bluuebunny/crossref_metadata_2025_split huggingface dataset:
Growth and differentiation schedule of mouse embryos obtained from delayed matings
Authors: Ishikawa Hitoshi , Omoe Katsuhiko , Endo Akira 
Published: June 2005

AbstractWe previously showed that digit formation in mouse embryos from early morning mating seemed to progress faster than those from overnight mating. In this study, to confirm this phenomenon, we examine whether the embryos from normal (0 hr from ovulation to fertilization) and delayed matings (3, 6, or 9 hr from ovulation to fertilization) respond differently to some acute teratogens when they are treated at the same time point from mating.Five mg/kg of cytosine arabinoside (Ara‐C) was given to pregnant mice intraperitoneally at 246, 249, or 252 hr (day of gestation (dg) 10) after mating. The patterns of Ara‐C induced digit malformations in embryos from the delayed mating groups were those of more advanced stages, when compared with normal mating groups with the same time intervals from mating to Ara‐C treatment. In other words, oocytes fertilized up to 9 hr after the presumed time of ovulation could grow similarly to those of normally fertilized oocytes. This catch‐up phenomenon suggests that the ovulation clock should be used for the startpoint of the time scale of the growth and differentiation of embryos rather than fertilization clock. © 1992 Wiley‐Liss, Inc.
Further genetic studies of the cause of exencephaly in SELH mice
Authors: Gunn T. M. , Juriloff D. M. , Harris M. J. 
Published: June 2005

AbstractWe have developed an inbred stock of mice called SELH that has a high frequency of the neural tube defect exencephaly at birth. A previous genetic study indicated that the exencephaly is due to two to three additive loci differing between SELH and a closely related normal strain, ICR/Bc, but this analysis was not designed to detect genetic maternal effects. Recently, we demonstrated that there is genetic polymorphism among normal mouse strains leading to differences in site of initiation of closure of the cranial neural tube. In the present study, an inbred substrain of SELH mice, with 24% exencephaly among embryos, was crossed with an unrelated normal strain, SWV/Bc, and the frequency of exencephaly in subsequent generations used to extend our understanding of the genetic cause of exencephaly in SELH mice.The purposes of the genetic studies reported here were twofold. First, based on the influence of genetic maternal effects on other genetically complex birth defects in mice, we hypothesized that the exencephaly of SELH mice would exhibit strong genetic maternal effects. This hypothesis was tested by comparisons among the four possible reciprocal backcrosses to SELH. The result was an overall frequency of 2.3% exencephaly in first backcross embryos with no difference among the four crosses and no evidence of genetic maternal effects. Second, the frequency of exencephaly recovered in the backcross and F1 embryos was compared with the previous genetic study and with various genetic models. The frequencies were similar to those obtained from the cross to ICR/Bc mice and were compatible with a hypothesis of additive gene action at a few loci. The similarity of results between a wide outcross to SWV/Bc and a narrow outcross to ICR/Bc suggests that the exencephaly‐causing genes in SELH are mutations, not polymorphisms. © 1992 Wiley‐Liss, Inc.
Effects of a 48 hour continous intravenous infusion of CGS 13080‐primagrel, a selective thromboxane synthetase inhibitor, on the perinatal and early postnatal period in the guinea pig
Authors: Keith J. , Rowles T. , Warwick K. , Yau E. 
Published: June 2005

AbstractCGS 13080, imidazo[1,5‐a]pyridine‐5‐hexanoic acid, was evaluated for perinatal and postnatal effects in third trimester pregnant guinea pigs and their offspring. The compound was administered via 48 hour continous intravenous infusion to a group of pregnant guinea pigs (n = 16) at a dose of 3 mg/kg/hr starting on gestational day 52 (via chronically implanted indwelling jugular venous cannulas). A saline control group (n = 12) received equivalent volumes of normal saline 0.5 ml/kg/hr throughout the dosing period. A third group (surgery‐sham, n = 16) was subjected to cannulation but not infused. A gross examination of each dam and piglets was conducted at necropsy on day 5 of lactation. The neonatal brains and all gross lesions (maternal and neonatal) were removed and fixed for histopathological examination. Compound‐related clinical signs were noted in dams during the dosing phase of gestation. Six guinea pigs developed cephalic lymphatic swelling during the infusion. This observation may be correlated to the reported redistribution of fluid volume to the thorax of guinea pigs given intravenous injections of CGS 13080. There were no compound‐induced effects on labor, delivery, or any of the examined reproductive parameters. There were no compound‐related clinical signs, or effects on survival, body weight and developmental parameters in the F1 generation. Histopathological examination of the brains and other organs did not reveal any compound‐related abnormalities. Based on these results, it was concluded that CGS 13080 did not elicit adverse perinatal and postnatal effects in guinea pigs. © 1992 Wiley‐Liss, Inc.
A case of agnathia, situs inversus, and a normal central nervous system
Authors: Stoler Joan M. , Holmes Lewis B. 
Published: June 2005

