC) I–V, ATP production, total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and thioredoxin peroxidase (TPx) in the C group were higher than those in the P group (<i>p</i> < 0.05), while they were lower than those in the P-GSH group (<i>p</i> < 0.05). Compared to the C group, the P group exhibited elevated levels of reactive oxygen species (ROS) and apoptosis (<i>p</i> < 0.05) and increased expression of ATG7 and ATG5 (<i>p</i> < 0.05). However, MRCC I–V, ATP, SOD, A-TOC, TPx, ROS, and apoptosis were decreased after the addition of glutathione (<i>p</i> < 0.05). The knockdown of either <i>L-PRLR</i> or <i>S-PRLR</i> in P group GCs resulted in a significant reduction (<i>p</i> < 0.05) in MRCC I–V, ATP, T-AOC, SOD and TPx, while the overexpression of either receptor showed an opposite trend (<i>p</i> < 0.05). Our findings suggest that high PRL concentrations induce apoptotic cell death in ovine ovarian GCs by downregulating <i>L-PRLR</i> and <i>S-PRLR</i>, activating oxidative stress and autophagic pathways.https://www.mdpi.com/1422-0067/24/19/14407ovine ovarian GCsapoptosisoxidative stressautophagymitochondriaROS |
| spellingShingle | Ruochen Yang Chunhui Duan Shuo Zhang Yunxia Guo Xinyu Shan Meijing Chen Sicong Yue Yingjie Zhang Yueqin Liu High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by <i>L-PRLR</i> and <i>S-PRLR</i> International Journal of Molecular Sciences ovine ovarian GCs apoptosis oxidative stress autophagy mitochondria ROS |
| title | High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by <i>L-PRLR</i> and <i>S-PRLR</i> |
| title_full | High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by <i>L-PRLR</i> and <i>S-PRLR</i> |
| title_fullStr | High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by <i>L-PRLR</i> and <i>S-PRLR</i> |
| title_full_unstemmed | High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by <i>L-PRLR</i> and <i>S-PRLR</i> |
| title_short | High Prolactin Concentration Induces Ovarian Granulosa Cell Oxidative Stress, Leading to Apoptosis Mediated by <i>L-PRLR</i> and <i>S-PRLR</i> |
| title_sort | high prolactin concentration induces ovarian granulosa cell oxidative stress leading to apoptosis mediated by i l prlr i and i s prlr i |
| topic | ovine ovarian GCs apoptosis oxidative stress autophagy mitochondria ROS |
| url | https://www.mdpi.com/1422-0067/24/19/14407 |
| work_keys_str_mv | AT ruochenyang highprolactinconcentrationinducesovariangranulosacelloxidativestressleadingtoapoptosismediatedbyilprlriandisprlri AT chunhuiduan highprolactinconcentrationinducesovariangranulosacelloxidativestressleadingtoapoptosismediatedbyilprlriandisprlri AT shuozhang highprolactinconcentrationinducesovariangranulosacelloxidativestressleadingtoapoptosismediatedbyilprlriandisprlri AT yunxiaguo highprolactinconcentrationinducesovariangranulosacelloxidativestressleadingtoapoptosismediatedbyilprlriandisprlri AT xinyushan highprolactinconcentrationinducesovariangranulosacelloxidativestressleadingtoapoptosismediatedbyilprlriandisprlri AT meijingchen highprolactinconcentrationinducesovariangranulosacelloxidativestressleadingtoapoptosismediatedbyilprlriandisprlri AT sicongyue highprolactinconcentrationinducesovariangranulosacelloxidativestressleadingtoapoptosismediatedbyilprlriandisprlri AT yingjiezhang highprolactinconcentrationinducesovariangranulosacelloxidativestressleadingtoapoptosismediatedbyilprlriandisprlri AT yueqinliu highprolactinconcentrationinducesovariangranulosacelloxidativestressleadingtoapoptosismediatedbyilprlriandisprlri |