Part Of Gestation Research Articles

Fetal development of primate chemosensory corpuscles. I. Synaptic relationships in late gestation

Fetal macaque chemosensory corpuscles during the last part of gestation contained chemosensory, sustentacular, and undifferentiated basal cells. Sustentacular cells had apical secretory granules and no specialized contacts with axons. Chemosensory cells contained basal collections of 80-100 nm dense core granules, and specialized axonal contacts of three types--afferent synapses, efferent synapses, and subsurface cisternae. Afferent synapses were commonly present on electron opaque cells with many 80-100-nm granules, typical 40-60-nm synaptic vesicles, and a few cisternae of smooth or granular endoplasmic reticulum. Cells with subsurface cisternae and/or efferent synapses were usually electron lucent, lacked vesicles and granules, and contained numerous intracytoplasmic cisternal elements. A continuum of intermediate forms was observed. It is postulated that transition of synaptic arrays accompanies the maturation of individual chemosensory cells.

Placental transport of the non-metabolisable alpha-aminoisobutyric acid in guinea-pigs given a commercial chlorobiphenyl preparation or a defined, pure chlorobiphenyl.

The placental transfer of the non-metabolisable alpha-aminoisobutyric acid was studied by means of a perfusion technique in pregnant guinea-pigs given the commercial chlorobiphenyl preparation, Clophen A50 (C-A50) or pure 2,2',4,4',5,5'-hexachlorobiphenyl (HCB), during different periods of gestation. It was shown that a total dose of 30 mg of HCB given during the latter part of gestation (day 45 to 61) decreased amino acid transport, while 30 mg of C-A50 did not. At a dose of 30 mg daily given from day 28 to day 61, again only HCB decreased the amino acid transfer. An amount of 60 mg C-A50 was required to reduce this transport. The concentration of the amino acid in blood from foetuses remaining in the uterus was significantly increased when the dams were given 60 mg of C-A50, indicating a reduced foetal uptake of the amino acid. It is suggested that the decreased placental transfer of the amino acid is dependent on physio-chemical interactions (e.g. caused by hydrophobic properties) between the chlorobiphenyls and the NaK-ATPase enzyme complex which is involved in amino acid transport.

Serum concentrations of testosterone throughout pregnancy in rats.

Testosterone concentrations in serum of rats bled throughout pregnancy and post partum were measured using Celite microcolumn chromatography and a radioimmunoassay for testosterone. Mean serum levels of testosterone ranged from about 170 to 340 pmol/l during the first 10 days of pregnancy. Significant increases in concentrations of testosterone in serum of pregnant rats were found on days 12, 15 and 18 of gestation. The highest testosterone concentrations occurred on days 18 and 20 of pregnancy when mean levels were 3228 and 3685 pmol/l respectively. Testosterone levels declined before parturition on day 22 (mean = 1449 pmol/l and declined further after parturition (mean = 315 pmol/l). In order to determine whether serum testosterone concentrations varied during the day in the pregnant rat, samples were collected at 6-h intervals on days 6–7 and 14–15 of gestation. Diurnal variations in serum testosterone concentrations were not evident during early or late pregnancy, unlike the rhythmic changes in serum prolactin levels found at these times during early pregnancy. The possible sources of the increased titres of serum testosterone during the second part of gestation in rats are discussed.

Plasma prolactin and progesterone responses to mating are altered in ages rats.

The effects of varying amounts of copulatory stimulation on patterns of plasma concentrations of prolactin and progesterone were evaluated in 3- and 12-month-old female rats. The 12-month-old group included rats which still exhibited oestrous cycles and rats in persistent vaginal oestrus (PVO). The extent of copulatory stimulation was defined by the number of intromissions received during mating: less than or equal to 5, 15 or greater than 50. Blood samples were drawn over the 8 days after mating through a cannula inserted into the right external jugular vein. Plasma from the samples was assayed for prolactin and progesterone. In aged but still cyclic rats, pregnancy rates were positively correlated with the number of intromissions received during mating. Only one rat in PVO became pregnant. All animals which became pregnant and rats in PVO which, after mating, exhibited a disruption of the pattern of PVO, showed the nocturnal surge of plasma prolactin characteristic of pregnant and pseudopregnant rats. While these surges persisted until day 8 after mating in pregnant animals, they were absent by this time in the rats in PVO. Prolactin surges were present in some but not all of the aged rats which did not become pregnant. Progesterone concentrations were raised in all pregnant animals except the one pregnant rat in PVO and, while not related to the number of intromissions, concentrations were higher 8 days after mating in young compared with those in aged pregnant rats. Plasma progesterone was low in rats in PVO regardless of disruption of the pattern of PVO. We have concluded that the failure of limited copulatory stimulation to induce pregnancy in older rats results, at least in part, from its failure to initiate nocturnal prolactin surges. Nevertheless, our data suggest that matings which are not experimentally limited should provide ample stimulation to establish such surges. Although reduced plasma concentrations of prolactin and progesterone at pro-oestrus and reduced plasma progesterone through part of gestation may contribute to decreasing fertility in aged rats, other unidentified factors appear to be involved in mediating the capacity of extensive copulatory stimulation to induce pregnancy in these animals.

