Intact Fetuses Research Articles

Role of vagosympathetic fibers in the control of adrenocorticotropic hormone, vasopressin, and renin responses to hemorrhage in fetal sheep.

Hemorrhage stimulates endocrine and cardiovascular reflex responses that are appropriate for returning blood volume and pressure to prehemorrhage levels. Fetal sheep respond to hemorrhage with increases in plasma adrenocorticotropic hormone (ACTH), cortisol, and vasopressin concentrations and plasma renin activity, but little is known about the afferent limb of the reflex(es) controlling these responses. Fetal sheep between 128 and 133 days' gestation were chronically prepared with vascular catheters. Five fetal sheep were subjected to bilateral section of the cervical vagosympathetic trunks; six fetal sheep were not vagotomized. Four to six days after surgery, the fetuses were subjected to withdrawal of 10 ml of blood every 10 minutes for 2 hours (130 ml total). Vagotomized fetal sheep responded to the hemorrhage with a greater decrease in central venous pressure than the intact fetuses and a slower restitution of fluid to the vascular space (estimated to be 17% of the hemorrhage volume in 2 hours) than the intact fetuses (estimated to be 28% of the hemorrhage volume in 2 hours). Both groups of fetuses, however, responded to the hemorrhage with increases in fetal plasma ACTH, cortisol, and vasopressin concentrations and plasma renin activity that were not significantly different. A posteriori analysis of the data by correlation analysis revealed that the fetal ACTH, vasopressin, and renin responses to the hemorrhage were more highly correlated to the changes in fetal arterial pH than to changes in fetal mean arterial pressure or central venous pressure. The results suggest that the ACTH, vasopressin, and renin responses to hemorrhage in the fetus be mediated by chemoreceptors, not by cardiovascular mechanoreceptors.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in the levels of growth hormones, insulin, cortisol, thyroxine and somatomedin-C/IGF-1, with increasing gestational age in the fetal pig, and the effect of thyroidectomy in utero

1. 1. Blood samples were taken from 30 chronically catheterized pig fetuses in utero. Levels of growth hormone, insulin, cortisol, thyroxine and somatomedin-C/IGF-1 were measured in the plasma of intact fetuses and the plasma of thyroidectomized fetuses at various gestational ages during the latter part of pregnancy. 2. 2. Growth hormone levels were high (mean ± SEM: 83 ± 9 ng/ml and remained constant throughout this period. 3. 3. Insulin levels were also constant and ranged between 4 and 14 mU/l. 4. 4. Cortisol levels showed a general increase from 400 nmol/l at 97 days to 1200 nmol/l at term and this increase was not affected by thyroidectomy. 5. 5. IGF-1 levels were lower than in the sows (8.0 ± 3.0 ng/ml) and did not change throughout this period. 6. 6. Thyroxine levels were also unchanged at about 92 ± 4 nmol/l. 7. 7. Thyroidectomy resulted in lower ( P < 0.001) thyroxine levels (28 ± 3 nmol/l) but had no effect on the levels of any other hormone.

Ultrastructural evidence that the negative feedback mechanism of the pituitary-thyroid axis can operate without the hypothalamus in fetal rats: observation of thyroid follicular cells.

Hypothalamus-independent negative feedback mechanism of the pituitary-thyroid axis was studied by electron microscopic observation of thyroid follicular cells of encephalectomized or hypophysectomized fetal rats under hypothyroidism induced by propylthiouracil (PTU). Fetal hypophysectomy or encephalectomy was performed on day 19 of gestation. Mother rats were given either a daily amount of 40 mg PTU or saline alone on the day of operation and on the next day. On day 21, their fetuses were obtained. As a result, PTU induced marked goiters even in encephalectomized fetuses, the goiters being comparable in weight to those induced in littermate intact fetuses. Electron microscopically, the follicular lumen was narrowed, microvilli were lengthened with a marked increase in number, and rER was extremely expanded. Follicular cells often confined colloid droplets and lysosomes. Fetal hypophysectomy, even in PTU-treatment, caused a reduction in the thyroid weight, accompanied by flattening of follicular cells, shortening of microvilli, widening of follicular lumen, and shrinkage of rER. These findings would support the view that the negative feedback mechanism of the pituitary-thyroid axis can operate without the hypothalamus in fetal rats.

