Runx3 Expression and Its Roles in Mouse Endometrial Cells

Tsuchiya, Yuta; Saito, Yuka; Taniuchi, Shusuke; Sakuma, Atsuko; Maekawa, Tetsuya; Fukamachi, Hiroshi; Tanaka, Sakae; Takahashi, Sumio

doi:10.1262/jrd.2012-066

Cited by 6 publications

(4 citation statements)

References 35 publications

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“…The significant decrease in Cyp11a1 mRNA levels in Runx3 −/− mouse ovaries may result in decreased androgen synthesis, leading to the diminished production of estrogen in granulosa cells. Atrophic uteri in Runx3 −/− mice also suggested a decrease in estrogen production in ovaries [13]. The increase in estrogen levels during the proestrous day triggers a preovulatory GnRH/LH surge.…”

Section: Discussionmentioning

confidence: 99%

“…The numbers of primary, secondary, and antral follicles were significantly lower in Runx3 −⁄− mouse ovaries than those in wt mouse ovaries, indicating that folliculogenesis was retarded. In addition, atrophic uteri were observed in Runx3 −/− mice, suggesting a decrease in estrogen and progesterone (P4) production [12, 13]. However, it is not clear how Runx3 deletion affects steroidogenesis in mouse ovaries.…”

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confidence: 99%

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Runx3 transcription factor regulates ovarian functions and ovulation in female mice

Ojima

Saito

Tsuchiya

et al. 2016

Journal of Reproduction and Development

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We previously demonstrated that the Runx3 transcription factor is expressed in the hypothalami, pituitaries, and ovaries of mice, and that Runx3 knockout (Runx3−/−) mice are anovulatory and their uteri are atrophic. Runx3 mRNA expression was detected in the granulosa cells of ovarian follicles, and in the anteroventral periventricular nucleus (AVPV) and arcuate nucleus (ARC). In the present study, we examined the effects of Runx3 knockout on the gene expression of enzymes associated with steroidogenesis. We found decreased Cyp11a1 mRNA expression in Runx3−/− mouse ovaries compared with that in wild-type (wt) mouse ovaries at the age of 8 weeks. In situ hybridization analysis showed that the percentages of Cyp11a1 mRNA-expressing theca cells in follicles of Runx3−/− mice were decreased compared with those of wt mice. In accord with the alterations in Runx3−/− mouse ovaries, Kiss1 mRNA levels in ARC were increased, whereas mRNA levels of kisspeptin in AVPV were decreased, and gonadotropin-releasing hormone in the preoptic area and follicle-stimulating hormone β subunit gene were increased in Runx3−/− mice. Following an ovarian transplantation experiment between Runx3−/− mice and wt mice, corpora lutea were observed when ovaries from Runx3−/− mice were transplanted into wt mice, but not when those from wt mice were transplanted into Runx3−/− mice, suggesting that Runx3 in the hypothalamo-pituitary system may drive gonadotropin release to induce ovulation in the ovary. These findings indicate that Runx3 plays a crucial role in the hypothalamo-pituitary-gonadal axis.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Runx3 transcription factor regulates ovarian functions and ovulation in female mice

Ojima

Saito

Tsuchiya

et al. 2016

Journal of Reproduction and Development

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“…5 suggests that vitamin D could act through VDR [23] upon both the epithelium and stroma in the developing mouse vagina. Considering the distribution of estrogen receptors (ERs) in the developing vagina [24] as well, vitamin D/VDR signaling may crosstalk and interfere with estrogen/ERs signaling within a cell or those of different cells through other peripheral cell signaling factors that mediate and/or influence on the estrogen effects in the genital tracts [25,26,27]. For example, vitamin D/VDR may inhibit KGF/KGFR signaling that is essential for estrogen to evoke permanent changes in the developing vagina [13, 19, 28].…”

Section: Discussionmentioning

confidence: 99%

Activated Vitamin D<sub>3</sub> and Pro-activated Vitamin D<sub>3</sub> Attenuate Induction of Permanent Changes Caused by Neonatal Estrogen Exposure in the Mouse Vagina

