Impaired fertility in female mice lacking urinary trypsin inhibitor.
Urinary trypsin inhibitor (UTI) is a serine proteinase inhibitor that is found in blood and urine. To investigate the physiological functions of UTI in vivo, we generated UTI-deficient mice by gene targeting. The mice showed no obvious abnormalities and appeared healthy. However, the females displayed a severe reduction in fertility. Wild-type embryos developed normally when transplanted into UTI-deficient female mice, suggesting that UTI-deficient females have a normal ability to maintain pregnancy. The number of naturally ovulated oocytes from UTI-deficient mice was greatly reduced compared with that from wild-type mice. Histologically, oocytes with disorganized corona radiata were frequently seen in the ovaries of UTI-deficient mice after hormonal stimulation. When ovaries from UTI-deficient mice were transplanted into wild-type mice, pups derived from the transplanted ovaries were obtained, suggesting that the ovary of UTI-deficient mice functions normally if UTI is supplied from the systemic circulation. These results demonstrate that UTI plays an important role in the formation of the stable cumulus-oocyte complex that is essential for oocyte maturation and ovulation.
Sato
H
H
Research Center, Mochida Pharmaceutical Company, Ltd., 722 Jimba-aza-uenohara, Shizuoka, Gotemba, 412-8524, Japan.
Kajikawa
S
S
Kuroda
S
S
Horisawa
Y
Y
Nakamura
N
N
Kaga
N
N
Kakinuma
C
C
Kato
K
K
Morishita
H
H
Niwa
H
H
Miyazaki
J
J
D000818:Animals; D004624:Embryo Transfer; D005260:Female; D006023:Glycoproteins / Q000235:genetics / Q000502:physiology*; D007246:Infertility / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010053:Ovary / Q000033:anatomy & histology / Q000637:transplantation; D010060:Ovulation; D011247:Pregnancy
D006023:Glycoproteins; C028665:urinastatin