Autonomic modulation of fetal atrial natriuretic factor and urine flow responses to vascular volume expansion

The present study was designed to test the hypothesis that the fetal autonomic nervous system modulates the fetal plasma atrial natriuretic factor and urine flow responses to vascular volume expansion. To do this, isotonic saline solution (2% of estimated body weight) was infused intravascularly over a 10-minute period into autonomically intact or autonomically blocked fetal sheep. The autonomically intact fetuses responded to the infusion with a significant rise in arterial and venous pressures (p < 0.0001), and atrial natriuretic factor increased by 36 ± 8 (SE) pg/ml (p < 0.05). In the autonomically blocked fetuses, the arterial pressure rise was greater (7.5 ± 1.3 vs 2.6 ± 0.7 mm Hg), whereas the venous pressure rise was not different from that seen in the intact fetuses. Atrial natriuretic factor increased by 44 ± 20 pg/ml (p < 0.05) in the blocked fetuses. Urine flow increased by similar amounts in the two groups (maximal increase above control of 0.33 ± 0.11 in the intact and 0.27 ± 0.10 ml/min in the blocked fetuses). Thus autonomic blockade did not significantly alter either the atrial natriuretic factor, urine flow, or venous pressure responses to volume loading in the fetal sheep. Therefore it appears that the autonomic nervous system does not play a major role in modulating atrial natriuretic factor, urine flow, or venous pressure responses to acute vascular volume expansion in the late gestational fetal sheep.

The effects of pancreatectomy on the rates of glucose utilization, oxidation and production in the sheep fetus.

The effects of fetal pancreatectomy on the uptake and metabolism of glucose were investigated in chronically catheterized sheep fetuses during late gestation by using tracer methodology. Rates of glucose uptake and metabolism were also measured in pancreatectomized fetuses during the infusion of insulin. Pancreatectomy produced hypoinsulinaemia and significantly reduced the rates of fetal glucose utilization and umbilical glucose uptake in comparison to intact fetuses of a similar gestational age. There was no significant alteration in the glucose oxidation fraction after pancreatectomy but because glucose utilization was low in the pancreatectomized fetuses, the rate of fetal glucose oxidation was significantly less after pancreatectomy than in intact animals. No apparent endogenous production of glucose was observed in the pancreatectomized fetuses. Insulin infusion into the pancreatectomized fetuses raised the rates of umbilical glucose uptake and of fetal glucose utilization and oxidation by 40-50% to values similar to those observed in intact animals. The endogenous production of glucose remained negligible during the infusion of insulin into the pancreatectomized fetuses. There was a net flux of radioactive glucose from the pancreatectomized fetus to the uteroplacental tissues and from the uteroplacental tissues into the uterine circulation. These net fluxes and the rate of placental metabolism of tracer glucose decreased significantly during the infusion of insulin into the pancreatectomized fetus. When all the data were combined, partial correlation analyses of the net uteroplacental uptake of tracer glucose and the fetal concentrations of plasma insulin and blood glucose showed that the fetal arterial glucose concentration was the major influence on the net flux of tracer from the fetus to the uteroplacental tissues. These observations demonstrate that the endogenous concentration of insulin has an important role in regulating glucose metabolism in sheep fetus during late gestation.

Transfer of 2,4,5,2′,4′,5′-hexachlorobiphenyl across the in situ perfused guinea pig placenta

