Details of a Researcher - BABA Tsuyoshi

Papers - BABA Tsuyoshi

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母児ともに救命し得た大動脈解離合併妊娠の3例

嶋田浩志, 岡村直樹, 染谷真行, 齋藤雅恵, 竹田倫子, 浅野拓也, 明石祐史, 馬場剛, 石岡伸一, 遠藤俊明, 齋藤豪

北日本産科婦人科学会総会・学術講演会プログラム・抄録集 ( 東北連合産科婦人科学会・北日本産科婦人科学会 ) 60回 90 - 90 2012.09

Simultaneous presentation of tubal and primary abdominal pregnancies following clomiphene citrate treatment.

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Naoko Takenami, Ayumi Shimizu, Miyuki Morishita, Hiroyuki Honnma, Hideyuki Ikeda, Tsuyoshi Saito

Archives of gynecology and obstetrics 286 ( 2 ) 395 - 8 2012.08 [International journal]

Abdominal pregnancy is a rare condition that is potentially life-threatening for the mother. We present a case of simultaneous ectopic pregnancies (EPs) in the right fallopian tube and in the vesicouterine pouch. A 26-year-old woman had undergone prior ovulation induction with clomiphene citrate and human chorionic gonadotropin (hCG) at an outside hospital for unexplained infertility. The patient was referred to our hospital for a suspected ectopic pregnancy at 6 weeks gestation. Transvaginal ultrasonography detected a viable fetus at the anterior left side of the uterus; therefore, we suspected a left tubal pregnancy. However, laparoscopic surgery revealed that EPs were located in both the left vesicouterine pouch and in the right fallopian tube. Resection of the right salpinx and abdominal implant were performed. Histopathological examination confirmed the simultaneous presentation of a primary abdominal pregnancy and a right tubal pregnancy. After surgery, the patient's serum hCG level returned to normal. Concurrent EPs and abdominal pregnancy are very rare. However, it should be noted that reproductive technologies sometimes cause unusual clinical situations. A thorough abdominal inspection is needed.

DOI PubMed

Trophectoderm morphology significantly affects the rates of ongoing pregnancy and miscarriage in frozen-thawed single-blastocyst transfer cycle in vitro fertilization.

Hiroyuki Honnma, Tsuyoshi Baba, Masahiro Sasaki, Yoshiki Hashiba, Hiroshi Ohno, Takanori Fukunaga, Toshiaki Endo, Tsuyoshi Saito, Yoshimasa Asada

Fertility and sterility 98 ( 2 ) 361 - 7 2012.08 [International journal]

OBJECTIVE: To determine which parameter of blastocyst morphology is the most important predictor of ongoing pregnancy or miscarriage. DESIGN: Retrospective analysis. SETTING: One in vitro fertilization (IVF) center. PATIENT(S): Women who underwent a total of 1,087 frozen-thawed single-blastocyst transfer cycles. INTERVENTION(S): First IVF treatment with blastocysts after frozen-thawed cycle. MAIN OUTCOME MEASURE(S): Ongoing pregnancy and miscarriage rates as related to blastocyst morphology (blastocyst expansion, inner cell mass, and trophectoderm), and interaction tests in unadjusted logistic regression models to assess clinical factors affecting outcomes. RESULT(S): After adjustment for trophectoderm, inner cell mass, and age as confounders, trophectoderm was determined to be statistically significantly related to the rate of ongoing pregnancy. Trophectoderm was also statistically significantly related to the miscarriage rate. By contrast, neither inner cell mass nor blastocyst expansion was statistically significantly related. CONCLUSION(S): In frozen-thawed embryo transfer cycles, trophectoderm morphology is statistically significantly related to the rates of ongoing pregnancy and miscarriage after adjusting for confounders. Trophectoderm morphology may be the most important parameter when selecting a single blastocyst for transfer.

DOI PubMed

Different ovarian response by age in an anti-Müllerian hormone-matched group undergoing in vitro fertilization.

