Eighth Day Of Gestation Research Articles

Embryopathic effects of mercuric salts

Various doses of mercuric acetate and phenylmercuric acetate were administered intravenously to anesthetized pregnant golden hamsters early on the eighth day of gestation in order to study their potential teratogenicity in this species. Fetuses removed from the females on either the twelfth or fourteenth day of gestation exhibited a delayed growth rate and varying degrees of a dorsally localized subcutaneous edema. All doses of mercuric acetate and the three larger doses of phenylmercuric acetate also induced resorption rates significantly higher than the control level of 4%. A small number of miscellaneous abnormalities including: exencephaly, encephalocele, anophthalmia, microphthalmia, cleft lip and palate, rib fusions and syndactylia were also observed in the fetuses from the treated females. Both mercurials also produced the following manifestations of toxicity in the maternal system: weight loss, kidney lesions, diarrhea, slight tremor and somnolence.

Angiotensin teratogenicity in the fetal hamster

The subcutaneous administration of a single dose of angiotensin to pregnant hamsters on the eighth day of gestation produced developmental anomalies of the cranium, brain and viscera. Edematous areas along the spinal axis were observed. The number of dead, resorbed and runt fetuses in the experimental litters was increased markedly over the number observed in control litters. The mechanism of action of angiotensin in the present study is postulated to include one or all of the following: (1) decrease in uterine blood flow by direct action on uterine smooth muscles and blood vessels; (2) release of catecholamines from adrenal gland, and their action on uterine smooth muscle and blood vessels; (3) imbalance of normal mitosis in fetus by the catecholamines released by angiotensin. Comparative studies using trypan blue were carried out simultaneously.

Fetal malformations produced in rats by N-isopropyl-alpha-(2-methylhydrazino)-p-toluamide hydrochloride (procarbazine).

AbstractSingle intraperitoneal injections of N‐isopropyl‐α‐(2‐methylhydrazino)‐p‐toluamide hydrochloride (procarbazine) at doses ranging from 5–550 mg/kg were given to pregnant rats on the fifth to twelfth, fourteenth, and seventeenth days of gestation. Malformations were seen in twenty‐first‐day fetuses exposed to doses that were slightly higher than one‐half (250 mg/kg on 17th day) to one forty‐fifth (12 mg/kg on 12th day) the single dose that was lethal to females (550 mg/kg) when they were treated once on the fifth, sixth, ninth to twelfth, fourteenth, or seventeenth day of gestation. Tail and appendicular defects were observed after treatment on all eight days, injury to the brain only after that on the ninth day, facial clefts on the ninth or tenth day, and cleft palate and shortened jaws on the sixth, ninth, twelfth, fourteenth, and seventeenth days. Malformations were not seen with any of the doses used on the seventh or eighth day of gestation. Attempts to protect the twelfth‐day fetus against the teratogenic effects of 100 mg/kg of procarbazine by administration of various amounts of L‐methionine were only partially successful.

Teratogenic effect of cadmium and its inhibition by zinc.

DURING a study of the teratogenic effects of heavy metals on mammalian embryos, we have been able to produce severe developmental malformations in golden hamster embryos by the intravenous injection of 2 mg/kg of cadmium sulphate into pregnant mothers on the eighth day of gestation. These malformations consisted of a specific effect on the face and upper jaw, ranging from a simple mid-line cleft to almost complete obliteration of normal facial architecture. A few other malformations apparently also induced by cadmium in this dose were occasionally found. These consisted of anophthakmia, digital and other limb defects, rib fusions and exencephaly. The simultaneous administration of 2 mg/kg zinc sulphate almost completely inhibited this marked teratogenic effect of cadmium. The particular susceptibility of the germinal epithelium of the testis and the rodent placenta to the toxic effects of cadmium has been described1,2. This toxic effect of cadmium has been attributed to alterations in the endothelium of the vascular beds in these affected organs2,3.

Effects of prenatal hypoxia upon activity and emotionality of the rat

Gravid female rats were made hypoxic on the eighth or twentieth day of term. Their progeny were found to be more active in an avoidance shuttle box. These results are contrasted to similar studies measuring activity in non-noxious circumstances. Also, the experimental Ss were found to be hypoemotional in comparison to their controls as measured by a rating scale and weight loss during avoidance training. The offspring of animals treated on the eighth day of gestation were less emotional than those receiving treatment on the twentieth day, confirming other studies demonstrating behavioral differences linked to prenatal age at treatment.

EFFECT OF TRANSPLACENTAL MITOTIC INHIBITORS ON THE FETAL HAMSTER EYE.

AbstractCongenital malformations of the hamster eye, consisting of microphthalmia and anophthalmia have been noted consistently in the offspring of pregnant hamsters treated with intravenous injections of colchicine, Vinacaleukoblastine (VLB) and Vincristine (VCR) on the eighth day of gestation. In an attempt to compare the mitotic‐arresting activity of these three compounds on the lens and retina of the fetal hamster eye, various concentrations of the drugs were injected into pregnant hamsters on the fourteenth day of gestation and the fetuses recovered after three hours. Mitotic counts were done on comparable sections of lens and retinas of the fetuses. Colchicine has the most marked mitosis‐inhibiting activity of these three drugs. The most effective mitosis‐inhibiting dosage of colchicine also correlates with its most effective teratogenic dose. VLB and VCR do not inhibit mitosis in the fetal hamster eye as markedly as colchicine and their most effective mitosis‐inhibiting dosages are equal to or above levels which cause a 95–100% embryonic mortality. It is possible that some common biological mechanism other than inhibition of mitosis may be responsible for the similar teratogenic activity of these compounds. The natural resistance of the golden hamster to colchicine does not appear to be manifest in the developing embryos in utero.

