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PubMed2003

Cellular immune response of fetuses to cytomegalovirus.

Primary infection with cytomegalovirus (CMV) in immunocompetent hosts is accompanied with activation and differentiation of naive CD8(+) T cells to effector/memory cells secreting interferon-gamma (IFN-gamma). Alteration of these responses during the perinatal period is suggested by a higher rate of CMV diseases in congenital infection. For addressing this issue, immunologic investigations were performed in 15 fetuses (22-36 wk of gestation) with documented congenital CMV infection. Results show that cellular immune responses can be detected as soon as the 22nd week of gestation (the youngest fetus analyzed). Compared with age-matched control subjects, infected fetuses evidence a dramatic increase in the percentages of activated and terminally differentiated CD8 T cells. Indeed, median percentages (interquartile range) of HLA-DR(+) and of CD28(-)CD8(+) T cells were 24% (19-34) and 38% (24-52), respectively in infected fetuses versus 3% (0-4) for each subset in control subjects. In addition, the percentages of T cells secreting IFN-gamma after in vitro stimulation with phorbol myristate acetate and ionomycin was significantly higher in infected fetuses [10% (5-25)] than in healthy fetuses [0.8% (0.6-1.2)] with IFN-gamma being mostly secreted by CD8(+) T cells and to a lesser extend by CD4(+) T cells. These cellular immune responses have clear similarities with responses previously reported in adults. Cellular immunity to CMV, however, might not be fully functional in fetuses. Indeed, the number of T cells capable of secreting IFN-gamma is strikingly lower after in vitro stimulation with the CMV-specific antigen than after in vitro stimulation with phorbol myristate acetate/ionomycin that bypasses signaling through the T-cell receptor.

Antigens, Viral↗
PubMed2006

Differential effects of maternal dexamethasone treatment on circulating thyroid hormone concentrations and tissue deiodinase activity in the pregnant ewe and fetus.

Clinically, treatment of pregnant women at risk of preterm delivery with synthetic glucocorticoids accelerates fetal maturation. This study investigated the effect of maternal dexamethasone treatment, in clinically relevant doses, on plasma thyroid hormone concentrations and tissue deiodinase activities (D1, D2, and D3) in ewes and their fetuses. From 125 d of gestation (term 145 +/- 2 d), pregnant ewes were injected twice im with either saline (2 ml of 0.9% NaCl, n = 11) or dexamethasone (2 x 12 mg in 2 ml of saline, n = 10) at 24-h intervals. Maternal dexamethasone treatment increased plasma T(3) and reverse T(3) (rT(3)), but not T(4), concentrations in the fetuses. In the dexamethasone-exposed fetuses, hepatic D1 activity was higher, and renal and placental D3 activities were lower, than in the saline-exposed fetuses. In the ewes, plasma concentrations of T(3) and T(4) were reduced, and rT(3) increased, by dexamethasone treatment without any change in tissue deiodinase activity. Therefore, maternal dexamethasone treatment has different effects on the thyroid hormone axis of the pregnant ewe and fetus. In the fetus, the dexamethasone-induced rise in circulating T(3) may be due to both increased hepatic production of T(3) from T(4), and reduced clearance of T(3) by the kidney and placenta. Changes in T(3) bioavailability may mediate some of the maturational effects of antenatal glucocorticoid treatment in the preterm fetus.

Animals↗
PubMed1980

Plasma testosterone and progesterone titers of pregnant rats, their male and female fetuses, and neonatal offspring.