The transplacental crossover of 14C-2,4,5,2′,4′,5′-hexachlorobiphenyl (6-CB) from the maternal circulation to the fetal side of the placenta was examined in intact fetuses and following the in situ perfusion of the guinea pig placenta. Fetal, late pregnant, and nonpregnant female guinea pig lipoprotein profiles and the association of 6-CB with these plasma constituents were also determined in vivo. Very low density lipoprotein (VLDL) concentrations were 10-fold higher in fetal than in maternal plasma, and the great majority of 6-CB which was transferred to intact fetuses became associated with this plasma fraction. 6-CB was found primarily in association with low density lipoproteins (LDL) in nonpregnant animals. In the late pregnant guinea pig, 6-CB became primarily associated with plasma protein in spite of circulating protein concentrations lower than those seen in the nonpregnant state. No differences in the levels of the three plasma lipoprotein classes were observed between pregnant and nonpregnant animals. It was found that an amount of 6-CB similar to that found in intact litter mates crossed the perfused placenta over the same time period. Despite the much higher VLDL concentrations on the fetal side of the placenta and the association of 6-CB with VLDL in intact fetuses, addition of 1000 mg/dl VLDL to the 5.4% bovine serum albumin perfusion medium failed to influence the magnitude of 6-CB crossover. 6-CB crossover was influenced by protein concentration in the perfusion media in a concentration-dependent fashion. It is hypothesized that 6-CB and free fatty acids traverse the placenta and are retained by the fetus via similar mechanisms.

Evidence that cortisol inhibits basal adrenocorticotropin secretion in the sheep fetus by 0.70 gestation.

To ascertain if reductions in fetal plasma cortisol cause increases in fetal plasma ACTH, we treated pregnant ewes or their fetuses with aminoglutethimide (10 mg/kg BW) and metyrapone (20 mg/kg BW) and measured the hormonal responses with RIAs. When given to fetuses (n = 9) at 0.90 +/- 0.01 gestation (term-145 days), the steroid synthesis inhibitors reduced fetal plasma cortisol from 35.1 +/- 11.9 to 18.5 +/- 6.2 ng/ml (P less than 0.01) and plasma ACTH increased from 37 +/- 7 to 189 +/- 74 pg/ml (P less than 0.02). Thus, late in gestation cortisol from the fetal adrenal suppresses basal fetal ACTH secretion. Blockade of steroid biosynthesis in pregnant ewes carrying intact fetuses at 0.76 +/- 0.02 gestation (n = 11) or adrenalectomized fetuses at 0.81 +/- 0.01 gestation (n = 6) also reduced cortisol and increased ACTH in fetal plasma. In intact fetuses cortisol declined from 9.4 +/- 2.0 to 3.6 +/- 0.9 ng/ml (P less than 0.05), and ACTH increased from 46 +/- 8 to 183 +/- 67 (P less than 0.01); cortisol declined in adrenalectomized fetuses from 2.1 +/- 0.4 to 1.1 +/- 0.3 ng/ml (P less than 0.01), and ACTH increased from 106 +/- 13 to 400 +/- 104 pg/ml (P less than 0.01). Cortisol infusions into intact and adrenalectomized fetuses prevented both the decline in steroid concentration caused by the biosynthesis inhibitors given to the ewe and the increase in fetal plasma ACTH concentration. These data indicate that reductions in plasma cortisol in adrenalectomized fetuses or intact fetuses at a time in development when the fetal adrenal produces little cortisol cause compensatory increases in fetal plasma ACTH concentration. The simplest explanation for these observations is that from approximately 0.70 gestation, basal fetal ACTH secretion is tonically inhibited by cortisol circulating in fetal plasma. This cortisol can originate from sources other than the fetal adrenal.

Evidence for a novel parathyroid hormone-related protein in fetal lamb parathyroid glands and sheep placenta: comparisons with a similar protein implicated in humoral hypercalcaemia of malignancy.

