Transferrin overexpression alters testicular function in aged mice.
Many studies have shown a correlation between transferrin (Tf) concentration and sperm yield in several mammalian species. We have used transgenic mice expressing human Tf (hTf) to investigate if overexpression of Tf increases the efficiency of mouse spermatogenesis. We demonstrated that a 36% increase of Tf does not ameliorate the efficiency of mouse spermatogenesis but on the contrary resulted in a 36% decrease of testis sperm reserves. Tf overexpression had no effect on testicular determination and development, however testicular function of these transgenic mice was affected in an age-dependent manner. At 16 months of age, testicular and epididymal weights were significantly reduced. While spermatogenesis was qualitatively normal, testicular functions were perturbed. In fact, testosterone rate after human chorionic gonadotropin (hCG) stimulation was lower in Tf overexpressing mice. Intratesticular concentration of estradiol-17beta was increased and fluid accumulation after ligation of rete testis was more abundant in these transgenic mice. Surprisingly, we found that endogenous Tf levels were also increased in Tf overexpressing mice and we demonstrated for the first time that Tf may serve to upregulate its own expression in testis. Collectively, our data show that Tf overexpression has negative effects on testicular function and that Tf levels require strict regulation in the testis.
Lécureuil
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UMR 6175 Institut National de la Recherche Agronomique, Centre National de Recherche Scientifique, Université de Tours, Haras Nationaux Physiologie de la Reproduction et des Comportements, Nouzilly, France.
Staub
C
C
Fouchécourt
S
S
Maurel
M C
MC
Fontaine
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I
Martinat
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N
Gauthier
C
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Daudignon
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A
Delaleu
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Sow
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A
Jégou
B
B
Guillou
F
F
D000818:Animals; D003433:Crosses, Genetic; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D005786:Gene Expression Regulation; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010902:Pituitary Gland / Q000378:metabolism; D012098:Reproduction / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology; D013737:Testis / Q000187:drug effects / Q000254:growth & development / Q000502:physiology*; D013739:Testosterone / Q000378:metabolism; D014168:Transferrin / Q000235:genetics* / Q000494:pharmacology / Q000502:physiology
D014168:Transferrin; D013739:Testosterone; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone