Renal responses of the fetal lamb to fetal or maternal volume expansion

Fetal and maternal glomerular filtration rate (GFR), renal plasma flow (RPF), urine volume, sodium excretion, and fractional sodium reabsorption were measured in a chronically instrumented sheep preparation. Fetal GFR was essentially stable between 110 and 135 days of gestation (term = 147 days). There was a significant increase in GFR after 135 days. After the infusion of 50 ml of normal saline over a 30-minute period, fetal GFR and sodium excretion increased significantly. Fractional sodium reabsorption was significantly decreased. Thus, the fetus is capable of responding to volume expansion with saline with an increase in GFR and a decrease in fractional sodium reabsorption. After the infusion of 1000 ml of normal saline into the ewe in 1 hour, maternal GFR and RPF rose significantly. Sodium excretion rose 6-fold and fractional sodium reabsorption fell significantly. After the infusion of saline into the ewe, there was no change in fetal GFR, RPF, sodium excretion, urine volume, or fractional sodium reabsorption. Since there were no changes in fetal renal function after maternal volume expansion with saline there was no evidence for the transplacental passage of a natriuretic factor from ewe to fetus.     

Role of luminal volume changes in the increase in pulmonary blood flow at birth in sheep

The mechanism by which pulmonary blood flow increases and pulmonary vascular resistance decreases after birth is not fully understood. The aim of this study was to simulate the decrease in lung volume caused by the onset of air-breathing at birth and determine whether it can duplicate the changes in pulmonary blood flow and vascular resistance that occur at this time. In chronically catheterized fetal sheep near term (145 days of gestation), fetal pulmonary arterial blood flow was measured, using coloured microspheres, before and after fetal lung liquid volumes were reduced from 52.2 +/- 2.7 to 21.2 +/- 1.6 ml kg-1. During the 30 min period following the reduction in lung liquid volume, the pulmonary-to-systemic arterial pressure difference decreased from 6.8 +/- 1.2 mmHg (pulmonary > systemic) to 1.6 +/- 0.5 mmHg. Reducing the volume of fetal lung liquid increased pulmonary blood flow from 59.1 +/- 10.5 to 204.2 +/- 40.4 ml min-1 (100 g tissue)-1 and reduced pulmonary vascular resistance from 0.53 +/- 0.20 to 0.14 +/- 0.04 mmHg min ml-1 (100 g tissue)-1. We conclude that a reduction in fetal lung liquid volume, which simulates the reduction in lung volume that occurs at birth, causes a 3- to 4-fold increase in pulmonary blood flow and a reduction in pulmonary vascular resistance of a similar magnitude. Thus, the reduction in lung volume associated with the lung changing from a liquid- to an air-filled organ, may partly account for the increase in pulmonary blood flow and decrease in pulmonary vascular resistance at birth.     

Single dose fetal betamethasone administration stabilizes postnatal glomerular filtration rate and alters endocrine function in premature lambs

These studies determined the effects of fetal treatment with betamethasone alone, or in combination with thyroid hormone (thyroxine; T4), on postnatal renal and endocrine adaptations in preterm newborn lambs. Ovine fetuses (126 d of gestation; term = 150 d) received single, ultrasound-guided intramuscular injections of saline, 0.5 mg/kg betamethasone (Celestone Soluspan, or 0.5 mg/kg betamethasone plus 60 micrograms/kg T4. After 48 h, lambs were delivered, treated with surfactant (Survanta, 100 mg/kg), and ventilated for 3 h. Due to maintained urine flow in the betamethasone-treated animals and a significant decrease in the saline group, betamethasone versus saline urine flow values (0.11 +/- 0.03 versus 0.03 +/- 0.004 mL.min-1.kg-1) were significantly elevated by the end of studies. GFR (1.5 +/- 0.3 versus 0.8 +/- 0.2 mL.min-1.kg-1) and mean blood pressure (61 +/- 4 versus 42 +/- 3 mm Hg) values also were higher in the betamethasone-treated animals. Although renal blood flow, renal plasma flow, and fractional sodium excretion rates did not differ, betamethasone versus saline values for the filtration fraction (11.9 +/- 1.5 versus 7.4 +/- 1.5%) and total sodium reabsorption (196 +/- 38 versus 81 +/- 16 microEq.min-1.kg-1) were increased. Betamethasone versus saline treatment also was associated with significant reductions in plasma angiotensin II (125 +/- 23 versus 550 +/- 140 pg/mL) and AVP (116 +/- 19 versus 230 +/- 77 pg/mL) levels. Overall, the effects of combined betamethasone + T4 treatment were similar to the effects of betamethasone alone. Conclusions: 1) fetal betamethasone injection 48 h before delivery stabilizes GFR and significantly alters endocrine function in preterm newborn lambs, and 2) the addition of T4 does not augment betamethasone-induced renal and endocrine responses.     