Parathyroid hormone (PTH)-like bioactivity, assayed as adenylate cyclase response in UMR 106-01 osteogenic sarcoma cells, was present in extracts of sheep fetal and maternal parathyroid glands and placenta. Preincubation of extracts with PTH(1-34) antiserum inhibited approximately 40% of the bioactivity in fetal parathyroid extracts, 50% in maternal parathyroid extracts, but only 10% of the bioactivity in the placental extract. Partial purification of placental extracts by chromatography yielded fractions containing PTH-like bioactivity which were similar in behaviour to that of PTH-related protein (PTHrP) from a human lung cancer cell line (BEN). An antiserum against synthetic PTHrP(1-16) partially inhibited the bioactivity of the placental extract and synthetic PTHrP(1-34), but had no effect on the bioactivity of bovine PTH(1-34) or bovine PTH(1-84). The placental PTH-like bioactivity was higher in mid- than in late gestation. Fetal parathyroid glands contained the highest PTH-like bioactivity. Thyroparathyroidectomy of one fetal twin lamb in each of 16 ewes between 110 and 125 days of gestation resulted in decreases of the plasma calcium concentration and reversal of the placental calcium gradient that existed between the ewe and the intact fetus. Perfusion of the placenta of each twin in anaesthetized ewes was carried out sequentially with autologous fetal blood in the absence of the exsanguinated fetus. The plasma calcium concentration in the blood perfusing the placenta of each twin increased, but reached a plateau at a lower concentration in the perfusing blood of thyroparathyroidectomized fetuses than in that of the intact fetuses. Addition of extracts of fetal parathyroid glands or of partially purified PTHrP resulted in further increases in plasma calcium in the autologous blood perfusing the placentae of thyroparathyroidectomized fetuses, but addition of bovine PTH(1-84) or rat PTH(1-34) had no effect. The presence of this PTH-like protein in the fetal parathyroid gland and placenta may contribute to the relative hypercalcaemia of the fetal lamb. This protein, which is similar to PTHrP associated with humoral hypercalcaemia of malignancy, stimulates the placental calcium pump responsible for maintaining a relative fetal hypercalcaemia during gestation.

The effect of fetal hypophysectomy and fetal death in gilts with small litters on concentrations of relaxin, progesterone and estradiol-17β

During late pregnancy concentrations of relaxin, progesterone (P) and estradiol-17β (E) in maternal plasma were measured in gilts with small litters of intact, hypophysectomized, partially hypophysectomized or dead fetuses and in gilts with litters of normal fetuses and numbers. To achieve a small litter size at parturition all but one or two fetuses were killed at surgery at Day 30 to 40 of gestation. Fetal hypophysectomy or sham procedures were attempted on Day 90 to 95. Gestation was prolonged in gilts carrying hypophysectomized or partially hypophysectomized fetuses ( P<0.01). Lactation and farrowing did not occur if hypophysectomy was complete. Basal concentrations of E in plasma were lower ( P<0.01), basal P appeared higher and basal relaxin was unchanged in gilts carrying hypophysectomized or dead fetuses as compared to gilts with intact fetuses. Near the end of pregnancy the concentration of E was 119.8 pg/ml in gilts with the normal number of fetuses, 32.6 pg/ml in the group with hypophysectomized fetuses, and 7.3 pg/ml in gilts with dead fetuses. The relaxin peak occurred near term in control pigs and was delayed in the groups with hypophysectomized and partially hypophysectomized fetuses. The concentration of relaxin at the peak in gilts with normal sized litters was 181.4±75.8 ng/ml as compared with 25.3±16.0 ng/ml in gilts with partially hypophysectomized fetuses and was 9.5±1.4 ng/ml in gilts with hypophysectomized fetuses and 10.6±3.3 ng/ml in gilts with one or two fetuses. In gilts with intact or partially hypophysectomized fetuses, or litters containing both types, which came into labor, the patterns of P and E were similar. In gilts with hypophysectomized fetuses, P and E at term showed little change from basal concentrations. The results confirm that the fetus influences basal concentrations of E and possibly P in late normal gestations. In addition, the presence of the fetal pituitary is associated with the peak in relaxin expected at term. These associations are likely to be related to pituitary function and/or the mass of the conceptus. Fetal hypophysectomy is clearly associated with maternal concentrations of P and E at Day 114 that are different from those in normal sows, suggesting that these two hormones may have an effect on the initiation of parturition in the pig.

INFLUENCE OF FETAL NUMBERS AND HYPOPHYSECTOMY ON THE LENGTH OF GESTATION IN THE PIG

Parturition was not delayed in gilts carrying intact and hypophysectomized fetuses when four or more intact fetuses were present but its timing varied when fewer were present. In normal farrowings, gestation periods were longer for litters of two or three but not for litters of four. It is suggested that four fetuses are required for consistent delivery at the expected time. Key words: Gestation length, litter size, hypophysectomy

Fetal expression of muscle-specific isoactins in multiple organs of the Wistar-Kyoto rat.

