收稿日期: 2024-08-15
网络出版日期: 2024-12-16
基金资助
国家自然科学基金青年科学基金项目(82101733);广州市科技计划项目(2023A04J0543)
The effect of melatonin on the maturation level of oocytes and mitochondrial dynamics in mice exposed to benzophenone⁃3
Received date: 2024-08-15
Online published: 2024-12-16
目的 探讨褪黑素（melatonin，MT）改善二苯酮-3（benzophenone-3，BP-3）暴露小鼠卵母细胞质量的作用及机制。 方法 试验将6 ~ 12周龄的ICR雌鼠GV期卵母细胞分别在M16培养液、0.8 μmol/L BP-3培养液以及1 × 10-7 mol/L MT + 0.8 μmol/L BP-3混合培养液中进行体外培养。将ICR雌鼠随机分为3组：对照组、BP-3组、BMT组；对照组灌胃0.5 mL纯净水、BP-3组灌胃0.5 mL含0.8 μmol/L BP-3的药物溶液、BMT组灌胃0.5 mL含0.8 μmol/L BP-3以及15 mg/kg MT的药物溶液，每天1次，连续灌胃4周，进行体内实验。随后通过检测3组小鼠的MⅡ期卵子成熟率，线粒体动力学相关基因Mfn1、Opa1、Fis1、Drp1的转录水平及其蛋白表达水平，线粒体膜电位及纺锤体形态来探讨MT对BP-3暴露小鼠卵母细胞线粒体的挽救作用。 结果 与对照组相比，MT处理显著增加了BP-3组卵母细胞中线粒体融合基因Mfn1和Opa1的转录及蛋白水平表达，同时下调了线粒体分裂基因Fis1和Drp1的mRNA与蛋白表达。此外，BMT组的卵母细胞ROS水平和纺锤体形态异常比例明显低于BP-3组，但其线粒体膜电位显著升高。 结论 生理浓度BP-3暴露具有生殖毒性，但添加适当浓度的MT可以明显改善BP-3暴露小鼠卵母细胞的线粒体动力学及其发育潜能。
史若锦 , 熊钰莹 , 张雪玲 , 金龙 , 朱海瑛 . 褪黑素对二苯酮-3暴露小鼠卵母细胞成熟水平及线粒体动力学的影响[J]. 实用医学杂志, 2024 , 40(23) : 3275 -3283 . DOI: 10.3969/j.issn.1006-5725.2024.23.001
Objective To investigate the effects and mechanisms of melatonin （MT） on improving oocyte quality in mice exposed to benzophenone-3 （BP-3）. Methods In this study， 6 ~ 12-week-old female ICR mice were cultured in vitro in M16 culture， 0.8 μmol/L BP-3 medium and 1 × 10-7 mol/L MT + 0.8 μmol/L BP-3 mixed culture. Female ICR mice were randomly segregated into three groups： control， BP-3， and BMT. The control group received 0.5 mL of purified water， the BP-3 group was administered 0.5 mL of a 0.8 μmol/L BP-3 solution， and the BMT group received 0.5 ml of a combination of 0.8 μmol/L BP-3 and 15 mg/kg MT solution via gavage once daily for four weeks， to facilitate in vivo experimentation. Subsequently， the oocyte maturity rate， transcription levels and protein expression levels of mitochondrial dynamics-related genes Mfn1， Opa1， Fis1 and Drp1， mitochondrial membrane potential and spindle morphology were detected in the three groups to explore the rescue effect of MT on the mitochondria of BP-3-exposed mice. Results Compared to the control group， MT treatment markedly enhanced the transcription and protein levels of the mitochondrial fusion genes Mfn1 and Opa1 in oocytes， while concurrently down-regulating the mRNA and protein levels of the mitochondrial fission genes Fis1 and Drp1. Additionally， the BMT group exhibited significantly lower levels of ROS and abnormal spindle morphology in their oocytes compared to the BP-3 group， yet their mitochondrial membrane potential was notably elevated. Conclusion Physiological concentration of BP-3 exposure was toxic for reproduction， but the addition of appropriate concentrations of MT could significantly improve the mitochondrial dynamics and developmental potential of oocytes in BP-3-exposed mice.
