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Biomedical subjects

A Endo

Publications and source records attributed to A Endo.

At least 217 records · Page 12Linked to original sources

Effects of delayed mating on preimplantation embryos in spontaneously ovulated mice.

The effects of delayed mating on mouse preimplantation embryos (78 +/- 1 hours) were studied by setting up different mating periods in relation to the estimated time of spontaneous ovulation. Copulation occurred even in the late morning and early afternoon after the night of spontaneous ovulation. However, females mated in the early afternoon had no viable embryos at the time of laparotomy. Although embryonic development was not affected in the groups mated 6 or 10 hours after estimated ovulation, the percentage of degenerated embryos was increased in these groups. These results suggest that prolonged intervals between the estimated time of ovulation and mating have some deleterious effects on preimplantation embryos.

Animals↗

Interlitter variability in fetal body weight in mouse offspring from continuous, overnight, and short-period matings.

When female mice of the Jcl:ICR strain were mated with a male either (1) continuously throughout the day or (2) overnight or (3) during 2 hours in the morning at light period, the interlitter variability of fetal body weight on the 18th day of gestation was smallest in the group with short-period mating. Thus, in the embryonic stage-specific teratological experiments, this mating schedule is advised. Even for routine reproductive toxicity testing protocols, the short-period mating may be preferable for the purpose of increasing test sensitivity.

Animals↗

Digit development and embryonic weight in mice: analysis of sex-related time difference and mating period-related interlitter variability.

The embryonic growth and digit formation in limb buds were more advanced in male embryos than in female embryos at a specific time (day 12.0) of midgestation. Furthermore, when the number of digits was compared between the sexes according to their body weight, male embryos were found to be more advanced than females in the differentiation of the digit in limb buds. This is the first demonstration of the presence of a time difference in digit development between the sexes of mouse embryos. In the short-period, morning-mating group, embryonic weights at day 12.0 were lower than those in the overnight-mating group. However, the digit development was not very much delayed in proportion to the difference in body weights, and some "catch-up" phenomena were observed in this group. Interlitter and intralitter variability in body weights of mouse embryos at day 12.0 was greater in the overnight-mating group than in the short-period-mating group. These findings suggest that, in embryonic stage-related teratological experiments in mice, a short-period-mating schedule is advised and that the incidence of developmental anomalies should be analyzed separately for male and female fetuses.

Animals↗

Analysis of protective activity of N-acetylcysteine against teratogenicity of heavy metals.

N-acetylcysteine (NAC) is known to enhance the renal excretion of heavy metals. Therefore, we investigated whether the teratogenicity of metals (Hg, Cr, and Cd) can be ameliorated by NAC in mice. Contrary to our expectation, the incidence of congenital malformations produced by these metals was two to three times higher in the mice that were fed NAC (0.2% in the diet). The underlying mechanism or mechanisms are unknown and should be investigated.

Abnormalities, Drug-Induced↗

Overaccumulation of 3-hydroxy-3-methylglutaryl-coenzyme-A reductase in a compactin(ML-236B)-resistant mouse cell line with defects in the regulation of its activity.

Using a stepwise selection procedure, we have developed a line of mouse FM3A cells which is resistant to compactin (ML-236B), a competitive inhibitor of 3-hydroxy-3-methyl-glutaryl-coenzyme-A (HMG-CoA) reductase. This line, designated CR200, expressed a stable phenotype of a greater than 100-fold higher resistance to the inhibitor and a 160-fold higher HMG-CoA reductase activity than did the parental FM3A cell line when grown in the presence of low-density lipoprotein (LDL). In contrast to its action in the parental cells, HMG-CoA reductase in CR200 cells was not suppressed by human LDL. The activity of both cell-surface binding and degradation of 125I-LDL was approximately 10% in CR200 cells as compared with that in parental cells. Affinity of the 125I-LDL binding in CR200 cells was similar to that in the parental cells. In addition, HMG-CoA reductase was not suppressed normally by mevalonate and 25-hydroxycholesterol in CR200 cells; suppression was 50-60% by both compounds under conditions where suppression was about 99% in the parental cells. Sterol synthesis from [3H]mevalonate was normal in the variant cells. These observations demonstrate two defects in CR200 cells: decreased levels of LDL receptor and a defective regulation of HMG-CoA reductase by one or more products derived from mevalonate. When grown without compactin for 21 weeks, the variant cells became slightly sensitive to compactin and concomitantly recovered partly from both defects. However, these phenotypes of CR200 cells were stable up to 15 months when exposed to compactin. These two defects may account for the overaccumulation of HMG-CoA reductase in CR200 cells and thereby for the resistance to compactin.

Animals↗

Distribution by sex of mouse fetuses in the intrauterine position.

We examined whether or not the sex of the fetuses of polytocous animals distributes randomly in the position along the uterine horn in 255 mouse litters. The fetal sex ratio did not differ significantly among the three intrauterine segments (ovarian, middle, and cervical). Based on the number of fetuses examined in this study, it can be stated that even if sex ratio differences exist among the segments, the ratio in individual segments would fall mostly inside the +/- 0.1 range, when the overall sex ratio (M/(M + F] is around 0.5.

Animals↗

Effects of induced ovulation by pregnant mare's serum and human chorionic gonadotropin on the sex ratio of mouse fetuses.