Hiroyuki Honnma, Tsuyoshi Baba, Masahiro Sasaki, Yoshiki Hashiba, Hisanori Oguri, Takanori Fukunaga, Toshiaki Endo, Yoshimasa Asada

Journal of assisted reproduction and genetics 29 ( 2 ) 117 - 25 2012.02 [International journal]

BACKGROUND: Recently, serum anti-Müllerian hormone (AMH) has been used as a good marker of ovarian response during in vitro fertilization (IVF). However, in the clinical setting, we felt that ovarian response was clearly different by age with the same AMH level. Then in this study we evaluated the relationship between serum AMH, age and parameters related to ovarian response and compared these parameters in regard to age within serum AMH-matched group. METHODS AND RESULTS: The relationship of these parameters were evaluated retrospectively in patients undergoing their first IVF cycle under a GnRH agonist flare up protocol (n = 456) between October 2008 and October 2010 in our clinic. To understand the relations between variables described above, principal component analysis (PCA) was performed. PCA revealed patients' age was at the different dimension from serum AMH and other variables. Therefore at first we segregated all patients into Low, Normal and High responder groups by their serum AMH using cut-off value of receiver operator characteristics curve analysis. Secondary, we divided each responder group into four subgroups according to patients' age. The high aged subgroups required a significantly higher dose of gonadotropin and a longer duration of stimulation; however, they had significantly lower peak E2 and a smaller number of total oocytes as well as M2 oocytes compared to the low aged subgroups. CONCLUSIONS: The influence of aging on the ovarian response was clearly seen in all groups; the ovarian response tended to decrease as patients' age increased with the same AMH level. Therefore serum AMH in combination with age is a better indicator than AMH alone.

DOI PubMed

Continuous follicle-stimulating hormone exposure from pituitary adenoma causes periodic follicle recruitment and atresia, which mimics ovarian hyperstimulation syndrome.

Mika Kanaya, Tsuyoshi Baba, Yoshimitsu Kitajima, Keiko Ikeda, Ayumi Shimizu, Miyuki Morishita, Hiroyuki Honnma, Toshiaki Endo, Tsuyoshi Saito

International journal of women's health 4 427 - 31 2012 [International journal]

CONTEXT: Follicle-stimulating hormone (FSH)-secreting pituitary adenoma is usually a nonfunctioning tumor, but in rare cases it may develop into ovarian hyperstimulation. Several reports have revealed that serum FSH levels are normal to slightly high in patients with combined FSH-secreting pituitary adenoma with ovarian hyperstimulation. This finding is different from iatrogenic ovarian hyperstimulation syndrome (OHSS), which is associated with extremely high levels of FSH. OBJECTIVE: To describe the clinical course of two patients who developed OHSS from FSH-secreting pituitary adenoma. RESULTS: Endocrine studies of the two cases revealed that FSH levels were normal or slightly increased, but luteinizing hormone levels were low to undetectable. Their estradiol (E2) levels were intriguing: levels fluctuated drastically over 6 weeks in Case 1, but stayed flat in Case 2. Ultrasonographic examinations showed bilaterally enlarged multicystic ovaries, and magnetic resonance imaging indicated pituitary tumors. Transsephenoidal resection of the tumors ameliorated the symptoms and pathological diagnosis revealed FSH-secreting pituitary adenomas. CONCLUSION: As is not the case in iatrogenic OHSS, even a small to moderate amount of FSH stimulation, which is continuously secreted by a pituitary adenoma, can cause ovarian hyperstimulation. Although FSH-secreting pituitary adenoma can cause ovarian hyperstimulation, an extremely high amount of E2 biosynthesis from granulosa cells seldom occurs.