Key words： melatonin; benophenone-3; mitochondrial dynamics; oocyte maturation
| 1 | ESHGHIFAR N， DEHGHAN B K， DO A A， et al. Infertility cell therapy and epigenetic insights［J］. Hum Antibodies，2021，29（1）： 17-26. doi:10.3233/hab-200438 |
| 2 | BLAKE B E， COPE H A， HALL S M， et al. Evaluation of Maternal， Embryo， and Placental Effects in CD-1 Mice following Gestational Exposure to Perfluorooctanoic Acid （PFOA） or Hexafluoropropylene Oxide Dimer Acid （HFPO-DA or GenX） ［J］. Environ Health Perspect， 2020，128（2）： 27006. doi:10.1289/ehp6233 |
| 3 | RICHARDSON S D， KIMURA S Y. Water Analysis： Emerging Contaminants and Current Issues［J］. Anal Chem，2020，92（1）： 473-505. doi:10.1021/acs.analchem.9b05269 |
| 4 | SADR N， QAYYUM R. Sunscreen compound benzophenone-3 and its relationship with white blood cell counts［J］. Skin Res Technol， 2024，30（5）： e13744. doi:10.1111/srt.13744 |
| 5 | JOVANOVIC N， MUSTIELES V， ALTHUSER M， et al. Associations between synthetic phenols， phthalates， and placental growth/function： a longitudinal cohort with exposure assessment in early pregnancy［J］. Hum Reprod Open， 2024，2024（2）： hoae018. doi:10.1093/hropen/hoae018 |
| 6 | ORTIZ-ROMáN MI， CASIANO-MU?IZ I M， ROMáN-VELáZQUEZ F R. Toxicity of UV Filter Benzophenone-3 in Brine Shrimp Nauplii （Artemia salina） and Zebrafish （Danio rerio） Embryos［J］. J Xenobiot， 2024，14（2）： 537-553. doi:10.3390/jox14020032 |
| 7 | MATTA M K， FLORIAN J， ZUSTERZEEL R， et al. Effect of Sunscreen Application on Plasma Concentration of Sunscreen Active Ingredients： A Randomized Clinical Trial［J］. JAMA， 2020， 323（3）： 256-267. doi:10.1001/jama.2019.20747 |
| 8 | 尹锦雯，朱海瑛，肖国宏.生理浓度二苯酮-3暴露对小鼠卵母细胞体外成熟及其质量的影响［J］.实用医学杂志， 2022，38（9）： 1051-1055. doi:10.3969/j.issn.1006-5725.2022.09.002 |
| 9 | JIN L， ZHU H Y， KANG X J， et al. Melatonin protects against oxybenzone-induced deterioration of mouse oocytes during maturation［J］. Aging （Albany NY）， 2020，13（2）： 2727-2749. doi:10.18632/aging.202323 |
| 10 | XU Y， ZHANG K H， SUN M H， et al. Protective Effects of Melatonin Against Zearalenone Toxicity on Porcine Embryos in vitro［J］. Front Pharmacol， 2019，10： 327. doi:10.3389/fphar.2019.00327 |
| 11 | WATANABE K， HATTORI A. Aging-induced memory loss due to decreased N1-acetyl-5-methoxykynuramine， a melatonin metabolite， in the hippocampus： a potential prophylactic agent for dementia［J］. Neural Regen Res， 2025， 20（6）：1705-1706. doi:10.4103/nrr.nrr-d-24-00379 |
| 12 | SAMIR H， NYAMETEASE P， ELBADAWY M， et al. Administration of melatonin improves testicular blood flow， circulating hormones， and semen quality in Shiba goats［J］. Theriogenology， 2020，146： 111-119. doi:10.1016/j.theriogenology.2020.01.053 |
| 13 | NIU Y J， ZHOU W， NIE Z W， et al. Melatonin enhances mitochondrial biogenesis and protects against rotenone-induced mitochondrial deficiency in early porcine embryos［J］. J Pineal Res， 2020，68（2）： e12627. doi:10.1111/jpi.12627 |
| 14 | YONG W， MA H， NA M， et al. Roles of melatonin in the field of reproductive medicine［J］. Biomed Pharmacother， 2021，144： 112001. doi:10.1016/j.biopha.2021.112001 |
| 15 | GAO S， HU J. Mitochondrial Fusion：The Machineries In and Out［J］. Trends Cell Biol， 2021，31（1）： 62-74. doi:10.1016/j.tcb.2020.09.008 |
| 16 | GIACOMELLO M， PYAKUREL A， GLYTSOU C， et al. The cell biology of mitochondrial membrane dynamics［J］. Nat Rev Mol Cell Biol， 2020， 21（4）： 204-224. doi:10.1038/s41580-020-0210-7 |
| 17 | GOGLIA I， W?GLARZ-TOMCZAK E， GIOIA C， et al. Fusion-fission-mitophagy cycling and metabolic reprogramming coordinate nerve growth factor （NGF）-dependent neuronal differentiation［J］. FEBS J， 2024， 291（13）：2811-2835. doi:10.1111/febs.17083 |