Actin, a cytoskeletal and contractile protein, is expressed in six different isoforms that exhibit striking specificity. No studies have considered the muscle-specific actin expression in multiple organ systems in the intact fetus. Using a monoclonal antibody (B4) which reacts specifically with the isoactins of the smooth and skeletal muscle our immunohistochemical study examined whole fetal body sections to follow the development of actin expression throughout the last third of gestation in the Wistar-Kyoto rat. B4 staining was exclusively localized to muscle, confirming its high specificity and its usefulness for studying the ontogeny of muscle-specific isoactins. At 15 days of gestation, B4 staining was detected in the heart, the thoracic aorta and the skeletal muscle of the chest wall. The distribution and intensity of staining in the heart were initially higher than in the aorta or skeletal muscle and remained unchanged throughout the remainder of gestation, suggesting that the maturation of cardiac actin expression is well developed, although not fully completed before birth. Expression of muscle-specific actins in skeletal muscle was age-dependent and correlated with the maturational changes of muscle cell precursors. B4 staining in the fetal kidney was not apparent until day 20 of gestation and was localized to the inner cortical vessels. in association with the most mature nephrons, suggesting a centrifugal maturation of the intrarenal vasculature. The intensity of B4 staining in most tissues including bronchi, bowel, diaphragm, chest wall muscle and peripheral and pulmonary arteries increased by the end of gestation.

Cardiorespiratory response to cyanide of arterial chemoreceptors in fetal lambs.

Cardiorespiratory response to the stimulation of the carotid and aortic receptors by sodium cyanide was examined in fetal lambs in utero at 0.8 (120 days) gestation. Injections of 50-400 micrograms cyanide into the inferior vena cava or the carotid artery of intact fetuses elicited bradycardia and respiratory responses that varied from a single gasp to rhythmic respiratory movements but no significant change in arterial blood pressure. Carotid sinus denervation eliminated the cardiorespiratory response to intracarotid injection of cyanide and sinoaortic denervation abolished the response to inferior vena caval injection. It is concluded that in fetal lamb in utero the aortic and carotid bodies are active, and hypoxic stimulation of these chemoreceptors results in cardiorespiratory response characterized by slowing of fetal heart rate, respiratory effort, and no consistent change in arterial blood pressure.

Pre-adipocyte proliferation and differentiation in response to hormone supplementation of decapitated fetal pig sera.

Growth hormone and thyroid hormones have been implicated as important serum factors for adipocyte development in cell culture. Fetal decapitation removes these factors from serum of the growing fetal pig and results in development of fewer adipocytes than in intact fetuses. These experiments examined the effects of growth hormone or thyroxine supplementation to decapitated fetal pig sera upon pre-adipocyte proliferation and differentiation. Hormones were supplemented to concentrations present in sera from intact pig littermates (reference). Sera +/- hormones were analyzed for their effects upon pre-adipocyte proliferation as determined by [3H]-thymidine incorporation; enzyme expression as determined by sn-glycerol-3-phosphate dehydrogenase activity; and induction of complete differentiation into lipid filled adipocytes as based upon a pre-adipocyte proliferation and enzyme expression than reference sera. Growth hormone had no effect in decap sera upon these parameters. Decap sera permitted detection of 54% more lipid-accumulating, newly formed adipocytes on percol gradients than reference sera, but growth hormone reduced detection to 29% of reference sera. Thyroxine specifically stimulated pre-adipocyte proliferation more than decap sera, but not to the level of reference sera. Complete differentiation, a formation of lipid-accumulating adipocytes was promoted also by thyroxine in comparison to basal decap sera. The results of these experiments indicate thyroid hormones are an important component of fetal sera for regulation of adipocyte development, whereas growth hormone may only affect cellular metabolism and not promote pre-adipocyte growth and development.

Central endocrine regulation of the development of hormone responses in porcine fetal adipose tissue.

