Kaoru Suzumori

Embryonic karyotype of abortuses in relation to the number of previous miscarriages

OBJECTIVE To examine the frequency of chromosomal abnormalities in products of conception from patients with recurrent miscarriages in relation to the number of previous miscarriages. DESIGN Retrospective analysis. SETTING Nagoya City University Medical Hospital. PATIENT(S) A total of 1,309 women with a history of 2-20 consecutive first-trimester abortions. INTERVENTION(S) Chromosomal analysis performed on products of conception with use of a standard G-banding technique. MAIN OUTCOME MEASURE(S) The frequencies of abnormal and normal embryonic karyotypes for each number of previous abortions were studied. The subsequent pregnancy outcome of patients whose previous miscarriages were karyotyped were studied along with the predictive value of karyotyping of previous miscarriages for subsequent miscarriages. RESULT(S) The miscarriage rate increased with the number of previous spontaneous abortions. The frequency of abnormal embryonic karyotypes significantly decreased and that of normal embryonic karyotypes significantly increased with the number of previous abortions. Among 71 patients whose embryonic karyotypes were normal, 44 aborted subsequently, and 23 of 60 patients whose embryonic karyotypes were abnormal aborted subsequently. Patients with a previous normal embryonic karyotype aborted more frequently than those with an abnormal karyotype. CONCLUSION(S) The frequency of normal embryonic karyotypes significantly increases with the number of previous abortions, and a normal karyotype in a previous pregnancy is a predictor of subsequent miscarriage.

Isolation, mapping, and functional analysis of a novel human cDNA (BNIP3L) encoding a protein homologous to human NIP3

We have isolated a novel cDNA that encodes a product showing significant sequence homology (56% identity) to human NIP3, a protein thought to interact with adenovirus E1B19kD and human BCL2 proteins. This cDNA contains an open reading frame of 657 nucleotides encoding a 219 amino acid polypeptide. The gene, designated BNIP3L, was expressed in all 16 normal human tissues examined; we mapped it to chromosome band 8p21 by fluorescence in situ hybridization. Introduction of the BNIP3L gene into six different cancer‐cell lines caused significant growth suppression in each of them, while no such effect occurred when the antisense cDNA or the vector DNA was transfected, indicating that BNIP3L may function as a tumor suppressor. Genes Chromosomes Cancer 21:230–235, 1998.

Distributions of endometrial NK cells, B cells, T cells, and Th2/Tc2 cells fail to predict pregnancy outcome following recurrent abortion.

PROBLEM: To evaluate the ability of immunophenotypes of endometrial leukocytes from patients with histories of recurrent abortion to predict outcome of subsequent pregnancy.

Factor XII but not protein C, protein S, antithrombin III, or factor XIII is a predictor of recurrent miscarriage.

OBJECTIVE To investigate whether a decrease in the values of protein C (PC), protein S (PS), antithrombin III (ATIII), factor XII (FXII), or factor XIII (FXIII) has predictive value for subsequent miscarriages. DESIGN Prospective study. SETTING Nagoya City University Medical School. PATIENT(S) A total of 536 patients with a history of two or more first-trimester miscarriages. INTERVENTION(S) One hundred and twelve patients treated with low-dose aspirin were excluded from the analysis. MAIN OUTCOME MEASURE(S) The subsequent pregnancy outcome of 424 patients was compared for abnormal and normal levels of each parameter. RESULT(S) There were no differences in the subsequent miscarriage rates between abnormal and normal values of PC, PS, ATIII, and FXIII. However, the rate with abnormal FXII is significantly higher than that with normal FXII. CONCLUSION(S) A decrease in FXII (but not in PC, PS, ATIII, or FXIII) predicts subsequent miscarriage in patients with a history of first-trimester recurrent miscarriages.

No association of C677T methylenetetrahydrofolate reductase and an endothelial nitric oxide synthase polymorphism with recurrent pregnancy loss

Problem:  It is controversial whether polymorphisms of methylenetetrahydrofolate reductase (MTHFR) and the endothelial nitric oxide synthase (eNOS) are associated with recurrent pregnancy loss.

Molecular analysis of five independent Japanese mutant genes responsible for hypoxanthine guanine phosphoribosyltransferase (HPRT) deficiency

Five independent mutations in the hypoxanthine guanine phosphoribosyltransferase (HPRT) gene were identified in a partially HPRT deficient patient with gout and in four Lesch-Nyhan patients. Using the polymerase chain reaction (PCR) technique coupled with direct sequencing, the nucleotide sequences of the entire HPRT coding region amplified from the cDNA and also of each exon amplified form the genomic DNA were analyzed. Three independent point mutations in the coding region were detected in the partially HPRT deficient patient (Case 1) and in two Lesch-Nyhan patients (Case 2 and 3), resulting in single amino acid substitutions. The family study of Case 3, utilizing a PvuII restriction site created in the mutant gene, indicated that the mother was a heterozygote, and a sister and a fetal brother had inherited the normal HPRT gene from the mother. In two other mutants causing Lesch-Nyhan syndrome, a portion of the HPRT gene was deleted, and RNA splicing was missing in both mutants. A 4-bp deletion at the 5′ end of exon 4 resulted in formation of three different types of abnormal mRNA (Case 4). The other mutant (Case 5) produced abnormal mRNA including 26bp of intron 8 instead of the deleted 58bp at the 5′ end of exon 9, because of a 74-bp deletion from intron 8 to exon 9.

