Connexin-43 is a promising target for lycopene preventing phthalate-induced spermatogenic disorders
Introduction: Male infertility is a multifactorial pathological condition and may be a harbinger of future health. Phthalates are ubiquitous environmental contaminants that have been implicated in the global decline in male fertility. Among them, di-(2-ethylhexyl) phthalate (DEHP) is the most preval...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-07-01
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| Series: | Journal of Advanced Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S209012322200203X |
| _version_ | 1827913839156396032 |
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| author | Yi Zhao Ming-Shan Chen Jia-Xin Wang Jia-Gen Cui Hao Zhang Xue-Nan Li Jin-Long Li |
| author_facet | Yi Zhao Ming-Shan Chen Jia-Xin Wang Jia-Gen Cui Hao Zhang Xue-Nan Li Jin-Long Li |
| author_sort | Yi Zhao |
| collection | DOAJ |
| description | Introduction: Male infertility is a multifactorial pathological condition and may be a harbinger of future health. Phthalates are ubiquitous environmental contaminants that have been implicated in the global decline in male fertility. Among them, di-(2-ethylhexyl) phthalate (DEHP) is the most prevalently used. Lycopene (LYC) is a possible preventive and therapeutic agent for male infertility owing to its antioxidant properties. The blood-testis barrier (BTB) is formed between Sertoli cells where it creates a unique microenvironment for spermatogenesis. Objectives: We hypothesize that phthalate caused male infertility and LYC plays an important role in phthalate-induced male fertility disorders. Methods: Hematoxylin-eosin (H&E) staining, ultrastructure observation, and fluorescence microscopy were used to examine the morphological changes. RNA-Seq, and western blotting were conducted to detect gene and protein levels. Routine testing for sperm morphology and sperm-egg binding assay were conducted to examine the morphological structure and function of sperm. Cell scratch assay and transepithelial electrical resistance (TER) were used to detect cell migration capacity and barrier integrity. Results: In vivo experiments, we showed that LYC prevented DEHP-induced impairment of BTB integrity, which provided a guarantee for the smooth progress of spermatogenesis. LYC improved DEHP-induced change in sperm parameters and fertilization ability. Subsequent in vitro experiments, LYC alleviated MEHP-induced disruption of intercellular junctions in mouse Spermatogonia cells (GC-1 cells) and mouse Sertoli cells (TM4 cells). In MEHP-induced BTB impairment models of Sertoli cells, treatment with LYC or overexpressing connexin-43 (Cx43) promoted cell migration capacity and normalized BTB integrity. Cx43 knockdown inhibited cell migration capacity and perturbed BTB reassembly in LYC preventing DEHP-induced BTB impairment. Conclusion: Our study provides evidence for the role of LYC in phthalates-induced spermatogenic disorders and points to Cx43 as a potential target for male fertility. |
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| format | Article |
| id | doaj.art-c09d9f3f33ed4a2d84f003bb60de3a94 |
| institution | Directory Open Access Journal |
| issn | 2090-1232 |
| language | English |
| last_indexed | 2024-03-13T02:36:39Z |
| publishDate | 2023-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Advanced Research |
| spelling | doaj.art-c09d9f3f33ed4a2d84f003bb60de3a942023-06-29T04:14:14ZengElsevierJournal of Advanced Research2090-12322023-07-0149115126Connexin-43 is a promising target for lycopene preventing phthalate-induced spermatogenic disordersYi Zhao0Ming-Shan Chen1Jia-Xin Wang2Jia-Gen Cui3Hao Zhang4Xue-Nan Li5Jin-Long Li6College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, P.R. China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, P.R. ChinaCollege of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. China; Key Laboratory of the Provincial Education Department of Heilongjiang for Common Animal Disease Prevention and Treatment, Northeast Agricultural University, Harbin 150030, P.R. China; Heilongjiang Key Laboratory for Laboratory Animals and Comparative Medicine, Northeast Agricultural University, Harbin 150030, P.R. China; Corresponding author at: College of Veterinary Medicine, Northeast Agricultural University, Harbin 150030, P.R. China. Tel.: +86 451 55190407; fax: +86 451 55190407.Introduction: Male infertility is a multifactorial pathological condition and may be a harbinger of future health. Phthalates are ubiquitous environmental contaminants that have been implicated in the global decline in male fertility. Among them, di-(2-ethylhexyl) phthalate (DEHP) is the most prevalently used. Lycopene (LYC) is a possible preventive and therapeutic agent for male infertility owing to its antioxidant properties. The blood-testis barrier (BTB) is formed between Sertoli cells where it creates a unique microenvironment for spermatogenesis. Objectives: We hypothesize that phthalate caused male infertility and LYC plays an important role in phthalate-induced male fertility disorders. Methods: Hematoxylin-eosin (H&E) staining, ultrastructure observation, and fluorescence microscopy were used to examine the morphological changes. RNA-Seq, and western blotting were conducted to detect gene and protein levels. Routine testing for sperm morphology and sperm-egg binding assay were conducted to examine the morphological structure and function of sperm. Cell scratch assay and transepithelial electrical resistance (TER) were used to detect cell migration capacity and barrier integrity. Results: In vivo experiments, we showed that LYC prevented DEHP-induced impairment of BTB integrity, which provided a guarantee for the smooth progress of spermatogenesis. LYC improved DEHP-induced change in sperm parameters and fertilization ability. Subsequent in vitro experiments, LYC alleviated MEHP-induced disruption of intercellular junctions in mouse Spermatogonia cells (GC-1 cells) and mouse Sertoli cells (TM4 cells). In MEHP-induced BTB impairment models of Sertoli cells, treatment with LYC or overexpressing connexin-43 (Cx43) promoted cell migration capacity and normalized BTB integrity. Cx43 knockdown inhibited cell migration capacity and perturbed BTB reassembly in LYC preventing DEHP-induced BTB impairment. Conclusion: Our study provides evidence for the role of LYC in phthalates-induced spermatogenic disorders and points to Cx43 as a potential target for male fertility.http://www.sciencedirect.com/science/article/pii/S209012322200203XLycopeneDi (2-ethylhexyl) phthalateConnexin-43Blood-testis barrierSpermatogenic disorders |
| spellingShingle | Yi Zhao Ming-Shan Chen Jia-Xin Wang Jia-Gen Cui Hao Zhang Xue-Nan Li Jin-Long Li Connexin-43 is a promising target for lycopene preventing phthalate-induced spermatogenic disorders Journal of Advanced Research Lycopene Di (2-ethylhexyl) phthalate Connexin-43 Blood-testis barrier Spermatogenic disorders |
| title | Connexin-43 is a promising target for lycopene preventing phthalate-induced spermatogenic disorders |
| title_full | Connexin-43 is a promising target for lycopene preventing phthalate-induced spermatogenic disorders |
| title_fullStr | Connexin-43 is a promising target for lycopene preventing phthalate-induced spermatogenic disorders |
| title_full_unstemmed | Connexin-43 is a promising target for lycopene preventing phthalate-induced spermatogenic disorders |
| title_short | Connexin-43 is a promising target for lycopene preventing phthalate-induced spermatogenic disorders |
| title_sort | connexin 43 is a promising target for lycopene preventing phthalate induced spermatogenic disorders |
| topic | Lycopene Di (2-ethylhexyl) phthalate Connexin-43 Blood-testis barrier Spermatogenic disorders |
| url | http://www.sciencedirect.com/science/article/pii/S209012322200203X |
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