Tomoko Nakamura

Nagoya University, Nagoya, Aichi, Japan

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Publications (11)28.98 Total impact

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    ABSTRACT: Since serum anti-Müllerian hormone (AMH) levels enable quantitative evaluation of ovarian damage, we conducted a computer-based search, using key words, of all articles published in English through the PubMed database from inception until September 2013 to summarize available studies evaluating ovarian reserve after ovarian toxic interventions to discuss the usefulness of serum AMH levels. We found that most of the studies demonstrated a decline in serum AMH levels when compared to control or pretreatment levels, with levels dependent on the type of treatment modality. Measurement of serum AMH levels enables quantitative evaluation of ovarian damage caused by ovarian toxic interventions, such as chemotherapy and radiotherapy, instead of qualitative evaluation using menstrual condition or basal follicle-stimulating hormone levels. Serum AMH levels are becoming indispensable to assess the ovarian reserve of patients who desire preservation of ovarian function for fertility and endogenous sex steroid hormones.
    Reproductive sciences (Thousand Oaks, Calif.) 09/2014; · 2.31 Impact Factor
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    ABSTRACT: Abstract Anti-Müllerian hormone (AMH) is a relatively novel method for examining the ovarian reserve that reflects female reproductive function. In the era in which the number of women delaying attempts to conceive has increased, a good predictor for long-term fecundability has been explored. We performed the retrospective cohort study to investigate whether initial serum AMH levels are useful for predicting long-term fertility during infertility treatments. We recruited 149 women in the retrospective cohort, and 52 women were gravid during the follow-up period. According to the multiple logistic analyses, only age was found to have a significant correlation with pregnancy success in all women. In women ≥38 years, significantly higher serum AMH levels were detected in the pregnant group (median = 2.83 ng/mL, range = 1.11-6.29 ng/mL) than the non-pregnant group (median = 1.22 ng/mL, range = 0-9.46 ng/mL; p = 0.015). None of the women with serum AMH levels <0.7 ng/mL were pregnant during treatment. AMH may be used to identify poor pregnancy prospects in women who are above 38 years.
    Gynecological endocrinology : the official journal of the International Society of Gynecological Endocrinology. 07/2014;
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    ABSTRACT: Growth differentiation factor 9 (GDF9), an oocyte-secreted factor, whose receptors exist in granulosa cells, is involved in follicle progression. Therefore, GDF9 is considered to potentially mediate signals necessary for follicular growth. However, the effect of GDF9 on human granulosa cells is not fully understood. Human immortalized nonluteinized granulosa cell line (HGrC1) which we have previously reported was stimulated with GDF9 and/or follicle-stimulating hormone (FSH). Granulosa cells obtained from in vitro fertilization (IVF) patients were also evaluated with quantitative reverse transcription polymerase chain reaction (RT-PCR). Real-time RT-PCR showed that GDF9 increased messenger RNA (mRNA) levels of enzymes required for cholesterol biosynthesis, such as 3-hydroxy-3-methylglutanyl-CoA synthase 1 (HMGCS1), farnesyl-diphosphate farnesyltransferase 1, squalene epoxidase, lanosterol synthase, and cytochrome P450, family 51, subfamily A, polypeptide 1 (CYP51A1). A greater increase in mRNA levels of HMGCS1 and CYP51A1 was observed by combined treatment with GDF9 and FSH. Clinical samples showed a significant increase in CYP51A1 mRNA in the group of granulosa cells connected with unfertilized oocytes. Our results suggest that GDF9, possibly with FSH, may play significant roles in the regulation of cholesterol biosynthesis and the expression of CYP51A1 which might be a predictor for unfertilization.
    Reproductive sciences (Thousand Oaks, Calif.) 04/2014; · 2.31 Impact Factor
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    ABSTRACT: Human follicular fluid constitutes the microenvironment of follicles and includes various biological active proteins that can affect follicle growth and oocyte fertilization. Conducting proteomic evaluations of human follicular fluid may be helpful for identifying potential biomarkers possibly possessing a predictive value for oocyte quality and the success of in vitro fertilization. We performed proteomic profiling of human follicular fluids containing oocytes that were fertilized and resulted in pregnancy and follicular fluids containing oocytes that were not fertilized in the same patients undergoing intracytoplasmic sperm injection using the LTQ Orbitrap coupled with liquid chromatography-tandem mass spectrometry (LC/MS/MS) analyses. We identified a total of 503 proteins in human follicular fluids containing fertilized and non-fertilized oocytes obtained from 12 patients. We also found that 53 proteins exhibited significantly different spectral counts between the two groups, including heparan sulfate proteoglycan perlecan, which showed significant upregulation in the follicular fluids containing fertilized oocytes in comparison with that observed in the follicular fluids containing non-fertilized oocytes. Our results suggest a possibility that proteins identified by LC/MS/MS in follicular fluid might not only be involved in folliculogenesis, but also function as biomarkers possessing predictive potential for oocyte maturation and the success of IVF when their expression levels are significantly different between fertilized and non-fertilized oocytes, although no distinctive biomarkers were identified in the current study.