AbstractWe reprot here a premature female infant with agnathia, lowset but normally formed ears, a downward eye slant, choanal atresia and a cleft palate. She had severe respiratory distress and died despite maximum intervantion at 5 days of age. Autopsy revealed situs inversus totalis; crossed fused renal ectopia; agnathia; normal thyroid, larynx, trachea, and bronchi; incomplete lobation of the lungs; immature pulmonary development with early hyaline membranes; and a normal central nervous system. This lack of significant central nervous system abnormalities distinguishes this infant from the majority of previously reported infants with agnathia and situs inversus. © 1992 Wiley‐Liss, Inc.
Ischemia/reperfusion: A new hypothesis for the developmental toxicity of cocaine
Authors: Fantel Alan G. , Barber Charles V. , Mackler Bruce 
Published: June 2005

AbstractIt has been shown that multiple exposures of gravid rats to cocaine during late gestation result in significant incidences of severe malformations. Hind limb reduction defects were frequent findings in this study. Other studies have shown that comparable abnormalities can be induced in experimental animals by various procedures including vascular clamping, direct fetal exposure to epinephrine, uterine handling following laparotomy, as well as by exposure to hyperbaric oxygen. This paper reviews these and other studies, and presents a novel mechanistic hypothesis that explains their common findings. It is proposed that in each instance, conceptual hypoxia results from hypoperfusion caused by transient vasoconstriction. Following the resumption of normal perfusion, reactive oxygen species are generated by the ischemia/reperfusion mechanisms thought to underlie many pathobiologic lesions. It is proposed that the conceptus is particularly vulnerable to the toxicity of oxygen radicals because of its low antioxidant activities and the highly reduced state of its undifferentiated cells. Sensitivity to cocaine and uterine handling appears to be enhanced during late gestation and it is hypothesized that this results from changes in oxygenation and iron content that increase both the substrate and catalyst for generation of reactive oxygen species. © 1992 Wiley‐Liss, Inc.
Accumulation of heat shock protein 72 (hsp 72) in postimplantation rat embryos after exposure to various periods of hyperthermia (40°–43°c) in vitro: Evidence that heat shock protein 72 is a biomarker of heat‐induced embryotoxicity
Authors: Mirkes Philip E. , Doggett Barbara 
Published: June 2005

AbstractA monoclonal antibody to the 72 kDa heat shock protein and Western blot analysis blot analysis were used to determine the induction, accumulation and turnover of hsp 72 after day 10 rat embryos were exposed to elevated temperatures (40°–43°C) for various lengths of time (2.5 minutes to 18 hours). Embryos exposed to temperatures that exceed the normal culture temperature (37°C) by 4°C or more for as little as 2.5 minutes (43°C) or 15 minutes (41, 42°C) synthesized and accumulated detectable amounts of heat‐inducible hsp 72. Hsp 72 could not be detected by Western blot analysis of proteins from embryos cultured at 40°C or below. Once induced, hsp 72 can be detected in embryos for 24–48 hours after they are removed from the hyperthermic conditions and returned to normothermic conditions. Our results also indicate that hsp 72 is induced by all hyperthermic exposures that induce alterations in rat embryo growth and development; therefore, hsp 72 is a potential biomarker for heat‐induced embryotoxicity. © 1992 Wiley‐Liss, Inc.
Embryotoxicity studies of norfloxacin in cynomolgus monkeys. II. Role of progesterone
Authors: Cukierski M. A. , Hendrickx A. G. , Prahalada S. , Tarantal A. F. , Hess D. L. , Lasley B. L. , Peter C. P. , Tarara R. , Robertson R. T. 
Published: June 2005