300 ONTOGENESIS OF GAMMA-GLUTAMYL TRANSPEPTIDASE (GGTP) IN RAT TISSUES

One of the mechanisms for amino acid active transport into the cell is GGTP. In order to map its developmental patterns this enzyme was studied in Wistar rat tissues before and after birth. Glycylglycine was the acceptor and L-δ-glutamyl-p-nitroanilide the donor in the assays. Placental GGTP activity (as nmoles/min × mg protein) decreased from 2.06 ± 0.15 to 0.69 ± 0.07) between the 14th and 21st day of gestation. Fetal kidney GGTP had the highest mean sp. act. than any other tissue at every stage of development. It doubled from the 20th day of gestation to birth (200 to 409), and then increased to 1,452 at 21 d. of age. GGTP in the small intestinal mucosa reached a peak by the middle of the lactation period (106 at 12 d. of age), returning to lower, fetal levels (22) at three weeks of age. Brain GGTP was minimal in utero (2.8 at the 20th day of gestation), and fell to zero at birth, increasing again during lactation and adulthood. Liver GGTP was measurable only in the gestational period, but after birth it became almost negligible. These data suggest that GGTP may play a role in amino acid transport into cells of various tissues in the later part of gestation. After birth, the only organ with significant GGTP activity is the kidney, where its physiologic role has been well studied (Supported in part by USPHS NIH grant S08 RR-09128-02).

Viability and sensorimotor development of mice exposed to prenatal short-term ethanol

The identification of the fetal alcohol syndrome in man has led to an abundant, but sometimes contradictory body of research examining the effects of prenatal ethanol exposure in animals. The present study examines the early sensorimotor development of heterogenous stock mice after ethanol exposure during one of two time periods in gestation, days 8–12, or days 14–18. Animals received either a liquid diet containing 20% ethanol derived calories, an isocalorically balanced yoked control diet or a lab chow control diet. Results indicated no apparent effects due to administration of alcohol during the middle of gestation, but a marked decrease in offspring viability, birthweight, and growth due to administration during the last part of gestation. The late gestation treatment group also showed a slight delay in the rate of development of the grasping and horizontal screen tasks. Overall, animals that survived showed relatively normal sensorimotor development.

Ontogeny of PHA and Con A responses in the fetal lamb

Twenty-three lambs from 10 ewes at 38 to 135 days of gestation (total gestation period is 150 days) were tested for PHA and Con A responses using cells from the liver, thymus, bone marrow, and spleen. The Ficoll-Isopaque technique was applied for the separation of cells from the liver, bone marrow, and spleen. During ontogeny, the first responses both to PHA and Con A were obtained with liver cells at 38 days of gestation. With thymus cells the first responses to PHA were observed at 68 days of gestation, whereas Con A responses were not detected before the 90th day. In the spleen, both responses were first found even later, at 98 days. With the bone marrow cells, significant responses were observed only occasionally during the later part of gestation. These results indicate that (excluding the fetal liver) PHA-responsive cells appear during ontogeny before Con A-responsive cells and that mitogen responses are observed in the spleen a few weeks later than in the thymus.

Alveolar lavage and lavaged lung tissue phosphatidylcholine composition during fetal rabbit development.