DOI PubMed

A Remarkably Easy Knot-Tying Technique for Single-Incision Laparoscopic Surgery with the SILS Port for Gynecologic Diseases

Toshiaki Endo, Kunihiko Nagasawa, Kota Umemura, Tsuyoshi Baba, Hirofumi Henmi, Tsuyoshi Saito

JOURNAL OF MINIMALLY INVASIVE GYNECOLOGY ( ELSEVIER SCIENCE INC ) 18 ( 4 ) 500 - 502 2011.07 [Refereed] [International journal]

Single-incision laparoscopic surgery (SILS) has been quickly accepted, especially for women, because the cosmetic benefits may be greater than with ordinary laparoscopic surgery. In gynecologic disease, SILS is appropriate for diagnostic laparoscopy, oophorectomy, and salpingectomy, among other conditions. In addition, the knot-tying process for intracorporeal suturing during SILS is a major rate-limiting step and a key determinant of the popularity of SILS. Although a roticulator instrument is useful for creating the needed operative angle, knot tying is still believed to be difficult. We have devised a remarkably simple knot-tying technique that can be applied during SILS with a SILS Port with a Roticulator and a straight-type needle driver. We determined that, after transfixing the needle, the long tail of the thread should be grasped at around 90 degrees relative to the long axis of tip of the Roticulator, which is articulated at 80 degrees. This automatically forms an ideal C-loop because of gravitation. The needle attached to the long tail should face the distal side from the tip of Roticulator (from the surgeon's perspective). The apex of the C-loop is then toward the proximal side from the tip of the Roticulator (from the perspective of the surgeon). This thread position is important during the knot-tying process. The upper arm of the C-loop should then be entwined by applying a series of axial spinning movements to the rod of the needle driver. At this time, the jaws of the needle driver should be kept open so the thread does not slip off of the rod. The benefit of this technique is that it does not require any special skills; any surgeon able to perform intracorporeal suturing should also be able to easily tie knots during SILS. Journal of Minimally Invasive Gynecology (2011) 18, 500-502 (C) 2011 AAGL. All rights reserved.

DOI PubMed

Distinctive features of female-to-male transsexualism and prevalence of gender identity disorder in Japan.

Tsuyoshi Baba, Toshiaki Endo, Keiko Ikeda, Ayumi Shimizu, Hiroyuki Honnma, Hiroshi Ikeda, Naoya Masumori, Tousei Ohmura, Tamotsu Kiya, Takashi Fujimoto, Motoiki Koizumi, Tsuyoshi Saito

The journal of sexual medicine 8 ( 6 ) 1686 - 93 2011.06 [International journal]

INTRODUCTION: The prevalence of transsexualism is thought to differ among socio-geographic backgrounds, and little is known about its prevalence in Japan. Polycystic ovary syndrome (PCOS), which is known to be associated with insulin resistance and metabolic syndrome, is often seen in female-to-male (FTM) transsexual patients. Consequently, detection of PCOS is an important part of health care for these individuals. AIM: The purpose of this study was to assess the prevalence of transsexuality in Japan, as well as the incidences of PCOS and insulin resistance among Japanese FTM transsexual patients. METHODS: One hundred four male-to-female (MTF) and 238 FTM Japanese transsexual patients were studied. Medical histories, including histories of menstrual cycling and hormone treatment, were taken. To exclude other diseases, such as congenital adrenal hyperplasia and hormone-secreting tumors, thorough medical assessments, including transvaginal or transrectal ultrasonography and measurement of serum hormone levels and insulin resistance indexes, were performed. MAIN OUTCOME MEASURES: The diagnosis of PCOS was based on the Rotterdam 2003 criteria. RESULTS: Based on demographic statistics, the prevalences of MTF and FTM transsexuality are about 3.97 and 8.20 per 100,000 people, respectively, making the MTF-to-FTM ratio about 1:2. Of the FTM transsexual patients studied, 128 had not taken hormones before their initial assessment (untreated group); the remaining 50 self-administered androgen. Among the untreated group, 32.0% were diagnosed with PCOS, 30.1% were insulin-resistant, and 31.1% showed hypoadiponectinemia. CONCLUSIONS: The sex ratio among Japanese transsexuals is different than among Caucasians. PCOS and insulin resistance are common findings in FTM transsexual patients at initial presentation.