Testosterone and progesterone titers were determined by RIA in the plasma of pregnant rats and their male and female fetuses from day 17 of gestation through the day of birth and in male and female neonates on days 3 and 5 post partum. Males had significantly higher mean testosterone levels than females from day 18 of gestation through day 5 post partum. Sex differences in plasma testosterone concentrations were greatest in the fetuses on days 18 and 19 of gestation when testosterone levels peaked in the males. Instances in which female fetuses had testosterone titers equal to or greater than their male littermates were found on every day of gestation except day 18. Mean testosterone concentrations in plasma of female fetuses were high throughout gestation (greater than 1000 pcg/ml). Testosterone concentrations decreased in both sexes after birth. Differences between the sexes remained significant, and although there was an overlap in the values for males and females, testosterone concentrations in females exceeded those of their male littermates in only one out of nine pairs of samples on day 5 and in none of seven pairs on day 3 post partum. There were no significant differences in progesterone levels in plasma of males and females, either pre- or postnatally. Progesterone titers changed as a function of days post conception in both the fetuses and their mothers. In the fetuses, progesterone levels declined progressively from day 18 post conception through the day of birth, while in the mother they rose from days 18 to 19 then declined between days 20 and 21 of pregnancy. Fetuses had lower progesterone titers than their mothers. From these data, we conclude that day 18 and possibly day 19 post conception represent a critical period during which the central nervous system of the male is primed by high levels of testosterone. Thereafter, the process of masculinization is completed by exposure to testosterone levels that are relatively low and need not be consistently higher than those of female littermates.

Aging↗
PubMed1983

Hormone ontogeny in the ovine fetus: XIV. The effect of 17 beta-estradiol infusion on fetal plasma gonadotropins and prolactin and the maturation of sex steroid-dependent negative feedback.

17 beta-Estradiol (E2; 100 micrograms/kg X day) was infused iv for 6 days into three chronically catheterized ovine fetuses beginning at 105-106 days of gestation (term, 147 days) and into four younger fetuses for 3 days commencing at 87-92 days. Control studies were performed on three fetuses at each age. At 90 days, E2 had no effect on the basal concentration of either LH or FSH. In both control and E2-infused fetuses, repeated LHRH testing was associated with a decreased LH response, but the decrease was not greater in the E2-infused fetuses. The FSH response was unaffected in either group. At 105 days, E2 caused suppression of the mean basal concentration of plasma LH from 1.2 +/- 0.1 to 0.1 +/- 0.1 ng/ml (P less than 0.01) and of basal FSH from 5.6 +/- 0.5 to 3.3 +/- 0.6 ng/ml (P less than 0.05). The LH response to LHRH administration (50-micrograms iv bolus) also was suppressed by E2. The maximal incremental LH response fell from 7.1 +/- 0.4 to 3.3 +/- 0.5 ng/ml (P less than 0.01); the integrated response decreased from 5.8 +/- 0.2 to 1.8 +/- 0.2 ng/ml X h (P less than 0.01). However, no effect was observed on the rise in FSH concentration evoked by LHRH. In control studies at 105 days, basal and LHRH-stimulated gonadotropin concentrations remained constant during the experiment. These results indicate that the capacity for exogenous E2 to suppress fetal pituitary gonadotropin secretion in the ovine fetus develops between 90 and 105 days of gestation, before the normal ontogenic decrease both in the basal concentration of fetal pituitary gonadotropins and in LHRH-stimulated FSH and LH secretion, which occur later in gestation. We suggest that the development of the E2-sensitive negative feedback mechanism in the fetal hypothalamic-pituitary unit is a major factor in this decrease. At 90 days gestational age, the mean fetal plasma concentration of PRL was not affected by the infusion of E2 into the fetus (5.9 +/- 1.5 ng/ml before E2 infusion 8.1 +/- 3.2 ng/ml during E2 infusion). However, at 105 days, the mean PRL concentration rose from 49.3 +/- 18.2 to 101.6 +/- 26.1 ng/ml (P less than 0.01) after the infusion of E2. The capacity for E2 to stimulate PRL release develops in parallel with the rise in fetal plasma PRL and estrogen concentrations. The results provide evidence that circulating estrogens are a determinant of fetal PRL concentrations in late gestation.