Experiments were performed to determine whether central endocrine or neural regulation is primarily involved with the development of endocrine responses in fetal adipose tissue metabolism. Fetuses within one uterine horn were either decapitated (decap) or spinally cauterized at 45 d of gestation, with fetuses in the other horn serving as sham controls (intact). Fetuses were removed by cesarean section at 110 d of gestation. Slices of subcutaneous adipose tissue (100 mg) were incubated in media supplemented with radioactive glucose and insulin (1.0 mU/ml) to measure the metabolic response of the tissue to insulin. Other slices were incubated in medium supplemented with norepinephrine bitartrate (1 microgram/ml) to measure lipolytic response by glycerol release. Basal glucose utilization for oxidation, total lipid and fatty acid synthesis was higher in decap adipose tissue than intact adipose tissue. Cauterized and intact fetuses did not differ in adipose tissue glucose metabolism. Only decap adipose tissue demonstrated an insulin stimulation of glucose oxidation and lipogenesis. Norepinephrine stimulated lipolysis in both cauterized and intact adipose tissue but had no effect upon decap adipose tissue lipolysis. These results demonstrate central endocrine regulation but not central neural regulation has an important function in the development of porcine fetal adipose tissue metabolism and its responses to systemic hormones.

Effect of hypophysectomy on tissue glycogen concentrations in the fetal pig.

The glycogen content was estimated in the liver, lung, cardiac ventricle and skeletal muscle of fetal pigs which had been hypophysectomized between 69-84 days of gestation, decapitated between 35-42 days of gestation or left intact. Comparisons made preterm (103-108 days) or at term (112-114 days) indicated that both liver and skeletal muscle glycogen content were significantly lower in the absence of the fetal pituitary, whereas concentrations in the fetal lungs were significantly higher. There were no significant differences in cardiac glycogen content between hypophysectomized and intact fetuses. Plasma glucose concentrations in both umbilical artery and vein were similar, but plasma arterial fructose concentrations were significantly higher in the hypophysectomized fetuses.

Influence of the fetal pituitary-adrenal axis on fetal and maternal progesterone and unconjugated oestrogen concentrations in the pig.

Fetal and maternal plasma progesterone and unconjugated oestrone and oestradiol-17 beta concentrations were measured in intact pig fetuses and those in which the pituitary had been destroyed. Progesterone concentrations were significantly higher (P less than 0.05) and oestrogen concentrations significantly lower (P less than 0.01) in hypophysectomized fetuses than in intact fetuses. When fetuses in one uterine horn only were hypophysectomized, oestrogen concentrations in the uterine vein draining this horn were lower than those from the contralateral vein. The results indicate that both fetal and maternal oestrogen concentrations are influenced by the fetal pituitary. When dexamethasone was infused (at 27 micrograms/h for 96 h) into 5 chronically-catheterized hypophysectomized fetuses no changes in peripheral fetal progesterone or oestrone were observed.

The effect of fetal thyroparathyroidectomy on the transport of calcium across the ovine placenta to the fetus

The ovine fetal placenta has been perfused with autologous fetal blood under controlled conditions in eleven experiments in which the fetus was first removed. Eight of these experiments involved four pairs of twins, one lamb of which had been thyroparathyroidectomized (TXPTX) three to seven days earlier. By this time the normal placental calcium gradient from mother to fetus had either decreased or been reversed. The mean rate of transport of calcium from the mother was unchanged by previous fetal TXPTX, but the final calcium gradient achieved from the mother to the perfusing blood was significantly less than with placentae from intact fetuses. No significant alteration in fetal plasma I,25-dihydroxyvitamin D (I,25(OH)2D) concentration was observed as a result of the fetal TXPTX, indicating that hypocalcaemia can compensate for the lack of PTH in fetal production of I,25(OH)2D. Fetal thyroidectomy with replacement of thyroxine did not lead to reversal of the placental calcium gradient, indicating that calcitonin was not involved. It is suggested that in the ovine fetus, parathyroid hormone promotes the active transport of calcium from mother to fetus, so that in its absence the fetus must obtain its calcium for growth by reducing its calcaemia and thereby allow net diffusion of calcium to replace the action of the placental calcium pump. The price paid for this compensation is marked hypocalcaemia and defective calcification of osteoid.

Effects of hypercapnia and hypoxemia on fetal breathing after decortication.

