Impaired female fertility in tubulointerstitial antigen-like 1-deficient mice

Tubulointerstitial nephritis antigen-like 1 (Tinagl1, also known as adrenocortical zonation factor 1 [AZ-1]or lipocalin 7) is a matricellular protein. Previously, we demonstrated that Tinagl1 expression was restrictedto extraembryonic regions during the postimplantation period and detected marked expression in mouseReichert’s membranes. In uteri, Tinagl1 is markedly expressed in the decidual endometrium during thepostimplantation period, suggesting that it plays a physical and physiological role in embryo developmentand/or decidualization of the uterine endometrium during pregnancy. In the present study, in order todetermine the role of Tinagl1 during embryonic development and pregnancy, we generatedTinagl1-deficient mice. Although Tinagl1^–/– embryos were notlethal during development to term, homologous matings of Tinagl1^–/– females andTinagl1^–/– males showed impaired fertility during pregnancy, including failureto carry pregnancy to term and perinatal lethality. To examine ovarian function, ovulation was induced withequine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG); the number of ovulated oocytes didnot differ between Tinagl1^–/– and Tinagl1^flox/flox.In vitro fertilization followed by embryo culture also demonstrated the normaldevelopmental potential of Tinagl1-null embryos during the preimplantation period. Ourresults demonstrate that Tinagl1 deficiency affects female mice and results in subfertility phenotypes, andthey suggest that although the potential of Tinagl1^–/– oocytes is normal, Tinagl1is related to fertility in adult females but is not essential for either fertilization or preimplantationdevelopment in vitro.