{"title":"脂多糖诱导炎症对小鼠睾丸kisspeptin系统的调节作用","authors":"Jaldhi , Shweta , Shashank Kumar Maurya , Amrita Bakshi","doi":"10.1016/j.reprotox.2025.109005","DOIUrl":null,"url":null,"abstract":"<div><div>Kisspeptin, a neuropeptide hormone, plays an indispensable role in regulating reproduction. Acting upstream of gonadotropin-releasing hormone, it controls gonadotropin release, and concomitant gonadal functions, and in turn, is regulated by gonadal steroid hormones. Nevertheless, expression of kisspeptin (Kiss1) and its receptor (Kiss1r) is reported in tissues other than hypothalamus, including testes. Since immune-challenged conditions lead to compromised reproductive functions, the present work emphasizes on investigating regulation of the testicular kisspeptin system in adult mice by lipopolysaccharide (LPS)-induced inflammation. <em>In vivo</em> chronic treatment of LPS for 7 days caused irregularly-shaped seminiferous tubules with reduced perimeter, diameter and cross-sectional area, distorted arrangement of spermatogenic cells, disrupted connective tissue leading to increased interstitial space and reduced sperm count. Further, elevated expression level of pro-inflammatory cytokine, <em>Tnfα,</em> in the testis validated the induction of inflammation. Regarding the kisspeptin system, a significant increase in testicular Kiss1 but a decrease in Kiss1r expression was observed at both gene and protein levels, implying a possible compensatory role of testicular kisspeptin to control reproductive functions under an infectious state. Further, an <em>in vitro</em> treatment of testicular fragments with LPS was conducted for 3 h and 6 h to understand the direct effect of inflammation on the testicular kisspeptin system. An increased <em>Tnfα</em> but decreased <em>Tgfβ1</em> expression was observed at both time points. At the transcript level, <em>Kiss1</em> showed a reduced expression at 6 h but no change at 3 h of LPS treatment. Regarding <em>Kiss1r</em>, an increased expression at 3 h but decreased at 6 h was seen. At the protein level, decreased levels of testicular Kiss1 was observed at both the time points while Kiss1r exhibited no significant change. Hence, the present work demonstrated modulation of the testicular kisspeptin system by LPS-induced inflammation.</div></div>","PeriodicalId":21137,"journal":{"name":"Reproductive toxicology","volume":"137 ","pages":"Article 109005"},"PeriodicalIF":2.8000,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Lipopolysaccharide-induced inflammation modulates testicular kisspeptin system in mice\",\"authors\":\"Jaldhi , Shweta , Shashank Kumar Maurya , Amrita Bakshi\",\"doi\":\"10.1016/j.reprotox.2025.109005\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Kisspeptin, a neuropeptide hormone, plays an indispensable role in regulating reproduction. Acting upstream of gonadotropin-releasing hormone, it controls gonadotropin release, and concomitant gonadal functions, and in turn, is regulated by gonadal steroid hormones. Nevertheless, expression of kisspeptin (Kiss1) and its receptor (Kiss1r) is reported in tissues other than hypothalamus, including testes. Since immune-challenged conditions lead to compromised reproductive functions, the present work emphasizes on investigating regulation of the testicular kisspeptin system in adult mice by lipopolysaccharide (LPS)-induced inflammation. <em>In vivo</em> chronic treatment of LPS for 7 days caused irregularly-shaped seminiferous tubules with reduced perimeter, diameter and cross-sectional area, distorted arrangement of spermatogenic cells, disrupted connective tissue leading to increased interstitial space and reduced sperm count. Further, elevated expression level of pro-inflammatory cytokine, <em>Tnfα,</em> in the testis validated the induction of inflammation. Regarding the kisspeptin system, a significant increase in testicular Kiss1 but a decrease in Kiss1r expression was observed at both gene and protein levels, implying a possible compensatory role of testicular kisspeptin to control reproductive functions under an infectious state. Further, an <em>in vitro</em> treatment of testicular fragments with LPS was conducted for 3 h and 6 h to understand the direct effect of inflammation on the testicular kisspeptin system. An increased <em>Tnfα</em> but decreased <em>Tgfβ1</em> expression was observed at both time points. At the transcript level, <em>Kiss1</em> showed a reduced expression at 6 h but no change at 3 h of LPS treatment. Regarding <em>Kiss1r</em>, an increased expression at 3 h but decreased at 6 h was seen. At the protein level, decreased levels of testicular Kiss1 was observed at both the time points while Kiss1r exhibited no significant change. Hence, the present work demonstrated modulation of the testicular kisspeptin system by LPS-induced inflammation.</div></div>\",\"PeriodicalId\":21137,\"journal\":{\"name\":\"Reproductive toxicology\",\"volume\":\"137 \",\"pages\":\"Article 109005\"},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2025-07-22\",\"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/S0890623825001765\",\"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/S0890623825001765","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
Lipopolysaccharide-induced inflammation modulates testicular kisspeptin system in mice
Kisspeptin, a neuropeptide hormone, plays an indispensable role in regulating reproduction. Acting upstream of gonadotropin-releasing hormone, it controls gonadotropin release, and concomitant gonadal functions, and in turn, is regulated by gonadal steroid hormones. Nevertheless, expression of kisspeptin (Kiss1) and its receptor (Kiss1r) is reported in tissues other than hypothalamus, including testes. Since immune-challenged conditions lead to compromised reproductive functions, the present work emphasizes on investigating regulation of the testicular kisspeptin system in adult mice by lipopolysaccharide (LPS)-induced inflammation. In vivo chronic treatment of LPS for 7 days caused irregularly-shaped seminiferous tubules with reduced perimeter, diameter and cross-sectional area, distorted arrangement of spermatogenic cells, disrupted connective tissue leading to increased interstitial space and reduced sperm count. Further, elevated expression level of pro-inflammatory cytokine, Tnfα, in the testis validated the induction of inflammation. Regarding the kisspeptin system, a significant increase in testicular Kiss1 but a decrease in Kiss1r expression was observed at both gene and protein levels, implying a possible compensatory role of testicular kisspeptin to control reproductive functions under an infectious state. Further, an in vitro treatment of testicular fragments with LPS was conducted for 3 h and 6 h to understand the direct effect of inflammation on the testicular kisspeptin system. An increased Tnfα but decreased Tgfβ1 expression was observed at both time points. At the transcript level, Kiss1 showed a reduced expression at 6 h but no change at 3 h of LPS treatment. Regarding Kiss1r, an increased expression at 3 h but decreased at 6 h was seen. At the protein level, decreased levels of testicular Kiss1 was observed at both the time points while Kiss1r exhibited no significant change. Hence, the present work demonstrated modulation of the testicular kisspeptin system by LPS-induced inflammation.
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.