Pulmonary surfactant, the major surface-active component of which in the adult is dipalmitoylglycerophosphocholine, can be obtained by lavaging lungs with physiological saline. We have previously shown that there is an increase in the amount of phosphatidylcholine in fetal rabbit lung lavage during the latter part of gestation. We have now measured the amount of disaturated phosphatidylcholine as well as the fatty acid composition of phosphatidylcholine in lung lavage from fetal rabbits during the period 27 days' gestation to full term (31 days). There was no developmental change in the amount of disaturated phosphatidylcholine during the period examined. About 50% of the total phosphatidylcholine was disaturated which is approximately the same as in adult rabbit lung lavage. The fatty acid composition, however, did change. There was an increase in the amount of 16:0 from about 20% of the total fatty acids in phosphatidylcholine at 27-28 days to about 60% at full term, after birth, and in the adults. There was a corresponding decrease in the amounts of 14:0, 18:0, and longer chain fatty acids, most of which were saturated. In the lavaged lung tissue, there was a 2.6-fold increase in the percentage of phosphatidylcholine which was disaturated during the period 27-31 days' gestation. It had not decrease to the adult value 24 hr after birth.

Regulation of fetal lung phosphatidyl choline synthesis by cortisol: role of glycogen and glucose.

Twenty pregnant rabbits were studied in pairs. Half were given cortisol subcutaneously on days 24, 25, and 26 of gestation in dosage of 2 mg/kg/day. Half served as controls and received saline. The fetal lungs were studied on the 27th day of gestation by incubating lung slices in the presence of [6-14C]glucose. Glucose consumption significantly increased in the tissue from animals treated with cortisol, 17.61 "/- 5.56 (SD) mumol/g in the controls (P less than 0.05). The glycogen content of tissue treated with cortisol was significantly reduced compared to the controls, 2.42 +/- 0.97 (SD) mg/g wet lung versus 3.81 +/- 1.05 (SD) mg/g (P less than 0.05). Treatment with cortisol resulted in significantly enhanced incorporation of the 14C label into glycogen and phosphatidyl choline (Tables 3 and 4). These data suggest that glucocorticoids affect fetal lung phosphatidyl choline production by promoting glycogenolysis and increasing glucose incorporation into phosphatidyl choline.

Stimulation of adrogen biosynthesis in rat fetal testes in vitro by gonadotropins.

Rt fetal testes in the latter part of gestation (Days 17-21) have enzyme systems for the de novo synthesis of androgen. Under the conditions of these in vitro experiments the major androgen produced was testosterone, with lesser amounts of androstenedione and 5n-dihydrotestosterone. As little as 10 m IU of hCG added in vitro significantly increased androgen synthesis in the fetal testis on Day 19. Bovine, ovine or human LH but not bovine or ovine FSH also stimulated the synthesis of androgens by the rat fetal testis. The synthesis of testosterone was increased by the addition of precursors: 15-fold by the addition of pregnenolone, 20-fold by progesterone, and 47-fold by dehydroepiandrosterone. However, the increase was marginal in the presence of sulfates of pregnenolone or dehydroepi- androsterone. These results suggest that �5-isomerase-3�3-hydroxysteroid dehydrogenase and 1 713-hydroxysteroid dehydrogenase are active in the fetal testes; in contrast, the activity of steroid sulfatase was relatively low.

Fetal death in eclampsia: I. Its relation to low gestational age, retarded fetal growth and low birthweight.

Of 173 eclamptics admitted to the only public maternity hospital in Cali, Colombia 44 had stillbirths making a rate of 25-4 per cent. Fetuses delivered before 32 weeks had nearly four times the stillbirth rate of those delivered at term. Those weighing less than 1600 g. had stillbirth rates about six times higher than those weighing above 2500 g. An attempt was made to divide the risk conveyed by low birthweight into two components; that which was due to low gestational age, and that which was due to an abnormally low rate of growth during the gestational time available. Deviation of birthweight below that expected for age (retarded fetal growth, RFG) was used as a measure of the latter component. RFG became more common as gestation progressed and was associated with fetal death only in the latter part of gestation and with marginal statistical significance. After 35 weeks, fetuses at or below two standard deviations from Gruenwald's mean weight for gestational age (Gruenwald, 1966) had a fetal death rate five times higher than those at the mean. The risk of fetal (intrauterine) death conveyed by low gestational age has not been definitively explained. Alternative pathophysiological mechanisms are discussed.

Growth of adipose tissue in the fetal rabbit.

(1) Fetal rabbits of different gestational ages (20-29 days) were obtained by Caesarian section and term rabbits (31 days) by natural delivery. After dissection, organ weights were obtained and growth curves drawn. Brown adipose tissue was first visible at 22 days gestation and increased relatively more quickly than the body weight till day 26 after which it formed a constant percentage of the body weight. Growth of white adipose tissue followed a similar pattern, except that it was not visible until day 24. (2) The percentage triglyceride content of both types of adipose tissue increased throughout the latter part of gestation. (3) Fetuses of low birth weight had depressed fat stores in brown adipose tissue. (4) Some, but not all, of the high birth weight fetuses had relatively enlarged fat stores. (5) It is suggested that the conditions which produce fetuses of unusually low or high birth weight tend to have a greater corresponding effect on the fetal fat stores.