The effects of hypercapnia and hypoxemia on breathing movements were studied in 12 chronically decorticated fetal sheep, 127-140 days gestation. The fetal state of consciousness was defined in terms of activity of the lateral rectus and nuchal muscles. Arterial blood pressure was monitored. Fetal breathing was determined by integrated diaphragmatic electromyogram (EMG) and analyzed in terms of inspiratory time (TI), expiratory time (TE), electrical equivalent of tidal volume (EVT), breath interval (TT), duty cycle (TI/TT), mean inspiratory flow equivalent (EVT/TI), and instantaneous ventilation equivalent (EVT/TT). Fetal breathing occurred only during episodes of rapid-eye movements, and the response to hypercapnia consisted of an increase in EVT, TI, EVE, and EVT/TI and a decrease in the coefficient of variation of all measured parameters. Induction of hypoxia during episodes of spontaneous fetal breathing produced a decrease in the rate of breathing and an increase in EVT and TI with no change in the variability of all parameters studied. Since similar responses to hypercapnia and hypoxemia are seen in the intact fetus, we conclude that the cerebral cortex has no obvious effect on the chemical control of fetal breathing.

Effects of progesterone induced postmaturity on CBG and pituitary-adrenal activities in the rat foetus.

CBG and pituitary-adrenal activities were investigated in intact rat foetuses, in newborns spontaneously delivered by vaginal way and in postmature foetuses from mothers with delayed parturition caused by daily progesterone injection from day 20 of gestation. The postmature foetuses had lower body weights and higher adrenal weights on day 22, 23 and 24 of gestation than newborns of the same conceptional age. The corticosterone binding capacity of the plasma as well as the binding capacity of CBG for corticosterone decreased in intact foetuses for the last 3 days of gestation and stayed very low in pups from day 0 to day 8 postpartum. These parameters decreased more slowly in postmature foetuses; however, the differences between the latter and intact foetuses or newborns were not statistically significant. Similar evolution occurred in intact pregnant and suckling females as well as in females with prolonged gestation. The fall in CBG activity in normal rat pups and the subsequent rise in free steroids could explain a sharp decrease in plasma ACTH levels as well as the drop in adrenal and plasma corticosterone concentration. In foetuses with prolonged gestation, the same phenomenon did not occur. Stress conditions produced by maintaining growing foetuses in utero and the development of severe jaundice maintained high ACTH levels. In contrast, the fall in adrenal and plasma corticosterone concentrations in spite of the high level of circulating ACTH could be mainly due to the progesterone inhibition of the steroidogenic activity of the foetal adrenals.

Regulation of rabbit fetal glycogen: effect of in utero fetal decapitation on the metabolism of glycogen in fetal heart, lung, and liver.

To understand the control mechanisms involved in the regulation of fetal glycogen, we have studied the effect of in utero fetal decapitations on glycogen metabolism in rabbit fetal heart, lung, and liver. In utero fetal decapitations were performed between days 18 and 21 of gestation. Two to four fetuses on one side of the horn were decapitated. Fetuses were delivered between days 23 and 26 or between days 28 and 30 of gestation. Fetal heart, lungs, and liver were analyzed for DNA, protein, glycogen, glycogen synthase (I and D forms), glycogen phosphorylase (a and b forms), phosphofructokinase, pyruvate kinase, and lactic dehydrogenase. In fetal heart and lung, no difference was observed in any of the above measurements in the intact and decapitated fetuses. In contrast, fetal liver does not appear to develop the glycogen system as indicated by the very low levels of glycogen (0.02 mg/mg DNA) in decapitated fetuses as compared with intact fetuses (0.4 mg/mg DNA). Similarly the levels of glycogen synthase and phosphorylase were two to three times lower in livers from decapitated fetuses as compared with the livers from intact fetuses. The three enzymes phosphofructokinase, pyruvate kinase, and lactic dehydrogenase were not affected by fetal decapitation in all three tissues. These results indicate that the fetal hypothalamic-pituitary-adrenal (thyroid) axis is not required at least after day 18 of gestation for the normal accumulation and subsequent utilization of glycogen in fetal heart and lungs, while it is an absolute requirement for the development of the fetal liver glycogen system.(ABSTRACT TRUNCATED AT 250 WORDS)