Oncocytic adrenocortical neoplasm arising from adrenal rest in the broad ligament of the uterus.

Oncocytic adrenocortical neoplasm is characterized by abundant eosinophilic cytoplasm containing mitochondria, occasional nuclear atypia and diffuse growth pattern. Oncocytic adrenocortical neoplasm arising in adrenal rest is, however, extremely rare. We report a case of oncocytic adrenocortical neoplasm arising in adrenal rest of the broad ligament with associated marked lipomatous metaplasia. A well circumscribed tumor was accidentally detected in the pelvic cavity of a 29 year old Japanese woman, adjacent to the broad ligament of the uterus. The tumor was composed of large eosinophilic cells associated with diffuse growth pattern and abundant mature adipose tissue admixed with foci of clear cells. Both steroidgenic factor 1 (SF-1) and alpha-inhibin were immunohistochemically positive in tumor cells. Abundant mitochondria detected by immunohistochemical and electron microscopic examination confirmed the diagnosis of oncocytic adrenocortical neoplasm. The absence of necrosis, capsular and vascular invasion as well as the low mitotic index indicated the benign potential of this tumor. The tumor cells were also positive for dehydroepiandrosteron-sulfotransferase (DHEA-ST), 17ß-hydroxysteroid dehydrogenase type 5 (17ß-HSD5), 3ß-hydroxysteroid dehydrogenase (3ß-HSD) and steroid 17α-hydroxylase (P450-c17), suggesting a possible production of testosterone of this tumor. This is the first reported case of oncocytic adrenocortical adenoma arising in adrenal rest of the broad ligament.

Guidelines for office gynecology in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2011 edition.

Gynecology in the office setting is developing worldwide. Clinical guidelines for office gynecology were first published by the Japan Society of Obstetrics and Gynecology and the Japan Association of Obstetricians and Gynecologists in 2011. These guidelines include a total of 72 clinical questions covering four areas (Infectious disease, Malignancies and benign tumors, Endocrinology and infertility, and Healthcare for women). These clinical questions were followed by several answers, backgrounds, explanations and references covering common problems and questions encountered in office gynecology. Each answer with a recommendation level of A, B or C has been prepared based principally on evidence or consensus among Japanese gynecologists.These guidelines would promote a better understanding of the current standard care practices for gynecologic outpatients in Japan.

Detection of dicofol and related pesticides in human breast milk from China, Korea and Japan.

Previously, we demonstrated that the concentrations of DDTs were greater in breast milk collected from Chinese mothers than from Japanese and Korean mothers. To investigate dicofol as a possible source of the DDTs in human breast milk, we collected breast milk samples from 2007 to 2009 in China (Beijing), Korea (Seoul, Busan) and Japan (Sendai, Takarazuka and Takayama). Using these breast milk samples, we quantified the concentrations of dichlorobenzophenone, a pyrolysis product of dicofol (simply referred to as dicofol hereafter), dichlorodiphenyltrichloroethane and its metabolites (DDTs) using GC-MS. Overall, 12 of 14 pooled breast milk samples from 210 mothers contained detectable levels of dicofol (>0.1 ng g⁻¹ lipid). The geometric mean concentration of dicofol in the Japanese breast milk samples was 0.3 ng g⁻¹ lipid and significantly lower than that in Chinese (9.6 ng g⁻¹ lipid) or Korean breast milk samples (1.9 ng g⁻¹ lipid) (p<0.05 for each). Furthermore, the ΣDDT levels in breast milk from China were 10-fold higher than those from Korea and Japan. The present results strongly suggest the presence of extensive emission sources of both dicofol and DDTs in China. However, exposure to dicofol cannot explain the large exposure of Chinese mothers to DDTs because of the trace levels of dicofol in the ΣDDTs. In the present study, dicofol was confirmed to be detectable in human breast milk. This is the first report to identify dicofol in human samples.

Levels and regional trends of persistent organochlorines and polybrominated diphenyl ethers in Asian breast milk demonstrate POPs signatures unique to individual countries.

Human breast milk samples collected in 2007-2008 from four countries, Vietnam (Hanoi), China (Beijing), Korea (Seoul) and Japan (Sendai, Kyoto and Takayama), were analyzed for persistent organic pollutants (POPs) such as dichlorodiphenyltrichloroethane and its metabolites (DDTs), chlordane-related compounds (CHLs), hexachlorocyclohexanes (HCHs), hexachlorobenzene (HCB), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs). Comparing with previous surveys, the present study indicates that the DDTs in breast milk from China and Vietnam had gradually decreased during the last decade, but were still 5-10 times higher than those in other nations. The ratios of p,p'-DDE/p,p'-DDT and o,p'-DDT/p,p'-DDT were higher in Beijing than in the other countries, suggesting that there is less fresh intake of commercial DDT products and a possible exposure to dicofol in China. CHL and PCB levels were relatively higher in mothers from Japan, whereas beta-HCH and HCB were more common in Chinese women. In Japan, it is suspected that mothers in the urban/coastal area (Sendai) were more continuously exposed to organochlorine pesticides (OCPs) than mothers in the rural/inland area (Takayama). In addition, OCP levels in primiparae were significantly higher than those in multiparae from Japan and Korea. These indicate that both parity and regional factors are major determinants of the levels of OCPs and PCBs in human milk. On the other hand, higher concentrations of PBDEs were observed in mothers' milk from Korea. The congener was dominated by BDE-47 (43-54%), followed by BDE-153 (23-33%) in all regions except for Beijing where BDE-28 (23%) was relatively abundant. In Japanese breast milk, regional and parity-dependent distributions were not observed for PBDEs. Among PBDE congeners, age-dependency was observed for BDE-153, which was negatively correlated (p<0.05) to the age of mothers in Kyoto (17 participants were housewives), while it increased with age in Sendai (10 participants were clerks). No such correlation was seen for BDE-47, indicating that BDE-47 was ingested and assimilated via different kinetics or routes from BDE-153 in Japan.