Differential effects in vivo of thyroid hormone on the expression of surfactant phospholipid, surfactant protein mRNA and antioxidant enzyme mRNA in fetal rat lung

Antenatal administration of triiodo-L-thyronine (T3) to late gestation rats resulted in decreased lung antioxidant enzyme (AOE) activity but increased surfactant phospholipids. In fetal rat lung explant cultures, T3 decreased the expression of surfactant proteins (SP) A and B. There have been no reported studies of the simultaneous in vivo developmental influence of T3 on both pulmonary AOE and SP gene expression. We hypothesized that antenatal T3 treatment would cause differential regulation of surfactant phospholipid, SP, and AOE genes in the late gestation fetal rat. Timed pregnant rats received intramuscular injections of either T3 (7 mg/kg) or placebo on days 19 and 20 of gestation and fetuses were delivered on day 21. Fetal lung SP-A, SP-B, SP-C, and AOE mRNA levels were studied by Northern analysis. AOE mRNA levels were further quantitated by solution hybridization. Total lung phospholipids (TPL) and disaturated phosphatidylcholine (DSPC) content were quantitated by a phosphorus assay. T3 significantly increased TPL and DSPC content, and significantly decreased the expression of SP-A, SP-C, CuZnSOD, and catalase genes. Because of a crucial interplay of these factors for normal lung function at the time of birth, the molecular mechanisms by which these apparently opposing changes are accomplished warrant further investigation.     

Carbonate dehydratase (carbonic anhydrase) and the fetal lung

Carbonic anhydrase activity (carbonic dehydratase, EC 4.2.1.1) has been detected in the fetal lungs of stillborn human infants and rhesus monkeys, but a role for this enzyme in the fetal lung has not been elucidated. In utero the mammalian lung develops as a liquid-filled structure, the liquid being secreted by the lung. In the fetal lamb this liquid, when compared with plasma, has a high chloride and a low bicarbonate concentration, suggesting a possible role for carbonate dehydratase. Studies on 10 fetal lambs confirmed the presence of carbonate dehydratase in the lung. Levels at 60-66 days were negligible and rose to 0.30 Meldrum Roughton units/mg protein at about 140 days (term 147 days), with little change after birth. In another six fetal lambs at 135-136 days, inhibition of this enzyme with 100 mg acetazolamide suppressed the mean rate of secretion of lung liquid by 64.5% (P less than 0.005), which correlated with a significant drop in chloride concentration (P less than 0.001). This magnitude of changes in secretion after acetazolamide is of the same order as that occurring in the secretion of cerebrospinal fluid when carbonate dehydratase is inhibited. This observation supports the hypothesis that carbonate dehydratase in fetal lung affects the secretion of lung liquid, although its mechanism is as yet unknown.     

