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Biomedical subjects

B Colenbrander

Publications and source records attributed to B Colenbrander.

At least 73 records · Page 4Linked to original sources

Effects of adrenergic agonists and antagonists on the blood pressure and heart rate of the pig fetus.

The effects of adrenergic agonists and antagonists on blood pressure and heart rate were investigated in 18 chronically catheterised pig fetuses aged between 102 and 109 days of gestation (term is 114 days). One fetus had been decapitated in utero at 42 days of gestation. The alpha adrenergic agonist methoxamine produced a small but dose dependent hypertension and a dose related slowing in heart rate. The beta adrenergic agonist isoprenaline decreased mean arterial pressure in a dose related manner and produced tachycardia. Propranolol, a beta adrenergic blocker, increased mean arterial pressure and decreased heart rate. The response to subsequent alpha adrenergic blockade with phentolamine was hypotension and a slight bradycardia. Decapitation at 42 days of gestation did not seem to change the fetal responsiveness to adrenergic agonists but removed the blood pressure response to beta blockade. These observations indicate that the heart and circulation of the pig fetus are under adrenergic vasomotor control during late gestation.

Adrenergic Agonists

Cytoplasmic filaments in fetal and neonatal pig testis.

Leydig cells in developing fetal pig testis contained during the fetal regressive phase large accumulations of intermediate filaments. Before and after this period these filaments were arranged in a criss-cross fashion. In the pig as well as in the dog testis these filaments have been characterized as vimentin. Within the vimentin aggregates occasionally a weak positive actin reaction was seen in pig but not in dog Leydig cells. Microfilaments were hardly observed. Most Sertoli cells contained a layer of actin microfilaments close to the basal cell membrane. In the lower cell compartment and around the nucleus (intermediate) vimentin filaments could be observed in a criss-cross configuration.

Aging

Development of nervous tissue in the heart of the fetal and neonatal pig and the effect of decapitation in utero.

The development and distribution of the nerves in the heart of the pig was studied macroscopically and by light microscopy. Hearts were collected from 86 fetuses between 31 and 114 days of gestation (term = 114 days), from 12 neonatal pigs aged 9 and 20 days and from 6 adult sows of the Dutch Landrace breed. The effect of vagotomy produced by decapitation in utero at 40-43 days was studied in an additional 24 hearts from fetuses aged between 51 and 114 days of gestation. The amount of acetyl-thiocholine reactive fibres increases in the atria, A-V node and ventricles throughout gestation. At every age the amount of nervous tissue is highest in the A-V node and lowest in the ventricles. Hearts from decapitated fetuses have smaller amounts of nerve tissue than those from intact fetuses at every age studied. Ganglia are present in both intact and decapitated fetuses. Fluorescent cells containing catecholamines are observed in hearts from fetuses as young as 35 days gestation. Although fluorescent nerve fibres are rarely seen in hearts at 70 days gestation, more fibres are present near birth and thereafter there appears to be a considerable increase in the number of fibres and in the intensity with which they fluoresce. These results show that there is substantial nerve growth into the heart of the pig during gestation and that catecholamine containing nerve fibres develop later than those reactive to acetyl-thiocholine.

Animals

The effects of gestational age and chronic fetal decapitation on arterial blood pressure in the pig fetus.

Blood pressure was measured in anaesthetized pig fetuses decapitated at 40-43 days of gestation and in intact fetuses between 35 and 112 days of gestation (term is 114 days). In the intact fetuses arterial blood pressure increased significantly from 0.8 +/- 0.1 kPa (mean +/- SEM) at 35 days to 5.8 +/- 0.2 kPa at 112 days (P less than 0.05). The arterial blood pressure of decapitated fetuses was similar to that of intact fetuses at 70 days of gestation (2.7 +/- 0.4 kPa vs. 2.5 +/- 0.1 kPa, respectively) but did not change with increasing gestational age thereafter. Hence in late gestation (greater than 90-100 days) the arterial blood pressure of the decapitated fetuses was significantly less than that of intact fetuses (P less than 0.05). These observations demonstrate that the control of blood pressure in the pig varies with gestational age and suggest that the developmental changes occurring after about 100 days gestation require tissues within the head.

