It has been well documented that pre-eclampsia and unexplained fetal growth restriction (FGR) have a common etiological background, but little is known about their linkage at the molecular level. The aim of this study was to further investigate the mechanisms underlying pre-eclampsia and unexplained FGR.

Nectins are cell adhesion molecules that play a pivotal role in adherens junctions and tight junctions. Our previous study using whole-genome oligonucleotide microarrays revealed that nectin-4 was upregulated in pre-eclamptic placentas. We investigated the role of nectin-4 in the etiology of pre-eclampsia. We investigated the expression of nectin-4 using real-time RT–PCR, western blot and immunostaining. Additionally, we performed matrigel invasion assay and cytotoxicity assay using cells overexpressing the nectin-4. NECTIN4 transcripts were elevated in pre-eclamptic placentas relative to uncomplicated pregnancies. Nectin-4 protein levels in pre-eclamptic placentas were higher on a semi-quantitative western blot. Nectin-4 was localized at the apical cell membrane in syncytiotrophoblast cells and not at the adherens junctions. Nectin-4 was also detected in cytotrophoblasts and a subset of cells in the decidua. Nectin-4 overexpressing trophoblast cells migrated normally in the matrix. However, Natural killer (NK) cells showed a strong cytotoxic effect against nectin-4 overexpressing trophoblast cells. No causative genetic variation was evident in the NECTIN4 gene from a pre-eclamptic placenta. There are as yet unknown factors that induce nectin-4 overexpression in trophoblast cells that may contribute to abnormal placentation via an aberrant immune response and the onset of a pre-eclamptic pregnancy.

Background: FLT1 is one of the significantly overexpressed genes found in a pre-eclamptic placenta and is involved with the etiology of this disease. Methods: We conducted genome-wide expression profiling by RNA-seq of placentas from women with pre-eclampsia and those with normotensive pregnancy. Results: We identified a lncRNA gene, MG828507, located ~80 kb upstream of the FLT1 gene in a head-to-head orientation, which was overexpressed in the pre-eclamptic placenta. MG828507 and FLT1 are located within the same topologically associated domain in the genome. The MG828507 mRNA level correlated with that of the FLT1 in placentas from pre-eclamptic women as well as in samples from uncomplicated pregnancies. However, neither the overexpression nor knockdown of MG828507 affected the expression of FLT1. Analysis of pre-eclampsia-linking genetic variants at this locus suggested that the placental genotype of one variant was associated with the expression of MG828507. The MG828507 transcript level was not found to be associated with maternal blood pressure, but showed a relationship with birth and placental weights, suggesting that this lncRNA might be one of the pivotal placental factors in pre-eclampsia. Conclusion: Further characterization of the MG828507 gene may elucidate the etiological roles of the MG828507 and FLT1 genes in pre-eclampsia in a genomic context.

In the present study, we report on a couple who underwent prenatal genetic diagnosis for autosomal recessive polycystic kidney disease (ARPKD). This healthy couple had previously had a healthy boy but had experienced two consecutive neonatal deaths due to respiratory distress resulting from pulmonary hypoplasia caused by oligohydramnios. The woman consulted our facility after she realized she was pregnant again. We promptly performed a carrier test for the PKHD1 gene by target exome sequencing of samples from the couple. A pathogenic mutation was identified only in the paternal allele (c.9008C>T, p.S3003F). The mutation was confirmed by Sanger sequencing of the DNA from formalin-fixed, paraffin-embedded, kidney tissue of the second neonate patient and was not found in the healthy sibling. We then performed haplotype analyses using microsatellite markers scattered throughout the PKHD1 gene. DNA from the amniocentesis was determined to belong to a carrier, and the couple decided to continue with the pregnancy, obtaining a healthy newborn. Subsequent detailed examination of the exome data suggested higher read depth at exons 45 and 46. Multiplex ligation-dependent probe amplification allowed identification of duplication of these two exons. This case suggests the potential usefulness of target exome sequencing in the prenatal diagnosis of the PKHD1 gene in ARPKD. This is the first report of intragenic duplication in the PKHD1 gene in ARPKD.

Objectives: We previously reported a high prevalence of hypovitaminosis D (25OHD < 20 ng/mL) in Japanese pregnant women with threatened premature delivery. This study aimed to assess nutritional status and its relationship with bone-related markers and microarchitecture, as measured using quantitative ultrasonography (QUS), in Japanese women during the perinatal period. Methods: We recruited Japanese women who had just delivered at Fujita Health University Hospital (n = 103, cesarean/vaginal delivery = 50/53, age 33.9 ± 4.9 years). On the third day postpartum, their calcaneal QUS was measured, and fasting blood samples were collected. Results: The mean total energy intake (1720 ± 298 kcal/day) was lower than the normal range for Japanese women (2100 kcal/day). Their calcium intake (446 ± 130 mg/day) was significantly below the recommended daily intake (RDI) in Japan (660 mg/day), with 95% of participants consuming less than the RDI. Although the average vitamin D intake (8.7 ± 1.8 μg/day) met the Japanese RDI (8.5 μg/day), 36% of participants consumed less than the RDI. Calcium intake was positively associated with the intake of lipids, protein, and vitamins A, D, and K. Additionally, calcium intake but not vitamin D intake tended to correlate with serum 25-hydroxyvitamin D (25OHD) levels. The QUS indices showed no significant association with calcium or vitamin D intake. Conclusions: During the perinatal period, Japanese women had low calcium intake and relatively low vitamin D intake, accompanied by reduced 25OHD levels. These findings highlight the need for public health recommendations and policies to promote adequate calcium and vitamin D intake during pregnancy.