Cortisol differentially regulates pituitary-adrenal function in the sheep fetus after disconnection of the hypothalamus and pituitary

We have investigated the effects of a 5 day infusion of cortisol into fetal sheep, in which the hypothalamus and pituitary were surgically disconnected (HPD), on fetal pituitary-adrenal function. Fetal HPD and vascular catheterization were carried out at between 104 and 124 days gestation. Cortisol was administered (3.5 mg 24 h-1) for 120 h between 134 and 140 days (HPD + F group; n = 5) and saline was administered during the same gestational age range to HPD (HPD group; n = 12) and intact fetal sheep (Intact group; n = 6). Cortisol infusion into the HPD fetal sheep did not suppress the mRNA levels for Proopiomelanocortin (POMC) in the fetal anterior pituitary at 139/140 days gestation (POMC mRNA: 18S rRNA: Intact 0.40 +/- 0.05; HPD 0.56 +/- 0.07; HPD + F 0.49 +/- 0.07). Similarly, there was no significant effect of either HPD or cortisol infusion on the plasma concentrations of immunoreactive (ir) ACTH or ACTH(1-39). The adrenal: fetal body weight ratio was significantly higher, however, in the HPD + F (88.4 +/- 8.7 mg kg-1) and Intact groups (84.1 +/- 5.6 mg kg-1) when compared with the HPD fetal sheep (63.7 +/- 5.4 mg kg-1). The ratio of total IGF-II mRNA: 18S rRNA was similar in the adrenals of the Intact (0.48 +/- 0.09), HPD (0.78 +/- 0.09) and HPD + F (0.71 +/- 0.11) groups. The ratios of CYPIIA1, 3 beta-HSD and CYP21A1 mRNA: 18S rRNA were significantly lower in adrenals from the HPD group when compared to those in the Intact group and were not restored to normal by cortisol infusion. We have therefore demonstrated that cortisol does not act directly at the fetal pituitary to suppress POMC synthesis or ACTH secretion in late gestation. Cortisol does, however, stimulate fetal adrenal growth after HPD in the absence of any effects on adrenal IGF-II or steroidogenic enzyme mRNA levels. The data provide evidence that an intact hypothalamic-pituitary axis and cortisol each play an important role in the stimulation of adrenal growth and steroidogenesis which occurs during the last 10-15 days of gestation in the sheep.     

bcl-2 protein downregulation is not required for differentiation of multidrug resistant HL60 leukemia cells

Maternal administration of thyrotropin-releasing hormone, alone or in combination with corticosteroid, accelerates functional, morphologic and biochemical fetal lung maturation. However, the dose-response relationship of maternal thyrotropin-releasing hormone treatment and acceleration of fetal lung ultrastructural maturation or disaturated phosphatidylcholine content has not been investigated. We administered (i.p.) saline or thyrotropin-releasing hormone (0.2, 0.4 or 0.6 mg/kg/dose) to the pregnant Balb/c mouse on days 16 and 17 (b.i.d.) and on day 18 of gestation (1 h prior to killing). Morphometric ultrastructural analysis and quantitation of disaturated phosphatidylcholine content was done on the 18-day gestation fetal lung. Maternal thyrotropin-releasing hormone treatment resulted in an increase in the number of lamellar bodies and depletion of glycogen in fetal lung type II cells, and an increase in the lung airspace to parenchymal ratio. In addition, a striking difference in the pattern of lung growth was noted in the thyrotropin-releasing-hormone-treated (0.4 and 0.6 mg/kg/dose) groups. These lungs had larger air spaces, thinner alveolar septae and more air-blood barriers. Maternal thyrotropin-releasing hormone treatment did not influence fetal lung disaturated phosphatidylcholine content. We conclude that in the mouse, maternal thyrotropin-releasing hormone treatment enhances fetal lung structural maturation and propose that thyrotropin-releasing hormone plays a role in mammalian fetal lung growth.     

