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T Iguchi

Publications and source records attributed to T Iguchi.

211 records · Page 12Linked to original sources
PubMedDate not supplied

Effect of neonatal exposure to DES in Fas and Bcl-2 expression in the adult mouse vagina and approach to the DES syndrome.

Neonatal exposure to a synthetic estrogen, diethylstilbestrol (DES), induces the ovary-independent persistent proliferation of vaginal epithelium in mice. Mouse vagina at the estrous stage in the normal estrous cycle shows 10 to 15 layers of epithelium with superficial keratinized layers, and ovariectomy induces a decrease of these epithelial cell layers and lymphocyte infiltration. Thus, cell proliferation and regression of vaginal epithelium are ovary dependent. Neonatally DES-treated mouse vagina showed the same phenotype as normal mouse vagina at the estrous stage, but ovariectomy did not induce a decrease of epithelial cell layers or a lymphocyte infiltration, and there was persistent proliferation of vaginal epithelium even after ovariectomy. In addition, apoptotic cell death characterized by oligonucleosomal DNA fragmentation, Fas expression, and Bcl-2 downregulation were induced after ovariectomy in normal mouse vagina, but not in DES-treated mouse vagina. These results suggest that neonatal DES-exposure in mice prevents vaginal Fas-mediated apoptosis following the downregulation of Bcl-2, and these abnormalities in expression are involved in persistent proliferation of the vaginal epithelium.

Animals↗
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Metallothionein expression in transplantable mouse mammary tumors.

BACKGROUND: The metal binding protein, metallothionein (MT) is involved in various physiological processes. In various human tumors, moreover, MT is reported to play an important role in carcinogenesis. MATERIALS AND METHODS: MT expression was investigated immunohistochemically and chromatographically in a transplantable pregnancy-dependent mouse mammary tumor (TPDMT-4) and related autonomous tumor sublines (T4-OI320 and -OI320CY). RESULTS: All tumor lines showed MT expression in the nucleus and/or cytoplasm of tumor cells. However, adenoacanthomatous T4-OI320 whose structure was different histopathologically from the remaining adenocarcinomas showed over-expression of MT in the basal layer of squamous metaplastic nodules. Cell proliferation activity estimated by the BrdU labeling method (BrdU index) was highest in the squamous nodules and correlated with the degree of MT expression (r = 0.96). By contrast, the BrdU index in T4-OI320CY was inversely correlated with the MT index (r = -0.91). CONCLUSIONS: The present investigation suggests expression of isotype MT in the transplantable mouse mammary tumors which may be involved in the carcinogenesis.

Adenocarcinoma↗
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Metallothionein expression and apoptosis in pregnancy-dependent and -independent mouse mammary tumors.

BACKGROUND: A metal binding protein, metallothionein (MT), may be involved in the regulation of carcinogenesis and apoptosis in addition to various physiological processes. MATERIALS AND METHODS: MT and sex hormone receptors (estrogen and progesterone receptors, ER and PR) expressions, and apoptosis were investigated immunohistochemically in pregnancy-dependent (PDMT) and -independent mammary tumors (PIMT) in GR/A mice in order to evaluate the possible role of MT in the genesis and regression of tumors. RESULTS: In PDMT and PIMT, MT was localized in the nucleus and/or cytoplasm of tumor cells. In PDMT, MT expression and apoptotic figures were increased during the regression period after parturition. MT and ER expressions in PIMT were approximately the same as those in the growing PDMT, while PR expression was lower in PIMT than in the PDMT. A significant correlation was observed between MT expression and apoptosis in PDMT, but not in PIMT. CONCLUSION: The present study suggests that MT involvement in the PDMT regression is associated with apoptosis.

Animals↗
PubMedDate not supplied

Effects of neonatal exposure to diethylstilbestrol on protein expression by vagina and uterus in mice.

