Analysis of molecular regulation on female reproductive tract during fertilization using genetic model mice

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The mammalian fertilization process takes place in a complex microenvironment within the female genital tract. A member of the chitinase protein family, oviduct-species glycoprotein (OGP), has been identified in oviductal fluid from various mammalian species including humans. Although it is thought that OGP is widely believed to involve in the process of mammalian fertilization, including sperm function and gamete interactions based on experimental results obtained in vitro, its physiological significance remains controversial. In this study, we generated transgenic mice using a 2.2-kilobase (kb) segment of the 5'-flanking sequence of the OGP gene for expression of the SV 40 T antigen (Tag). These mice spontaneously developed tumors in the female reproductive tract. Analysis using RT-PCR showed that the 2.2-kb OGP 5'-flanking region drove Tag mRNA expression in the oviduct, uterus, vagina and ovary, but not in other tissues. Ovariectomy suppressed Tag expression and thereby blocked tum … More origenesis in the transgenic mice. Estradiol administration to ovariectomized transgenic mice led to dramatic hyperplasia of the reproductive tract tissues in association with enhanced Tag expression, both in intensity and distribution. These results demonstrated that a 2.2-kb fragment of the 5'-flanking sequence of the mouse OGP gene was capable of directing the expression of Tag and inducing tumorigenesis in female reproductive tract tissues in an estrogen-dependent the expression of Tag and inducing tumorigenesis in female reproductive tract tissues in an estrogen-dependent manner. Estrogen response elements present in the promoter region were functional in vivo. In In addition, we eatablished OGP gene-null (ogp^<-/-> mice, and primarily characterized their reproductive properties to study the physiological function(s) of OGP. Data obtained from studies using in vivo or in vitro system showed that the fertility of ogp^<-/-> females was within normal limits. These results indicate that OGP is dispensable for the process of in vivo fertilization, at least in mice Less