Levels and concentration ratios of polychlorinated biphenyls and polybrominated diphenyl ethers in serum and breast milk in Japanese mothers.

Blood and/or breast milk have been used to assess human exposure to various environmental contaminants. Few studies have been available to compare the concentrations in one matrix with those in another. The goals of this study were to determine the current levels of polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) in Japanese women, with analysis of the effects of lifestyle and dietary habits on these levels, and to develop a quantitative structure-activity relationship (QSAR) with which to predict the ratio of serum concentration to breast milk concentration. We measured PBDEs and PCBs in 89 paired samples of serum and breast milk collected in four regions of Japan in 2005. The geometric means of the total concentrations of PBDE (13 congeners) in milk and serum were 1.56 and 2.89 ng/g lipid, respectively, whereas those of total PCBs (15 congeners) were 63.9 and 37.5 ng/g lipid, respectively. The major determinant of total PBDE concentration in serum and milk was the geographic area within Japan, whereas nursing duration was the major determinant of PCB concentration. BDE-209 was the most predominant PBDE congener in serum but not in milk. The excretion of BDE 209 in milk was lower than that of BDE 47 and BDE 153. QSAR analysis revealed that two parameters, calculated octanol/water partition and number of hydrogen-bond acceptors, were significant descriptors. During the first weeks of lactation, the predicted partitioning of PBDE and PCB congeners from serum to milk agreed with the observed values. However, the prediction became weaker after 10 weeks of nursing.

A trial to restore defective human sperm centrosomal function.

BACKGROUND: In human fertilization, sperm centrosome function is essential for male and female pronuclear movement and fusion. In this study, we investigated the possibility of restoring human sperm centrosomal function in sperm exhibiting abnormalities in microtubule organization. METHODS: Semen was obtained from both a fertile donor and a patient with dysplasia of the fibrous sheath (DFS). Following heterologous ICSI using human sperm, we examined microtubules and chromatin configuration in bovine oocytes. Sperm were treated with dithiothreitol (DTT) prior to ICSI, while the oocytes were treated with the cytoskeletal stabilizer paclitaxel after ICSI. RESULTS: The combination of DTT and paclitaxel treatment induced microtubule organization in dead sperm from the fertile donor following heterologous ICSI. This treatment, however, was not effective for DFS sperm. In addition, expression of centrin, a protein functioning within the sperm centrosome, was reduced in DFS sperm from that of the normal levels observed in fertile donor sperm. CONCLUSION: These results indicate that sperm centrosomal function could be induced by the treatment of sperm with DTT before ICSI and of oocytes with paclitaxel after ICSI. DFS sperm are likely to exhibit such severe dysfunction of sperm centrosome that cannot be compensated for by this treatment; therefore, this method may be a practical way to discern the degree of sperm centrosomal dysfunction.

Cervical cytologic examination during physical checkup of pregnant women: cervical cancer screening in women under the age of thirty.

Recently, the Ministry of Health, Labor and Welfare proposed that cervical cancer screening should be conducted for women aged 20 to 29 years old in Japan. However, there are insufficient data available in Japan concerning the screening conducted for women under the age of 30. Therefore, we made a survey of the results of cervical cytologic examination for pregnant women. 28,616 pregnant women were examined as subjects of a study group. A group of 108,289 women, subjected to group screening for cervical cancer in Miyagi Prefecture, were studied as a control group. The rate of subjects who required close examination in the pregnant women's group was significantly higher than that in the mass screening group (1.12% vs. 0.84%). The rate of close examination was significantly higher in the women 19 years old or younger compared to those in the age group of 25 to 39 years old. The rate was also significantly higher in women aged 20 to 24 years old than those who are 25 to 34 years old. Of the 321 subjects who required close examination, 34 cases underwent treatment, and 17 cases were under age 30. Moreover, all three cases of microinvasive and/or invasive carcinoma were under the age of 30 years (23, 23, 27 years old, respectively). Our results suggest that screening for cervical cancer in pregnancy is a useful means to find cervical neoplasia in young women and is effective in reducing the cervical cancer morbidity rate.

Genetic significance of skewed X-chromosome inactivation in premature ovarian failure.

