Days Of Intrauterine Life Research Articles

Adrenocortical function in foetal, neonatal and young pigs.

SUMMARY Absolute and relative adrenal weight, blood plasma concentrations of 17-hydroxycorticosteroids and their production in vitro on incubation of adrenal slices with corticotrophin (ACTH), were measured in foetal pigs, piglets and older pigs. These criteria all indicated that adrenocortical activity was highest on the day of birth. It developed intensely in about the last 10 days of intra-uterine life. After birth it decreased progressively with age, approaching the adult level after weaning in the second month of life. The adrenal cortex of pigs of all developmental stages investigated in this study was capable of responding markedly to stimulation with ACTH. No significant differences in adrenocortical activity were found between sexes up to 90 days of age.

Prenatal development of the testicular artery in the rat.

The morphogenesis of the testicular artery of the rat was studied using the Indian ink injection technique and histology. 1. The first primitive vasculature of the gonad appears on the dorsal side of the plica genitalis on the 14th day of intrauterine life. 2. On the 16th day the permanent testicular artery with transient superficial branches is seen under the tunica albuginea. 3. The first convolutions of the artery appear at 17 days and on the 19th day the characteristic unbranched convolutions have developed fully. 4. The site of entrance of the testicular artery into the testis shifts cranially during the prenatal period. 5. The development of the functional vasculature cincides with the endocrine activation of the testis.

The ontogenesis of haematoencephalic cation transport processes in the rhesus monkey.

1. This investigation was undertaken to determine the time course of development of cation transport processes between blood and the extracellular fluid compartments of the central nervous system (C.N.S.) of the foetal rhesus monkey. The development of concentration gradients within the cerebrospinal fluid (c.s.f.) system was also studied in an attempt to gain information on regional variations in transport activities.2. Cerebrospinal fluid samples were obtained from the lateral ventricle, the cisterna magna, the cortical subarachnoid space and the lumbar region of the spinal subarachnoid space of adult monkeys. Foetal c.s.f. samples were obtained from the cisterna magna and the frontal region of the cortical subarachnoid space. Blood samples were taken within 3-10 min of the c.s.f. samples. The concentration of K, Mg and Ca were determined on appropriately diluted samples by atomic absorption spectrophotometry.3. The concentrations of K, Mg, and Ca in the plasma and c.s.f.s of the adult monkey are similar to those of other mammalian species. The c.s.f./blood concentration gradients of these cations are in the same direction but generally of greater magnitude than those in non-primate mammals. The indicated [Mg] in the extracellular fluid of the adult monkey's cerebral cortex is high (more than 2 m-equiv/kg H(2)O) and the [K] is low (less than 2 m-equiv/kg H(2)O).4. Accumulation of Mg into the c.s.f. system against a concentration gradient is evident in the earliest foetuses studied (50 days of intrauterine life) and by the second half of gestation the concentration gradients of this cation are similar to that of the adult.5. In the second trimester foetus, the [K] in the cisternal fluid is near the plasma ultrafiltrate level. It then decreases gradually throughout the remainder of gestation, approximating the adult value at birth.6. The very low [K] typical of the adult cortical subarachnoid fluid is observed by the sixth month following birth but not during foetal life or within the first few weeks of post-natal life. This indicates that the transport processes at the cortical region of the haematoencephalic interphase do not fully develop until well after birth.7. It is concluded that the various transport processes responsible for the elaboration and maintenance of adult type of K, Ca and Mg concentrations within the extracellular fluid compartments of the monkey C.N.S. do not develop at the same time. This temporal dissociation provides strong evidence against any direct association or coupling between the haematoencephalic K and Mg transport systems.8. Existence of normal cation concentration gradients between c.s.f. and blood may serve as a criterion for the normality of the (foetal) blood-brain barrier.

Body Composition in Experimental Intrauterine Growth Retardation in the Rat

The body compositions of a normally growing rat fetus were measured in the fetuses of eight pregnant rats during the last 5 days of intrauterine life. As the fetus grew in utero, there was a progressive contraction of body water and an increase in body protein (measured as nitrogen), fat, calcium and phosphorus contents. These changes were similar to those observed during postnatal growth. Intrauterine growth retardation was experimentally induced in five pregnant rats by ligating the uterine artery supplying one of the two uterine horns at 17 days of gestation. Intrauterine growth retardation (IUGR) was evident in 21 rat fetuses when delivered at 21 days of gestation, since their body weights were significantly lower than those of 21 control fetuses located in the unligated uterine horns. Chemical compositions were measured by tissue analysis. In IUGR fetuses, the total body water content was significantly higher, whereas the fat and protein contents were significantly lower than the control. The calcium and phosphorus contents were similar. The Ca/P ratio was lower in IUGR fetuses. The placental chemical compositions were similar between IUGR and control fetuses. It is suggested that the difference in chemical composition is probably a result of decreased placental transport of essential nutrients for fetal assimilation in utero.