Roles of gastrin and somatostatin in the regulation of gastric acid secretion in the fetal rabbit

In adult gastric epithelium, gastrin and somatostatin regulate parietal cell acid secretion; however, their expression and function in the fetus are largely unknown. We defined the developmental expression of gastrin and somatostatin in the fetal rabbit stomach and determined their effects on fetal acid secretion. To define peptide expression, fetuses from 12 time-mated New Zealand white rabbit does were analyzed at successive ages during the third trimester (term is 31 days). Peptides were extracted from fetal gastric tissue by boiling in water and then in acetic acid. Amidated gastrin and somatostatin levels were measured by radioimmunoassay using antisera 1296 for gastrin and 8402 for somatostatin. To determine the effects of gastrin and somatostatin, pentagastrin (64 microg/kg/hr) or octreotide (35 microg/kg/hr) were infused intravenously in conscious pregnant rabbits at 28 days of gestation for 3 hr. Fetuses (n = 45) were harvested and gastric acid was titrated with 0.02 N NaOH. Gastrin and somatostatin tissue content were 12 +/- 3 and 51 +/- 6 pmol/g at gestational day 20, respectively, and increased to 146 +/- 10 and 162 +/- 5 pmole/g by day 30 (P < 0.05). Between days 24 and 26, when gastric acid was first detectable, the molar ratio of somatostatin to gastrin decreased from 5.0 +/- 1.0 to 1.1 +/- 0.1 (P < 0.05). Fetal gastric acid content (micromole) was 28.5 +/- 1.7 in controls, 27.5 +/- 1.9 with pentagastrin treatment, and 15.8 +/- 1.4 micromole with octreotide (P < 0.05). In summary, 1) In fetal gastric tissue, gastrin increased 12-fold and somatostatin increased 3-fold between days 20 and 30 of gestation. 2) The decreased ratio of somatostatin to gastrin between days 24 and 26 of gestation coincides with the onset of fetal gastric acid secretion in the fetal rabbit. 3) Maternal administration of octreotide inhibited fetal gastric acid content; however, pentagastrin had no effect. We conclude that, in the fetal rabbit stomach, the relative expression of gastrin and somatostatin may regulate the onset of parietal cell acid secretion.     

Constrictive effect of thyroxine on the ductus arteriosus in fetal rats

This work was conducted to know whether thyroxine (T4) when injected into fetal rats would induce a constriction of the ductus arteriosus (DA). In Experiment 1, fetal rats on day 20 of gestation were given a subcutaneous injection of 1 or 10 micrograms T4 through the maternal uterine wall, and were autopsied 3 or 6 hr later. Similarly, in Experiment 2, the mother rats were given an injection of hydrocortisone (10 mg/kg) just after fetal T4 injections. In either series of experiments, uninjected littermates served as controls. According to the whole-body freezing and shaving method, the DA was exposed and calibrated under a dissecting microscope. In Experiment 1, the DAs of the T4-injected fetuses, 3 hr later, were significantly smaller in caliber than those of their controls, but recovered 6 hr later. In Experiment 2 with fetal T4 injection followed by maternal hydrocortisone injection, the DAs of the T4-injected fetuses were further smaller in caliber than those of their controls which were clearly shrunken as compared with those of controls in Experiment 1. These results indicate that T4 exerts a constrictive effect on the DA, an effect which is strengthened in the presence of hydrocortisone.     

Immunoreactive thromboxane synthase is measurable in ovine fetal hypothalamus as early as 86 days' gestation

Thromboxane A2 (TxA2) augments hypothalamus-pituitary-adrenal axis activity in both fetal and adult animals. We have proposed that TxA2 acts as a neuromodulator within the brain to stimulate the release of corticotropin releasing hormone (CRH) or arginine vasopressin (AVP) into the hypophyseal-portal blood. We performed the present experiments to identify immunoreactive thromboxane synthase (TxS) within fetal brain regions and to quantify developmental changes in the TxS immunoreactivity measurable within those regions. We found that immunoreactive TxS was present in fetal hypothalamus, pituitary, brainstem, and lung. In fetal hypothalamus, we found immunoreactive TxS in three identifiable molecular weights, approximately 65, 42, and 35 kD. In fetal pituitary and lung, we found the 65 and 35 kD forms, and in the brainstem we found only the 35 kD form. In fetal pituitary, there was a clear ontogenetic change in TxS immunoreactivity. The 42 kD TxS immunoreactivity was not present in the youngest fetal sheep studied (86-90 days' gestation), but was expressed in the other age groups (125-128, 135-139, 141-term, and postnatal ages). The other molecular weight forms appeared to increase in the older fetuses, but the changes were not significant. In the hypothalamus, all three forms of TxS were measurable at all ages, and there was no significant change in relative abundance. We conclude that immunoreactive TxS is present in the fetal brain throughout the last half of fetal gestation, but that the significance of multiple molecular weight forms is not clear.     