    Journal of Assisted Reproduction and Genetics 07/2013; · 1.82 Impact Factor
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    ABSTRACT: A reduced response to progesterone in the eutopic endometrium with endometriosis and in endometriotic tissues is considered to be the underlying factor for endometriosis. CD10 is known to be expressed by endometrial and endometriotic stromal cells and may be induced by progestins, although the function of CD10 is not fully revealed in endometrial or endometriotic tissues. In the current study, the expression of CD10 was significantly increased by treatment of the cells with progesterone, 17β-estradiol, and dibutyryl cyclic adenosine monophosphate (cAMP) in the endometrial stromal cells. On the other hand, the expression of CD10 following treatment with progesterone, 17β-estradiol, and dibutyryl cAMP was not significantly increased in endometriotic stromal cells. The adhesion assay for endometrial and endometriotic stromal cells to hyaluronan using 5- or 6-(N-succinimidyloxycarbonyl)-fluorescein 3', 6'-diacetate-labeled cells demonstrated that the CD44-dependent adhesion of stromal cells was inhibited by CD10. As far as the induction of CD10 is concerned, the effect of progesterone was different between endometrial stromal cells and endometriotic stromal cells. CD10 might be involved in the development of endometriosis due to its influence on CD44-dependent cell adhesion.
    Reproductive sciences (Thousand Oaks, Calif.) 05/2013; · 2.31 Impact Factor
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    ABSTRACT: OBJECTIVE: To investigate whether the serum antimüllerian hormone (AMH) levels recover within 1 year after cystectomy for endometriomas, and to analyze the pattern of sequential changes in the serum AMH levels. DESIGN: Prospective study. SETTING: University hospital. PATIENT(S): Thirty-nine patients undergoing cystectomy for unilateral endometrioma (n = 22) and bilateral endometriomas (n = 17). INTERVENTION(S): Serum samples collected 2 weeks before, and 1 month and 1 year after surgery were assayed for AMH levels. MAIN OUTCOME MEASURE(S): Assessment of the ovarian reserve damage based on alterations in the serum AMH levels and the association with parameters of endometriosis and surgery for endometriomas. RESULT(S): The median AMH levels were 3.56, 1.90, and 2.10 ng/mL before, 1 month after, and 1 year after surgery, respectively. Twenty patients showed higher AMH levels 1 year after surgery than 1 month after surgery (increase group); 19 patients showed lower AMH levels (decrease group). We found a statistically significant difference in the number of follicles removed by surgery between the two groups. CONCLUSION(S): The decrease in the serum AMH levels caused by cystectomy can recover. Our results suggest that removal of ovarian cortex might be involved in the decrease of the ovarian reserve just after surgery, and that a continuous decrease of the ovarian reserve after cystectomy might be attributed to other mechanisms.
    Fertility and sterility 04/2013; · 3.97 Impact Factor
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    ABSTRACT: OBJECTIVE: The loss of primordial follicles from gonadal damage caused by chemotherapy results in decreased ovarian reserve. To assess the impact of chemotherapy for patients with gestational trophoblastic neoplasia (GTN) on the ovarian reserve, we evaluated the post-chemotherapy serum anti-Müllerian hormone (AMH) levels. STUDY DESIGN: In 22 patients with GTN receiving chemotherapy, serum AMH levels were measured after the administration of chemotherapy and compared with serum AMH levels measured in patients with hydatidiform mole who did not receive chemotherapy, as a control. We also analyzed differences in the serum AMH levels following the administration of different anti-cancer agents. RESULTS: The serum AMH levels measured in the GTN group after chemotherapy was administered (median 1.18, range 0.32-3.94ng/mL) significantly decreased in comparison to those measured in the control group (median 4.22, range 0.77-6.53ng/mL, P=0.002). Serum AMH levels were significantly lower in the patients who had received a regimen including etoposide than in the patients who had not received treatment with etoposide (0.71 vs. 1.30ng/mL, P=0.027). CONCLUSION: Our results suggest that chemotherapy administered to treat GTN does indeed affect the ovarian reserve, especially in patients who receive a medication regimen that includes etoposide. Measuring their serum AMH levels might therefore be helpful for counseling GTN patients regarding their ovarian reserve.
    European journal of obstetrics, gynecology, and reproductive biology 12/2012; · 1.97 Impact Factor
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    ABSTRACT: To investigate the protective effect of sphingosine-1-phosphate (S1P) against H(2)O(2)-induced apoptosis in human granulosa cell cultures with freshly harvested granulosa cells. Experimental study. Academic medical center for reproductive medicine. Cultures of primary granulosa cells isolated from women undergoing in vitro fertilization (IVF). None. Cell apoptosis and Western blot analysis of signaling pathway proteins. We found that S1P (1 and 10 mM) statistically significantly decreased granulosa cell apoptosis after H(2)O(2) treatment. The decreased cell apoptosis induced by S1P was abolished after treatment with VPC23019, an inhibitor of S1P1 and S1P3 receptors, W146, an inhibitor of S1P1 receptors, and CAY10444, an inhibitor of S1P3 receptors. A Western blot analysis revealed that the level of phospho-Akt increased and peaked at 10 minutes after 10 mM S1P exposure. Treatment with S1P can inhibit the apoptosis of granulosa cells in response to oxidative stress induced by H(2)O(2). The protective effect of S1P is mediated by activating the PI3K/Akt pathway, and the antiapoptotic effect of S1P is mainly mediated through the S1P1 and S1P3 receptor.