Neonatal treatment of female mice with diethylstilbestrol (DES) results in genital tract abnormalities including ovary-independent vaginal proliferation and cornification. Protein profiles were examined in vagina and uterus from 45-day-old, ovariectomized C57BL/Tw mice which had been given 5 daily injections of 2 micrograms DES or oil vehicle alone from the day of birth, and in those from 45-day-old, ovariectomized mice given 3 daily injections of 0.1 microgram DES from 42 days of age. Proteins extracted were analyzed by two-dimensional polyacrylamide gel electrophoresis. In the vagina, expression of 37 non-keratin proteins was altered by postpubertal injections of DES as compared with the controls. In the neonatally DES-exposed vagina, expression of 26 of 37 proteins was altered as compared with controls. In the uterus, expression of 22 proteins was altered in the postpubertally DES-exposed group as compared with that in the control; however, the protein expression pattern of the neonatally DES-exposed group closely resembled that of the control except for one protein (no. 23, pI = 6.1, MW = 39.5 kDa) which was specifically increased in the neonatally DES-exposed group. By immunoblot analysis, 6 keratin polypeptides (49.5, 50, 52, 53, 57 and 58 kDa) were identified in vaginae of ovariectomized mice exposed neonatally and postpubertally to DES and of the controls. These results indicate that neonatal DES exposure induces organ specific alterations in the synthesis of proteins in mouse vagina and uterus.

Animals↗
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Effects of postpubertal treatment with progesterone on protein expression in the vagina and uterus of mice exposed neonatally to diethylstilbestrol.

Postpubertal progesterone injections slightly inhibited the proliferation and cornification of the vaginal epithelium induced by neonatal injections of diethylstilbestrol (DES). In vaginae of neonatally DES-exposed mice (DES mice), 9 protein expressions (PEX) appeared newly; 13 PEX decreased; 5 PEX increased compared to those in the controls. In vaginae of DES mice, PEX were altered by postpubertal injections of progesterone (DES-P); 3 PEX disappeared; 11 PEX were reversed to those in the controls. Progesterone injections impaired the proliferation of the vaginal epithelium, reversing 11 PEX compared to those in DES mice. In uteri of DES-P mice, 3 PEX increased, 2 PEX decreased, 2 PEX appeared and 1 PEX disappeared compared to those in DES mice. In conclusion, it was shown that postpubertal injections of progesterone alter the protein expression in the vagina and uterus of DES mice.

Animals↗
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Effects of postpubertal treatment with diethylstilbestrol and tamoxifen on protein expression in the vagina and uterus of neonatally diethylstilbestrol-exposed mice.

Postpubertal injections of a synthetic estrogen, diethylstilbestrol (-DES), and an anti-estrogen, tamoxifen (-Tx), stimulate proliferation of vaginal and uterine epithelial cells of ovariectomized (OVX) adult mice. In vaginae of two groups of OVX mice treated neonatally with DES (DES-) and oil vehicle alone (Oil-), postpubertal injections of DES altered all and 25 out of 37 protein expressions examined, except for keratin polypeptides, respectively. Twenty-one of the DES- and Tx-altered protein expressions showed the same behavior, suggesting that Tx acts as an estrogen agonist on these proteins. Both neonatally Oil- and DES-treated OVX mice given postpubertal injections of DES (Oil-DES and DES-DES) and Tx (Oil-Tx and DES-Tx) showed similar histological changes in the vagina. Epithelial proliferation and superficial cornification were observed in vaginae of five groups of Oil-DES, Oil-Tx, DES-DES, DES-Tx and DES-Oil (given oil postpubertally) OVX mice. In these groups, 13 proteins showed the same behavior, implying that these proteins are related to proliferation and cornification of mouse vagina. The histology of the uterus in DES-Oil OVX mice closely resembled that in Oil-Oil OVX mice; in protein expressions of the uterus, 5 proteins in DES-DES and 7 proteins in DES-Tx OVX mice were different from those in Oil-DES and Oil-Tx OVX mice, respectively. These findings indicate that neonatal DES treatment alters the behavior of the vagina and uterus in response to postpubertally administered DES and Tx.