THE EFFECT OF TRYPAN BLUE ON THE SERUM PROTEINS OF THE FETAL RAT.

AbstractPregnant rats were injected intraperitoneally with a teratogenic dose of trypan blue (14 mg/100 g or 20 mg/100 g body weight) on the eighth day of gestation. Fetal blood was collected from control and experimental fetuses on the twentieth day of pregnancy. Serum was obtained from pooled blood samples of two to three fetuses. Paper electrophoresis was carried out in a Spinco model R system using barbital buffer at pH 8.6. The paper strips were subsequently stained with bromphenol blue and their density measured in a Spinco Analytrol to determine the relative concentration of each component. Total protein was measured in a Bausch and Lomb Serum Protein Meter. The predominant malformations seen in abnormal fetuses were apparent anophthalmia, 59%; hydrocephalus, 37%; and exencephaly, 19%. Other malformations were noted but with less frequency. Twenty‐day fetuses from trypan blue treated mothers had a significantly lower total protein concentration (1.50 g/100 ml) than control fetuses (1.95 g/100 ml). A comparison of the absolute protein concentration of the serum fractions revealed significant differences between control and experimental fetuses in beta globulin, alpha‐1 globulin, and albumin. In each instance the absolute concentration was less in the fraction from fetuses of trypan blue treated mothers. Fetal gamma, alpha‐2, and alpha‐3 globulins were not affected by the maternal treatment.

Modification of Irradiation Effects on Rat Embryos by Uterine Vascular Clamping

Uterine vascular clamping of the pregnant rat uterus for 45 minutes protects against the lethal and growth-retarding effects of irradiation on the eighth day of gestation and against the lethal, growth-retarding, and probably teratogenic effects of irradiation on the ninth day of gestation. If the clamping procedure is continued for more than an hour on the eighth and ninth days; it results in a high incidence of malformations. The most likely basis for the protective effect of the clamping procedure is the resultant hypoxia, but the definitive answer is not yet available. The inability of irradiation to induce malformations in the 8-day 0-hour-old rat embryo was confirmed. The discrepancy between the teratogenic action of vascular clamping and irradiation on the eighth day is presented and discussed. (auth)

The Effects of Irradiation with Phosphorus-32 on the Viability and Growth of Rat Embryos

It has been recently shown by Russell (1), Wilson et al. (2-4) and Hicks (5) that the sensitivity of the mouse and rat embryo to X-irradiation changes throughout gestation, with respect to both lethality and the production of malformations. The work of Wilson and his collaborators, on the rat, showed that when irradiation was administered after 9 or 10 days of gestation, 100 r would greatly increase the percentage of dead and resorbed embryos as well as produce abnormalities characteristic of the day, the ninth day having a greater effect in this respect as well as producing a greater depression of weight. On the eighth day of gestation, however, doses up to and including 100 r did not increase mortality above control levels nor produce any malformations, although weight depression was greater than on either of the other 2 days. Irradiation at this time with 200 r killed almost all the embryos within 3 days. This was a greater lethal effect than that produced by the same exposure on the subsequent days. Hicks found similar results at these times and extended the work to later stages. Russell had previously found that irradiation at comparable times during the gestation of the mouse produced the same effect in a qualitative sense, but that slightly higher doses were required. Warren and Dixon (6, 7) had earlier studied the effects of continuous radiation of the chick embryo at various times during gestation by injecting radioactive phosphorus (p32) into the yolk. The effects of this irradiation were not so striking as those of X-irradiation on rodents; there was a great reduction in size, but very few deaths and no malformations were produced. There are many possible explanations

Amount of luteal tissue required for the maintenance of pregnancy in the rat.

ConclusionsThe albino rat of the Holtz-man strain was used to determine the minimum number of corpora lutea required to maintain pregnancy. It was found 2 corpora will maintain pregnancy from the eighth day of gestation, but one corpus will not, nor will one corpus and part of another. In animals where all corpora but one were removed on the 15th day of pregnancy, two-thirds either had litters of normal fetuses or some of the fetuses were normal while others were being resorbed. All of the fetuses of the other one-third of the animals were being resorbed at the time of autopsy. Pregnancy was maintained in a group of animals in which all but 2 corpora were removed on the eighth day and hypophysectomized on the 12th day of pregnancy.There is no evidence that the placentae are adequate supplementary sources of progesterone in those groups where the corpora were reduced below two at the eighth day, since pregnancy was terminated in all cases. However, when the corpora were reduced to one on the 15th day of pr...

The Endometrial Mole

It is well known since the classical experiments of Loeb that the uterine mucosa is sensitized by the corpus luteum hormone in such a manner that it reacts to traumatization with the formation of a deciduoma, a tumor closely resembling in its structure the maternal part of the placenta. It has been noted, however, that while deciduomata form readily during the first part of gestation, they will not form during the later stages of pregnancy although active corpora lutea are present in the ovary. We have repeated and confirmed these observations on rats, placing silk threads into the uterus as a local irritant, and we found that deciduomata may only be produced if the threads are placed between the fifth and eighth day of gestation, while later on in pregnancy the trauma does not call forth any local reaction. This, however, does not mean that the uterus is insensitive to trauma during the second half of gestation, for in another group of animals in which we slit the uterus open on one side, instead of mere...