{"title":"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","authors":"Nazli Pinar Arslan , Zuleyha Akpinar , Havva Aybek , Meryem Doymus , Gulsum Asilkan-Kaldik , Nevzat Esim , Mesut Taskin","doi":"10.1016/j.reprotox.2025.109067","DOIUrl":null,"url":null,"abstract":"<div><div>In mammalian cells, nicotinamide adenine dinucleotide (NAD<sup>+</sup>) 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<sup>+</sup> 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<sup>+</sup> and its precursors have critical importance for the <em>in vivo</em> and <em>in vitro</em> 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 <em>in vivo</em> models, such as the meiotic defects and the reductions in cellular NAD<sup>+</sup> level, mitochondrial functions, sperm and oocyte quality, blastocyst and embryo formation rate, implantation success, whereas the intragastric, intraperitoneal or oral administration of NAD<sup>+</sup> precursors prevents or attenuates these detrimental effects. Similarly, the supplementation of NAD<sup>+</sup> precursors can protect the oocytes and sperms against the cryopreservation process, aging and toxic compounds in the <em>in vitro</em> and also enhances blastocyst and embryo formation <em>in vitro</em>. This review study also revealed that the ability of NAD<sup>+</sup> precursors-loaded drug delivery systems to prevent reproductive defects has not yet been investigated in literature. Therefore, we recommend the development of NAD<sup>+</sup> 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<sup>+</sup>) can be used to specifically target mitochondria.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"138 ","pages":"Article 109067"},"PeriodicalIF":2.8000,"publicationDate":"2025-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"NAD+ precursors mitigate the in vitro and in vivo reproductive defects: Limitations and possible solutions\",\"authors\":\"Nazli Pinar Arslan , Zuleyha Akpinar , Havva Aybek , Meryem Doymus , Gulsum Asilkan-Kaldik , Nevzat Esim , Mesut Taskin\",\"doi\":\"10.1016/j.reprotox.2025.109067\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>In mammalian cells, nicotinamide adenine dinucleotide (NAD<sup>+</sup>) 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<sup>+</sup> 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<sup>+</sup> and its precursors have critical importance for the <em>in vivo</em> and <em>in vitro</em> 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 <em>in vivo</em> models, such as the meiotic defects and the reductions in cellular NAD<sup>+</sup> level, mitochondrial functions, sperm and oocyte quality, blastocyst and embryo formation rate, implantation success, whereas the intragastric, intraperitoneal or oral administration of NAD<sup>+</sup> precursors prevents or attenuates these detrimental effects. Similarly, the supplementation of NAD<sup>+</sup> precursors can protect the oocytes and sperms against the cryopreservation process, aging and toxic compounds in the <em>in vitro</em> and also enhances blastocyst and embryo formation <em>in vitro</em>. This review study also revealed that the ability of NAD<sup>+</sup> precursors-loaded drug delivery systems to prevent reproductive defects has not yet been investigated in literature. Therefore, we recommend the development of NAD<sup>+</sup> 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<sup>+</sup>) can be used to specifically target mitochondria.</div></div>\",\"PeriodicalId\":21137,\"journal\":{\"name\":\"Reproductive toxicology\",\"volume\":\"138 \",\"pages\":\"Article 109067\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-09-19\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Reproductive toxicology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0890623825002382\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"REPRODUCTIVE BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Reproductive toxicology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0890623825002382","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
NAD+ precursors mitigate the in vitro and in vivo reproductive defects: Limitations and possible solutions
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.
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.