Editorial: Opportunistic infections due to Aspergillus

Changes in plasma thyroxine (T4) concentrations were followed in 27 fetal sheep after surgical implantation of catheters. Fourteen days were required before stable concentrations of T4 were achieved, whether surgery was performed between 90 and 96 days or 109 and 120 days gestation. Twenty-three fetuses were followed to birth, and during the last four days the T4 concentrations showed no change in 11 fetuses and a significant decrease in the other 12. Birth occurred between 142 and 157 days gestation in both groups. There was a significant rise in T4 concentration during labour in all 23 fetuses. There were large differences among the plasma T4 concentrations of individual ewes which were not related to ambient temperature.     

Ontogeny of 11 beta-hydroxysteroid dehydrogenase in ovine fetal kidney and lung

Eleven-beta-hydroxysteroid dehydrogenase (11 beta-HSD) is an enzyme which degrades 11-hydroxycorticosteroids to biologically inactive 11-oxocorticosteroids (cortisone and 11-dehydrocorticosterone). In some tissues, the activity of this enzyme prevents binding of cortisol to mineralocorticoid receptors. The present experiments were designed to test the hypothesis that the fetal kidney contains 11 beta-HSD, that the activity of 11 beta-HSD in fetal kidney increases near term, and that the fetal lung does not contain significant 11 beta-HSD activity. In kidney and lung tissue from 23 fetal sheep ranging in age between 86 and 145 days' gestation, we measured 11 beta-HSD activity. We found significant activity in fetal kidney (14-85% conversion from cortisol to cortisone) but no measurable activity in fetal lung (0-9%). The activity of 11 beta-HSD was significantly related to fetal gestational age (r = 0.76, n = 14). We conclude that 11 beta-HSD activity in the fetal kidney develops as a function of fetal gestational age, and that activity cannot be demonstrated in fetal lung. We speculate 11 beta-HSD in the fetus might function to alter the sensitivity of target organs to glucocorticoids, as well as to mineralocorticoids, and that the absence of activity in the lung allows a high sensitivity of pulmonary tissue to cortisol at the end of gestation.     

Selective mutation of K-ras by N-ethylnitrosourea shifts from codon 12 to codon 61 during fetal mouse lung maturation

Fetal mouse lung before gestation day 17 shows unique sensitivity to causation of rapidly growing tumors by N-ethylnitrosourea (ENU). Since mouse lung tumors present a mutated K-ras oncogene, we hypothesized that this special susceptibility might reflect an unusual vulnerability of the K-ras gene. Of the lung tumors caused by ENU exposure of BALB/c mice on gestation day 14, 8/25 had a codon 12 mutation in K-ras, vs 4/25 in codon 61. Of 15 tumors after day 16 exposure, three had codon 12 and four codon 61 changes. Tumors from day 18 exposure had only codon 61 mutations (11/16), all A:T to G:C changes (CGA). By contrast, codon 12 (GGT) changes included G:C to T:A, to A:T, and to C:G. These results show significant (P<0.01) shift in the sensitivity of particular K-ras codons to ENU mutation, during fetal mouse lung maturation. In a test of a possible relationship to expression of K-ras, K-ras p21 was measured in lungs of fetal mice, and found to increase markedly on day 18 in comparison to days 14 and 16. Both alkylation of DNA and base damage due to reactive oxygen species are postulated as mechanisms for mutation by ENU, whose efficacies vary with state of fetal lung maturation and K-ras expression.     

