Shinobu Goto

Role of Indoleamine 2,3-Dioxygenase and Tryptophan 2,3-Dioxygenase in Patients with Recurrent Miscarriage

An indoleamine 2,3‐dioxygenase (IDO) and a tryptophan 2,3‐dioxygenase (TDO) lead to dysfunction of T cell and immunological tolerance between fetus and mother in early pregnancy. We investigated the role of IDO and TDO in patients with recurrent miscarriage.

Prenatal findings of omphalocele–exstrophy of the bladder–imperforate anus–spinal defects (OEIS) complex

Omphalocele–exstrophy of the bladder (cloaca)–imperforate anus–spinal defects (OEIS) complex describes a rare grouping of more commonly occurring component malformations. We report two cases of OEIS complex diagnosed prenatally by ultrasound and magnetic resonance imaging (MRI). In both cases, OEIS complex was suspected by conventional sonography in the second trimester, and fetal MRI was performed at 27 and 32 weeks of gestation. Conventional sonography revealed low abdominal wall mass, spina bifida, absent bladder and ambiguous genitalia, but those findings were inconclusive. Using fetal MRI, we were able to detect omphalocele, imfraumbilical mass connected to gut tract, absent bladder, ambiguous external genitalia and spinal defect. Our findings suggest that fetal MRI is a useful tool for prenatal diagnosis of OEIS complex. MRI helps prenatal counseling and planning of postnatal early treatment strategy.

Role of cathepsin E in decidual macrophage of patients with recurrent miscarriage.

In a previous study, we reported that the cathepsin-cystatin system caused endometrial dysfunction in early pregnancy. Here, we investigated the existence and contribution of cathepsin E in early pregnancy in patients with recurrent miscarriage (RM). The effect of cathepsin deficiency on fertility and female reproductive organs were also analyzed in CatE(-/-) mice. Human studies were conducted in a hospital setting, with informed consent. Cervical mucus was collected from RM patients in early pregnancy (4-6 gestational weeks, n = 21), and the pregnancy outcome was compared prospectively. The cathepsin E expression in decidua of RM patients (n = 49) and normal pregnant women undergoing elective surgical abortion (n = 24) was measured using SDS-PAGE, and western blot analysis. Decidual macrophages were isolated from RM patients (n = 6) and stimulated by lipopolysaccharide (LPS) and interferon gamma (IFN-γ). Results from the mouse model showed that CatE(-/-) mice were fertile, but the litter number was significantly smaller. The uterus of CatE(-/-) mice showed granulation tissue. In human samples, protease activity of cathepsin E measured with Fluorescence-Quenching Substrate (KYS-1) in cervical mucus of patients who developed miscarriage was markedly decreased compared with patients without RM. The expression of cathepsin E in decidua, semi-quantified by SDS-PAGE, western blot analysis was significantly lower in RM patients compared with patients without RM. By double staining immunofluorescence, the staining of cathepsin E was observed in CD14 or CD68 positive cells in all deciduas. Upon stimulation with LPS and IFN-γ, the expression of cathepsin E in cell lysate of decidual macrophages was markedly reduced in RM patients compared with controls. The results suggested that decreased activity of cathepsin E produced by decidual macrophages might be responsible for the induction of miscarriages in some RM patients.

A Case of Microangiopathic Antiphospholipid-Associated Syndromes during Pregnancy: Review of the Literature

Microangiopathic antiphospholipid-associated syndromes (MAPSs) are reported as encompassing several conditions mainly affecting the microvasculature of selected organs: the liver in HELLP syndrome (hemolysis, elevated liver enzymes, and low platelet); kidney, brain, and skin in TTP (thrombotic thrombocytopenic purpura). It is predominant in patients with catastrophic antiphospholipid syndrome (APS). A recent report suggests that APS is not only a thrombotic disease but also associated with microangiopathic features, and it can explain the greater prevalence of HELLP syndrome in these patients. We here report a case of MAPS during pregnancy associated with systemic lupus erythematosus (SLE) in early second trimester.

Two cases of prenatally diagnosed sacrococcygeal teratoma type I with different clinical features

Sacrococcygeal teratoma (SCT) is a rare congenital disease and prognostic factors have not been entirely established. We report two cases of fetal SCT with different clinical courses. Case 1 was a cystic, slow growing tumor with mild vascularity. The tumor was removed one week after delivery at 35 weeks, and there was no recurrence at 1.5‐year follow‐up. Case 2 was a solid, rapid growing tumor with rich vascularity. Cesarean section was performed due to severe fetal hydrops and mirror syndrome in the mother at 27 weeks. The tumor had ruptured and was removed soon after delivery to control bleeding, but the baby died the next day. Our cases suggest that solid component and rich vascularity might correlate with poor prognosis.

Clinical and molecular findings in a patient with 46,XX/47,XX,+14 mosaicism caused by postzygotic duplication of a paternally derived chromosome 14

Clinical and Molecular Findings in a Patient with 46,XX/47,XX,þ14 Mosaicism Caused by Postzygotic Duplication of a Paternally Derived Chromosome 14 Nobuhiro Suzumori,* Masayo Kagami,** Kyoko Kumagai, Shinobu Goto, Keiko Matsubara, Shinichiro Sano, and Mayumi Sugiura-Ogasawara Department of Obstetrics and Gynecology, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Division of Clinical and Molecular Genetics, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan

1141651467 Role of calpain in human sperm

We evaluated the role of calpain in human sperm for fertilization. Semen collected manually from healthy donors with informed consent was liquefied and following percoll gradient centrifugation. After exposure to different concentration of progesterone (P) or under hypoxic condition (H), the samples were used for immunostaining, SDS‐PAGE and western blot analysis. The increase of calcium ion concentration in the sperm was observed by fluorescent microscope (ARGUS‐50CA) system using Fura 2‐AM. The role of calpain for fertilization was speculated from the results of Hamster penetration test, Hamilton Motility Analyzer, Triple satin method and Acrobeads test using calpain inhibitors. Immunostaining in human sperm was observed using antibodies against the micro‐calpain in the types of whole acrosome, equatorial segment, head segment, neck segment or neck and tail segment. Most of these demonstrated acrosome type staining with anti‐pro micro‐calpain antibody. Western blot analysis revealed P or H treatment to cause a concentration or time‐dependent activation of micro‐calpain. In addition, calpain inhibitors significantly reduced the acrosome reaction and penetration. The results suggest that micro‐calpain in human sperm plays an important role for the fertilization.