Levels of testosterone, androstenedione, estrone and estradiol-17 beta in the testes of fetal sheep.

Testosterone, androstenedione, estrone and estradiol-17β were determined in the testes of fetal sheep ranging in age from 30 to 132 days of intrauterine life. These steroids were measured by micromethods using gas-liquid chromatography with electron capture detection. The presence of testosterone and androstenedione was demonstrated in the fetal testis on the 30th day of gestation, 5 days before onset of sexual differentiation and the earliest period studied. The amounts of testosterone and androstenedione were similar in 46- to 65-day-old testes, while the levels of testosterone were much higher than those of androstenedione at the 30th and 35th days and after the 65th day of intrauterine life. Detectable amounts of estrone were present in 70-day-old testes. (Endocrinology 85: 280, 1969)

Effect of prenatal administration of androgen on the reproductive function in female rats.

Studies were made on the effects of prenatal administration of androgen on the development of sexual function in female rats. Pregnant rats at the middle or late stage of gestation were injected subcutaneously with testosterone propionate (T. P.) or methyltestosterone (M. T.) and their embryos at the late stage of intra-uterine life were given a single direct injection of T.P. In pregnant rats, an injection of 3 or 6mg M. T. or T. P., given for 6 successive days beginning on the 12th or the 15th day of gestation did not affect ovarian function of the offspring, although it was effective in causing masculinization of the genital tract. The female young became pregnant by artificial insemination.An injection of 30 or 50mg of the hormones given to pregnant rats for 3 consecutive days between the 15th and the 17th day of gestation, and a single direct injection of 40μg of T. P. to fetuses on the 16th day of intra-uterine life gave rise not only to marked masculinization of the genital tract, but also to abnormal sexual function in female offspring. Many of these females exhibited constant cornification in vaginal smears and tended to display a persistent, opulatory response of low grade or failed to display any sexual reflex. The ovaries of these animals contained no normal nor freshly developing corpora lutea, but various types of follicles, some of which showed atresia.These results suggest that the prenatal administration of androgen does not always alter the ovarian activity of the female rats, though it effectively induces masculinization of the genital tract. However, with large doses, it may induce phenomenon corresponding to androgen sterility in later life.

Localization of Fibrinolytic Activity in the Developing Rat Eye

The histological localization of fibrinolytic activity in the developing eye of rat was studied by means of the histochemical fibrin slide technique. The observation that fibrinolytic activity is related to small vessels provided a means of following the developing vascularization of the eye. The hyaloid vascular system was found fully developed, together with the tunica vasculosa lentis, at the 18th day of intrauterine life. Involution of these vessels begins between the third and the seventh day after birth. The retinal vessels begin to develop between the 16th and the 18th day of intrauterine life. The choroid acquires fibrinolytically active vessels in the second week of life. At this time also the ciliary body becomes vascularized. The patterns of appearance and disappearance of sites of fibrinolytic activity observed during the development of the eye are related to the functional morphology of the involved tissues.

Synthesis and breakdown of rat liver RNA during the neonatal period

The incorporation of radioactivity from labeled pyrimidine precursors (6- 14C-orotic acid and 2- 14C-uridine) and from 32P into liver RNA has been evaluated in fetuses and newborn rats. Very low values were recorded in the last days of intrauterine life and at birth. Soon after birth, there was a very sharp increase of the incorporation, and maximum values were attained at three days of life. Nuclear DNA-dependent RNA polymerase activity was also found to be very low in fetuses, but increased gradually after birth and reached the adult values only at about 25 days of of life. Ribonuclease activity of isolated nuclei and microsomal fractions were very high at birth and decreased in the first days of extrauterine life, attaining the lowest values in adult life. Similarly, autohydrolysis of endogenous nuclear or microsomal RNA was higher in young than in adult animals but did not undergo appreciable change during the first 3 weeks of life. Newborn liver nuclei and microsomes contained ribonuclease essentially in a free form, whereas in adult ones the latent form of enzyme was predominant. The significance of these findings in relation to the labeling of RNA, and with the changes in enzyme activities, liver size, and liver protein content in the perinatal period, is discussed.

The two types of alpha cells during the development of the guinea-pig pancreas.