DOI PubMed

Changes of uterine blood flow after vaginal radical trachelectomy (VRT) in patients with early-stage uterine invasive cervical cancer.

Kota Umemura, Shin-ichi Ishioka, Toshiaki Endo, Tsuyoshi Baba, Yoshiaki Ezaka, Kunihiko Nagasawa, Madoka Takahashi, Masahito Mizuuchi, Nanako Iwami, Hidefumi Adachi, Noriko Takeda, Mitsuharu Tamagawa, Tsuyoshi Saito

International journal of medical sciences 7 ( 5 ) 260 - 6 2010.08 [International journal]

BACKGROUND: Vaginal radical trachectomy (RT) ligates and cuts several arteries supplying the uterus. Changes of blood supply to the uterus in two patients who experienced pregnancy and delivery were studied by using 3-D CT scanning. Effects of changes of blood supply to the uterus on the pregnancy courses were also examined. METHODS: Vascular distribution in the uterus was studied in two patients who received vaginal RT after delivery. Effects of changes of vascular distribution after vaginal RT were studied with respect to pregnancy courses and cervical functions. RESULTS: New arterial vascularization from the ascending branches of uterine arteries or other arteries occurred, and these new vessels seemed to supply blood to the remaining cervix. Differences of fetal growth and histopathological changes in the placenta between the two patients could not be detected. CONCLUSION: Ligation and cutting of several supplying arteries by RT induces new arterial vascularization and it does not seem to affect fetal growth and placental function.

PubMed

Remarkable features of ovarian morphology and reproductive hormones in insulin-resistant Zucker fatty (fa/fa) rats.

Hiroyuki Honnma, Toshiaki Endo, Tamotsu Kiya, Ayumi Shimizu, Kunihiko Nagasawa, Tsuyoshi Baba, Takashi Fujimoto, Hirofumi Henmi, Yoshimitsu Kitajima, Kengo Manase, Shinichi Ishioka, Eiki Ito, Tsuyoshi Saito

Reproductive biology and endocrinology : RB&E 8 73 - 73 2010.06 [International journal]

BACKGROUND: Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. METHODS: In this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7). RESULTS: Ovaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats. CONCLUSIONS: Our findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.

DOI PubMed

Spontaneous ovarian hyperstimulation syndrome and pituitary adenoma: incidental pregnancy triggers a catastrophic event.

Tsuyoshi Baba, Toshiaki Endo, Yoshimitsu Kitajima, Hirofumi Kamiya, Osamu Moriwaka, Tsuyoshi Saito

Fertility and sterility 92 ( 1 ) 390.e1-3 2009.07 [International journal]

OBJECTIVE: To report a rare case of spontaneous ovarian hyperstimulation syndrome (OHSS) associated with spontaneous pregnancy and a FSH-secreting pituitary adenoma. DESIGN: Case report. SETTING: University hospital. PATIENT(S): A 32-year-old woman with spontaneous OHSS. INTERVENTION(S): Transsphenoidal resection of the tumor. MAIN OUTCOME MEASURE(S): Regression of the symptoms of OHSS and hyperestrogenemia. RESULT(S): At presentation, the patient's ovaries were markedly enlarged and massive ascites was seen. Her serum E(2) level was markedly elevated, but her LH level was low, and FSH was within the normal range. In addition, her TSH level was normal, and hCG was appropriate for the date of pregnancy. Subsequently, the patient developed massive thrombophlebitis in her right internal jugular and subclavian veins. Termination of the pregnancy ameliorated the accumulation of ascites, but ovarian enlargement and hyperestrogenemia persisted. No mutations of the FSH receptor, LH receptor, or aromatase genes were detected, but magnetic resonance imaging (MRI) of the head revealed a pituitary adenoma. After transsphenoidal resection of the tumor, the patient got better. CONCLUSION(S): A gonadotropin-secreting adenoma caused ovarian hyperstimulation (ovarian enlargement and hyperestrogenemia). In addition, spontaneous pregnancy and intrinsic hCG increased vascular permeability, which complicated the patient's disease.

