Placenta

Placental extracellular vesicles induce ovarian tumour cell death in an ex vivo explant model: Possible therapeutic potential

Placental extracellular vesicles (EVs), lipid-enclosed particles released from the placenta, can facilitate intercellular communication and are classified as micro- or nano-EVs depending on size. Placental EVs contain molecules associated with cell proliferation and death. In this study, we investigated whether treating human ovarian tumour explants with placental EVs could induce ovarian tumour cell death. Human ovarian tumours were collected. After directly treating human ovarian tumour explants with placental EVs, cellular necrosis was observed in ovarian tumour explants by HE stains. Cell death-associated miRNAs were measured. Expression of apoptosis and senescence-associated proteins, including NF-κβ and γ H2AX, were significantly increased, while proliferation-associated proteins were significantly reduced in the explants after exposure to placental EVs. Furthermore, miRNA-519a-5p, miRNA-512-3p and miRNA-143-3p, which were reported to promote ovarian cancer cell apoptosis or inhibition of ovarian cancer cell growth, were significantly increased, and the target genes of miRNA-519a-5p and miRNA-512-3p were significantly reduced in the explants after exposure to placental EVs. Transfection of SK-OV-3 ovarian cancer cells with a mimic of miRNA-519a-5p or miRNA-143-3p reduced the viability of these cells. Our study demonstrated that placental EVs could induce necrosis in ovarian tumour explants. Increased levels of apoptosis and senescence-associated proteins and miRNAs could contribute to this change in ovarian tumour cell phenotype after exposure to placental EVs.

Natural-killer-cell–dominant immune landscape and HLA-E–mediated immune evasion in choriocarcinoma

Choriocarcinoma is a rare cancer associated with antecedent pregnancy. Therefore, its development may be influenced by an immune-evasive tumor microenvironment. In this study, we focused on natural killer (NK) cells to elucidate the immune microenvironment of choriocarcinoma. Peripheral blood and intratumoral NK cells were isolated from six samples of four patients with choriocarcinoma. Flow cytometry was used to analyze the NK cell proportion. Immunohistochemistry was performed to assess the expression of NK cell inhibitory ligands using choriocarcinoma tissues from 17 patients. In addition, choriocarcinoma cell lines (JAR, BeWo, and JEG-3) were cocultured with interleukin-2-stimulated NK cells, and loss-of-function analyses of HLA-E were conducted to investigate the impact of NK cells on choriocarcinoma cells. Flow cytometry revealed that NK cells were more abundant in choriocarcinoma tissues than in the peripheral blood. Immunohistochemistry confirmed the expression of NK cell inhibitory ligands, including HLA-E. Moreover, JAR cells were cocultured with NK cells, and viable JAR cells were isolated by flow cytometry. Subsequent mRNA sequencing showed that HLA-E was upregulated, and multiple cytokine-related pathways were activated in the cocultured JAR cells compared with monocultured JAR cells. Functional assays demonstrated that HLA-E knockdown enhanced NK-cell-mediated cytotoxicity, whereas interferon-gamma treatment increased HLA-E expression and promoted tumor cell survival. These findings suggest that NK cells may play an important role in the tumor immune microenvironment of choriocarcinoma through HLA-E expression.

MALAT1 overexpression contributes to choriocarcinoma by binding with RBM10 and promoting p53 degradation

Choriocarcinoma (CC), a highly aggressive and malignant subtype of gestational trophoblastic disease (GTD), arises from the dysregulated proliferation of trophoblastic cells, which normally mediate placental development during pregnancy. This study aimed to characterize the expression and functional significance of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), a nuclear-enriched long non-coding RNA, in CC pathogenesis. We analyzed MALAT1 expression levels in 30 normal placental villi, 46 hydatidiform moles (repressive subtype), and 52 CC specimens. To identify MALAT1-interacting proteins, we performed RNA antisense purification followed by immunoblotting, with subsequent validation via co-immunoprecipitation (Co-IP) and immunofluorescence (IF) assays. MALAT1 was significantly upregulated in CC tissues compared to controls. In vivo xenograft experiments further revealed that MALAT1 overexpression enhanced tumor growth. Mechanistically, we identified RNA-binding motif protein 10 (RBM10), a key spliceosomal regulator, as a novel MALAT1-binding partner. Strikingly, MALAT1 promoted p53 protein degradation without affecting its transcriptional levels, and this oncogenic effect was mediated through an RBM10-dependent mechanism. In conclusion, our findings establish MALAT1 as a critical oncogenic driver in CC, functioning through its interaction with RBM10 to destabilize p53 and accelerate tumor progression. These insights highlight the potential of the MALAT1-RBM10-p53 axis as a therapeutic target in CC.