| 18 | CHAN D C. Mitochondrial Dynamics and Its Involvement in Disease［J］. Annu Rev Pathol， 2020，15： 235-259. doi:10.1146/annurev-pathmechdis-012419-032711 |
| 19 | LIU W J， LI L S， LAN M F， et al. Zinc deficiency deteriorates ovarian follicle development and function by inhibiting mitochondrial function［J］. J Ovarian Res， 2024，17（1）： 115. doi:10.1186/s13048-024-01442-z |
| 20 | NADRI P， ZAHMATKESH A， BAKHTARI A. The potential effect of melatonin on in vitro oocyte maturation and embryo development in animals［J］. Biol Reprod， 2024， 111（3）：529-542. doi:10.1093/biolre/ioae077 |
| 21 | DING M， FENG N， TANG D， et al. Melatonin prevents Drp1-mediated mitochondrial fission in diabetic hearts through SIRT1-PGC1α pathway［J］. J Pineal Res， 2018，65（2）： e12491. doi:10.1111/jpi.12491 |
| 22 | YONG W， MA H， NA M， et al. Roles of melatonin in the field of reproductive medicine［J］. Biomed Pharmacother， 2021，144： 112001. doi:10.1016/j.biopha.2021.112001 |
| 23 | 熊钰莹，史若锦，朱海瑛，等. 褪黑素提高二苯酮-3暴露小鼠早期胚胎体外发育潜能的研究［J］. 实用医学杂志， 2024， 40（7）： 904-909. |
| 24 | UTSUNOMIYA H， HIRAISHI R， KISHIMOTO K， et al.Cytotoxicity of benzophenone-3， an organic ultraviolet filter， caused by increased intracellular Zn2+ levels in rat thymocytes［J］. Chem Biol Interact， 2019，298： 52-56. doi:10.1016/j.cbi.2018.10.029 |
| 25 | ZHANG L， ZHANG Z， WANG J， et al. Melatonin regulates the activities of ovary and delays the fertility decline in female animals via MT1/AMPK pathway［J］. J Pineal Res，2019，66（3）： e12550. doi:10.1111/jpi.12550 |
| 26 | CHAKRABARTY R P， CHANDEL N S. Mitochondria as Signaling Organelles Control Mammalian Stem Cell Fate［J］. Cell Stem Cell， 2021，28（3）： 394-408. doi:10.1016/j.stem.2021.02.011 |
| 27 | PASQUARIELLO R， ERMISCH A F， SILVA E， et al. Alterations in oocyte mitochondrial number and function are related to spindle defects and occur with maternal aging in mice and humans?［J］. Biol Reprod， 2019，100（4）： 971-981. doi:10.1093/biolre/ioy248 |
| 28 | YILDIRIM R M， SELI E. The role of mitochondrial dynamics in oocyte and early embryo development［J］. Semin Cell Dev Biol， 2024，159-160： 52-61. doi:10.1016/j.semcdb.2024.01.007 |
| 29 | CHITIMUS D M， POPESCU M R， VOICULESCU S E， et al. Melatonin's Impact on Antioxidative and Anti-Inflammatory Reprogramming in Homeostasis and Disease［J］. Biomolecules， 2020，10（9）： 1211. doi:10.3390/biom10091211 |
| 30 | XING C H， WANG Y， LIU J C， et al. Melatonin reverses mitochondria dysfunction and oxidative stress-induced apoptosis of Sudan I-exposed mouse oocytes［J］. Ecotoxicol Environ Saf， 2021，225： 112783. doi:10.1016/j.ecoenv.2021.112783 |
| 31 | LEI X， XU Z， HUANG L， et al. The potential influence of melatonin on mitochondrial quality control： a review［J］. Front Pharmacol， 2024， 14：1332567. doi:10.3389/fphar.2023.1332567 |
| 32 | SALAGRE D， RAYA áLVAREZ E， CENDAN C M， et al. Melatonin Improves Skeletal Muscle Structure and Oxidative Phenotype by Regulating Mitochondrial Dynamics and Autophagy in Zücker Diabetic Fatty Rat［J］. Antioxidants （Basel）， 2023， 12（8）：1499. doi:10.3390/antiox12081499 |
| 33 | LIU W J， LI L S， LAN M F， et al. Zinc deficiency deteriorates ovarian follicle development and function by inhibiting mitochondrial function［J］. J Ovarian Res， 2024，17（1）： 115. doi:10.1186/s13048-024-01442-z |
| 34 | MEI N H， GUO S M， ZHOU Q， et al. H3K4 Methylation Promotes Expression of Mitochondrial Dynamics Regulators to Ensure Oocyte Quality in Mice［J］. Adv Sci （Weinh）， 2023，10（12）： e2204794. doi:10.1002/advs.202204794 |
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