Elevation of Transforming Growth Factor-β1 Is Associated with Recurrent Miscarriage

To investigate the significance of transforming growth factor-β1 (TGF-β1) in reproduction we have compared plasma levels in normal pregnant women and patients suffering miscarriages. We examined 188 normal pregnant women and 12 pregnant women with miscarriages. Eight women with severe recurrent miscarriages (mean ± SD of previous number of miscarriages; 10.4 ± 2.4 times) were also examined before conception; 34 nonpregnant women served as controls. Plasma TGF-β1 level increased with the gestational week and returned within the normal range 1 month after delivery. The levels among pregnant women with miscarriages (mean ± SD; 2.44 ± 0.83 ng/ml) were significantly higher than those of pregnant controls (1.74 ± 0.95 ng/ml) of matched gestational weeks; levels among nonpregnant women with severe recurrent miscarriages were extremely elevated (4.1 ± 3.04 ng/ml) compared to the control value (1.34 ± 0.59 ng/ml). These data suggest that TGF-β1 may be necessary to maintain pregnancy but also may be a risk factor for recurrent miscarriages.

Sex Chromosomal Analysis of Spermatozoa from Infertile Men Using Fluorescence In Situ Hybridization

AbstractPurpose: To confirm an association between male infertilityand chromosome aberrations of spermatozoa, wedemonstrated the frequency of numerical abnormalities ofspermatozoa from infertile men with abnormal semen parameterscompared with fertile controls. Method: Sperm cells from 10 infertile patients wereinvestigated for disomy rates of sex chromosomes and chromosome18 and diploidy by fluorescence in situ hybridization (FISH).All patients showed oligoasthenozoospermia with spermcounts 3–20 × 106/ml and motile rates 0–40%. Results: Regarding XY disomy, a significantly higherfrequency was found in 8 of 10 patients as compared to normalfertile men. The disomy rates of chromosome 18, XX, YY,and diploidy rate were not increased. Conclusions: There is an association between maleinfertility and embryo with aneuploidy of sex chromosomes.Counseling about possible genetic risks should be provided to theinfertile couples planning assisted reproduction treatment.

Progesterone inhibits apolipoprotein-mediated cellular lipid release: a putative mechanism for the decrease of high-density lipoprotein.

In order to investigate the mechanism for female gonadal hormones to regulate the plasma high-density lipoprotein (HDL) level, the effect of 17 beta-estradiol and progestogens was examined in vitro on the assembly of HDL by free apolipoprotein A-I (apoA-I) with cellular cholesterol and phospholipid. ApoA-I generated HDL particles by removing cholesterol and phospholipid from human fibroblasts, MRC-5. While 17 beta-estradiol did not influence this reaction, progesterone suppressed the removal by apoA-I of both cholesterol and phospholipid, with the extent of the inhibition more for cholesterol than phospholipid. Three other synthetic progestogens showed the similar inhibitory effect on the cellular cholesterol release. Cellular cholesterol de novo-synthesized from mevalonolactone entered more into the acyl-esterified cholesterol compartment and less to the unesterified compartment in the presence of progesterone. On the other hand, progesterone did not influence the overall mass ratio of free and esterified cholesterol in the cell. Cell-surface cholesterol was also uninfluenced by progesterone when probed by extracellular cholesterol oxidase reaction or by diffusion-mediated cellular cholesterol release to cyclodextrin. Neither caveolin-1 nor ABCA1 expression was influenced by progesterone. Progesterone thus seems primarily to alter the specific intracellular cholesterol compartment that is related to the apoA-I-mediated HDL assembly. This mechanism might contribute to the decrease of plasma HDL by administration of progestogen in women under hormone replacement therapy.

Mechanisms underlying the reduced endothelium-dependent relaxation in human omental resistance artery in pre-eclampsia

1 In pre‐eclampsia, a functional change occurs in the role played by endothelium‐derived nitric oxide (NO) in the regulation of smooth muscle contraction in resistance arteries. We investigated the underlying mechanism in human omental resistance arteries from normotensive pregnant and pre‐eclamptic women in the presence of diclofenac (an inhibitor of cyclo‐oxygenase). 2 In endothelium‐intact strips, the sensitivity to 9,11‐epithio‐11,12‐methano‐thromboxane A2 (STA2) was significantly higher in pre‐eclampsia, and this was not modified by either NG‐nitro‐l‐arginine (l‐NNA, an inhibitor of NO synthase) or removal of the endothelium. 3 Bradykinin and substance P each produced an endothelium‐dependent relaxation of the STA2‐induced contraction in both groups, although the relaxation was significantly smaller for pre‐eclampsia. l‐NNA markedly attenuated the endothelium‐dependent relaxation in the normotensive pregnant group but not in the pre‐eclamptic group. 4 In the presence of l‐NNA, the relaxation induced by sodium nitroprusside (SNP) on the STA2 contraction was significantly smaller for pre‐eclamptic than for normotensive pregnant women. 5 In endothelium‐denuded strips, the relaxation induced by 8‐para‐ chlorophenyl thio‐guanosine‐3′,5′‐cyclic monophosphate (8‐pCPT‐cGMP) on the STA2 contraction was significantly less for pre‐eclampsia. 6 In β‐escin‐skinned strips from both groups of women, 8‐pCPT‐cGMP (1–10 μm) concentration‐dependently attenuated the contraction induced by 0.5 μm Ca2+. However, its relaxing action was significantly weaker in pre‐eclampsia. 7 It is suggested that the weaker responsiveness to NO seen in strips from pre‐eclamptic women may be partly due to a reduced smooth muscle responsiveness to cyclic GMP.