    Fertility and sterility 07/2012; 98(4):1001-1008.e1. · 3.97 Impact Factor
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    ABSTRACT: The ovary is a complex endocrine organ responsible for steroidogenesis and folliculogenesis. Follicles consist of oocytes and two primary steroidogenic cell types, the granulosa cells, and the theca cells. Immortalized human granulosa cells are essential for researching the mechanism of steroidogenesis and folliculogenesis. We obtained granulosa cells from a 35-yr-old female and immortalized them by lentivirus-mediated transfer of several genes so as to establish a human nonluteinized granulosa cell line (HGrC1). We subsequently characterized HGrC1 and investigated its steroidogenic performance. HGrC1 expressed enzymes related to steroidogenesis, such as steroidogenic acute regulatory protein, CYP11A, aromatase, and gonadotropin receptors. Stimulation with FSH increased the mRNA levels of aromatase, which consequently induced the aromatization of androstenedione to estradiol. Activin A increased the mRNA levels of the FSH receptor, which were synergistically up-regulated with FSH stimulation. HGrC1 also expressed a series of ligands and receptors belonging to the TGF-β superfamily. A Western blot analysis showed that bone morphogenetic protein (BMP)-4, BMP-6, and BMP-7 phosphorylated small mother against decapentaplegic (Smad)1/5/8, whereas growth differentiation factor-9 phosphorylated Smad2/3. BMP-15 and anti-Müllerian hormone phosphorylated Smad1/5/8 while also weakly phosphorylating Smad2/3. These results indicate that HGrC1 may possess the characteristics of granulosa cells belonging to follicles in the early stage. HGrC1 might also be capable of displaying the growth transition from a gonadotropin-independent status to gonadotropin-dependent one.
    Endocrinology 03/2012; 153(6):2851-60. · 4.72 Impact Factor
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    ABSTRACT: Inflammatory mediators, including chemokines, may play crucial roles in the development of endometriosis. Therefore, we investigated the expression and localization of CXCL16 and its receptor, CXCR6, in ovarian endometriotic tissues. We also examined whether CXCL16 induces IL-8 production in endometriotic stromal cells. We performed immunohistochemical and Western blotting analyses of in vivo and in vitro samples. IL-8 production was assayed using an ELISA. Both CXCL16 and CXCR6 were expressed by endometriotic epithelial cells and stromal cells, but not normal ovarian stroma. A Western blotting analysis using primary cultured endometriotic stromal cells showed a constant expression of CXCL16 and CXCR6 in the proliferative phase, secretory phase and during gonadotropin-releasing hormone agonist therapy. CXCL16 induced IL-8 production in several endometriotic stromal cells in vitro. CXCL16 and CXCR6 might be involved in the pathophysiology of endometriosis through regulation of the inflammatory response.
    Archives of Gynecology 07/2011; 284(6):1567-72. · 0.91 Impact Factor
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    ABSTRACT: BACKGROUND To assess the impact of ovarian cystectomy for endometriomas on the ovarian reserve, we evaluated the pre- and post-operative levels of serum anti-Müllerian hormone (AMH). We also analyzed the correlations between factors related to endometriosis and surgery for endometriomas and the serum AMH levels to investigate which factors affect ovarian reserve. METHODS Thirty-eight patients who were undergoing ovarian cystectomy for unilateral endometrioma (n = 20) and bilateral endometriomas (n = 18) participated. Preoperative and post-operative serum samples were collected and assayed for AMH levels, and changes between the two samples were analyzed in association with parameters of endometriosis and surgery for endometriomas. RESULTS The mean AMH level was 3.9 ng/ml prior to surgery, and was reduced to 2.1 ng/ml at 1 month post-surgery. The rate of decline of the serum AMH level was significantly higher in the bilateral group than the unilateral group (62.8 ± 29.6 versus 24.7 ± 32.5%, P < 0.001). The rate of decline in the serum AMH levels showed a significant correlation to the revised American Society for Reproductive Medicine (rASRM) score (P = 0.003), but not age, cyst diameter, blood loss during the operation or the number of follicles removed in the specimens. CONCLUSIONS Our results suggest that the decrease in ovarian reserve should be taken into account in patients indicated for cystectomy for bilateral endometriomas or unilateral endometrioma with high rASRM scores.
    Human Reproduction 02/2011; 26(4):904-10. · 4.67 Impact Factor