Animals

Ovarian development in control and decapitated pig fetuses.

Ovarian development was studied in control and decapitated pig fetuses. Fetuses were decapitated at 42 days postcoitum. At 51, 61, 74, 90 and 112 days postcoitum decapitated and control females were collected. Ovarian weight gradually increased during development in control animals. Deprivation of pituitary hormones as a result of fetal decapitation did not cause a decline in ovarian weight increase. Germ cell maturation in control and decapitated fetuses proceeded in a similar fashion, with secondary follicles being the most advanced stage. Enzyme histochemical activity was present in the primary interstitial gland cells and in granulosa cells and was similar in normal and decapitated fetuses. Both NADH diaphorase activity and 3 beta-hydroxysteroid dehydrogenase activity increased from 51 to 74 days and remained relatively constant thereafter. Since fetal decapitation in the pig hardly influences ovarian development, pituitary dependency of the fetal ovary in the pig is unlikely.

3-Hydroxysteroid Dehydrogenases

Lack of effect of chronic hyperinsulinaemia on growth and body composition in the fetal pig.

Chronic hyperinsulinaemia in the presence of euglycaemia was obtained in pig fetuses using implanted osmotic minipumps to deliver 3 U of insulin per day over 14 days (90-104 days gestational age); term is 114 days. Total body growth (length and weight) was unaffected by insulin administration, although some changes in organ weights were observed. There was a significant retardation of lung growth (apparently as a result of operative stress) and, in the insulin-treated fetuses, an increase in liver weight which was attributable to enhanced glycogen deposition. Two of the insulin-treated fetuses appeared to have an increase in subcutaneous fat at delivery, but overall there was no statistically significant change in body fat, water, or protein content of the carcases. Growth hormone levels in all the fetuses were high, but there were no differences between treatment groups. Bioassayable plasma somatomedin activity was increased in the insulin-treated fetuses. It is proposed that this increase may be a result of insulin-induced enhancement of liver growth hormone receptors. From these data we conclude that a 14-day period of hyperinsulinaemia towards the end of gestation does not stimulate growth of the pig fetus despite producing an increase in somatomedin activity. The growth enhancement seen in offspring from diabetic mothers is probably due to increased nutrient availability rather than a direct effect of fetal insulin. Insulin does, however, significantly increase glycogen deposition in the fetus.

Adipose Tissue

Glucose, growth hormone, somatomedin, cortisol and ACTH changes in the plasma of unanaesthetised pig foetuses following intravenous insulin administration in utero.

Insulin tolerance tests were carried out in chronically catheterised foetal pigs. The experiment was carried out 7 days after catheterisation. The foetuses were, therefore, considered to be free from the effects of anaesthetics and stress. Under these conditions growth hormone levels were high compared with post-natal growth hormone levels but, under the favourable conditions in this study, both growth hormone and ACTH levels were lower than those found in anaesthetised or stressed foetuses. By contrast, cortisol levels were somewhat higher than those mentioned in previous reports. Somatomedin activity measured by post-natal cartilage bioassay was low. Following iv insulin administration there was a marked depression in plasma glucose (P less than 0.01), an elevation in growth hormone (P less than 0.05) and an increase in ACTH (P less than 0.01). Levels of cortisol and somatomedins did not change significantly. From these data it is concluded that insulin is an hypoglycaemic factor in the foetal pig and that, for the most part, the foetal pig pituitary responds to an insulin challenge in a similar way to the post-natal pig.

Adrenocorticotropic Hormone

Somatomedin activity and growth hormone levels in body fluids of the fetal pig: effect of chronic hyperinsulinaemia.

Chronic hyperinsulinaemia in the presence of euglycaemia was obtained in pig fetuses between 90 and 104 days gestational age (term is 114 days) by the implantation of insulin-filled osmotic minipumps. At 104 days these fetuses were compared with both saline-implanted controls and with unoperated fetuses from the same sows. Mean plasma GH levels were the same in all three treatment groups and were much greater than in the maternal peripheral venous circulation. Levels of GH in amniotic fluid were low, and even lower levels were measured in lung fluid. Glucose and protein levels were also lower in amniotic fluid than in plasma and lower still in lung fluid. In contrast, somatomedin activity was higher in amniotic and lung fluids than in fetal plasma and, when expressed relative to protein content, was highest in lung fluid. Insulin-treated fetuses had significantly (P less than 0.05) higher levels of somatomedin activity than control fetuses, but despite this were neither longer nor heavier than control fetuses. From these data it is concluded that neither insulin nor somatomedin directly affect fetal growth.