Animals↗
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Estrogen receptor expression in the genital tract of female mice treated neonatally with diethylstilbestrol.

The distribution of the estrogen receptor (ER) was investigated immunohistochemically in the genital tract of 0 (day of birth)--to 50-day-old C57BL/Tw female mice given 5 daily injections of 2 micrograms diethylstilbestrol (DES) from the day of birth using an anti-ER monoclonal antibody. In the oviduct, cervix and vagina of control mice, both epithelial and stromal cell nuclei showed positive ER immunoreaction at 0 day. Nuclei of uterine stromal cells also showed strong ER immunostaining even at 0 day. In contrast, the ER in uterine epithelial cells began to appear by day 5. The number of positive epithelial cells and staining intensity gradually increased until 10 days. In neonatally DES-exposed mice, ER appeared in uterine epithelial cells 24 h after the injection. Polygonal cells appearing in the vaginal epithelium of DES-exposed 3-day-old mice showed weak ER staining. Neonatal DES exposure reduced staining intensity of columnar vaginal epithelial cells and uterine stromal cells at 3 days. Vaginal epithelial cells undergoing ovary-independent stratification and cornification in neonatally DES-exposed mice and normal estrous mice showed ER immunoreaction only in the basal cells.

Animals↗
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In vitro fertilization of oocytes from polyovular follicles in mouse ovaries exposed neonatally to diethylstilbestrol.

In 35-day-old female ICR/JCL mice given 5 daily injections of 1 microgram diethylstilbestrol (DES) from the day of birth, a significantly higher incidence of polyovular follicles was found in the ovaries than in those of age-matched control mice. Gap junctions of granulosa cells of mature follicles in neonatally DES-exposed mice were larger than those of the controls. When stimulated by gonadotropins (PMSG and hCG) and caged with males, the number of tubal embryos in DES-exposed mice was less, but the rate of fertilization and development was not different compared to the controls. Division of oocytes collected from the ovaries of 40-day-old DES-exposed and control mice after stimulation of gonadotropins was examined 24 to 72 h after in vitro insemination to ascertain whether fertilization had occurred in oocytes from polyovular follicles. Seventy-seven % of oocytes from uniovular follicles of control mice developed up to 8-cell stage embryos following in vitro insemination; 66% of those from similar follicles of DES-exposed mice developed into the same stage. By contrast, only 47% of oocytes from polyovular follicles of DES-exposed mice showed the division up to 8-cell stage 72 h after insemination, indicating a significantly lower fertilization rate compared to the oocytes from uniovular follicles of control and DES-exposed mice. Without insemination, oocytes taken from the same pools in these experiments never divided during the period of manipulation and incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
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Critical period of induction by tamoxifen of genital organ abnormalities in female mice.

Genital organs of C57BL/Tw female mice given 5 daily injections of 100 micrograms tamoxifen (Tx) from the day of birth (day 0) were examined at 5, 10, 15, 20, 30 and 60 days of age. The incidence of polyovular follicles (PF) in Tx mice was higher, but the development of uterine glands and tunica muscularis uteri in Tx mice was lower than in the age-matched controls. Uteri of 15-day-old Tx mice underwent a weight increase resulting from edematous change in the stromal tissue lacking type I collagen and fibronectin. Adenosis-like lesions were found in the vaginae of 5- to 30-day-old Tx mice. Mice given neonatal injections of 100 micrograms clomiphene (Clm) and nafoxidine (Naf) were also examined at 60 days. Tx caused much greater damage to the ovary and uterus than did Clm and Naf. In order to examine the critical period of induction by Tx of female genital organ abnormalities, mice were given 5 daily injections of Tx starting at different early postnatal ages. Tx injections starting within 5 days caused a high incidence of PF in the ovary and aplasia of tunica muscularis in the uterus. The Tx treatment also induced atrophy of the uterine luminal epithelium when started within 7 days. The present study suggests, therefore, that the postnatal limit of the critical period for the female genital organs lies within 7 days after birth.

Age Factors↗
PubMedDate not supplied

Development and mitotic activity of the metrial gland in rat uterus during mid-pregnancy.