DOI PubMed

The contributions of resistin and adiponectin gene single nucleotide polymorphisms to the genetic risk for polycystic ovary syndrome in a Japanese population

Tsuyoshi Baba, Toshiaki Endo, Fumihiro Sata, Kunihiko Nagasawa, Hiroyuki Honnma, Yoshimitsu Kitajima, Takuhiro Hayashi, Kengo Manase, Mika Kanaya, Osamu Moriwaka, Hirofumi Kamiya, Hideto Yamada, Hisanori Minakami, Reiko Kishi, Tsuyoshi Saito

GYNECOLOGICAL ENDOCRINOLOGY ( INFORMA HEALTHCARE ) 25 ( 8 ) 498 - 503 2009 [Refereed] [International journal]

Polycystic ovary syndrome (PCOS) is a heterogeneous group of disorders that occur fairly commonly in women of reproductive age and are characterized by a variety of clinical manifestations, including insulin resistance that is independent of obesity. Recent studies suggest that altered adipocytokine gene expression is closely associated with insulin resistance and that single nucleotide polymorphisms (SNPs) modulate the expression and/or function of these genes, thereby affecting insulin sensitivity. With that in mind, we investigated whether SNPs at position 7420 of the resistin gene (RETN) and/or 711377 of the adiponectin gene (ADIPOQ) modulate the susceptibility to PCOS. We evaluated the genotypes of 117 women with PCOS and 380 healthy fertile controls and measured the index of insulin resistance and hormonal profiles in the PCOS women. The RETN 7420G/G homozygous variant genotype occurred significantly more frequently among the PCOS group than among the control group (15.4% vs. 8.4%, p = 0.035). PCOS women with the RETN 7420G/ G genotype also showed significantly higher BMIs and greater insulin resistance than those with RETN 7420 C/C or C/G genotypes. The ADIPOQ SNP at 711377 showed no association with PCOS. We conclude that the RETN G/G at 7420 genotype is associated with PCOS in Japanese women.

DOI PubMed

Advanced epithelial ovarian carcinoma during pregnancy.

Shin-ichi Ishioka, Takuhiro Hayashi, Toshiaki Endo, Tsuyoshi Baba, Hiroyuki Honma, Tsuyoshi Saito

International journal of clinical oncology 12 ( 5 ) 375 - 8 2007.10 [Domestic journal]

We report a rare case of advanced ovarian mucinous adenocarcinoma in a pregnant woman. A 28-year-old pregnant Japanese woman was diagnosed with an ovarian tumor 8 cm in diameter at a local hospital. She was sent to a private hospital at 25 weeks of gestation because of the growing ovarian tumor. Advanced ovarian carcinoma with widespread intraabdominal dissemination was detected by laparotomy at the hospital and she was referred to our hospital for further management. At 27 weeks of gestation, she underwent cesarean section, followed by abdominal total hysterectomy, and bilateral salpingo-oophorectomy. A girl weighing 879 g was delivered, with Apgar scores of 4 and 6 at 1 and 5 min, respectively. The pathological diagnosis of the tumor was mucinous cystadenocarcinoma grade 2. Although chemotherapy was not effective for her and she died of the disease 4 months after the surgery, her baby grew well and weighed 3750 g 3 months after delivery. For the treatment of such patients, we believe we should choose operative therapy as early as possible after the maturation of the fetus, although there are several reports of successful treatment with the administration of chemotherapy during pregnancy. To determine a better approach for such patients, multidisciplinary staff meetings, including gynecological oncologists, obstetricians, neonatologists, psychologists, and the patient are important.

PubMed

Polycystic ovary syndrome is associated with genetic polymorphism in the insulin signaling gene IRS-1 but not ENPP1 in a Japanese population.

