Bell Research Center for Reproductive Health and Cancer

Nagoya-shi, Japan

Bell Research Center for Reproductive Health and Cancer

Nagoya-shi, Japan
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Komatsu K.,Bio database Institute of Reproductive and Developmental Medicine | Iwase A.,Nagoya University | Mawatari M.,Bell Research Center for Reproductive Health and Cancer | Wang J.,Bell Research Center for Reproductive Health and Cancer | And 2 more authors.
Reproduction | Year: 2014

Hormonal stimulation in superovulation induces female mice to ovulate more oocytes than spontaneous ovulation. Because the superovulated oocytes contain a number of oocytes that normally regress before spontaneous ovulation or immature oocytes, the development of some embryos that derive from these oocytes by IVF is prevented. Therefore, the quality of superovulated oocytes should differ from that of spontaneously ovulated oocytes. In this study, we evaluated the quality of superovulated oocytes, by examining 1- and 2-cell stage embryos, in which the development mainly depends on the maternal mRNA, proteins, and mitochondria that are contained in the oocytes, and we then measured the mitochondrial membrane potential (ΔΨm) of the 1- and 2-cell stage, in vivo-fertilized, and IVF embryos. The ΔΨm of 1-cell stage IVF embryos was lower than that of in vivo-fertilized embryos; however, there was no difference between IVF embryos. During the developmental process from 1- to 2-cell stage, the ΔΨm of in vivo-fertilized embryos was highly upregulated, whereas a number of IVF embryos remained unchanged. As a result, 2-cell stage embryos were divided into two groups: high- and low- ΔΨm 2-cell stage IVF embryos. The development of low-ΔΨm 2-cell stage IVF embryos tended to be arrested after the 2-cell stage. These results indicated that the upregulation of ΔΨm during the 1- to 2-cell stage was important in the development of early preimplantation embryos; there were some defects in the mitochondria of superovulated oocytes, which prevented their development. © 2014 Society for Reproduction and Fertility.


Luo C.,Bio Databases Institute of Reproductive and Developmental Medicine | Shibata K.,Nagoya University | Suzuki S.,Nagoya University | Kajiyama H.,Nagoya University | And 5 more authors.
Oncology Reports | Year: 2014

Glypican-3 (GPC3) is specifically expressed in ovarian clear cell carcinoma (OCCC), hepatocellular carcinoma (HCC), and melanoma and lung cancer. GPC3 is being explored as a potential candidate for OCCC and HCC immunotherapy. As a tumor-associated antigen, induction of immune response of GPC3 in ovarian cancer remains elusive. We established a GPC3 transgenic mouse ovarian cancer cell line, OV2944-HM-1 (HM-1), and used the intraperitoneal ovarian cancer mouse model to investigate immune response in GPC3-expressing tumor. We found that GPC3 expression in the tumor increased F4/80+CD86+ macrophage (M1) proportion and caused GPC3-specific CD8+ T cell immune responses, and prolonged mouse survival. Our results demonstrated that GPC3 expression induced T cell-mediated immune response in this mouse ovarian cancer model and also provided supportive evidence that GPC3 is an ideal target for ovarian cancer immunotherapy.


Shiomi-Sugaya N.,Bell Research Center for Reproductive Health and Cancer | Komatsu K.,Bell Research Center for Reproductive Health and Cancer | Wang J.,Bell Research Center for Reproductive Health and Cancer | Yamashita M.,Bell Research Center for Reproductive Health and Cancer | And 2 more authors.
Journal of Reproduction and Development | Year: 2015

Ovaries contain follicles at various stages of development, including primordial, primary, secondary, antral and Graafian follicles. Although the growth of these follicles is controlled to maintain regular ovulation, the mechanism through which this occurs remains unclear. In our study, we found that the growth rate of cultured secondary follicles separated from mice ovaries differed between follicles. After 4 days of culture, the size of some secondary follicles was markedly increased, while that of others had either slightly increased, remained unchanged or shrunk. We compared the expression levels of growth factors between these secondary follicles and found that the growth rate of cultured secondary follicles correlated with the expression level of insulin-like growth factor 1 (Igf1) mRNA. Igf1 mRNA expression level in secondary follicles containing theca cells was higher than that in secondary follicles without theca cells, and the granulosa cell proliferation around follicles containing theca cells was increased. Furthermore, an IGF1 inhibitor also inhibited the granulosa cell proliferation, and administration of IGF1 to secondary follicles without growth promoted granulosa cell proliferation. These results indicated that the theca cells of secondary follicles induced the expression of IGF1 and promoted the follicle growth. © 2015 by the Society for Reproduction and Development.