Maturational effects of cortisol on the exocrine abomasum and pancreas in fetal sheep

The role of cortisol in the prenatal development of digestive enzymes in the abomasum (prochymosin and pepsinogen) and pancreas (amylase, trypsin, chymotrypsin) has been investigated in the fetal lamb during late gestation. The abomasum and pancreas were collected from 22 unoperated control fetuses (99-145 days gestation; term, 145 +/- 2 days), from seven pairs of twins infused with either saline or cortisol for five days preceding delivery at 127-133 days, and from four 139-143-day-old fetuses adrenalectomized at 120-123 days. Developmental increases (2-8-fold) occurred in protease concentrations in the fetal abomasum and in amylase and chymotrypsin contents in the fetal pancreas. These increases paralleled the normal prepartum rise in fetal plasma cortisol. In addition, the enzyme values were significantly higher in cortisol-infused than in saline-infused fetuses (with the exception of pancreatic amylase) and were significantly lower in adrenalectomized fetuses than in control fetuses at term. The pH of abomasal fluid remained neutral (pH 6.8-8.0) during late gestation and was not affected by cortisol treatment or adrenalectomy. The results suggest that cortisol stimulates the development of the exocrine abomasum and pancreas in fetal sheep and may, thereby, increase the digestive capacity in neonatal lambs. Compared with the pig, another long-gestation species, the sheep has an early development of gastric pepsinogen but a late development of gastric acidity and pancreatic protease activities.     

Effect of thyrotropin-releasing hormone on secretion of thyrotropin, prolactin, thyroxine, and triiodothyronine in pregnant and fetal rhesus monkeys

The effect of thyrotropin-releasing hormone (TRH) on the pituitary-thyroid axis and on prolactin secretion was studied in pregnant Rhesus monkeys during the latter period of gestation and in non-pregnant female controls. The baseline plasma concentrations of TSH, T3, T4, and prolactin (PRL) of pregnant monkeys did not differ from those of non-pregnant monkeys. After administration of TRH, plasma prolactin rose to higher levels in pregnant monkeys than in non-pregnant monkeys whereas there was a similar response of plasma TSH, T4 and T3 in both groups. The baseline plasma TSH was elevated and plasma T3 was decreased in the fetus compared with the mother. Administration of TRH iv to the maternal monkey caused a larger response in the fetal plasma TSH than in that of the mother and was followed by larger increments in plasma T4 and T3 concentrations in the fetuses than in the mothers. The larger increments of plasma TSH and thyroid hormones in the fetus compared with the mother also occurred when TRH was given iv to the fetus. There was a significant rise of plasma prolactin in both mother and fetus after administration of TRH to mother or fetus; the increase of plasma PRL was much higher in the mother than in the fetus. The data show that TRH can cross the primate placenta in either the maternal to fetal or fetal to maternal direction. The fetal thyroid of the Rhesus monkey during the latter period of gestation can release both T4 and T3 in response to TSH.     

The effects of thyroxine on serum and tissue concentrations of insulin-like growth factors (IGF-I and -II) and IGF-binding proteins in the fetal pig

We have extensively studied the effect of hypophysectomy on the growth and development of tissues in the fetal pig. However, little is known about the effect of hypophysectomy on tissue levels of insulin-like growth factors I and II (IGF-I and -II) and how these growth factors are affected by T4 replacement. Fetal pigs were hypophysectomized (Hypox) at 70 days of gestation, and pellets containing 15 mg T4 were implanted into the lateral musculature of the hind limb at either 70 or 90 days of gestation. Fetuses were removed at either 90 or 105 days of gestation, respectively. Control (non-Hypox), Hypox, and T4 (Hypox-T4) fetal weights were similar at 90 days, but Hypox-T4 weighted less than control and Hypox fetuses at 105 days. Hypophysectomy decreased levels of serum T4, LH, cortisol, and IGF-I (105 days) when compared with controls. Heart and liver (105 days and 90 days) and fat, muscle, and kidney (90 days) IGF-I levels were lower in Hypox fetuses when compared with controls. Hypophysectomy decreased concentrations of IGF-II in only 105-day fetal kidneys. Hypophysectomy decreased serum levels of IGF binding protein 1 (IGFBP-1) (90 days) and IGFBP-2 (105 days) and increased IGFBP-4 (105 days) in comparison with control. T4 treatment of Hypox fetuses increased serum concentrations of T4 and IGF-I over Hypox levels at both 90 and 105 days gestation. Cortisol levels remained decreased in the T4-treated fetuses. Levels of IGF-I in the heart (90 and 105 days) and liver (90 days) of Hypox fetuses were increased by T4 treatment. T4 did not effect tissue IGF-II levels when compared with Hypox. T4 increased serum IGFBP-1, -2, and -4 levels over Hypox values. We suggest that T4 enhances production of IGF-I (as opposed to IGF-II), which in turn mediates some of T4's capability to enhance tissue development in the fetal pig.     

