KCTD19 and its associated protein ZFP541 are independently essential for meiosis in male mice.

Meiosis is a cell division process with complex chromosome events where various molecules must work in tandem. To find meiosis-related genes, we screened evolutionarily conserved and reproductive tract-enriched genes using the CRISPR/Cas9 system and identified potassium channel tetramerization domain containing 19 (Kctd19) as an essential factor for meiosis. In prophase I, Kctd19 deficiency did not affect synapsis or the DNA damage response, and chiasma structures were also observed in metaphase I spermatocytes of Kctd19 KO mice. However, spermatocytes underwent apoptotic elimination during the metaphase-anaphase transition. We were able to rescue the Kctd19 KO phenotype with an epitope-tagged Kctd19 transgene. By immunoprecipitation-mass spectrometry, we confirmed the association of KCTD19 with zinc finger protein 541 (ZFP541) and histone deacetylase 1 (HDAC1). Phenotyping of Zfp541 KO spermatocytes demonstrated XY chromosome asynapsis and recurrent DNA damage in the late pachytene stage, leading to apoptosis. In summary, our study reveals that KCTD19 associates with ZFP541 and HDAC1, and that both KCTD19 and ZFP541 are essential for meiosis in male mice.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology.

"Welcome to OBGYN World!" A novel recruitment event for medical students organized by the Japan Society of Obstetrics and Gynecology. Since 2012, the number of doctors in Japan who specialize in obstetrics and gynecology has shown a decreasing trend. To increase the number of doctors majoring in obstetrics and gynecology, the Japanese Trainees in Obstetrics and Gynecology subcommittee developed a new recruitment event called Welcome to OBGYN World! (WOW!); the aim of this event was to focus on lower grades of medical students. The present report describes the content of WOW! and the results of a post-event questionnaire administered to participating students and tutors. WOW! was held online in order to avoid the risk of Coronavirus Disease 2019 infection for participants. Sixty of the 82 medical schools nationwide (73.2%) participated in this event. Overall, there were 285 participating students, ranging from first to fourth grade in medical school, and 106 tutors were involved to teach material at the event. In the post-event questionnaire survey, 97.6% (248/254) and 100% of the participants stated they now had a high degree of interest in obstetrics and gynecology and found the specialty attractive, respectively. Furthermore, 93.6% (90/94) of the tutors stated that WOW! had helped recruitment activities in their universities. Based on this outcome, members of the Japanese Trainees of Obstetrics and Gynecology subcommittee will now try to increase the number of doctors specializing in obstetrics and gynecology by holding WOW! annually.

Clinical manifestations of placental mesenchymal dysplasia in Japan: A multicenter case series.

AIM: This study aimed to evaluate the clinical features and pregnancy outcomes of placental mesenchymal dysplasia (PMD) in Japan. METHODS: We requested detailed clinical information and placental tissue of PMD cases in 2000-2018 from Japanese facilities with departments of obstetrics and gynecology and analyzed the pregnancy course and neonatal outcomes. RESULTS: We collected 49 cases of PMD. Of 18 patients with measured maternal serum alpha-fetoprotein (MSAFP) levels, 15 (83.3%) had elevated levels. Maternal serum human chorionic gonadotropin (MShCG) levels were transiently elevated in five (17.8%) of 28 patients. Forty-seven patients continued their pregnancies. All pregnancies were singleton and 40 (85.1%) were associated with adverse events including fetal growth restriction (FGR), threatened premature delivery, fetal demise, and hypertensive disorder of pregnancy in 34 (72.3%), 14 (29.8%), eight (17.0%), and six (12.8%) patients, respectively. Of 47 infants, there were eight stillbirths. There were 40 (85.1%) female infants, and eight (17.0%) had Beckwith-Wiedemann syndrome. Of 39 live births, 23 (59.0%) were associated with premature induction of labor or cesarean section for obstetric indications related to FGR. Eighteen (46.2%) neonates had complications. PMD-affected placentas were pathologically heterogeneous in both grossly PMD-affected and non-affected areas. CONCLUSIONS: Our study included the largest number of PMD cases with detailed clinical information. PMD is a high-risk condition for both the mother and the child. Elevated MSAFP levels with normal MShCG levels indicate PMD. Conventional perinatal management of FGR in Japan might be effective in reducing the fetal mortality rate.

Attitudes toward overtime work and self-training: A survey on obstetricians and gynecologists in Japan.