Development and mitotic activity of metrial gland in rat uterus were investigated focusing on the point of implantation during mid-pregnancy. In decidua basalis, the granulated metrial gland (GMG) cells slightly increased in number during days 8-12 of pregnancy and then decreased, while the cells appearing in the mesometrial triangle on day 9 continued to increase until day 16, forming the metrial gland in situ. By contrast, the mitotic change in the mesometrial triangle was similar to that in the other 2 regions, decidua basalis and the inner layer of myometrium. In all 3 regions, mitotic rate rose drastically on day 9, and then gradually decreased until day 16. However, most of the mitotic cells lacked the PAS-positive cytoplasmic granules in any regions. Mitotic activity in GMG cells was very low and almost unchanged throughout the gland development. These results suggest that the rapid rise of mitotic rate is due to the active mitosis of PAS-negative cells, presumably GMG precursor cells, existing widely in the implantation point of rat uterus during the early development of the gland. Immunocytochemical study revealed that progesterone receptors were localized in decidual and muscle cells and fibroblasts, but not in GMG cells during the development of the gland. The present study suggests that the metrial gland cells are proliferated, differentiated and maintained by the progesterone-sensitive stromal cells, such as decidual cells and/or fibroblasts.

Animals↗
PubMedDate not supplied

Persistent changes in protein synthesis by vagina of ovariectomized mice exposed neonatally to diethylstilbestrol.

Neonatal treatment of female mice with a synthetic estrogen, diethylstilbestrol (DES), results in adenosis, ovary-independent epithelial proliferation and cornification, and downgrowths in the vagina. Protein synthesis was examined in the vagina of 45-day-old, ovariectomized C57BL/Tw mice which had been given 5 daily injections of 2 micrograms DES or the oil vehicle alone from the day of birth, and in those of age-matched, ovariectomized mice given 3 daily injections of 0.1 microgram DES from 42 days of age. [35S]Methionine-labeled proteins of the vagina were analyzed by two-dimensional polyacrylamide gel electrophoresis. Major changes were observed in 11 proteins of the vagina in both neonatally and postnatally DES-exposed groups. Six of the 11 proteins were increased in expression, but one of the remaining proteins was decreased. In the group of neonatally DES-exposed mice alone, expressions of 4 proteins (MW. 128, 90, 46 and 44 kDa) were markedly increased. These results indicate that neonatal exposure of mice to DES induced ovary-independent, persistent alteration in the protein synthesis of the vagina.

Animals↗
PubMedDate not supplied

Effect of ovariectomy on histological change and protein expression in female mouse reproductive tracts.

Proliferation of the vagina and uterus in rodents is stimulated by ovarian estrogen, and ovariectomy induces regression of these tracts. In mouse, reproductive tracts, organ weights, vaginal epithelial thickness, the number of epithelial cell layers, and uterine epithelial cell height were significantly reduced 1 to 20 days after ovariectomy when compared with those of intact, mice taken at the estrous stage. No significant differences in those parameters were found between ovariectomized mice implanted with estradiol and intact estrous mice. Vaginal epithelium at estrus was composed of 10-15 layers of epithelial cells with superficial keratinized layers, however, the vaginal epithelium began to regress one day after ovariectomy. Infiltration of leukocytes was encountered in the vaginal epithelium 2-3 days after ovariectomy. Protein expression in the regressing vagina and uterus after ovariectomy was examined by two-dimensional polyacrylamide gel electrophoresis. After ovariectomy, new proteins appeared in the regressing vagina, but not in the regressing uterus. Expressions of 7 and 6 proteins in the vagina and uterus, respectively, reached peak levels 2-3 days after ovariectomy. The expression of ovariectomy-specific proteins and infiltration of leukocytes in vaginal epithelium was inhibited by the injection of cycloheximide, an inhibitor of protein synthesis. These results suggest that some proteins participate in the regression of mouse reproductive tracts after estrogen withdrawal induced by ovariectomy.

Animals↗