AbstractNorfloxacin, an orally active fluoroquinolone antimicrobial, has been reported to be embryolethal but not teratogenic when administered to pregnant cynomolgus macaques prior to gestational day (GD) 36 at doses ≤200 mg/kg/day. Additional studies have been performed in an effort to examine the mechanism responsible for this effect, particularly regarding the role of progesterone (P). The first study (Study I) investigated the effect of norfloxacin administration during early pregnancy (200 mg/kg/day; daily GD 20–30) in the absence of a functional corpus luteum (CL). The CL was surgically removed from 16 gravid females on GD 19 in order to focus on placental‐derived P; ten were dosed with norfloxacin and six received vehicle only. Embryolethality was observed for 7/10 (70%) of the treated animals during GD 25–31 versus 0/6 (0%) for controls. A reduction in serum P was noted prior to embryonic loss, although no significant effects on chorionic gonadotropin (CG), 17β‐estradiol (E2), or P or E urinary metabolites were observed. A second study (Study II) was performed in order to evaluate the capacity of norfloxacin (200 mg/kg) to reduce CL‐derived P in both normally cycling and CG‐stimulated nonpregnant females (ten treated, ten controls; daily for 8 days). No effects on P production or on luteal phase or menstrual cycle lengths were observed. The third study (Study III) was designed to examine the effect of norfloxacin on the metabolism and excretion of P in nonpregnant females. Silastic P implants were placed subcutaneously in order to maintain constant P levels during a 10 day treatment regimen (200 mg/kg/day; ten controls, nine treated). Five of the controls and four of the norfloxacin‐treated females also received 14C‐P intravenously within 1 hr of the last dose of norfloxacin in order to study excretory patterns. No significant differences between control and treated groups were observed. The results of these studies combined suggest that the developmental toxic effects observed in prior studies and Study I are specific to pregnancy and directly related to placental‐derived P production. © 1992 Wiley‐Liss, Inc.
Histochemical and immunohistochemical distribution of glycosaminoglycans, type II collagen, and fibronectin in developing fetal cartilage of congenital osteochondrodysplasia rat (ocd/ocd)
Authors: Kikukawa Keiichiro , Suzuki Katsushi 
Published: June 2005

AbstractThe osteochondrodysplasia rat (ocd/ocd) is a lethal dwarfism. The ocd/ocd shows histological abnormalities of the epiphysis, characterized by a decrease in amount of glycosaminoglycans (GAGs) in the extracellular matrix (ECM). The present study describes histochemical and immunohistochemical distributions of GAGs, type II collagen, and fibronectin (FN) in abnormal humeral cartilage of the ocd/ocd fetuses on days 16–21 of gestation. A wide‐spread region with severe necrosis was observed in the cartilage on days 20 and 21. The affected cartilage has small amounts of ECM, irregular columnizations, thinner hypertrophic zones, and expanded and pyknotic chondrocytes on days 16–21 of gestation. The severely expanded chondrocytes did not have cytoplasmic glycogens on days 19–21. Reactions for chondroitin sulfate (CS) and hyaluronic acid (HA) in the ECM were consistently lower in ocd/ocd than in +/+ during the entire period of observation, although there were granules immunoreactive to CS within the chondrocytes of ocd/ocd. The distribution of type II collagen seemed normal in relatively normal regions in the affected cartilage. Strong reactions for CS, HA, type II collagen, and FN were present in the necrotic region on days 20 and 21 of gestation. These findings suggest that the affected chondrocyte may have some defects in releasing ECM substances, which may be released by the process of cell rupture. We hypothesize that some defects in releasing processes inherent to the ocd/ocd cartilage may relate to cellular differentiation and cell death. © 1992 Wiley‐Liss, Inc.
Occurrence of embryotoxicity in mouse embryos following in utero exposure to 2′‐deoxycoformycin (pentostatin)
Authors: Airhart Mark J. , Robbins Charles M. , Knudsen Thomas B. , Church Joyce K. , Skalko Richard G. 
Published: June 2005

