Male reproductive phenotype alterations in heterozygous β-globin gene knockout thalassemia (BKO) mice as a model for β-thalassemia patients
Abstract Heterozygous β-globin gene knockout thalassemia (BKO) mice derived from C57BL/6 wild-type (WT) mice have phenotypic of β-thalassemia (BT) and have been widely used for studying this disease except reproductive disorders. The present study determined whether male BKO mice recapitulate reprod...
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Nature Portfolio
2025-02-01
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| Series: | Scientific Reports |
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| Online Access: | https://doi.org/10.1038/s41598-025-87619-y |
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| author | Suparada Aiemongkot Sukanya Ruschadaariyachat Chinarat Changsangfa Khanita Nuamsee Kittikun Viwatpinyo Pornthip Chaichompoo Saovaros Svasti Kakanang Buranaamnuay |
| author_facet | Suparada Aiemongkot Sukanya Ruschadaariyachat Chinarat Changsangfa Khanita Nuamsee Kittikun Viwatpinyo Pornthip Chaichompoo Saovaros Svasti Kakanang Buranaamnuay |
| author_sort | Suparada Aiemongkot |
| collection | DOAJ |
| description | Abstract Heterozygous β-globin gene knockout thalassemia (BKO) mice derived from C57BL/6 wild-type (WT) mice have phenotypic of β-thalassemia (BT) and have been widely used for studying this disease except reproductive disorders. The present study determined whether male BKO mice recapitulate reproductive problems as BT men. Mice were randomly assigned into groups depending on the genotype (WT vs. BKO) and intervention (control vs. iron-loaded). Euthanized mice were collected blood, testes, epididymides, hypothalamus, and anterior pituitary for assessing hematological parameters, plasma iron and testosterone levels, testis iron levels, sperm characteristics, and histological alterations. Iron administration caused significant increases of plasma and testis iron levels (p < 0.001) but had no significant influence on the hematological profile of BKO mice, which indeed had fewer erythrocyte, hemoglobin, and hematocrit but had greater reticulocyte than WT (p < 0.001 to p = 0.017). Furthermore, irrespective of the genotype, iron administration decreased plasma testosterone levels (p = 0.03 to p > 0.05), total sperm count (p < 0.001), and percent normal sperm morphology (p ≤ 0.01). Based on Perls’ Prussian blue staining, excess iron was ubiquitously present in the anterior pituitary and testicular interstitium of iron-loaded mice. This mineral, however, caused no significant changes in reproductive organs microstructure as visualized by hematoxylin and eosin staining. In conclusion, besides physiological dysfunction of many organ systems, iron-loaded male BKO mice exhibit reproductive problems and abnormal sperm characteristics similar to BT men. Therefore, this animal model seems invaluable for future biomedical research involved in various aspects of BT-related male reproductive disorders. |
| first_indexed | 2025-03-17T01:42:23Z |
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| issn | 2045-2322 |
| language | English |
| last_indexed | 2025-03-17T01:42:23Z |
| publishDate | 2025-02-01 |
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| series | Scientific Reports |
| spelling | doaj.art-a29f7a5aca5545d988bc8349d9638bb62025-02-16T12:25:05ZengNature PortfolioScientific Reports2045-23222025-02-0115111410.1038/s41598-025-87619-yMale reproductive phenotype alterations in heterozygous β-globin gene knockout thalassemia (BKO) mice as a model for β-thalassemia patientsSuparada Aiemongkot0Sukanya Ruschadaariyachat1Chinarat Changsangfa2Khanita Nuamsee3Kittikun Viwatpinyo4Pornthip Chaichompoo5Saovaros Svasti6Kakanang Buranaamnuay7Thalassemia Research Center, Institute of Molecular Biosciences, Mahidol UniversityOffice of Research and Innovation Affair, Institute of Molecular Biosciences, Mahidol UniversityOffice of Research and Innovation Affair, Institute of Molecular Biosciences, Mahidol UniversityThalassemia Research Center, Institute of Molecular Biosciences, Mahidol UniversityDapartment of Medical Science, School of Medicine, Walailak UniversityDepartment of Pathobiology, Faculty of Science, Mahidol UniversityThalassemia Research Center, Institute of Molecular Biosciences, Mahidol UniversityMolecular Biosciences Cluster, Institute of Molecular Biosciences, Mahidol UniversityAbstract Heterozygous β-globin gene knockout thalassemia (BKO) mice derived from C57BL/6 wild-type (WT) mice have phenotypic of β-thalassemia (BT) and have been widely used for studying this disease except reproductive disorders. The present study determined whether male BKO mice recapitulate reproductive problems as BT men. Mice were randomly assigned into groups depending on the genotype (WT vs. BKO) and intervention (control vs. iron-loaded). Euthanized mice were collected blood, testes, epididymides, hypothalamus, and anterior pituitary for assessing hematological parameters, plasma iron and testosterone levels, testis iron levels, sperm characteristics, and histological alterations. Iron administration caused significant increases of plasma and testis iron levels (p < 0.001) but had no significant influence on the hematological profile of BKO mice, which indeed had fewer erythrocyte, hemoglobin, and hematocrit but had greater reticulocyte than WT (p < 0.001 to p = 0.017). Furthermore, irrespective of the genotype, iron administration decreased plasma testosterone levels (p = 0.03 to p > 0.05), total sperm count (p < 0.001), and percent normal sperm morphology (p ≤ 0.01). Based on Perls’ Prussian blue staining, excess iron was ubiquitously present in the anterior pituitary and testicular interstitium of iron-loaded mice. This mineral, however, caused no significant changes in reproductive organs microstructure as visualized by hematoxylin and eosin staining. In conclusion, besides physiological dysfunction of many organ systems, iron-loaded male BKO mice exhibit reproductive problems and abnormal sperm characteristics similar to BT men. Therefore, this animal model seems invaluable for future biomedical research involved in various aspects of BT-related male reproductive disorders.https://doi.org/10.1038/s41598-025-87619-yβ-thalassemiaHypogonadismIron overloadMouseTesticular histologySperm characteristics |
| spellingShingle | Suparada Aiemongkot Sukanya Ruschadaariyachat Chinarat Changsangfa Khanita Nuamsee Kittikun Viwatpinyo Pornthip Chaichompoo Saovaros Svasti Kakanang Buranaamnuay Male reproductive phenotype alterations in heterozygous β-globin gene knockout thalassemia (BKO) mice as a model for β-thalassemia patients Scientific Reports β-thalassemia Hypogonadism Iron overload Mouse Testicular histology Sperm characteristics |
| title | Male reproductive phenotype alterations in heterozygous β-globin gene knockout thalassemia (BKO) mice as a model for β-thalassemia patients |
| title_full | Male reproductive phenotype alterations in heterozygous β-globin gene knockout thalassemia (BKO) mice as a model for β-thalassemia patients |
| title_fullStr | Male reproductive phenotype alterations in heterozygous β-globin gene knockout thalassemia (BKO) mice as a model for β-thalassemia patients |
| title_full_unstemmed | Male reproductive phenotype alterations in heterozygous β-globin gene knockout thalassemia (BKO) mice as a model for β-thalassemia patients |
| title_short | Male reproductive phenotype alterations in heterozygous β-globin gene knockout thalassemia (BKO) mice as a model for β-thalassemia patients |
| title_sort | male reproductive phenotype alterations in heterozygous β globin gene knockout thalassemia bko mice as a model for β thalassemia patients |
| topic | β-thalassemia Hypogonadism Iron overload Mouse Testicular histology Sperm characteristics |
| url | https://doi.org/10.1038/s41598-025-87619-y |
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