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The authors add to our knowledge of the transcriptional regulation of the meiotic program in mice spermatocytes, showing ZFP541 regulates meiotic prophase and transition to the division phase by being the target for upstream factors MEIOSIN/STRA8.

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 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.

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.