AbstractPrevious investigations had shown that i.p. injection of 2′‐deoxycoformycin (dCF; pentostatin; 5 mg/kg) on either E7 or E8 into pregnant mice results in a 61–81% resorption rate at E17. The incidence of visible gross malformations among the surviving conceptuses was exceptionally low (3%) at the time of necropsy on E17 and was unrelated to dCF dose (Knudsen et al., Teratology, 40:5–626, '89; Teratology, 45:91–103, '92). These findings demonstrated the embryotoxicity of dCF but provided no clues as to the site(s) of dCF action. To define the lesion site(s), we have now examined embryos at 72 h(E10), 96 h (E11), and 120 h (E12) following administration of a highly embryotoxic dose of 5 mg dCF/kg to dams on E7. Deoxycoformycin caused multiple abnormalities and growth retardation, and the temporal sequence between maximal abnormal embryo incidence and resorption frequency was established. The quantitative data show that the maximal occurrence of abnormal embryos on E10 (71%) was followed by a maximal resorption rate on E12 (78%). There was a strong correlation (r = −0.82; P < 0.05) between the rapid decline of percent abnormal embryos over E10–E12 and the simultaneous increase in resorption rate, with linear regression analysis showing nearly equal but opposite slopes (−31.2% vs. +35.8% per gestational day, respectively). This suggests that one or more of the abnormalities seen at E10 is associated with the death and resorption of the embryo at E12. The dCF treatment perturbed a wide spectrum of developmental events, including neural tube closure, craniofacial and limb development, turning of the embryo, and growth retardation. None of the individual abnormalities, however, can quantitatively account for the high percentage of dead and resorbed embryos. Therefore, the specific cause of dCF‐induced embryolethality is not clear. There is evidence both for direct dCF toxicity at specific embryonic sites as well as for a generalized retardation in the rate of development. © 1993 Wiley‐Liss, Inc.
Comparative teratogenicity and metabolism of all‐trans retinoic acid, all‐trans retinoyl β‐glucose, and all‐trans retinoyl β‐glucuronide in pregnant Sprague‐Dawley rats
Authors: Gunning Desirée B. , Barua Arun B. , Olson James Allen 
Published: June 2005

AbstractWhen single large equimolar doses (0.38–0.41 mmol/kg BW) of all‐trans retinoic acid (RA), all‐trans retinoyl β‐glucose (RBGL), and all‐trans retinoyl β‐glucuronide (RBG) are administered orally in oil on day 8.5 of pregnancy to Sprague‐Dawley rats, RA and RBGL proved highly teratogenic, whereas RBG was not. Indeed, fetuses from RBG‐treated dams were 16% heavier (P < 0.01) than control fetuses. After dosing with RA and RBGL, RA appeared in large amounts within 0.5 h in the maternal plasma and within 1.0 h in the embryo. In contrast, orally administered RBG seemed to be absorbed much more slowly, to be converted very slowly to RA, and not to accumulate either as RBG or as RA in the embryo. When incubated in vitro with embryos and attached membranes, however, both all‐trans RBG and all‐trans RA were partially converted to 13‐cis RA. The nonteratogenicity of RBG, in contrast to RA, seems to be due to a much slower rate of GI absorption, a slow rate of hydrolysis to RA, a limited passage from the maternal circulation into the embryo, and a lower inherent toxicity. © 1993 Wiley‐Liss, Inc.
Development of in vitro fertilized mouse embryos exposed to ethanol during the preimplantation period: Accelerated embryogenesis at subtoxic levels
Authors: Leach Richard E. , Stachecki James J. , Armant D. Randall 
Published: June 2005

AbstractThis study examined the effects of ethanol (EtOH) on mouse preimplantation development using an in vitro culture method. Embryos at the 1‐cell, 2‐cell, or 4‐cell stage were exposed for 24 h to medium containing EtOH, then further cultured without EtOH to determine their ability to form blastocysts and to eventually hatch from the zona pellucida. EtOH exposure either arrested or enhanced normal development, depending on dose and embryonic stage of exposure. Exposure of 1‐cell and 2‐cell embryos to 1.6% (w/v) EtOH decreased blastocyst formation and hatching, and exposure of 1‐cell embryos to 0.4% EtOH inhibited their development. At 0.1%, EtOH had an opposite effect, causing an increase in the percent blastocyst formation of treated 1‐cell and 2‐cell embryos. Neither inhibition nor stimulation of blastocyst formation occurred in 4‐cell embryos exposed to 0.1–1.6% EtOH. Using an in vitro outgrowth model of implantation, embryos that reached the blastocyst stage were further tested for their ability to produce differentiated trophoblast cells. Blastocysts previously exposed to 0.1% EtOH during the 1‐cell stage appeared to form adhesive trophoblasts earlier than control embryos, indicating that EtOH exposure can induce precocious differentiation of the trophoblast cells. The EtOH treated blastocysts contained significantly more cells than control blastocysts. These results indicate that EtOH can alter preimplantation development by either inhibiting or accelerating cell growth and differentiation. © 1993 Wiley‐Liss, Inc.
Renal dysplasia, megalocystis, and sirenomelia in four siblings
Authors: Selig Abby M. , Benacerraf Beryl , Greene Michael F. , Garber Mary‐Frances , Genest David R. 
Published: June 2005