AIM: The Ministry of Health, Labour, and Welfare of Japan proposed a regulation of overtime work as a reform in work style. However, the regulation may deteriorate the quality of medical services due to the reduction in training time. Thus, the study aimed to reveal perceptions in terms of generation gaps in views on self-training and overtime work, among members of the Japan Society of Obstetrics and Gynecology (JSOG). METHODS: A web-based, self-administered questionnaire survey was conducted among members of the JSOG. In total, 1256 respondents were included in the analysis. Data were collected on age, sex, experience as a medical doctor, location of workplace, work style, the type of main workplace, and number of full-time doctors in the main workplace. The study examined the attitudes of the respondents toward overtime work and self-training. The respondents were categorized based on experience as a medical doctor. RESULTS: According to years of experience, 112 (8.9%), 226 (18.0%), 383 (30.5%), 535 (42.6%) doctors have been working for ≤5, 6-10, 11-19, and ≥ 20 years, respectively. Although 54.5% of doctors with ≤5 years of experience expected the regulation on working hours to improve the quality of medical services, those with ≥20 years of experience expressed potential deterioration. After adjusting for covariates, more years of experience were significantly related with the expectation of deterioration in the quality of medical services. CONCLUSIONS: The study revealed a generation gap in the views about self-training and overtime work among obstetricians and gynecologists in Japan.

Anesthetic Management of a Cesarean Delivery in a Patient With MYH11 Mutation Who Underwent Aortic Replacement.

We report a case of a pregnant woman with a history of ascending arch replacement for aortic dissection who still had a residual descending aortic dissection. She underwent urgent genetic testing to identify hereditary aortic-related diseases that might be useful in perinatal management. A mutation in the myosin heavy chain gene (MYH11), indicating a high risk of aortic dissection but a low impact on other vascular systems and organs, was identified. Due to concerns about the development of residual aortic dissection, cesarean delivery with combined spinal-epidural anesthesia was selected. Predelivery genetic testing might be useful for perinatal anesthetic management.

Progressive idiopathic juvenile osteoporosis in pregnancy: A case report of two successive pregnancies in the same woman.

A 33-year-old primiparous woman with progressive idiopathic juvenile osteoporosis (IJO) who had had multiple vertebral compressions and bilateral femoral neck fractures since the age of 15 years presented for perinatal management at 11 weeks of gestation. Her vertebral bone mass was 0.634 g/cm2 before pregnancy. The target calcium intake was set at 800 mg/day. Cephalopelvic disproportion led to the patient having an elective cesarean section at 39 weeks 3 days of gestation and she delivered a female infant weighing 2785 g. After the delivery, her vertebral bone mass had increased to 0.700 g/cm2. At 34 years of age, she conceived her second child. With similar perinatal management, she delivered a female infant weighing 2580 g at 38 weeks of gestation by elective cesarean section. Her vertebral bone mass had increased again after the second pregnancy. Few cases of pregnancy complicated by progressive IJO have been reported. However, an uneventful pregnancy course can be expected with proper management, and pregnancy can be a good opportunity to increase bone mass.

Meiosis-specific ZFP541 repressor complex promotes developmental progression of meiotic prophase towards completion during mouse spermatogenesis.

During spermatogenesis, meiosis is accompanied by a robust alteration in gene expression and chromatin status. However, it remains elusive how the meiotic transcriptional program is established to ensure completion of meiotic prophase. Here, we identify a protein complex that consists of germ-cell-specific zinc-finger protein ZFP541 and its interactor KCTD19 as the key transcriptional regulators in mouse meiotic prophase progression. Our genetic study shows that ZFP541 and KCTD19 are co-expressed from pachytene onward and play an essential role in the completion of the meiotic prophase program in the testis. Furthermore, our ChIP-seq and transcriptome analyses identify that ZFP541 binds to and suppresses a broad range of genes whose function is associated with biological processes of transcriptional regulation and covalent chromatin modification. The present study demonstrates that a germ-cell specific complex that contains ZFP541 and KCTD19 promotes the progression of meiotic prophase towards completion in male mice, and triggers the reconstruction of the transcriptional network and chromatin organization leading to post-meiotic development.

Sac-Type Congenital Diaphragmatic Hernia: A Case Report of Two Siblings.

Congenital diaphragmatic hernia (CDH), a herniation of the abdominal contents through a defect or hypoplasia of the diaphragm, is a relatively common, severe congenital anomaly. Here we present the first case of two siblings with possibly isolated sac-type CDH and with a suspected genetic etiology. Although sibling recurrence of isolated CDH is rare, the incidence is higher than in the general population. Additionally, the second child had a more severe respiratory disorder than the first child. It is to be noted that siblings of children having isolated CDH are at risk for CDH, and prenatal evaluation should be considered individually.