Amniotic Fluid

Morphological development of the thyroid gland and serum T4-concentration in the intact and decapitated pig fetus.

The morphological and functional development of the fetal pig thyroid gland between 50 and 110 days post coitum have been examined in the normal pig fetus and after fetal decapitation at 42 days postcoitum. Body length and body weight developed at the same rate, comparing control and decapitated animals. Thyroid gland weight increased between 50 days and 110 days from 1.3 +/- 0.5 mg (SD) to 130.0 +/- 35.0 mg in control fetuses and from 0.9 +/- 0.2 mg to 113.4 +/- 23.0 mg in decapitated fetuses. A number of histomorphometrical parameters in thyroid tissue were measured. No significant differences in follicular epithelial height were observed between decapitated and control animals at 75 and 110 days. In control animals follicles increased both in size and number. In decapitated animals the follicles increased strikingly in number, but only slightly in size. Although colloid was formed in glands of decapitated animals, it was much less than in control fetuses. The gland of decapitated animals of 110 days resembled histologically the gland of much younger control animals (60 to 75 days). Gland development after fetal decapitation at 42 days may represent autonomous development when Thyroid Stimulating Hormone (TSH) is depleted. Serum thyroxine concentration (T4) was determined by radioimmunoassay and increased in control animals from 0.06 +/- 0.01 micrograms/100 ml to 4.18 +/- 0.87 micrograms/100 ml at 110 days, the greatest rate of increase being observed between 64 and 90 days. In decapitated fetuses serum T4 remained very low, namely less than 0.20 micrograms/100 ml. It is very unlikely that any significant transfer of T4 from mother to fetus or from one fetus to another occurred. Both the rise in serum T4 and the enlargement of the follicles may be TSH dependent events in fetal pig thyroid gland development, whereby the sudden rise is serum T4 precedes the greatest rate of increase in follicle size.

Animals

Leydig cell development of pig testis in the early fetal period: an ultrastructural study.

Leydig cell development in the pig testis occurs in three periods (an early fetal, the perinatal period, and the period from puberty onward). The earliest of these periods was investigated ultrastructurally. The early fetal period starts immediately after gonadal differentiation, approximately 27 days postcoitum (p.c.), and finishes at about 60 days postcoitum. Dates of observation were 35, 52, and 62 days p.c. At 42 days p.c. some animals were decapitated. Leydig cells at 35 days p.c. are characterized by an oval nucleus, vesicular or branched tubular smooth endoplasmic reticulum (SER), and a small quantity of rough endoplasmic reticulum (RER). The RER has two forms: a short and a long profile. The latter is closely coupled with mitochondria. The mitochondria mostly have tubular cristae. From 52 days p.c. onward the degree of coupling lessens, and it vanishes at 62 days p.c. At 52 and 62 days p.c. a very large amount of 10 nm filaments and a slight decrease in SER can be observed. The SER now has a branched tubular form, and the presence of polygonal dense bodies is also characteristic. Decapitation does not disturb normal development of the Leydig cells in the observation period. No obvious differences from controls can be observed.

Animals

Changes in serum FSH concentrations in the pig during development.

Serum FSH concentrations were measured in fetal and prepubertal pigs between 40 days postcoitum and 25 weeks after birth. In addition, serum FSH was estimated in prepubertal, unilaterally cryptorchid, freemartin and castrated pigs. The average serum FSH concentrations in male and female fetuses was low (less than 2 ng/ml) until 80 days p.c. During the remaining fetal period, concentrations in females were elevated (7.9 +/- 0.4 ng/ml) and remained fairly constant after birth (16.3 +/- 0.8 ng/ml). In the male, serum FSH concentrations gradually rose to 22.5 +/- 5.5 ng/ml during the first 3 weeks after birth and declined thereafter. The changes in FSH concentrations in male pigs are reflected in gonadal-development. In contrast, in fetal and prepubertal females, ovarian development seems not to be influenced by changes in serum FSH concentrations. Unilateral cryptorchidism did not affect serum FSH concentrations. After castration, however, concentrations rose significantly. In freemartin pigs concentrations were similar to those in female pigs.