The prenatal and postnatal development of the two types of pancreatic A cells was examined in guinea-pigs. The A1 and A2 cells appeared at about the same time and were first seen in 26 days old fetuses, while B cells could not be recognized earlier than on the 39th day of intrauterine life. In all age groups examined with quantitative methods (65 days old fetuses to 9 months old guinea-pigs) the proportion of parenchyma in the pancreatic gland appeared higher in the cauda than in the caput. In the 3 months and 9 months old animals the proportions of the different types of islet cells were also higher in cauda than in caput. In each case the total weights of the A1, A2 and B cell fractions showed a similar growth rate relative to that of the body weights. The results are discussed in the light of previous observations in man and rat.

THE SHORT-TERM EFFECTS OF ACUTE X-IRRADIATION ON OOGONIA AND OOCYCTES.

Foetal rats were exposed to 100 r (acute X-irradiation) at 15.5, 16.5 and 17.5 days of intrauterine life, and killed at daily intervals up to 20.5 daysp.c. The populations of normal and degenerating germ cells in irradiated ovaries were estimated by the volumetric method of Beaumont & Mandl (1962). The chromosomal configurations of germ cells were examined in both histological and squash preparations. Irradiation appears to disturb the close developmental synchronization of germ cells. Many irradiated cells also show transient changes in chromosomal morphology, and an increase in cell and nuclear volumes. The treatment induces both immediate cell death (i.e. within 24 h of exposure) and delayed cell death. The latter becomes manifest by an increase in the incidence of degenerating cells of the same type as arise spontaneously during normal development (‘atretic divisions’; ‘Z’ cells). The most severe depletion in the total population of germ cells occurs following exposure at 15.5 days, only some 13 000 germ cells being present 24 h later (cf. 37 000 in coeval controls). Their number is further reduced to about 5000 at 20.5 days (cf. 56 000 in controls). In contrast, the mean populations at 20.5 days following irradiation at 16.5 and 17.5 days areca. 16 000 and 42 500 respectively. Most degenerating germ cells are eliminated from the ovary by 20.5 days. The subsequent loss of oocytes with age (up to 25 and 100 daysp.p.) occurs at alowerrate in irradiated than in normal animals.

Concentration of 5-hydroxytryptamine in the small intestine and platelets of the developing guinea pig

In guinea-pigs, 5-hydroxytryptamine first appeared in the small intestine in measurable amounts after 30–40 days of intra-uterine life. The rise in concentration of the 5-hydroxytryptamine in the platelets followed the rise in the intestine. These results support the view that platelet 5-hydroxytryptamine is derived from the intestine. They are compared with previous observations on the concentration of 5-hydroxytryptamine in the developing guinea-pig brain.

SERUM GLYCOPROTEINS IN OFFSPRING OF NORMAL AND ALLOXAN-DIABETIC RABBITS

Serum protein bound hexose, hexosamine, and sialic acid were determined in pregnant normal and alloxan-diabetic rabbits and their offspring. The young were delivered by cesarean section on the 26th day of gestation and close to term on the 30th day of gestation.In the mothers, pregnancy did not lead to an increase in the concentration of serum glycoproteins, with the exception of the seromucoid hexose, which was found to be elevated in both normal and diabetic rabbits at the time of delivery.In the young, the concentration of total protein bound hexose did not appreciably change, while the concentrations of hexosamine, sialic acid, and seromucoid hexose were increasing moderately and nearly to the same extent in both groups of fetuses over the last 4 days of intrauterine life. During the same period of time the average increment in body weight was 26 g in the normal series and 17 g in the diabetic series.

SERUM GLYCOPROTEINS IN OFFSPRING OF NORMAL AND ALLOXAN-DIABETIC RABBITS

Serum protein bound hexose, hexosamine, and sialic acid were determined in pregnant normal and alloxan-diabetic rabbits and their offspring. The young were delivered by cesarean section on the 26th day of gestation and close to term on the 30th day of gestation.In the mothers, pregnancy did not lead to an increase in the concentration of serum glycoproteins, with the exception of the seromucoid hexose, which was found to be elevated in both normal and diabetic rabbits at the time of delivery.In the young, the concentration of total protein bound hexose did not appreciably change, while the concentrations of hexosamine, sialic acid, and seromucoid hexose were increasing moderately and nearly to the same extent in both groups of fetuses over the last 4 days of intrauterine life. During the same period of time the average increment in body weight was 26 g in the normal series and 17 g in the diabetic series.

The radiosensitivity of germ-cells at various stages of ovarian development.