To determine the relationship between premature ovarian failure (POF) and skewed X-chromosome inactivation (XCI), karyotype, and XCI status in 43 patients with POF (group I) and 43 age-matched control women with regular menstrual cycles (group II) were evaluated. Evaluation of XCI status was based on the CAG triplet repeat polymorphism assay in the androgen receptor gene after sodium bisulfite treatment of DNA samples, and XCI patterns were classified as random (XCI < 70% skewing) or skewed (> or =70%). Furthermore, skewed XCI was classified under three different thresholds (> or =70, > or =80, or > or =90%). Karyotyping by G-banding and fluorescence in situ hybridization (FISH) on peripheral blood lymphocytes showed that one patient in group I had a deletion of Xq22, and another was 47,XXX. The frequency of low-level 45,X/46,XX mosaicism was nearly equal in both groups. In women without any X-chromosomal aberrations, the incidence of skewed XCI in group I was significantly higher than in group II on all threshold levels. Furthermore, extremely skewed XCI (> or =90%) was observed only in group I. These results indicate that POF may be caused by some underlying genetic disorders, which may induce skewed XCI.

CpG dinucleotide methylation patterns in the human androgen receptor gene and X-chromosome inactivation in peripheral blood leukocytes of phenotypically normal women.

To evaluate methylation patterns in CpG dinucleotides (CpGs) of the human androgen receptor gene ( HUMARA) and X-chromosome inactivation (XCI) status in phenotypically normal women in a general population, bisulfite genomic sequencing and methylation-specific PCR of genomic DNA extracted from peripheral blood samples of 124 phenotypically normal women were examined. CpGs methylation patterns were based on bisulfite genomic sequencing of the region containing nine CpGs in the HUMARA exon 1. The results of methylation status in CpGs from 43 independent colonies of 14 women revealed that not all CpGs were methylated even in highly methylated HUMARA alleles, and that the methylation status in CpGs varied between clones, by the position of CpGs methylation and in each subject. Evaluation of XCI was based on the method of an HUMARA (CAG)n polymorphism assay after bisulfite modification of DNA samples. The HUMARA allele size ratios of the women (82 heterozygotes) varied over a wide range and the distribution patterns of the ratios approached a 'normal distribution'. Since excessive skewing of XCI was observed in 11-12% of women, female carriers of an X-linked hereditary disease manifest its clinical symptoms or signs possibly in maximum 5-6%.

Complete XY gonadal dysgenesis and aspects of the SRYgenotype and gonadal tumor formation.

XY gonadal dysgenesis can be classified as either complete or incomplete according to gonadal morphology. The disease is a sex-reversal disorder resulting from embryonic testicular regression sequences and is induced by mutations in the sex-determining region Y ( SRY) gene. The incidence of SRY mutations is thought to be approximately 20%. As the disease is characterized by a frequent complication of gonadal tumors, patients are usually advised to undergo prophylactic gonadectomy. In this study, we searched for mutations in SRY open reading frames from three patients with the complete form of XY gonadal dysgenesis, and detected missense mutations in two patients. Combined with the results of our previous study, in which SRY abnormalities were also detected in two out of three complete-type patients, the final incidence of SRY abnormalities was 67% (four of six patients), which is much higher than previously thought. The incidence of gonadal tumor formation in patients with SRY abnormalities was 50% (two of four patients), which is similar to the result of a metanalysis of patients with SRY abnormalities that revealed an incidence of 52.5%. Therefore, it is possible that the lower incidences of SRY abnormalities previously reported were caused by the inclusion of patients with the incomplete form or other sex-reversal disorders. Moreover, our results suggest that clinicians should carefully examine patients with SRY abnormalities.

Erythropoietin and erythropoietin receptor expression in human endometrium throughout the menstrual cycle.

Erythropoietin (Epo) is an important regulator of erythropoiesis. Recent studies have demonstrated non-classical sites of Epo and Epo-receptor (Epo-R) expression, suggesting new physiological roles unrelated to erythropoiesis. Other studies have shown that the mouse uterus expresses Epo and its receptor, and produces Epo protein in an estrogen-dependent manner. We therefore hypothesized that Epo is one of the growth factors involved in cyclic endometrial changes. We determined Epo and Epo-R mRNA expression in isolated endometrial epithelial and stromal cells using RT-PCR. While both Epo and Epo-R were detected in all samples of isolated epithelial cells analysed throughout the menstrual cycle, neither one was detected in isolated stromal cells. In addition, using quantitative real-time RT-PCR with the TaqMan detection system, we showed that isolated epithelial cells had higher Epo mRNA levels in the secretory phase than in the proliferative phase. Immunohistochemical analyses revealed that Epo and Epo-R protein expression in glandular epithelial cells was increased during the mid-proliferative phase and was maintained during the late proliferative and the early, mid- and late secretory phases. These findings suggest that Epo may be involved in cyclic proliferation and differentiation of endometrial glandular epithelial cells, acting in an autocrine manner. In addition, we also hypothesize that ovarian steroids may stimulate Epo production in human endometrial glandular epithelial cells.