BMAL1 positively correlates with genes regulating steroidogenesis in human luteinized granulosa cells.

In brief: In this study, we examined the relationship between BMAL1 expression and the genes regulating steroid biosynthesis in human luteinized granulosa cells. BMAL1 function is crucial for steroid production and proper ovarian function, highlighting the importance of circadian clock regulation in female reproductive health. Abstract: Human luteinized granulosa cells were collected to analyze circadian clock gene expression and its effect on the genes regulating steroid biosynthesis. We used siRNA to knock down the expression of BMAL1 in KGN cells. We measured the expression levels of genes regulating steroid biosynthesis and circadian clock RT-qPCR. We demonstrated that BMAL1 expression positively correlates with genes regulating steroid biosynthesis (CYP11A1, CYP19A1, STAR, and ESR2). The knockdown of BMAL1 in KGN cells revealed a significant decrease in steroid synthase expression. In contrast, when BMAL1 was overexpressed in KGN and HGL5 cells, we observed a significant increase in the expression of steroid synthases, such as CYP11A1 and CYP19A1. These results indicated that BMAL1 positively controls 17ß-estradiol (E2) secretion in granulosa cells. We also demonstrated that dexamethasone synchronization in KGN cells enhanced the rhythmic alterations in circadian clock genes. Our study suggests that BMAL1 plays a critical role in steroid biosynthesis in human luteinized granulosa cells, thereby emphasizing the importance of BMAL1 in the regulation of reproductive physiology.

Prevalence of and risk factors for chronic endometritis in patients with intrauterine disorders after hysteroscopic surgery.

OBJECTIVE: To identify the prevalence of and risk factors for chronic endometritis (CE) in patients with intrauterine disorders and the therapeutic efficacy of hysteroscopic surgery in the treatment of CE without antibiotic therapy. DESIGN: Prospective cohort study. SETTING: Hospital specializing in reproductive medicine. PATIENT(S): The study population consisted of 350 women with infertility, of whom 337 were recruited, who underwent hysteroscopic surgery between November 2018 and June 2021. Eighty-nine consecutive patients without intrauterine disorders were also recruited as controls. INTERVENTION(S): Endometrial samples were collected during the surgery for CD138 immunostaining for the diagnosis of CE. In women diagnosed with CE, endometrial biopsy was performed without antibiotic use in the subsequent menstrual cycle. MAIN OUTCOME MEASURE(S): Prevalence of and risk factors for CE in intrauterine disorders and therapeutic effects of hysteroscopic surgery on CE. RESULT(S): The prevalence of CE with ≥5 CD138-positive cells in women with no intrauterine disorder and with endometrial polyps, myomas, intrauterine adhesions (IUAs), and septate uterus was 15.7%, 85.7%, 69.0%, 78.9%, and 46.2%, respectively. A multivariate analysis revealed that CE was diagnosed significantly more often in the endometrial polyp (odds ratio, 27.69; 95% confidence interval, 15.01-51.08) and IUA groups (odds ratio, 8.85; 95% confidence interval, 3.26-24.05). The rate of recovery from CE with surgery in women with endometrial polyps, myomas, IUA, and septate uterus was 89.7%, 100%, 92.8%, and 83.3%, respectively. CONCLUSION(S): Endometrial polyp and IUA were risk factors for CE. Most CE cases with intrauterine disorders were cured with hysteroscopic surgery without antibiotic therapy, regardless of the type of intrauterine abnormalities.

A report on the 73th Annual Congress of the Japan Society of Obstetrics and Gynecology International Workshop for Junior Fellows: Risk-reducing surgery for hereditary breast and ovarian cancer.

At the 73rd Annual Congress of the Japan Society of Obstetrics and Gynecology, young doctors from Japan and South Korea made presentations on the present condition of risk-reducing surgery for hereditary breast and ovarian cancer (RRSO) in their respective country. RRSO was insured in Japan in April 2020, whereas in South Korea, it was insured 7 years earlier in 2013. In Japan, certification criteria have been set for facilities that perform RRSO, and the number of facilities is increasing, but regional disparities still exist in its distribution. The number of gBRCA1/2 testing facilities is larger, and the cost is more affordable in South Korea than in Japan. Additionally, South Korea provides genetic counseling to a wider range of relatives compared to Japan. In the future, as the indications for the gBRCA1/2 test have expanded as a companion diagnostic for the use of PARP inhibitors, it is expected that the number of candidates for the gBRCA1/2 mutation test and RRSO will increase in Japan. It is important to increase the number of BRCA tests while maintaining the quality of genetic counseling in order to provide adequate information on BRCA mutations and RRSO for patients to support their decision. For the development of hereditary breast and ovarian cancer (HBOC) medical care, it is necessary to publish a nationwide database in Japan and continue to analyze and discuss the data based on the results.

Circulating and tissue miR-100 acts as a potential diagnostic biomarker for cervical cancer.

BACKGROUND: MicroRNAs (miRNA) are promising biomarkers for cancer diagnosis and prognosis; miR-100 expression is decreased in cervical cancer tissues. OBJECTIVE: To determine whether miR-100 is a useful biomarker for early cervical cancer diagnosis. METHODS: Total RNA was extracted from the sera of 34 healthy controls (HC), 64 cervical intraepithelial neoplasia patients (CIN), and 46 cervical cancer patients (CC). miR-100 expression levels were measured with quantitative real-time PCR. Correlations between clinicopathological factors and miR-100 expression levels were also assessed. The cut-off value for miR-100 was calculated from the Receiver Operating Characteristic (ROC) curve. RESULTS: Relative expression levels of miR-100 in serum were 1.84 ± 1.72, 3.93 ± 2.52, and 5.32 ± 3.39 in CC, CIN, and HC, respectively; it was significantly lower in CC (p< 0.001). The area under the ROC curve was 0.879 and the cut-off value was 2.451. miR-100 expression levels were significantly higher in metastasis cases that were lymph node negative than positive (p< 0.05). CC patients with miR-100 expression levels below the cut-off value tended to have a poor prognosis. CONCLUSIONS: Serum miR-100 may be a useful diagnostic biomarker for CC, and for predicting lymph node metastasis and disease free survival in CC patients.