SummaryFemale rats were exposed to 50 and 100 r x-rays on the 8th, 10th and 12th days of intra-uterine life, at birth and on the 2nd and 5th days after birth.As judged by the survival of oocytes at the age of 25 days, germ-cells in the developing ovary undergo two periods of high radiosensitivity: the first at 15 days post coitum, when oogonial mitoses are frequent, and the second shortly after birth, when the oocytes attain the dictyate phase. The intervening period of relative refractoriness to radiation damage occurs while the oocytes undergo the prophase of meiosis.

Oogenesis in the mouse: A study of the meiotic prophase

In albino mice of the street strain ovaries from the 10th day of fetal life until the 5th day after birth were studied histologically and cytologically by the squash technique. The gonad is in the indifferent stage until the 13th day of intrauterine life, when differentiation into a male and a female gonad is recognizable. Germ cells stop oogonial division along with this differentiation and enter into meiosis on the 14th day. This happens in the ovary simultaneously for all oocytes, i.e. in the course of one or two days. Thus leptotene and zygotene figures are seen together with the last oogonial divisions on the 14th and 15th day of fetal life; on the 16th day a great number of pachytene nuclei appear and on the 17th and 18th day practically all oocytes are in the pachytene stage. Pachytene nuclei seem either to degenerate or to go into diplotene stage. From the 18th or 19th day diplotene figures increase in number, until by the 4th or 5th day of life all oocytes are in late diplotene, the so-called resting stage of the meiotic prophase. In this stage oocytes are arrested until they in a later period grow in size and enter maturation division. From the 16th day of intrauterine life and until the 3rd or 4th day after birth a massive degeneration of oocytes in the pachytene stage takes place. Different strains of mice (Bagg, dlb, hairless and naked) follow the same pattern of oogenesis.

Localization of Alkaline Phosphatase in the Histogenesis of Cartilage and Bone

1. Meckel's cartilages and the intramembranous sites of ossification in the mandible, tympanic ring, and the anterior process of the malleus of fetal rats between fifteen and twenty days of intrauterine life have been studied with respect to the localization of alkaline phosphatase during the normal differentiation of embryonic mesenchymal cells to osteoblasts and chondroblasts. 2. Alkaline phosphatase appears in the nuclei concurrent with the preliminary condensation of osteogenic mesenchymal cells in the primordium of an intramembranous ossification center. 3. With further differentiation of these osteogenetic precursors to bone-forming cells, the enzynme appears in the nucleoli and in the cytoplasm. At an osteoblastic stage it also appears intercellularly in the osteoid matrix. 4. Mesenchymal cells that have not differentiated in an osteogenetic direction are free of enzymatic activity in contrast to the mesenchymal osteogenic precursor cells. 5. No enzymatic activity was noted during the condensation and differentiation of mesenchymal cells in a chondrocytic direction until hypertrophy of chondrocytes took Place preparatory to ossification. 6. Enzymatic activity was demonstrable in the ossifying anterior portion of Meckel's cartilage but not in its nob-ossifying portion. 7. The preskeletal type of tissue, an internmediate between bone and cartilage, which may also be called secondary or hypertrophic cartilage, occurs in the ramus of the membranous bony mandible. This is a neomorphic product in the differentiation of rapidly proliferating osteogenetic on osteoblastic cells in a site of intramembranous ossification. This is well demonstrated by our studies of alkaline phosphatase activity.

THE FETAL BOVINE THYROID: MORPHOGENESIS AS RELATED TO IODINE ACCUMULATION1

In the fetal calf, which has a gestation period of approximately 285 days, thyroxine-like iodine can be detected in the thyroid gland on the sixtieth day of intrauterine life. Thereafter, the amounts of thyroxine-like and total iodine in the gland increase steadily, and the rates of increase of these two iodine fractions have been shown to be related exponentially to fetal body weight, length, and age (Wolff et al., 1949). Since, in addition, the concentration of iodine in the developing gland (i.e., mg. of iodine per 100 gm. fresh tissue) appeared to increase progressively, it was postulated that with increasing age, the fetal thyroid acquired an increased capacity for iodine storage. In the present investigation, we have attempted to correlate the morphogenesis of the gland with its iodine content. Since the follicle might be regarded as the structural and functional unit of the gland, we sought to determine the relation of its development to the capacity of the gland to store iodine.

II. The early development of the pericardium, diaphragm, and great veins

The history of the development of the pericardium, diaphragm, and great veins is traced by means of rabbit’s embryos ranging from the eighth to the seventeenth day of intrauterine life. The splanchnic origin of the two halves of the heart is briefly illustrated, and each separate half is shown to project into the fore­most end of the cœlom.