No abstract

PF20 was first identified in Chlamydomonas rheinhardtii as an essential component of the axoneme central apparatus. We discovered that the mouse Pf20 gene encodes two major transcripts (2.5 and 1.4 kb), which are expressed in different patterns during spermatogenesis, yielding proteins of 71 and 35 kDa, respectively. Both proteins contain contiguous WD repeats in their C termini. The meiotically expressed 71-kDa protein is incorporated into the central apparatus, whereas the 35-kDa protein, which accumulates in postmeiotic male germ cells, is abundant in the nucleus. We disrupted the Pf20 gene domains that encode the C-terminal WD repeats in embryonic stem cells. Highly chimeric mice carrying the mutant Pf20 allele had impaired spermatogenesis with a significant loss of germ cells at the round spermatid stage, in association with disorganization of sperm axoneme structure. The mutated Pf20 allele was never transmitted, indicating that Pf20 haploinsufficiency caused the defects in spermatogenesis. The 35-kDa PF20 protein was shown to bind to meiosis-expressed gene 1 (MEIG1), a chromosome͞chromatin-binding protein initially expressed during meiosis but retained in the germ cell nucleus throughout later stages of spermatogenesis. Our findings reveal an essential role for Pf20 in mouse spermatogenesis, sustaining postmeiotic germ cell viability. The different patterns of expression of the two PF20 proteins suggest the possibility that the Pf20 gene has multiple functions during spermatogenesis.A xonemes, critical components of cilia and flagella, have a structure consisting of nine outer doublet microtubules encircling a central pair of microtubules, which has remained virtually unchanged during evolution (1-3). Defective assembly or function of axonemes results in immotile cilia, which causes defects in lateralization, respiratory disease, hydrocephalus, and infertility (4-7). The best-studied mutations in mammals that cause immotile cilia are in genes encoding dynein arm proteins, which generate the force that drives axonemal motility (8-10). Less is known about other axonemal proteins, especially those of the central pair. However, studies of Chlamydomonas rheinhardtii revealed important roles for the central apparatus. Mutant Chlamydomonas strains lacking functional PF16, PF6, and PF20 have paralyzed flagella, and the C1 microtubule, the projections connecting the C1 microtubule and the entire central pair, respectively, are missing in isolated axonemes (11)(12)(13).To understand the function of the central apparatus in mammals, we cloned the human and mouse orthologues of Chlamydomonas, PF16 (SPAG6) (14, 15) and PF20 (16). SPAG6-deficient mice are hydrocephalic, and males surviving to maturity are infertile as a result of a marked sperm motility defect associated with disorganization of flagellar structures, including loss of the central pair microtubules and disorganization of the outer dense fibers and fibrous sheath (6). These observations suggested an important role for central apparatus proteins in mammali...

The StAR-related lipid transfer (START) domain, first identified in the steroidogenic acute regulatory protein (StAR), is involved in the intracellular trafficking of lipids. Sixteen mammalian START domain-containing proteins have been identified to date. StAR, a protein targeted to mitochondria, stimulates the movement of cholesterol from the outer to the inner mitochondrial membranes, where it is metabolized into pregnenolone in steroidogenic cells. MLN64, the START domain protein most closely related to StAR, is localized to late endosomes along with other proteins involved in sterol trafficking, including NPC1 and NPC2, where it has been postulated to participate in sterol distribution to intracellular membranes. To investigate the role of MLN64 in sterol metabolism, we created mice with a targeted mutation in the Mln64 START domain, expecting to find a phenotype similar to that in humans and mice lacking NPC1 or NPC2 (progressive neurodegenerative symptoms, free cholesterol accumulation in lysosomes). Unexpectedly, mice homozygous for the Mln64 mutant allele were viable, neurologically intact, and fertile. No significant alterations in plasma lipid levels, liver lipid content and distribution, and expression of genes involved in sterol metabolism were observed, except for an increase in sterol ester storage in mutant mice fed a high fat diet. Embryonic fibroblast cells transfected with the cholesterol side-chain cleavage system and primary cultures of granulosa cells from Mln64 mutant mice showed defects in sterol trafficking as reflected in reduced conversion of endogenous cholesterol to steroid hormones. These observations suggest that the Mln64 START domain is largely dispensable for sterol metabolism in mice.