The sex ratio of the fetuses from mice treated with pregnant mare's serum (PMS)/human chorionic gonadotropin (HCG) to induce ovulation did not differ appreciably from that of spontaneously ovulated controls. Rather, an intriguing observation was that the sex ratio in the right uterine horns tended to be lower than that in the left horns in both spontaneously ovulated controls and PMS/HCG-treated groups. We speculate on its possible relation to the observed right-left asymmetry of horn sizes (number of fetuses in the horn).

Animals↗

Analysis of diurnal difference in teratogen (Ara-C) susceptibility in mouse embryos by a progressive phase-shift method.

Our objectives were to determine whether the embryotoxic and teratogenic potential of cytosine arabinoside (Ara-C) differs depending on the time of day. Pregnant CD-1 (ICR) mice were placed in an environment where the phases of lighting and darkness were reversed by progressive phase-delay or phase-advance methods--2 h every day from day of gestation (dg) 2 to dg 7 (or 6). After it was confirmed that these progressive phase-shifting methods had no effect on embryonic growth and pregnancy outcome, 5 mg/kg body weight (bt) of Ara-C was injected intraperitoneally into these animals at 1000 or 1600 on dg 11, and the incidence of gross fetal malformations was compared with that in control dams treated similarly but under a regular lighting regimen (0600-1800). In contrast to previous reports on other teratogens, no diurnal difference was observed in fetal susceptibility to the teratogenic potential of Ara-C. The possible usefulness of the progressive phase-shifting method in the field of chronoteratology is proposed.

Animals↗

Dose- and stage-related sex difference in the incidence of cytosine arabinoside induced digit anomalies in the mouse fetus.

Pregnant mice of the Jc1:ICR strain were injected intraperitoneally with a single dose of 2.5, 5, or 10 mg/kg of cytosine arabinoside (Ara-C) on day 9.5 or 10.5 of gestation (dg). Mice were killed on 18.4 dg, and the incidences of digit anomalies were compared between male and female fetuses. In the group treated with 10 mg of Ara-C on 9.5 dg, oligodactyly of the hindlimbs was produced more frequently in male fetuses. In the group treated with 5 mg of Ara-C on 10.5 dg, oligodactyly of the forelimbs tended to occur more frequently in male fetuses. Also, in this group, oligodactyly of the hindlimbs occurred more frequently in male fetuses, whereas polydactyly occurred more frequently in female fetuses. The observed difference in the incidences of digit anomalies between male and female fetuses may be explained either in terms of the sex-related time lag in the critical period for digit development or by a probable sex difference in embryonic susceptibility to Ara-C.

Abnormalities, Drug-Induced↗

Potential teratogenicity of gonadotropin treatment for ovulation induction in the mouse offspring.

The teratogenic effects of induced ovulation were studied in mice by using three different doses of pregnant mare's serum (PMS)/human chorionic gonadotropin (HCG) (2.5, 5, or 10 IU) at two different stages of the estrous cycle. The PMS/HCG treatment induced high incidences of external congenital anomalies in the offspring in a dose-dependent manner. This was especially so when the treatment was "out of phase" to the naturally occurring ovulation schedule. The predominant malformations were open eyelids and cleft palate. The problems of extrapolating these findings to humans are discussed.

Abnormalities, Drug-Induced↗

The incidence of tail flexion to the left side in mouse embryos.

The tail was flexed towards the left side of the body in 5.2 and 6.2% of ICR mouse embryos at 10.5 and 11.5 days of gestation respectively. Body weights of these embryos did not differ from their littermates with right-sided tail flexion. The flexion to the left may be an easily detectable parameter of variation in the morphology of mouse embryos at midgestation.

Animals↗

Production of tetrodotoxin and its derivatives by Pseudomonas sp. isolated from the skin of a pufferfish.

Bacteria isolated from the skin of the pufferfish Fugu poecilonotus were screened for tetrodotoxin production. Tetrodotoxin and its derivatives were detected by HPLC analyses in broth cultures of a Pseudomonas sp. Upon alkali treatment the compounds yielded, as do tetrodotoxin and its derivatives, 2-amino-6-hydroxymethyl-8-hydroxyquinazoline, the identity of which was confirmed, after methylation or trimethylsilylation, by HPLC, mass spectrometry and gas chromatography - mass spectrometry.

Animals↗

Purification and properties of collagenase from a Streptomyces species.

A collagenase active against native, insoluble collagen was isolated from the culture filtrate of a streptomycete which has been designated Streptomyces sp. C-51. Collagenase was produced by growing this strain in media containing gelatin. Purification by ammonium sulfate fractionation and chromatographies on DEAE-Toyopearl and DEAE-Cellulofine columns produced active enzyme which was free of contaminating proteins, including nonspecific proteinases, but which contained two active subspecies (I and II). Both subspecies were purified by preparative slab gel electrophoresis. The apparent molecular weights were 100,000 for the homogeneous fraction I and 90,000-110,000 for the microheterogeneous fraction II. These two subspecies were most active at pH 8-9, very similar in amino acid composition and immunologically identical. Some other properties of the Streptomyces C-51 collagenase were compared with those of Clostridium histolyticum collagenase. Substrate specificity, insensitivity to N-ethylmaleimide and diisopropyl fluorophosphate, and sensitivity to certain metal ion complexing agents were similar for the collagenases from both microorganisms.

Amino Acids↗