NAD+ precursors mitigate the in vitro and in vivo reproductive defects: Limitations and possible solutions

IF 2.8 4区 医学 Q2 REPRODUCTIVE BIOLOGY
Nazli Pinar Arslan , Zuleyha Akpinar , Havva Aybek , Meryem Doymus , Gulsum Asilkan-Kaldik , Nevzat Esim , Mesut Taskin
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Abstract

In mammalian cells, nicotinamide adenine dinucleotide (NAD+) participates in the regulation of diverse cellular processes such as ATP production, oxidative stress resistance, DNA repair, metabolic homeostasis, and inflammation. Due to these properties, exogenously applied NAD+ precursors (nicotinic acid, nicotinamide, nicotinamide riboside, and nicotinamide mononucleotide) can protect organs and cells of mammalian against detrimental effects of various stress factors and diseases. For instance, NAD+ and its precursors have critical importance for the in vivo and in vitro fertilization success of mammals. This review summarizes that the natural aging process, diseases, and toxic compounds cause the detrimental effects in the reproductive parameters of the in vivo models, such as the meiotic defects and the reductions in cellular NAD+ level, mitochondrial functions, sperm and oocyte quality, blastocyst and embryo formation rate, implantation success, whereas the intragastric, intraperitoneal or oral administration of NAD+ precursors prevents or attenuates these detrimental effects. Similarly, the supplementation of NAD+ precursors can protect the oocytes and sperms against the cryopreservation process, aging and toxic compounds in the in vitro and also enhances blastocyst and embryo formation in vitro. This review study also revealed that the ability of NAD+ precursors-loaded drug delivery systems to prevent reproductive defects has not yet been investigated in literature. Therefore, we recommend the development of NAD+ precursor-loaded drug delivery systems targeting reproductive system organs and/or cell organelles (mitochondria, endoplasmic reticulum and nucleus). To achieve this, hormone receptors in testicular and ovarian cells can be targeted. Similarly, triphenylphosphonium (TPP+) can be used to specifically target mitochondria.
NAD+前体减轻体外和体内生殖缺陷:局限性和可能的解决方案
在哺乳动物细胞中,烟酰胺腺嘌呤二核苷酸(NAD+)参与多种细胞过程的调节,如ATP产生、氧化应激抵抗、DNA修复、代谢稳态和炎症。由于这些特性,外源应用NAD+前体(烟酸、烟酰胺、烟酰胺核苷和烟酰胺单核苷酸)可以保护哺乳动物的器官和细胞免受各种应激因素和疾病的有害影响。例如,NAD+及其前体对哺乳动物体内和体外受精的成功至关重要。本文综述了自然衰老过程、疾病和有毒化合物对体内模型生殖参数的不利影响,如减数分裂缺陷、细胞NAD+水平降低、线粒体功能降低、精子和卵母细胞质量降低、囊胚和胚胎形成率降低、着床成功率降低等,而灌胃、腹腔或口服NAD+前体可预防或减轻这些不利影响。同样,在体外,补充NAD+前体可以保护卵母细胞和精子免受低温保存过程、老化和有毒化合物的影响,并促进体外囊胚和胚胎的形成。本综述还发现,NAD+前体载药系统预防生殖缺陷的能力尚未见文献报道。因此,我们建议开发针对生殖系统器官和/或细胞器(线粒体、内质网和细胞核)的装载NAD+前体的药物递送系统。为了实现这一目标,睾丸和卵巢细胞中的激素受体可以成为目标。类似地,三苯基膦(TPP+)也可用于特异性靶向线粒体。
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来源期刊
Reproductive toxicology
Reproductive toxicology 生物-毒理学
CiteScore
6.50
自引率
3.00%
发文量
131
审稿时长
45 days
期刊介绍: Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.
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