Komatsu K.,Nagoya University | Komatsu K.,Bell Research Center for Reproductive Health and Cancer | Koya T.,Bell Research Center for Reproductive Health and Cancer | Wang J.,Bell Research Center for Reproductive Health and Cancer | And 3 more authors.
Biology of Reproduction | Year: 2015

Leukemia inhibitory factor (LIF) is expressed in the ovary and controls follicular growth. LIF has been reported to accelerate the primordial to primary follicle transition, the growth of cultured preantral follicles, and the maturation of oocytes. Previous reports on factors that regulate follicular growth have largely employed cultured follicles. However, there are several types of follicles and somatic cells in the ovary that are likely to interact with one another to regulate follicular growth. Therefore, a novel approach is essential for understanding the function of factors that regulate follicular growth in the ovary. In this study, we evaluated the function of LIF using cultured ovarian tissue. Ovarian tissue slices were cultured in the presence or absence of recombinant LIF and neutralizing anti- LIF antibody to enable continuous monitoring of follicular growth within the context of the ovary as well as analysis of the process of follicular growth. The results revealed that LIF inhibited the growth of primary, secondary, and antral follicles. Furthermore, we verified the inhibitory function of LIF using the neutralizing antibody, which accelerated follicular growth. These results suggest that LIF is likely to coordinate follicular growth in the ovary. The culture and analysis methods employed in this study are thus effective for clarifying the tissue-level functions of factors that regulate follicular growth within the ovary. © 2015 by the Society for the Study of Reproduction, Inc.


PubMed | Bell Research Center for Reproductive Health and Cancer and Nagoya University
Type: Journal Article | Journal: Biology of reproduction | Year: 2015

Leukemia inhibitory factor (LIF) is expressed in the ovary and controls follicular growth. LIF has been reported to accelerate the primordial to primary follicle transition, the growth of cultured preantral follicles, and the maturation of oocytes. Previous reports on factors that regulate follicular growth have largely employed cultured follicles. However, there are several types of follicles and somatic cells in the ovary that are likely to interact with one another to regulate follicular growth. Therefore, a novel approach is essential for understanding the function of factors that regulate follicular growth in the ovary. In this study, we evaluated the function of LIF using cultured ovarian tissue. Ovarian tissue slices were cultured in the presence or absence of recombinant LIF and neutralizing anti-LIF antibody to enable continuous monitoring of follicular growth within the context of the ovary as well as analysis of the process of follicular growth. The results revealed that LIF inhibited the growth of primary, secondary, and antral follicles. Furthermore, we verified the inhibitory function of LIF using the neutralizing antibody, which accelerated follicular growth. These results suggest that LIF is likely to coordinate follicular growth in the ovary. The culture and analysis methods employed in this study are thus effective for clarifying the tissue-level functions of factors that regulate follicular growth within the ovary.


PubMed | Bio Databases Institute of Reproductive and Developmental Medicine, Bell Research Center for Reproductive Health and Cancer and Nagoya University
Type: Journal Article | Journal: Oncology reports | Year: 2014

Glypican-3 (GPC3) is specifically expressed in ovarian clear cell carcinoma (OCCC), hepatocellular carci-noma (HCC), and melanoma and lung cancer. GPC3 is being explored as a potential candidate for OCCC and HCC immunotherapy. As a tumor-associated antigen, induction of immune response of GPC3 in ovarian cancer remains elusive. We established a GPC3 transgenic mouse ovarian cancer cell line, OV2944-HM-1 (HM-1), and used the intraperitoneal ovarian cancer mouse model to investigate immune response in GPC3-expressing tumor. We found that GPC3 expression in the tumor increased F4/80+CD86+ macrophage (M1) proportion and caused GPC3-specific CD8+ Tcell immune responses, and prolonged mouse survival. Our results demonstrated that GPC3 expression induced Tcell-mediated immune response in this mouse ovarian cancer model and also provided supportive evidence that GPC3 is an ideal target for ovarian cancer immunotherapy.


PubMed | Bell Research Center for Reproductive Health and Cancer
Type: Journal Article | Journal: The Journal of reproduction and development | Year: 2015

Ovaries contain follicles at various stages of development, including primordial, primary, secondary, antral and Graafian follicles. Although the growth of these follicles is controlled to maintain regular ovulation, the mechanism through which this occurs remains unclear. In our study, we found that the growth rate of cultured secondary follicles separated from mice ovaries differed between follicles. After 4 days of culture, the size of some secondary follicles was markedly increased, while that of others had either slightly increased, remained unchanged or shrunk. We compared the expression levels of growth factors between these secondary follicles and found that the growth rate of cultured secondary follicles correlated with the expression level of insulin-like growth factor 1 (Igf1) mRNA. Igf1 mRNA expression level in secondary follicles containing theca cells was higher than that in secondary follicles without theca cells, and the granulosa cell proliferation around follicles containing theca cells was increased. Furthermore, an IGF1 inhibitor also inhibited the granulosa cell proliferation, and administration of IGF1 to secondary follicles without growth promoted granulosa cell proliferation. These results indicated that the theca cells of secondary follicles induced the expression of IGF1 and promoted the follicle growth.

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