Women with antithrombin (AT) I11 deficiency are prone to pregnancy-associated venous thromboembolism. We report 2 cases with genetically confirmed ATIII deficiency, one with a mutation in exon 3A and the other with an exon 4 deletion, in whom the pregnancies were successfully managed with prophylactic therapies for thrombosis. A 35-year-old pregnant woman was treated with intravenous infusions of ATIII concentrate alone, and the other 22-year-old pregnant woman was mainly treated with subcutaneous injections of heparin and oral low-dose aspirin therapy. Both pregnancies resulted in vaginal deliveries of healthy neonates. The literature concerning prophylactic therapies for thrombosis in ATIII deficiencycomplicated pregnancy is reviewed, and the clinical problems, including the adverse effects of the therapies, are discussed.

There have been few reports on postpartum changes in the uterus during the three months after delivery. The aim of this study was to evaluate uterine morphological changes in women after vaginal delivery (n=262-351) and in women after cesarean section (n=64-82) and to evaluate the relation between breast-feeding and parity, and uterine involution at 1 and 3 months postpartum measured by vaginal ultrasonography. There were no significant differences in parity between the vaginal delivery group and the cesarean section group. The length of the uterus at one month (7.93+/-1.16 cm, mean+/-SD) and, three months (7.03+/-1.19 cm) and the width of the uterus at three months (3.83+/-0.94 cm) after delivery in the cesarean section group were greater than in the transvaginal group (7.64+/-1.03 cm, 6.65+/-0.99 cm, 3.57+/-0.62 cm, respectively). Increasing maternal parity was associated slightly with larger uterine size at one month post partum. The length of the uterus of women with a breast-feeding rate of 80% or more per day was 6.35+/-0.85 cm, and shorter than in women with a rate of 20% or less 7.03+/-1.04 cm, at three months after delivery. The width of the uterine body of women with a breast-feeding rate of 80% or more per day was 3.32+/-0.45 cm, and shorter than in women with a rate of 20% or less 3.87+/-0.66 cm, at 3 months after delivery. Stepwise regression and multiple regression analysis among parity, the history of cesarean section, the breast-feeding rate at one and three months after the delivery, and the restoration of the menses at three months after the delivery showed that the uterine size at one month after the delivery was related to the cesarean section and that the uterine size at three months after delivery was mostly related to the rate of breast-feeding. These results indicated that uterine involution was related to delivery mode at one and three months postpartum, feeding mode at three months postpartum, the menses restoration, and parity. The rate of breastfeeding was mostly related to the uterine size at three months postpartum.

MIVIg treatment was effective in all 14 pregnancies from RSA women of unexplained etiology, excluding 4 abortions with chromosome abnormality. Peripheral NK cell activity and subsets were suppressed by MIVIg treatment.

The aims of the present study were to determine recent trends in the prevalence of Down syndrome (DS) in Japan, and to determine whether recent changes in demographic and social habits and access to prenatal diagnosis have influenced the livebirth rates of DS. Livebirth statistics indicate that the birth rate in Japan has decreased for women in their 20s and has increased for those in their 30s and 40s. During an 18-year period between 1980 and 1997, 1,299 consecutive DS infants were born among a total of 2,232,694 births, a rate corresponding to approximately 10% of all births in Japan over the same period. The increasing risk of DS with advancing maternal age was confirmed. The overall prevalence was 5.82 DS births per 10,000 livebirths (8.3-9.7 per 10,000 after correction according to the estimated ascertainment ratio: 60-70%). The prevalence rate by year of child birth represents a statistically significant increase (P = 0.001). In conclusion, recent trends in the prevalence of DS in Japan from 1980 to 1997 failed to show a consistent tendency to decrease, probably because of the concomitant increase in pregnancy in advanced maternal age.

The aim of this study was to investigate the correlation between the cytokine levels in the amniotic fluid (AF) and the histological stage of chorioamnionitis (CAM) in premature labor. AF of 6 cases (7 samples of AF were obtained as one was a twin pregnancy) in whom CAM was diagnosed histologically, and 12 cases without CAM were included in this study. Amniotic fluid was obtained within 24 hours prior to delivery. Cytokine levels (IL-2, -4, -6, TNF-alpha, IFN-gamma) in AF were measured by an ELISA method. Levels of IL-2 and -6 in the CAM-positive group (mean +/-S.E., 52.9 +/- 83.9 pg/ml, and 20,537.9 +/- 8853.7 pg/ml, respectively) were higher than those in the CAM-negative group (i.e. undetectable, and 65.6 +/- 27.5, respectively) with a statistical significance of p < 0.05, p < 0.001, respectively. There was a positive linear relationship between IL-6 levels of AF and the placental histological inflammatory stages of Blanc in the CAM-positive group. From these results it would appear that the IL-6 level in AF is the most sensitive test in the detection of extraamniotic infection or intraamniotic infection in preterm labor with intact membranes and also indicates the severity infection.