Animals

Response of luteinizing hormone and follicle-stimulating hormone to luteinizing hormone releasing hormone in the fetal pig.

The responses of anesthetised fetal pigs (n=95) and chronically catheterized fetal pigs (n=10) to luteinizing hormone releasing hormone (LHRH) administration (2 micrograms/kg estimated fetal body weight) was investigated. Fetuses were studied at 55, 70, 85, 100, 106 (chronic) and 113 days. Plasma concentrations of follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were measured by radioimmunoassay. Blood samples were taken from the umbilical artery (anesthetised fetuses) or carotid artery (catheterized fetuses) every 10 min for 1 h except in the youngest age group. No significant sex difference in the LH response to LHRH treatment was observed. The LH response increased with gestational age; average pretreatment plasma concentrations were below 1.1 ng/ml. No response was observed at 55 days, and the highest response was seen at 113 days when plasma LH concentrations rose to 4.3 +/- 0.7 (mean +/- SEM) ng/ml 40 min after treatment. Pretreatment plasma FSH concentrations at 55 days were 1.6 +/- 0.1 ng/ml and gradually rose in males to 3.2 +/- 0.4 ng/ml at 113 days, which was significantly lower than in females where concentrations averaged 8.1 +/- 2.0 ng/ml. LHRH did not significantly affect FSH concentrations in males, while in females a gradually increasing response was observed; at 113 days plasma FSH was 12.5 +/- 2.9 ng/ml 40 min after treatment. The increase in response to LHRH with age of plasma LH concentrations in both sexes, and of plasma FSH concentrations in females indicates the maturation of the hypothalamo-pituitary system.

Animals

Renal response to hypotonic saline load in fetal and new-born pigs.

Kidney function has been studied in pig fetuses (105-109 d of gestation) and neonates (5-7 d old). Urine was collected by catheterization of the ureter. Inulin clearance, the excretion of electrolytes and the osmolality of urine and plasma were measured. In addition the response of the fetal neurohypophysis and fetal and neonatal kidney to a reduction of plasma osmolality was studied. The results show that the inulin clearance increases rapidly in the perinatal period, at a rate greater than would be expected from the gain in body weight. The re-absorption of Na and K is well developed. The fractional sodium excretion in fetuses is 2% and is 0.1% in the new-borns. The urine osmolality is high, probably due to high plasma lysine vasopressin levels persisting throughout the experiment. The infusion of hypotonic saline results in a significant decrease of plasma osmolality but only three out of nineteen animals showed an increase in urine flow. Although lysine vasopressin concentrations fell in some animals the urine stayed hyperosmotic as compared with plasma. The results show that fetuses and neonates may react to volume load but in the conditions of these experiments that regulation of plasma osmolality was inadequate.

Animals

Changes in serum testosterone concentrations in the male pig during development.

Serum testosterone concentrations were elevated between 40 and 60 days p.c. but were low between 60 and 100 days p.c. when the testis descends. Elevated concentrations occurred in the perinatal period and from the 18th week after birth. Between 60 days p.c. and 16 weeks after birth the changes in serum testosterone concentrations parallel those of testicular development, as determined by morphology and steroid histochemistry, and peripheral LH concentrations.

Animals

Gonadotrophic hormones and testicular descent.

The effect of fetal decapitation on gubernacular development and testicular descent was studied in the pig. Gubernacular development was unaffected and testicular descent occurred normally in decapitated fetuses. Neither testicular descent nor gubernacular development could be induced by HCG or LH-RH, administered to naturally unilateral cryptorchid prepuberal pigs in doses comparable to those used in human therapy. Gubernacular development and, subsequently, testicular descent seem to be independent of gonadotrophic stimulation.

Animals