Rescue of fertility in homozygous mice for the urokinase plasminogen activator transgene by the transplantation of mouse hepatocytes.
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.
Brezillon
Nicolas M
NM
INSERM, U845, 75015 Paris, France.
DaSilva
Lucie
L
L'Hôte
David
D
Bernex
Florence
F
Piquet
Julie
J
Binart
Nadine
N
Morosan
Serban
S
Kremsdorf
Dina
D
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
D014568:Urokinase-Type Plasminogen Activator