Takuhiro Hayashi

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

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.

Pregnancy-related complications after vaginal radical trachelectomy for early-stage invasive uterine cervical cancer

BackgroundPregnancy-related complications after vaginal radical trachelectomy (RT) for early-stage invasive uterine cervical cancer were studied in comparison with those occurring after laser conization. The strategy to reduce vaginal RT-related complications during pregnancy is also discussed.MethodsPregnancy courses after vaginal RT in two patients and those after laser conization in five patients, whose operations were performed during the same period, were studied with respect to symptoms, cervical length, and infectious signs.ResultsThe cervix shortened progressively both in patients with laser conization and in those with RT. However, throughout the pregnancy, the remaining cervix after the operation was longer in patients who had undergone conization than in those who had undergone vaginal RT. After laser conization, two of the five patients suffered from preterm rupture of the membrane (PROM) at 36 weeks of gestation, and both patients who had undergone vaginal RT had premature PROM (pPROM), at 32 and 24 weeks of gestation, respectively.ConclusionPrevention of preterm labor and the following occurrence of pPROM is a significant task to be resolved in order to improve pregnancy outcome after vaginal RT for early-stage invasive uterine cervical cancer. Daily vaginal disinfection with povidone iodine and the administration of a ulinastatin vaginal suppository, bed rest, and the use of ritodrine would be the best approach, and a more conservative approach for stage Ia2 also might be taken into consideration.

Coordinated elevation of membrane type 1-matrix metalloproteinase and matrix metalloproteinase-2 expression in rat uterus during postpartum involution

BackgroundThe changes occurring in the rodent uterus after parturition can be used as a model of extensive tissue remodeling. As the uterus returns to its prepregnancy state, the involuting uterus undergoes a rapid reduction in size primarily due to the degradation of the extracellular matrix, particularly collagen. Membrane type-I matrix metalloproteinase (MT1-MMP) is one of the major proteinases that degrades collagen and is the most abundant MMP form in the uterus. Matrix metalloproteinase-2(MMP-2) can degrade type I collagen, although its main function is to degrade type IV collagen found in the basement membrane. To understand the expression patterns of matrix metalloproteinases (MMPs) in the rat uterus, we analyzed their activities in postpartum uterine involution.MethodsWe performed gelatin zymography, northern blot analysis and immunohistochemistry to compare the expression levels of MT1-MMP, MMP-2, matrix metalloproteinase-9 (MMP-9) and the tissue inhibitors of MMPs-1 and 2 (TIMP-1 and TIMP-2) in the rat uterus 18 h, 36 h and 5 days after parturition with their expression levels during pregnancy (day 20).ResultsWe found that both MT1-MMP and MMP-2 localized mainly in the cytoplasm of uterine interstitial cells. The expression levels of MT1-MMP and MMP-2 mRNAs and the catalytic activities of the expressed proteins significantly increased 18 h and 36 h after parturition, but at postpartum day 5, their mRNA expression levels and catalytic activities decreased markedly. The expression levels of MMP-9 increased 18 h and 36 h after parturition as determined by gelatin zymography including the expression levels of TIMP-1 and TIMP-2.ConclusionThese expression patterns indicate that MT1-MMP, MMP-2, MMP-9, TIMP-1 and TIMP-2 may play key roles in uterine postpartum involution and subsequent functional regenerative processes.

Successful delivery after vaginal radical trachelectomy for invasive uterine cervical cancer.

A 32-year-old Japanese woman was diagnosed as having stage Ib1 adenocarcinoma by diagnostic laser conization at a local hospital. She was admitted to our hospital for fertility-sparing treatment. A radical trachelectomy (RT) was performed using the laparoscopic vaginal procedure. The procedure was started with a laparoscopic pelvic lymphadenectomy. As the lymph nodes were tumor free, RT was carried out transvaginally. The excised uterine cervix and lymph nodes were pathologically negative for cancer. Eight months after the operation, the patient became pregnant without any artificial reproduction techniques. At 17 weeks of gestation, she was admitted to our hospital again for a threatened abortion. Continuous tocolytic treatment with ritodrine and daily administration of a granulocyte elastase inhibitor vaginal suppository were given. At 32 weeks of gestation, she underwent emergency cesarean section because of sudden premature rupture of the membranes. A girl weighing 1991 g was delivered, with Apgar scores of 7 and 8 at 1 and 5 min, respectively. Both the mother and the baby were discharged without trouble. This is the first successful case in Japan of delivery after vaginal RT for invasive uterine cervical cancer.

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

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 −420 of the resistin gene (RETN) and/or −11377 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−420G/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−420G/G genotype also showed significantly higher BMIs and greater insulin resistance than those with RETN−420 C/C or C/G genotypes. The ADIPOQ SNP at −11377 showed no association with PCOS. We conclude that the RETN G/G at −420 genotype is associated with PCOS in Japanese women.

Antenatal diagnosis of prune belly syndrome at 11 weeks of gestation.

We present a case of prune belly syndrome diagnosed by ultrasonography at 11 weeks of gestation. We believe this case to be the earliest detection of this syndrome.

Successful twin pregnancy in panhypopituitarism caused by suprasellar germinoma.

BACKGROUND Pregnancy in a woman with hypopituitarism from a suprasellar germinoma is rare. CASE A 27-year-old woman presented with panhypopituitarism from a suprasellar germinoma. She had diabetes insipidus, hypothyroidism, adrenal cortex dysfunction, and hypogonadotropic ovarian failure. When treated with thyroxin, cortisol, antidiuretic hormone, human menopausal gonadotropin, and human chorionic gonadotropin, she conceived and gave birth to healthy twins. CONCLUSION Hormonal replacement therapy and ovulation induction resulted in a successful pregnancy in a woman with panhypopituitarism.

Advanced epithelial ovarian carcinoma during pregnancy

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.

Successful Uterus-Preserving Surgery for Treatment of Chemotherapy-Resistant Placenta Increta

Treatment of placenta increta often entails abdominal total hysterectomy. We present a case of placenta increta in which 3-dimensional computed tomography shows very high blood flow to the placenta, even after chemotherapy with methotrexate. Nonetheless, we were able to remove the region of the uterus that had been invaded by chorionic villi. Massive bleeding during the operation was prevented by ligation of the hypogastric artery and local injection of vasopressin. The combination of chemotherapy and partial resection of the uterus is quite a unique treatment for placenta increta patients. This approach enabled preservation of the uterus and the patient’s fertility. We suggest this procedure could be one of the treatments for patients who have placenta increta and wish to retain their fertility.

Hemorrhagic infarction of fibroma. MR imaging appearance.

Abstract We experienced a case of hemorrhagic infarction of the ovarian fibroma and that indicated the characteristic following appearance: exhibiting a high signal intensity area observed at the periphery of mass on T1-weighted MRI (magnetic resonance imaging). It was thought that this appearance developed because hemorrhagic infarction was caused by subacute ovarian torsion. This is a useful finding for suspecting hemorrhagic infarction preoperatively.