Several miRNAs are expressed in human gestational tissue, and some have been shown to be associated with placental dysfunction and complicated pregnancy outcomes. To investigate the roles of miR-346 and miR-582-3p in adverse obstetric events, we analyzed these 2 miRNAs in three samples (maternal blood, umbilical cord blood and placenta) obtained from pregnant women in four groups, including healthy control (n = 60), preeclampsia (n = 31), preterm delivery (n = 29) and small for gestational age (n = 19) patients. The expression levels of miR-346 and miR-582-3p in all included adverse obstetric outcome groups were significantly higher in the maternal plasma samples but lower in the placenta samples (all p value < 0.05). In addition, the miR-346 expression levels in fetal cord blood were also significantly lower in all of the included adverse obstetric outcome groups (all p < 0.05). Multivariate analysis of the three specimens after adjusting for maternal age and gestational age at delivery gave the same results. In conclusion, aberrant miR-346 and miR-582-3p expression level in pregnancy was associated with multiple maternal and fetal complications. Their differential expression in maternal blood, umbilical cord blood and placenta could be potential biomarkers or therapeutic targets for adverse obstetric outcomes

Background and Objective: In the first trimester of pregnancy, fetal growth, and abnormalities can be assessed using the exact middle sagittal plane (MSP) of the fetus. However, the ultrasound (US) image quality and operator experience affect the accuracy. We present an automatic system that enables precise fetal MSP detection from three-dimensional (3D) US and provides an evaluation of its performance using a generative adversarial network (GAN) framework. Method: The neural network is designed as a filter and generates masks to obtain the MSP, learning the features and MSP location in 3D space. Using the proposed image analysis system, a seed point was obtained from 218 first-trimester fetal 3D US volumes using deep learning and the MSP was automatically extracted. Results: The experimental results reveal the feasibility and excellent performance of the proposed approach between the automatically and manually detected MSPs. There was no significant difference between the semi-automatic and automatic systems. Further, the inference time in the automatic system was up to two times faster than the semi-automatic approach. Conclusion: The proposed system offers precise fetal MSP measurements. Therefore, this automatic fetal MSP detection and measurement approach is anticipated to be useful clinically. The proposed system can also be applied to other relevant clinical fields in the future.

Macrophage polarization, regulated appropriately, may play important roles in successful pregnancy. In the face of the vital roles of decidua macrophages in pregnancy, it is insufficient to recognize the trigger of macrophage differentiation and polarization. We aimed to explore the link between the NLRP7 gene and macrophage polarization in human deciduas. Here, we enrolled the endometrial tissues from eight pregnant women in the first trimester. We found that NLRP7 was abundant in endometrial tissues and that NLRP7 was expressed in decidual macrophages of the first-trimester pregnancy. NLRP7 was predominately expressed in the decidual M2 macrophages, as compared with the M1 macrophages. Furthermore, our results suggest that NLRP7 is associated with decidual macrophage differentiation. NLRP7 over-expression suppresses the expression of M1 markers and enhances the expression of the M2 markers. Considering that NLRP7 relates to decidualization and macrophage differentiation, we propose that NLRP7 is a primate-specific multitasking gene to maintain endometrial hemostasis and reproductive success. This finding may pave the way for therapies of pathological pregnancies.

Recurrent miscarriage is defined as more than three pregnancy failures occurring before 20 weeks of gestation. Poor differentiation of the endometrial stroma or defective trophoblast cell invasion at the maternal-fetal interface leads to recurrent miscarriages. Several miRNAs, including miR-20b-5p, are aberrantly regulated in recurrent miscarriages; however, the underlying molecular mechanisms remain unclear. Primary cilia are antenna-like organelles that coordinate signaling during development and differentiation. Defective primary cilia formation leads to complications, such as recurrent miscarriage or preeclampsia. Here, we demonstrated that miR-20b-5p inhibited trophoblast cell invasion by blocking primary cilia formation. Mechanistically, miR-20b-5p targeted and inhibited ATG16L1 and ATG7 expression, thereby blocking autophagy. Defective autophagy reduced primary cilia formation and stopped ERK activation, which is a crucial signaling pathway for trophoblast invasion. Aspirin is used to prevent recurrent miscarriages in clinical settings. Treatment with aspirin inhibited miR-20b-5p levels, thus restoring primary cilia formation and trophoblast invasion. Thus, our findings uncovered the molecular mechanism by which miR-20b-5p suppressed primary cilia formation and trophoblast invasion by reducing the expression of ATG16L1 and ATG7. Moreover, we found that the defective phenotypes could be rescued by aspirin in recurrent miscarriages.

Gestational diabetes mellitus (GDM) is a type of unbalanced glucose tolerance that occurs during pregnancy, which affects approximately 10% of pregnancies worldwide. Fetuin-A is associated with insulin resistance, and the concentration of circulating fetuin-A increases in women with GDM, however, the role of fetuin-A in the placenta remains unclear. In this study, we enrolled placental samples from twenty pregnant women with GDM and twenty non-GDM pregnant women and found that the abundance of fetuin-A was upregulated in terms of mRNA and protein levels. Fetuin-A inhibited placental cell growth by inducing apoptosis and inhibiting S phase entry. Irregular alignment of mitotic chromosomes and aberrant mitotic spindle poles were observed. In addition, centrosome amplification was induced by fetuin-A treatment, and these amplified centrosomes nucleated microtubules with disorganized microtubule arrays in placental cells. Furthermore, fetuin-A inhibited autophagy, and thus blocked the growth of the primary cilium, a cellular antenna that regulates placenta development and differentiation. Thus, our study uncovered the novel function of fetuin-A in regulating placental cell growth and ciliogenesis.