Tsuyoshi Baba, Toshiaki Endo, Fumihiro Sata, Hiroyuki Honnma, Yoshimitsu Kitajima, Takuhiro Hayashi, Kengo Manase, Mika Kanaya, Hideto Yamada, Hisanori Minakami, Reiko Kishi, Tsuyoshi Saito

Life sciences 81 ( 10 ) 850 - 4 2007.08 [International journal]

Recent studies indicate that insulin resistance resulting from altered post-receptor signaling is associated with polycystic ovary syndrome (PCOS). We hypothesized that insulin receptor substrate-1 (IRS-1) Gly972Arg polymorphism and/or ectonucleotide pyrophosphatase/phosphodiesterase 1 (ENPP1) Lys121Gln polymorphism predisposes women to PCOS and that these polymorphisms also affect anthropometric variables, glucose metabolism and androgen synthesis. To test those ideas, we studied the genotypes, indexes of insulin resistance, and hormone profiles in 123 Japanese women with PCOS and 380 healthy Japanese controls. We found that there were significantly more IRS-1 972Arg carriers among the PCOS patients than among the healthy controls (10.6% vs. 4.8%, p=0.029), which is consistent with our finding that women carrying the IRS-1 972Arg allele had a significantly increased risk of developing PCOS (odds ratio: 3.31, 95% confidence interval: 1.49-7.35). By contrast, the ENPP1 Lys121Arg polymorphism was distributed equally among PCOS patients and controls. In addition, neither of these polymorphisms studied affected the anthropometric variables, metabolic parameters or androgen levels of women with PCOS. We conclude that the IRS-1 Gly972Arg polymorphism is associated with PCOS in the Japanese population.

PubMed

Association between polycystic ovary syndrome and female-to-male transsexuality.

Tsuyoshi Baba, Toshiaki Endo, Hiroyuki Honnma, Yoshimitsu Kitajima, Takuhiro Hayashi, Hiroshi Ikeda, Naoya Masumori, Hirofumi Kamiya, Osamu Moriwaka, Tsuyoshi Saito

Human reproduction (Oxford, England) 22 ( 4 ) 1011 - 6 2007.04 [International journal]

BACKGROUND: The aim of this study is to understand the relationship between polycystic ovary syndrome (PCOS), altered hormonal characteristics and insulin resistance in female-to-male (FTM) transsexual patients. METHODS: We studied 69 Japanese FTM cases, aged 17-47 years, who were seen in the Gender Identity Disorder Clinic of Sapporo Medical University Hospital between December 2003 and May 2006. The subjects had never received hormonal treatment or sex re-assignment surgery. Prior to treatment, they received physical examinations entailing measurement of anthropometric, metabolic and endocrine parameters, after which we compared the values obtained according to the presence or absence of PCOS and/or obesity. Insulin resistance was determined using the homeostasis model assessment of insulin resistance (HOMA-IR). RESULTS: Of the 69 participating FTM cases, 40 (58.0%) were found to have PCOS. Of the 49 for whom HOMA-IR was calculated, 15 (30.6%) also showed insulin resistance, whereas of the 59 for whom adiponectin was measured, 18 (30.5%) showed hypoadiponectinaemia. Of 69 for whom androgens were measured, 29 (39.1%) showed hyperandrogenaemia. Insulin resistance was associated with obesity but not with PCOS. In contrast, hyperandrogenaemia was associated with both PCOS and obesity. CONCLUSION: FTM transsexual patients have a high prevalence of PCOS and hyperandrogenaemia.

PubMed

Significance of matrix metalloproteinases in the pathophysiology of the ovary and uterus.

Toshiaki Endo, Tamotsu Kiya, Taeko Goto, Hirofumi Henmi, Kengo Manase, Hiroyuki Honnma, Tsuyoshi Baba, Shinichi Ishioka, Takuhiro Hayashi, Manabu Chida, Kazuyo Arima, Kiyohiro Yamazaki, Mika Kanaya, Atsushi Azumaguchi, Osamu Moriwaka, Hirofumi Kamiya, Tsuyoshi Saito

Reproductive medicine and biology 5 ( 4 ) 235 - 243 2006.12 [Domestic journal]

