Journal of Developmental Medicine(Electronic Version)  2024, Vol. 12 Issue (3): 210-216,223 DOI: 10.3969/j.issn.2095-5340.2024.03.009 |
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| Mechanism of melatonin inhibiting chronic stress-induced follicular dysplasia in mice by inhibiting the PTEN/AKT/FOXO3a pathway |
| Xi Hong, Wang Yanqiu, Yu Hongqin, et al
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(Department of Gynaecology, Panjin Liaoyou BaoshihuaHospital, Liaoning, Panjin 124010, China)
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Abstract 【Abstract】 Objective To explore the mechanism of melatonin inhibiting chronic stress-induced folliculardysplasia by inhibiting the activation of PTEN/AKT/FOXO3a pathway in ovaries of mice. Method Sixty6-week-old female C57BL/6N mice were randomly divided into normal control group, chronic stress group,and melatonin group, 20 mouse in each group. The body mass and ovarian mass of the mice were recordedusing a laboratory balance. Enzyme-linked immunosorbent assay (ELISA) kits were used to measure theserum hormone levels in mice. Histological analysis was performed to determine the number of folliclesat different stages in ovaries of mice. ELISA and real-time fluorescence quantitative polymerase chainreaction (RT-qPCR) were used to detect the expression of anti-Müllerian hormone (AMH) in serum of
mice. Western blotting analysis was conducted to examine the expression of the phosphatidylinositol 3
kinase (PI3K)/protein kinase B (AKT)/Forkhead box transcription factor 3a (FOXO3a) signaling pathway.PCR was used to measure the transcription levels of PI3K/AKT/FOXO3a in ovaries of mice. Statistical methodswere used for LSD t-test, χ2 tests, one-way analysis of variance (ANOVA) or repeated measurement data analysisof variance. Result Chronic stress group were higher than those with normal control group in number ofprimary follicles (174±30 vs 107±17, t=-148.098), p-phosphatase and tensin homolog deleted on chromosometen (p-PTEN) proteins (2.03±0.19 vs 1.26±0.16, t=-32.207), p-AKT proteins (1.99±0.18 vs 1.07±0.05,t=-70.021), p-FOXO3a proteins (2.18±0.20 vs 1.18±0.11, t=-64.621), cortistatin (CORT) (137±12 vs83±7, t=-124.235), follicle-stimulating hormone (FSH) [(13.1±1.9) IU/L vs (8.2±1.6) IU/L, t=-25.388] (allP<0.001). Chronic stress group were lower than those with normal control group in body mass [(22.5±2.5) gvs (28.4±4.7) g, t=12.906], ovarian mass [(9±3) mg vs (23±5) mg, t=45.302], estradiol levels [(36±8) μg/Lvs (75±10) μg/L, t=88.937], androgen levels [(0.13±0.01) μg/L vs (0.20±0.02) μg/L, t=23.123], luteinizinghormone (LH) levels [(3.2±0.3) IU/L vs (4.6±0.5) IU/L, t=31.170] and the number of primary follicles(87±9 vs 143±27, t=111.829), secondary follicles (92±11 vs 150±21, t=130.837) and sinus follicles (43±5vs 96±8, t=144.851) (all P<0.001). Melatonin group were lower than those with chronic stress group in p-PTEN/PTEN (1.15±0.14 vs 2.03±0.19, t=4.983), p-AKT/AKT (1.21±0.13 vs 1.99±0.18, t=-12.108), p-FOXO3a/
FOXO3a (1.35±0.17 vs 2.18±0.20, t= -11.274), CORT[(106±10) μg/L vs (137±12) μg/L, t=-50.392)and
FSH levels [(10.2±1.5) IU/L vs (13.1±1.9) IU/L, t=-10.317)] (all P<0.001). Melatonin group were higher
than those with chronic stress group in body mass of mice [(26.5±4.1) g vs (22.5±2.5) g, t=5.182], ovarianmass [(17±5) mg vs (9±3) mg, t=19.588], estradiol levels [(66±6) μg/L vs (36±8) μg/L, t=20.485],androgen [(0.21±0.02) μg/L vs (0.13±0.01) μg/L, t=6.458], LH levels [(4.3±0.4) IU/L vs (3.2±0.3) IU/L,t=6.924] and the number of primary follicles [(125±15) vs (87±9), t=38.784], secondary follicles [137±16vs 92±11, t=29.063] and sinus follicles [76±6 vs 43±5, t=49.447] (all P<0.001). Conclusion Melatonininhibits the phosphorylation of PTEN/AKT/FOXO3a pathway members, increases the serum AMH levels inmice, and ultimately alleviates the loss of primordial follicles and follicular dysplasia in the ovaries of miceinduced by chronic stress.
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Received: 19 December 2022
Published: 31 May 2024
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