title: Impaired female fertility in tubulointerstitial antigen-like 1-deficient mice.
abstract: 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 restricted to extraembryonic regions during the postimplantation period and detected marked expression in mouse Reichert's membranes. In uteri, Tinagl1 is markedly expressed in the decidual endometrium during the postimplantation period, suggesting that it plays a physical and physiological role in embryo development and/or decidualization of the uterine endometrium during pregnancy. In the present study, in order to determine the role of Tinagl1 during embryonic development and pregnancy, we generated Tinagl1-deficient mice. Although Tinagl1(-/-) embryos were not lethal during development to term, homologous matings of Tinagl1(-/-) females and Tinagl1(-/-) males showed impaired fertility during pregnancy, including failure to carry pregnancy to term and perinatal lethality. To examine ovarian function, ovulation was induced with equine chorionic gonadotropin (eCG) and human chorionic gonadotropin (hCG); the number of ovulated oocytes did not differ between Tinagl1(-/-) and Tinagl1(flox/flox). In vitro fertilization followed by embryo culture also demonstrated the normal developmental potential of Tinagl1-null embryos during the preimplantation period. Our results demonstrate that Tinagl1 deficiency affects female mice and results in subfertility phenotypes, and they suggest that although the potential of Tinagl1(-/-) oocytes is normal, Tinagl1 is related to fertility in adult females but is not essential for either fertilization or preimplantation development in vitro.
authors.affiliation: Laboratory of Animal Breeding and Reproduction, Division of Animal Science, Faculty of Agriculture, Utsunomiya University, Tochigi 321-8505, Japan.
authors.forename: Akihito
authors.initials: A
authors.lastname: Takahashi
authors.forename: Ajalli
authors.initials: A
authors.lastname: Rahim
authors.forename: Miki
authors.initials: M
authors.lastname: Takeuchi
authors.forename: Emiko
authors.initials: E
authors.lastname: Fukui
authors.forename: Midori
authors.initials: M
authors.lastname: Yoshizawa
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Mukai
authors.forename: Makoto
authors.initials: M
authors.lastname: Suematsu
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Hasuwa
authors.forename: Masaru
authors.initials: M
authors.lastname: Okabe
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Matsumoto
mesh_terms: D000483:Alleles; D000818:Animals; D006063:Chorionic Gonadotropin / Q000378:metabolism; D003433:Crosses, Genetic; D046149:Embryo Culture Techniques; D010064:Embryo Implantation / Q000187:drug effects; D047108:Embryonic Development; D004717:Endometrium / Q000378:metabolism; D005260:Female; D005298:Fertility / Q000235:genetics*; D005307:Fertilization in Vitro; D005822:Genetic Vectors; D006801:Humans; D007150:Immunohistochemistry; D054834:Lipocalins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics*; D009865:Oocytes / Q000166:cytology; D010060:Ovulation; D010641:Phenotype; D014599:Uterus / Q000378:metabolism
chemical_list: D006063:Chorionic Gonadotropin; D054834:Lipocalins; D009363:Neoplasm Proteins; C484283:Tinagl1 protein, mouse