Miki Mori

Immune activation during the implantation phase causes preeclampsia-like symptoms via the CD40–CD40 ligand pathway in pregnant mice

The CD40 ligand (CD40L) is expressed by T cells and has a critical role in immune system regulation. Interventions targeting CD40L interactions following embryo implantation represent an approach to preventing preeclampsia (PE). To better understand the role of CD40L in PE, we developed a PE mouse model in which we examined how CD40L-induced immune activation affects embryo implantation. Blastocysts were incubated with CD40L-expressing adenovirus and then were transferred into the uterine horns of pseudopregnant ICR mice. Histology, biochemistry and flow cytometry experiments were performed to examine the characteristics of the mouse model. In early pregnancy, decidualization and spiral artery remodeling were reduced in CD40L-transfected mice (CD40L mice) compared with control mice. Hematoxylin–eosin (HE) staining revealed hemorrhaging and excess fibrin deposition at the labyrinth layer-junctional zone interface of the placenta, and PAS staining demonstrated prominent focal and segmental sclerosis with collapsed glomerular capillaries in the kidneys of the CD40L mice. Flow cytometry data showed that interferon-γ production derived from CD4+ T cells was elevated in the splenic cells of CD40L mice. Blood pressure (measured by the tail-cuff method) and urine albumin concentrations were significantly increased in CD40L mice compared with control mice. Furthermore, the plasma concentrations of soluble Flt-1 and soluble endoglin were increased in CD40L mice, as occurs in human patients with PE. Thus, CD40L-induced T-helper cell type 1 differentiation during embryo implantation may have a critical role in the pathogenesis of a PE-like presentation in a novel mouse model of PE.

Stromal Cell-Derived Factor-1α Plays a Crucial Role Based on Neuroprotective Role in Neonatal Brain Injury in Rats.

Owing to progress in perinatal medicine, the survival of preterm newborns has markedly increased. However, the incidence of cerebral palsy has risen in association with increased preterm birth. Cerebral palsy is largely caused by cerebral hypoxic ischemia (HI), for which there are no effective medical treatments. We evaluated the effects of stromal cell-derived factor-1α (SDF-1α) on neonatal brain damage in rats. Left common carotid (LCC) arteries of seven-day-old Wistar rat pups were ligated, and animals were exposed to hypoxic gas to cause cerebral HI. Behavioral tests revealed that the memory and spatial perception abilities were disturbed in HI animals, and that SDF-1α treatment improved these cognitive functions. Motor coordination was also impaired after HI but was unimproved by SDF-1α treatment. SDF-1α reduced intracranial inflammation and induced cerebral remyelination, as indicated by the immunohistochemistry results. These data suggest that SDF-1α specifically influences spatial perception abilities in neonatal HI encephalopathy.

A Case Report of a Pregnant Gene Carrier of Spinal Muscular Atrophy

Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by degeneration of spinal cord motor neurons, atrophy of skeletal muscles, and generalized weakness. It is caused by gene deletions or other mutations in the survival motor neuron 1 gene on chromosome 5q13. There are three types of SMA. Of these types, SMA type 1 (SMA1) is distinguished by the disease onset before 6 months of age and death within the first two years of life. We report a case study of a pregnant SMA1 gene carrier for whom a prenatal diagnosis was performed. The woman delivered a healthy baby, and she was free of anxiety due to the prenatal diagnosis. The case was a 34-year-old woman with a history of giving birth to children with SMA1(3 gravida 2 para). The first baby was diagnosed with SMA1 and died 9 months later. During her second pregnancy, the fetus was prenatally diagnosed with SMA1, and the parents chose to have an artificial abortion. In her third pregnancy, the fetus was prenatally diagnosed as a gene carrier of SMA1 and was delivered. During her fourth pregnancy, a prenatal diagnosis was performed using amniocentesis after genetic counseling, and the fetus was diagnosed as a gene carrier of SMA1. A 3.310 g female baby was delivered with Apgar scores of 9 at 1 minute and 9 at 5 minutes. When a prenatal diagnosis of SMA is performed, various guidelines should be followed, and the patient should be provided with genetic counseling.