Morphological development of the lung: a review.

SYNOPSISThis literature review compares the developing lung structure of several mammalian species and identifies those features which are common at birth. Potential air‐conducting structures are formed early in gestation with the bronchial tree being developed well before the alveoli and gas exchanging structures. The distal pulmonary epithelium differentiates into alveolar type I and II cells whilst capillaries proliferate in the pulmonary mesenchyme. Late in gestation structures similar in shape to adult alveoli form and potential gas exchanging areas are detectable. Cell inclusions associated with the production of pulmonary surfactant develop during the latter part of gestation and are abundant at term. Whilst the relative rates of development of these pulmonary structures vary between species, the lung has a common fundamental architecture at birth.

INDUCTION OF DRUG METABOLIZING ENZYME ACTIVITIES IN THE HUMAN FOETUS AND IN THE NEWBORN INFANT

The problem of induction of microsomal enzyme activities in the human fetus and in the neonate was studied by measuring diazepam metabolites in the urine of five subjects pretreated with phenobarbital, either during fetal life or after birth. A very considerable increase of urinary excretion of hydroxylated and conjugated compounds was observed. These findings may be considered as an indirect evidence of induction of drug metabolizing enzyme activities during the last part of gestation and shortly after birth. Present knowledge on liver enzyme induction in fetuses and neonates are critically reviewed.

Sequential foetal-maternal plasma cortisol levels in sheep.

SUMMARY Chronic foetal—maternal cortisol interrelationships were studied in five time-dated pregnant ewes. Serial blood samples were obtained from ewe and foetus simultaneously for several weeks before and including parturition. Plasma cortisol was measured by both fluorometry and isotopic competitive protein binding. The data indicate that maternal cortisol levels are slightly higher than those in the foetus during the latter part of gestation until approximately 1 week before parturition. During the last week of gestation, especially 4–5 days before delivery, a marked increase in foetal cortisol levels was noted. Administration of amino-glutethimide to the foetus 1 week before delivery did not alter cortisol levels in either foetus or ewe. The results suggest that parturition in sheep is a culmination of events initiated by active foetal adrenocortical secretion.

The composition of foetal and maternal blood during parturition in the ewe.

1. Changes in the composition of foetal and maternal blood have been followed during the last 5-10 days of gestation and throughout parturition in the conscious sheep.2. Catheters were placed in the foetal inferior vena cava through a tarsal vein and in a maternal uterine vein in ten ewes under sodium pentobarbitone anaesthesia. In four of the foetuses blood pressure and heart rates were recorded before and during parturition from an arterial catheter.3. Foetal blood gas tensions, pH and PCV remained stable during the latter part of gestation and throughout labour until 15 min before delivery, when P(O) (2) and pH fell while PCV and P(CO) (2) rose in about 50% of the foetuses examined.4. Metabolite levels were also relatively stable at the end of gestation. Plasma glucose in both maternal and foetal blood rose during the hour before birth, while foetal plasma lactate was elevated as early as 4 hr before birth and was unrelated to any maternal changes. Foetal fructose levels were maintained until after delivery.5. Rises in foetal blood pressure before birth were associated with uterine contractions. Foetal heart rate changes during labour varied in different individuals. The heart rate either fell gradually before birth or there was little change until a sudden drop at delivery.6. The most striking changes in the lamb occurred at, or a few minutes after, birth; pH and P(O) (2) fell, P(CO) (2) and PCV rose, and bradycardia at delivery was succeeded by prolonged tachycardia. There were marked increases in plasma glucose and lactic acid at this time.7. P(O) (2) rose rapidly once respiration was established, while pH and P(CO) (2) levels were restored within (1/2)-1 hr. Plasma FFA levels rose rapidly in the lambs 10-30 min after birth and remained high, while plasma glucose, lactate and fructose concentrations declined slowly in the 1-2 hr after birth, although suckling raised the plasma glucose levels. Considerable individual variation in the metabolite levels was found in both ewes and lambs.8. In the majority of ewes delivery was associated with an abrupt maternal hyperglycaemia, with a much smaller rise in lactate and virtually no change in maternal blood gases or pH.9. These findings are discussed in relation to existing information on new-born lambs and the human infant during birth.

