CDKN2AIP is critical for spermiogenesis and germ cell development.

BACKGROUND: As a member of RNA-binding protein, CDKN2AIP has been shown to play a critical role in stem cell pluripotency and somatic differentiation. Recent studies indicate that Cdkn2aip is essential for spermatogonial self-renewal and proliferation through the activating Wnt-signaling pathway. However, the mechanisms of how Cdkn2aip regulate spermatogenesis is poorly characterized. RESULTS: We discovered that the CDKN2AIP was expressed in spermatocyte as well as spermatids and participated in spermiogenesis. Cdkn2aip-/- mice exhibited multiple sperm head defects accompanied by age dependent germ cell loss that might be result of protamine replacement failure and impaired SUN1 expression. Loss of Cdkn2aip expression in male mice resulted in synapsis failure in 19% of all spermatocytes and increased apoptosis due to damaged DNA double-strand break (DSB) repair and crossover formation. In vitro, knockdown of Cdkn2aip was associated with extended S phase, increased DNA damage and apoptosis. CONCLUSIONS: Our findings not only identified the importance of CDKN2AIP in spermiogenesis and germ cell development, but also provided insight upon the driving mechanism.

CDKN2AIP-induced cell senescence and apoptosis of testicular seminoma are associated with CARM1 and eIF4ß.

Testicular seminoma is a relatively rare tumor which is mostly detected in male population aged from 15 to 35 years old. Although several molecular biomarkers have been identified to be associated with testicular seminoma pathogenesis, the exact mechanism for testicular seminoma progression remains largely unknown. CDKN2A interacting protein (CDKN2AIP) has previously been identified as a tumor suppressor in multiple malignant diseases. In this study, we aimed to further explore its role in testicular seminoma as well as the underlying molecular mechanisms. Retrospective testicular seminoma clinical samples, normal tissues, NTERA-2 cell line, and mouse xenograft models were used in this study. RT-qPCR, western blot analysis, immunofluorescence microscopy, Co-IP and IP-MS experiments were performed to detect the expression of CDKN2AIP and its interaction with CARM1 and eIF4ß. SA-ß-gal staining assay and H3K9me3 activity experiments were used to subsequently evaluate the cell senescence and apoptosis. Mouse xenograft animal model was used for in vivo study. The results showed that CDKN2AIP is highly expressed in normal testis samples, and is significantly suppressed in testicular seminoma clinical samples and cell line model. Up-regulation of CDKN2AIP is significantly associated with the inhibition of testicular seminoma tumor growth and the increase of cell senescence and apoptosis. CDKN2AIP exhibits anti-tumor activity by interacting with CARM1 and eIF4ß. CDKN2AIP induces testicular seminoma cell senescence by suppressing CARM1 expression and eIF4ß phosphorylation. The CDKN2AIP-CARM1 and CDKN2AIP-eIF4ß interactions, which induce tumor cell senescence and apoptosis, may be the potential druggable molecular pathways in testicular seminoma tumor pathogenesis and progression.

Maternal exposure to bisphenol A induces fetal growth restriction via upregulating the expression of estrogen receptors.

Bisphenol A (BPA) accumulation in the placenta leads to fetal growth restriction (FGR). Here we aimed to explore the effect and the underlying mechanism of BPA exposure on fetal development. ELISA was performed to measure estrogen levels in human placenta and BeWo cells. qRT-PCR and Western blotting were conducted to determine the expression of estrogen receptors (ERs), breast cancer resistance protein (BCRP), the key enzymes for ER synthesis, and DNA methyltransferases (DNMTs). Bisulfite-sequencing PCR analysis was performed to measure CpG methylation in ER genes. Flow cytometry was used to examine cell apoptosis. We found that human FGR placentae had significantly increased BPA and estrogen levels and decreased BCRP levels compared with healthy placentae. BPA downregulated BCRP expression via ERs, and BCRP silencing promoted ER expression in BeWo cells. Compared with vehicle treatment, BPA treatment significantly enhanced the expression of key enzymes for estrogen synthesis and ERs in BeWo cells. BPA treatment inhibited CpG methylation in ER genes, along with downregulated DNMT1 expression and upregulated DNMT3a and DNMT3b expression. BPA treatment significantly promoted BeWo cell apoptosis compared with vehicle treatment. Importantly, ER inhibitor ICI-182780 significantly reversed all the BPA-induced effects on BeWo cells. In conclusion, BPA promotes estrogen production and cell apoptosis in BeWo cells via upregulating ER expression, leading to FGR.

Pregnant women's psychological state and influence factors: anxiety, and depression during COVID-19 outbreak.

OBJECTIVES: The outbreak of COVID-19 affects both physical and mental health of pregnant women. This study focuses on their psychological status, and analyzes the main factors affecting their emotions of pregnant women so as to provide guidance for psychological counseling and social intervention during epidemics. METHODS: Multiple researchers distributed a questionnaire online via the Internet. Pregnant women volunteered, and the questionnaire was automatically collected in the background. RESULTS: The 298 valid questionnaires recovered showed that 82 cases of pregnant women were in states of anxiety, accounting for 27.51%, of which 78.05% were mild (82 cases), 19.51% were moderate (16 cases), and 2.44% were severe (2 cases). Moreover, 31.21% of pregnant women were in states of depression (93 cases), of which 52.69% were mild (49 cases), 40.86% were moderate (38 cases), and 6.45% were severe (6 cases). The risk factors for states of anxiety or depression were fear of fetal malformation or genetic disease, history of adverse pregnancy, can't do routine prenatal examination, and insufficient support and care from husbands and families. Besides, 16 cases had sought psychological help during the epidemic, among whom 62.50% (10 cases) experienced anxiety, 68.75% (11 cases) had depression. CONCLUSIONS: During the outbreak of COVID-19, obstetricians may take use of the Internet, based on the advantages in epidemic prevention, controlling health education, and popularizing science. In addition, husbands and family members should provide greater care for pregnant women, to protect their mental health during public health incidents.