Matrix metalloproteinases (MMP) are capable of degrading a variety of extracellular matrix (ECM) proteins and are also involved in the processing of a number of bioactive molecules. Our findings indicate that the functions of MMP in the ovary and uterus are organ-specific and time-dependently vary during the reproductive cycle. Prolactin induces structural luteolysis indicated by loss of luteal weight, protein and DNA within 36 h after pretreatment with ergot alkaloid. MMP activation appears crucial for the selective depletion of protein during luteal involution, which entails loss of ECM accompanied by apoptosis. During GnRHagonist-induced luteolysis, this response was also associated with marked increases in MMP-2, which degraded collagen type IV, and MT1-MMP, which in addition to activating MMP-2 also degrades collagen type I, III and V. We also found that the level of MT1-MMP and MMP-2 expression in the human CL is greater during the late luteal phase than during either the early mid luteal phases or during gestation, respectively. That dehydroepiandrosterone (DHEA) treatment caused the formation of cysts from antral follicles in the ovaries of immature rats while depressing MMP-2 collagenolytic activity and enhancing lysyl oxidase expression highlights the importance of collagen degradation in the process of ovulation and suggests that changes in the activities of these enzymes play a key role in ovarian cystogenesis in polycystic ovary syndrome patients. Furthermore, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive apoptotic granulosa cells in rats treated with DHEA, that the Fas/FasL/Caspase-8 (death receptor-dependent) pathway is pivotal for follicular atresia and that increased levels of MT1-MMP likely play an important role in tissue remodeling during follicular atresia. After parturition, the uterus undergoes involution, a conspicuous feature characterized by a rapid reduction in the collagen content mediated by degradation of extracellular collagen bundles. Our findings strongly suggest that MT1-MMP, MMP-2 and MMP-9 are each time-dependently regulated and play important roles in tissue remodeling during postpartum uterine involution. (Reprod Med Biol 2006; 5: 235-243).

DOI PubMed

Altered expression of Fas/Fas ligand/caspase 8 and membrane type 1-matrix metalloproteinase in atretic follicles within dehydroepiandrosterone-induced polycystic ovaries in rats.

Hiroyuki Honnma, Toshiaki Endo, Hirofumi Henmi, Kunihiko Nagasawa, Tsuyoshi Baba, Kiyohiro Yamazaki, Yoshimitsu Kitajima, Takuhiro Hayashi, Kengo Manase, Tsuyoshi Saito

Apoptosis : an international journal on programmed cell death 11 ( 9 ) 1525 - 33 2006.09 [International journal]

One of the characteristics of polycystic ovary syndrome (PCOS) is the presence of cystic follicles in various stages of growth and atresia, the latter of which is known to be the result of apoptosis and tissue remodeling. To further investigate the process of follicular atresia, we compared ovarian expression and localization of Fas, Fas ligand (FasL), casapse-8 and membrane-type1 matrix metalloproteinase (MT1-MMP) in rats treated with dehydroepiandrosterone (DHEA) as a model of PCOS, and in control rats. We found that the numbers of TdT-mediated dUTP-biotin nick end-labeling (TUNEL)-positive follicles were significantly higher in ovaries from PCOS rats than in those from control rats (P < 0.05), as were ovarian levels of FasL mRNA and protein, processed caspase-8 protein and MT1-MMP mRNA. Correspondingly, we also observed an increase in the level of MTI-MMP catalytic activity and a decrease in the level of pro-caspase-8 protein. In addition, immunohistochemical analyses showed that MT1-MMP and FasL co-localize with TUNEL-positive apoptotic granulosa cells within atretic follicles of PCOS ovaries. Our results suggest that under the PCOS-like conditions induced by DHEA, the Fas/FasL/Caspase-8 (death receptor dependent) pathway is pivotal for follicular atresia, and that increased levels of MT1-MMP likely play an important role in tissue remodeling during structural luteolysis.

PubMed

Hyperstimulation and a gonadotropin-releasing hormone agonist modulate ovarian vascular permeability by altering expression of the tight junction protein claudin-5.