Matsuda

Kurosaki

Okamura

2014

Journal of Reproduction and Development

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Exposure of mice to a high dose of estrogens including diethylstilbestrol (DES) during the neonatal period modifies the developmental plan of the genital tract, which leads to various permanent changes in physiology, morphology and gene expression. These changes include development of an abnormal vaginal epithelium lined with hyperplastic mucinous cells accompanied by Tff1 gene expression in mice. Here, the influence of vitamin D on the direct effect of estrogen on the developing mouse vagina was examined. The mid-vagina of neonatal mice was cultured in a serum-free medium containing estradiol-17β (E2) and various concentrations of 1,25-dihydroxyvitamin D3 (1,25(OH)2D) ex vivo and then was transplanted under the renal capsule of ovariectomized host mice for 35 days. Exposure to E2 alone caused the vaginal tissue to develop estrogen-independent epithelial hyperplasia and to express TFF1 mRNA, while addition of a low nanomolar amount of 1,25(OH)2D added at the same time as E2 to the culture medium attenuated the effects of estrogen. Expression of vitamin D receptor was also evident in the neonatal mouse vagina. Interestingly, addition of 25-hydroxyvitamin D3, a pro-activated form of vitamin D, at the micromolar level was found to be potent in disrupting the developmental effects of E2, while cholecalciferol was not at least at the dose examined. Correspondingly, expression of Cyp27B1, a kidney-specific 25-hydroxyvitamin D hydroxylase, was evident in the neonatal mouse vagina when examined by RT-PCR. In addition, simultaneous administration of 1,25(OH)2D successfully attenuated DES-induced ovary-independent hyperplasia in the vagina in neonatal mice in vivo. Thus, manipulation of vitamin D influenced the harmful effects of estrogens on mouse vaginal development.

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“…Estrogen production in follicular cells is regulated by FSH and LH (Adashi and Hsueh 1982;Fitzpatrick and Richards 1991). In Runx3 −/− mouse ovaries, mRNA expression of the gene encoding the cholesterol side-chain cleavage enzyme (SCC) gene Cyp11a1 in theca cells is decreased in mature female mice (Sakuma et al 2008;Tsuchiya et al 2012;Ojima et al 2016). Aromatase encoded by Cyp19a1 is a key enzyme of estrogen synthesis in granulosa cells, in which Runx3 is also expressed.…”

Section: Introductionmentioning

confidence: 99%

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice

et al. 2018

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We previously demonstrated that female Runx3 knockout (Runx3 −/−) mice were anovulatory and their uteri were atrophic, and that Runx3 mRNA was expressed in granulosa cells. To clarify how Runx3 regulates folliculogenesis and ovulation, we examined the effects of Runx3 knockout on the gene expression of growth factors associated with folliculogenesis and enzymes associated with steroidogenesis. In Runx3 −/− mouse ovaries, the numbers of primary and antral follicles were lower than those in wild type (wt) mice at 3 weeks of age, indicating that the loss of Runx3 affects folliculogenesis. The expression of genes encoding activin and inhibin subunits (Inha, Inhba, and Inhbb) was also decreased in ovaries from the Runx3 −/− mice compared with that in wt mice. Moreover, the expression of the genes Cyp11a1 and Cyp19a1 encoding steroidogenic enzymes was also decreased. In cultured granulosa cells from 3-week-old mouse ovaries, Cyp19a1 mRNA levels were lower in Runx3 −/− mice than those in wt mice. Follicle stimulating hormone (FSH) treatment increased Cyp19a1 mRNA levels in both wt and Runx3 −/− granulosa cells in culture, but the mRNA level in Runx3 −/− granulosa cells was lower than in wt ones, indicating that granulosa cells could not fully function in the absence of Runx3. At 3 weeks of age, gonadotropin α subunit, FSHβ subunit and Luteinizing hormone (LH)β subunit mRNA levels were decreased in Runx3 −/− mice. These findings suggest that Runx3 plays a key role in female reproduction by regulating folliculogenesis and steroidogenesis in granulosa cells.

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Runx3 Expression and Its Roles in Mouse Endometrial Cells

Cited by 6 publications

References 35 publications

Runx3 transcription factor regulates ovarian functions and ovulation in female mice

Runx3 transcription factor regulates ovarian functions and ovulation in female mice

Activated Vitamin D<sub>3</sub> and Pro-activated Vitamin D<sub>3</sub> Attenuate Induction of Permanent Changes Caused by Neonatal Estrogen Exposure in the Mouse Vagina

Runx3 regulates folliculogenesis and steroidogenesis in granulosa cells of immature mice

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