Massive subchorionic thrombohematoma (Breus’ mole): An exceedingly rare placental disorder—Case series and systematic review

Breus' mole, or massive subchorionic thrombohematoma (MST), is an exceedingly rare placental condition associated with adverse pregnancy outcomes. We aim to describe the clinical, ultrasonographic, and histopathological features of newly diagnosed MST cases and review those previously reported. We conducted a retrospective observational study of MST cases diagnosed between 2016 and 2024 in two Spanish referral hospitals for high-risk pregnancies. A systematic review of the literature was also performed. We identified 18 new MST cases. The mean maternal age was 32.5 years. Maternal heart disease was present in 42 % of cases. The mean gestational age at delivery was 35.1 weeks; 72.2 % of neonates were born preterm. Fetal growth restriction (FGR) was present in 55.2 %. No intrauterine fetal deaths occurred. Obstetric or maternal complications appeared in 77.1 % of pregnancies. The most common ultrasound findings included placental thickening (11.7 %), fetal surface hematomas (11.7 %), lacunar appearance (11.7 %), and amnion detachment (11.7 %). Doppler assessments were normal in 76.4 %. Placentomegaly or hypoplasia were observed in 11.6 % and 22.3 %, respectively. Histology showed yellowish, indurated areas on the fetal surface, affecting 30-100 % of the surface and measuring 1-2.3 cm in depth. Serous cysts were found in 11.2 %. Circumvallate/circummarginate insertion occurred in 22.3 %, and marginal/velamentous cord insertion in 33.4 %. Maternal vascular malperfusion pattern was present in 72.3 %. Seventy-four MST cases have been previously reported. MST should be considered in the differential diagnosis of FGR, especially when ultrasound findings show placental thikenning and hematoma in the chorionic plate in mothers with heart disease. Histological confirmation and close ultrasound follow-up are key for appropriate management.

Placental extracellular vesicles promoted cervical tumour tissue undergoing death

Cervical cancer is a leading cause of death in developing countries. Although the placenta is a tumor-like organ, the placental development, including invasive function, is well controlled. One mechanism is that extracellular vesicles (EVs) released from the placenta contribute to this regulation. Placental EVs carry functional proteins and regulatory RNAs. Our previous study reported that placental EVs inhibited ovarian cancer growth in vitro and in vivo. Whether the inhibitory effect induced by placental EVs also applies to cervical cancer, a non-endocrine-related cancer, in this study, we first co-cultured the cervical tumour tissues with placental explants. Co-culturing cervical tumour tissues (n = 7) with placental explants showed necrotic signs and increased levels of senescence-associated proteins and death-associated miRNAs, including miRNA-143-3p, miRNA-519a-5p and miRNA-199a-3p in tumour tissues. Additionally, treatment of HeLa cells with placental EVs reduced the viability of HeLa cells and inhibited the ability of invasion and migration of HeLa cells. Increased levels of senescence-associated proteins and reduced levels of proliferative proteins may contribute to the inhibitory effects in HeLa cells. placental EVs are involved in regulating placental development, and the delivery of cargo significantly impacts the functions of target cells. This study found that factors released from placental explants, likely placental EVs, had anti-tumour effects on the cervical tumour by inhibiting cervical cancer cell viability, invasion, and migration. Cargo in placental EVs, such as cellular death-associated miRNAs, may contribute to the inhibitory effects on cervical tumour.