Yoshimitsu Kitajima, Toshiaki Endo, Kunihiko Nagasawa, Kengo Manase, Hiroyuki Honnma, Tsuyoshi Baba, Takuhiro Hayashi, Hideki Chiba, Norimasa Sawada, Tsuyoshi Saito

Endocrinology 147 ( 2 ) 694 - 9 2006.02 [International journal]

We investigated the mechanism by which a GnRH agonist (GnRHa) affects ovarian vascularity, vascular permeability, and expression of the tight junction protein claudin-5 in a rat model of ovarian hyperstimulation syndrome (OHSS). Hyperstimulated rats received excessive doses of pregnant mare serum gonadotropin (PMSG; 50 IU/d) for 4 consecutive days, from d 25 to 28 of life, followed by 25 IU human chorionic gonadotropin (hCG) on d 29. Control rats received 10 IU PMSG on d 27 of life, followed by 10 IU hCG on d 29. GnRHa (leuprolide 100 microg/kg.d) was administered to some hyperstimulated rats either on d 29 and 30 (short-term GnRHa treatment) or from d 25 to 30 (long-term GnRHa treatment). Ovarian vascular density (vessels per 10 mm(2)) and vessel endothelial area (percent) were assessed by immunohistochemical analysis of the distribution of von Willebrand factor, whereas vascular permeability was evaluated based on leakage of Evans blue. High doses of PMSG and hCG significantly increased ovarian weight, vascular permeability, vascular density, and the vessel endothelial area and significantly reduced expression of claudin-5 protein and mRNA. All of these effects were significantly and dose-dependently inhibited by administration of GnRHa. This suggests that reduced expression of claudin-5 plays a crucial role in the increased ovarian vascular permeability seen in OHSS and that its expression can be modulated by GnRHa treatment. Indeed, preventing redistribution of tight junction proteins in endothelial cells and the resultant loss of endothelial barrier architecture might be the key to protecting patients against massive extravascular fluid accumulation in cases of OHSS.

PubMed

17th Symposium on Gynecology and Colposcopy July 15-16, 1998, Osaka, Japan. Characterization of subclonal cell lines showing high motility derived from an undifferentiated human endometrial cancer cell line

Motoiki Koizumi, Eiki Ito, Satoko Yamashita, Tsuyoshi Baba, Ikuhito Yamanaka, Takahiro Suzuki, Ryuichi Kudo

Gynecologic and Obstetric Investigation 48 ( 3 ) 206 - 210 1999

To examine the relationship between the morphology and the motility of cancer cells, we studied the difference between human endometrial undifferentiated cancer cell lines with different motilities, using light and electron microscopy, immunocytochemistry and RT-PCR. In a transplanted tumor of a cell line with high motility, many connective tissues and microvessels were observed and there were few intercellular spaces, which were ultrastructurally full of extracellular matrix. In the high-motility cell line only cytokeratin 19 was observed, and the level of cytokeratin 19 mRNA was elevated. Thus, motility is suggested to be related to the induction of connective tissues and cytoskeleton.

DOI PubMed

Cloning and characterization of a cDNA fragment coding β-casein-like protein preferentially expressed in cervical adenocarcinoma cell line CAC-1

Takahiro Suzuki, Motoiki Koizumi, Tsuyoshi Baba, Ryuichi Kudo

Cancer Letters ( Elsevier Ireland Ltd ) 124 ( 2 ) 165 - 171 1998.02

We generated new murine monoclonal antibodies against bovine β-casein. One of eight new monoclonal antibodies generated, 12G2, specifically reacted not only with β-casein, but also with human cervical adenocarcinoma cell line CAC-1. To identify the gene encoding the putative protein (BCLP) defined by monoclonal antibody (mAb) 12G2, a complementary DNA library was constructed. We obtained the inserted cDNA fragment that showed high homology to reported DNA sequences of unknown function in normal human placenta. We think that BCLP was overexpressed or changed its structure by carcinogenesis.

DOI PubMed

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Papers - BABA Tsuyoshi