Abnormal prenatal lung development resulting from maternal zinc deficiency in rats

The effect of maternal zinc deficiency during gestation on fetal lung development was studied. Sprague-Dawley rats were fed from the day of mating (day zero) a zinc deficient diet (0.4 +/- 0.1 ppm zinc) ad libitum, or a zinc supplemented control diet (100 ppm zinc) either ad libitum or with restricted intake. Fetuses were removed by cesarean section on days 17 to 21 of gestation. Fetuses of zinc deficient dams had smaller lungs both in absolute weight and relative to body weight on all days than did either ad libitum-fed or restricted-intake controls. On days 20 and 21 of gestation, concentration of fetal lung lecithin and phosphatidylethanolamine was lower in zinc deficient fetuses than in control groups, indicating a reduced production of pulmonary surfactant. The lecithin to sphingomyelin ratio of amniotic fluid was lower in zinc deficient rats than in controls on days 19, 20, and 21 of gestation. On days 18 through 21 of gestation, fetal lung DNA concentration in zinc deficient fetuses was lower than in controls, but there were no differences in fetal lung zinc concentration. Histological examination of lungs from zinc deficient fetuses at term showed air spaces that were slightly collapsed with smaller lumina of the alveolar ducts than in controls.     

Suppression of arousal by progesterone in fetal sheep

The high rate of progesterone synthesis by the placenta in late gestation exposes the ovine fetus to high concentrations of progesterone and its metabolites that may affect activity of the fetal brain. The aim of this study was to determine the effect of inhibiting maternal progesterone synthesis on sleep-wake activity in fetal sheep. Fetal and maternal vascular catheters, a fetal tracheal catheter, and electrodes for recording fetal electrocortical (ECoG), electro-ocular (EOG) and nuchal muscle electromyographic (EMG) activity were implanted. At 128-131 days gestation, progesterone production was inhibited by an injection of trilostane (50 mg), a 3beta-hydroxysteroid dehydrogenase inhibitor. Vehicle solution or progesterone (3 mg h(-1)) was then infused into the ewe between 6 and 12 h after the trilostane treatment. Maternal progesterone concentrations were significantly reduced from 1-24 h after trilostane treatment (P < 0.05) when followed by vehicle infusion. Fetal breathing movements (FBM), EOG, nuchal muscle EMG, and behavioural arousal increased 12 h after trilostane treatment (P < 0.05). In contrast, there was no change in fetal arousal, EOG, EMG or FBM activities when progesterone was infused after the trilostane treatment. These findings show that progesterone can influence fetal behaviour, and indicates that normal progesterone production tonically suppresses arousal, or wakefulness in the fetus.     

Asparaginylendopeptidase: an enzyme probably responsible to post-translational proteolysis and transpeptidation of proconcanavalin A

Nineteen ewes were injected subcutaneously with the agent of enzootic ovine abortion, Chlamydia psittaci serovar 1, at 50 days gestation. Placental and fetal tissues were examined at 15 days postinfection and thereafter at ten day intervals. Placental infection was detected at 15 days postinfection. Only postinoculation sera collected from postinfected ewes contained antibodies reactive to C. psittaci. Five (26%) chlamydial infected ewes experienced inapparent fetal loss before day 105 of gestation. This finding is significant since C. psittaci infection in sheep is commonly associated with abortion and not infertility.