title: Rescue of fertility in homozygous mice for the urokinase plasminogen activator transgene by the transplantation of mouse hepatocytes.
abstract: Development of the urokinase plasminogen activator/SCID (uPA/SCID) transgenic mouse model has opened new perspectives for the study of different biological mechanisms such as liver regeneration, stem cell differentiation, and human hepatic pathogens. We observed that homozygous uPA/SCID mice (uPA+/+/SCID) had a small offspring, indicating a fertility defect. The goal of this study was thus to rescue the fertility of homozygous uPA mice. A deregulation of ovarian function with an absence of corpus luteum was observed in female uPA+/+/SCID mice. In male uPA+/+/SCID mice, a decrease of the weight of the testes, epididymis, seminal vesicle, and prostate was measured. This was associated with an absence of seminal and prostatic secretions and a reduction in testicular sperm production. We hypothesized that the infertility of mice was the consequence of uPA-induced liver injury. Thus, in order to rescue liver function, hepatocytes from mice negative for the uPA transgene were transplanted into uPA+/+/SCID mice. Thirty days after cell transplantation, the livers of transplanted uPA+/+/SCID mice were totally repopulated and presented a normal morphology. Furthermore, transplantation restored normal body weight, life span, and reproductive organ function. In conclusion, we demonstrated that the transplantation of uPA+/+/SCID mice with healthy hepatocytes was sufficient to rescue the reproductive capacity of female and male uPA homozygous animals, highlighting the importance of normal liver function to reproductive capability.
authors.affiliation: INSERM, U845, 75015 Paris, France.
authors.forename: Nicolas M
authors.initials: NM
authors.lastname: Brezillon
authors.forename: Lucie
authors.initials: L
authors.lastname: DaSilva
authors.forename: David
authors.initials: D
authors.lastname: L'Hôte
authors.forename: Florence
authors.initials: F
authors.lastname: Bernex
authors.forename: Julie
authors.initials: J
authors.lastname: Piquet
authors.forename: Nadine
authors.initials: N
authors.lastname: Binart
authors.forename: Serban
authors.initials: S
authors.lastname: Morosan
authors.forename: Dina
authors.initials: D
authors.lastname: Kremsdorf
mesh_terms: D000818:Animals; D001835:Body Weight; D005260:Female; D005835:Genitalia / Q000033:anatomy & histology / Q000473:pathology; D022781:Hepatocytes / Q000502:physiology / Q000637:transplantation*; D006801:Humans; D007246:Infertility / Q000628:therapy*; D008099:Liver / Q000473:pathology / Q000502:physiology; D008115:Liver Regeneration / Q000502:physiology; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008822:Mice, Transgenic; D019076:Transgenes; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
chemical_list: D014568:Urokinase-Type Plasminogen Activator