AbstractFirst degree relatives of infants with bilateral renal agenesis or dysplasia have an increased risk of renal abnormalities including renal agenesis. We report a family in which four successive offspring exhibited a previously undescribed combination of congenital lethal renal disorders: bilateral renal dysplasia, megalocystis secondary to urethral obstruction and, sirenomelia with associated renal agenesis. © 1993 Wiley‐Liss, Inc.
Fetal dexamethasone exposure interferes with establishment of cardiac noradrenergic innervation and sympathetic activity
Authors: Bian Xiaopeng , Seidler Frederic J. , Slotkin Theodore A. 
Published: June 2005

AbstractEndogenous glucocorticoids provide natural differentiation signals for adrenergic neurons, and exposure to high exogenous steroid levels thus disrupts the timing of neuronal maturation. In the current study, pregnant rats were given 0.05, 0.2, or 0.8 mg/kg dexamethasone on gestational days 17, 18, and 19, and the effects on development of cardiac sympathetic function were assessed postnatally in the offspring. Dexamethasone produced a dose‐dependent retardation of body and heart weight gains; at the highest dose, heart weight deficits were smaller than those for body weight, producing a relative cardiomegaly. The weight effects were accompanied by abnormalities of noradrenergic innervation, as assessed with measurements of norepinephrine levels and turnover. Norepinephrine levels were significantly reduced at all doses of dexamethasone, with the magnitude of effect exceeding that on heart or body weights; thus the levels were reduced even when corrected for tissue weight (ng norepinephrine/g heart weight). Norepinephrine turnover, a measure of neuronal impulse activity, showed delayed development at the lowest dose of dexamethasone and displayed profound suppression throughout development at the higher doses. Adverse effects of dexamethasone on norepinephrine turnover were still apparent in young adulthood, despite the recovery of weight variables to within 15% of normal values. In light of the release of steroids during maternal stress and the use of steroids in the therapy of neonatal respiratory distress, developing adrenergic neurons are likely to be targeted for adverse effects even when standard growth indices have normalized. © 1993 Wiley‐Liss, Inc.
Embryotoxic effects of chlorobutanol in cultured mouse embryos
Authors: Smoak Ida W. 
Published: June 2005

AbstractChlorobutanol (CB) is a commonly used preservative which is added to numerous pharmaceutical preparations, and it is the active ingredient in certain oral sedatives and topical anesthetics. Chlorobutanol has demonstrated adverse effects in adult tissues, but CB has not been previously investigated for its effect on the developing whole embryo. The method of wholeembryo culture was used in this study to expose mouse embryos during two stages of organogenesis to CB at final concentrations of 0 (control), 10, 25, 50, 100, and 200 μg/ml. Embryos were evaluated for heart rate (HR), malformations, and somite number, and embryos and visceral yolk sacs (VYSs) were assayed for total protein content as a measure of overall growth. Neurulating (3–6 somite) embryos were malformed and growth retarded by exposure to CB concentrations ⩾25 μg/ml, with decreased VYS growth at ⩾50 μg/ml and decreased HR at ⩾100 μg/ml CB. Early limb‐bud stage (20–25 somite) embryos were malformed at CB concentrations ⩾50 μg/ml and growth retarded at ⩾100 μg/ml, with decreased VYS growth at 200 μg/ml and decreased HR at ⩾100 μg/m, CB. Thus, CB produces dysmorphogenesis in mouse embryos in vitro, and neurulating embryos are somewhat less sensitive than early limb‐bud stage embryos. The concentrations of CB that interfere with normal embryonic development are within the range of human blood levels measured following multiple doses of CB. Preparations containing CB should be used with caution during pregnancy, particularly when repeated dosing may allow accumulation of CB to potentially embryotoxic levels. © 1993 Wiley‐Liss, Inc.