A study of storage iron in the placental and foetal tissues of the rat.

SummaryPart of the iron entering the placenta late in gestation is stored as ferri‐tin and haemosiderin; the function of placental storage iron is not known. 50–60% of foetal iron is found within storage compounds. There are relatively few studies of the foetal tissues responsible for the synthesis of storage iron‐protein.In order to investigate these aspects of iron metabolism we measured the quantity and concentration of ferritin and haemosiderin iron in the placental and foetal tissues of the rat during the latter part of gestation; the incorporation of 59Fe into these compounds was also investigated.Placental ferritin and haemosiderin iron reached peak values on day 17. A 40% decrease in the quantity of ferritin iron by day 19, without a corresponding change in placental weight, indicated mobilization of iron from placental ferritin; haemosiderin iron remained unchanged. On day 21 (parturition) both iron storage compounds again increased in quantity. The amounts of storage iron deposited in the allantoic placenta and yolk sac were similar until day 21 when the former tissue contained 75% of the total quantity. The concentration of ferritin iron was higher in the yolk sac on days 17 and 19.The major portion of foetal ferritin and haemosiderin was deposited late in gestation. The carcass and liver were the principal sites involved although small amounts were found in the spleen and gastrointestinal tract. The incorporation of 59Fe by ferritin and haemosiderin confirmed the results obtained by chemical analysis and also showed that there was a steady addition of iron to both compounds throughout the latter part of gestation.

THE EFFECTS OF MATERNAL HYPOXIA AND HYPEROXIA UPON THE NEONATAL PULMONARY VASCULATURE

The fetal and newborn pulmonary artery has thickened media by comparison to that of the older infant. In this study we investigated the proposition that chronic maternal hypoxia during the latter part of gestation might induce further thickening of the neonatal pulmonary artery media. Relative medial thickness was determined by the ratio of the arterial media to external diameter. The mean ratio of small pulmonary arteries of progeny of hypoxic mothers was significantly thicker in each size group between 50 and 150 microns as compared to those born to mothers who spent their gestation in air or hyperoxic environments. Medial hypertrophy was most pronounced in the smaller arteries of the hypoxic group; no intersize variations were found between the control or hyperoxic groups. Medial thickness decreased in all arteries through 2 weeks of age; this decrease was greatest in control and hyperoxic arteries. The possible relationship of hypertrophied pulmonary arterial media and abnormally increased neonatal pulmonary vascular resistance is discussed.

Electron microscopy of the chorioallantoic placenta of the rabbit: II. The decidua and the maternal vessels

The ultrastructure of the decidual cells at different stages of gestation is described. The decidual cells are formed from the perivascular cells from the eight day of pregnancy. Their ultrastructure resembles that of fetal liver cells. The maternal vessels in the latter part of gestation are lined by multinucleated cells, the origin of which is unknown. The different possibilities are discussed, and evidence is presented in favor of the theory that they may be decidual in origin. The “zone of separation” at parturition is formed mainly by the degeneration of the multinucleated giant cells of the “intermediate zone,” but the debris of degenerated decidual cells also takes part in its formation.

Urinary Excretion of Estrogenic Compounds During Estrus and Gestation by the Bovine as Determined by Three Assay Methods

Summary Aliquots of 24-hr urine collections from cows during estrus and at the 50th, 100th, 200th, and 275th days of gestation were extracted and assayed for the estrogenic content by the Kober color reaction, fluorometrically, and with bioassay. The bioassay procedure gave results for estradiol-17 α that averaged 1.19 times higher than those obtained by the Kober color reaction and 1.74 times higher than the fluorometric results. However, in measuring estradiol-17 β , the bioassay results were 0.7 times greater than the Kober results and 0.54 times greater than, the fluorometric results. The greatest differences between the methods were revealed in measuring urinary estrone, in that the bioassay results averaged only 0.21 times greater than the Kober results and 0.42 times higher than the fluorometric results. Excretion of the three estrogens was lowest at 50 days, but after 100 days of gestation an increase in urinary estrogenic excretion occurred and it was at an accelerated rate during the last stages of pregnancy. The most pronounced increase was in the excretion of estradiol-17 α , although estrone excretion was also considerably higher during the latter part of gestation. The urinary excretion of estradiol-17 β increased at a much slower rate than did that of two other estrogens.