Animals↗
PubMed1985

Hormone ontogeny in the ovine fetus. XVIII. The effect of an opioid antagonist on luteinizing hormone secretion.

Endogenous opioid-like peptides influence gonadotropin release in adult animals and man; however, the role of these peptides in the regulation of fetal LH secretion is not known. We administered naloxone hydrochloride (1.3 mg/kg iv), a specific opioid receptor antagonist, to 22 chronically catheterized ovine fetuses of gestational ages 94-143 days (term = 147 days). As a control, each fetus also received the vehicle on a separate occasion, the sequence of the studies being randomized. After the administration of naloxone, LH secretion increased from 38.6 +/- 5.8 to 114 +/- 21 ng/h ml-1 (P less than 0.001); LH release was not affected by administration of the vehicle. Morphine (13 mg/kg) and naloxone (1.3 mg/kg) were administered together to three fetuses (gestational age 94-105 days); LH secretion was sharply reduced from 411 +/- 14.3 ng/h ml-1 after naloxone alone to 53 +/- 17.5 ng/h ml-1 after the administration of both naloxone and morphine (P less than 0.01). The response to naloxone varied with gestational age. Fetuses of 94-115 days showed a significantly higher increment in LH secretion when given naloxone (112.3 +/- 30.7 ng/h ml-1) than did older fetuses of gestational age 126-143 days (64.8 +/- 20.8 ng/h ml-1) (P less than 0.02). These findings indicate that, in the ovine fetus endogenous opioid-like peptides exert a tonic suppressive effect on LH secretion at least as early as 94 days gestation. Moreover, the effectiveness of naloxone in augmenting LH release decreases with advancing gestational age. This latter observation supports the concept that, in the ovine fetus, endogenous opioid tone is not the sole factor involved in the dampened fetal LH secretion which is characteristic of late gestation.

Animals↗
PubMed1986

Androstenedione metabolism in the late gestation sheep fetus.

We have determined metabolic parameters for androstenedione (A) in chronically catheterized late gestation (day 130) sheep fetuses. The MCR (MCRA) was 3210 +/- 229 (SEM, n = 12) ml/min, the fetal arterial whole blood concentration of A [A] was 65 +/- 5 pg/ml, and the blood production rate (PRA) was 204 +/- 20 ng/min. Pulsatile administration of ACTH in amounts that raised fetal arterial plasma cortisol concentrations by 5- to 7-fold increased [A] to 154 +/- 20 pg/ml and PRA to 471 +/- 31 ng/min with no change in MCRA. In the presence of metopirone to block fetal adrenal cortisol output, ACTH treatment still provoked elevations in [A] (to 198 +/- 23 pg/ml) and PRA (539 +/- 158 ng/min), without altering MCRA. The major radiolabeled product in blood of infused [3H]A was [3H]testosterone; smaller amounts of phenolic steroids were formed. Extensive metabolism of [3H]A occurred in whole blood in vitro. The major product was [3H]testosterone; the 17-oxidoreductase activity was associated with the red blood cells. Umbilical vein [A] was greater than umbilical artery [A]; ACTH treatment increased [A] in both vessels. Concomitant metopirone abolished the arteriovenous difference by eliminating the ACTH-induced increase in venous [A], although arterial [A] rose significantly. The venous [A] and the arteriovenous gradient were restored with exogenous glucocorticoid treatment to the fetus. Collagenase-dispersed fetal adrenal cells secreted A. Adrenal cells from fetuses pretreated with ACTH in vivo had higher basal and ACTH-induced output of A in vitro than cells from fetuses pretreated with saline in vivo. We conclude that the MCRA in fetal sheep is extremely high, in part due to conversion of A to testosterone in fetal blood. The elevated PRA after ACTH plus metopirone and the lack of an umbilical arteriovenous gradient of [A] in this, but not other groups of fetuses, suggests a source of A production independent of the cortisol-induced changes in the placenta. Direct evidence is provided for fetal adrenal secretion of A which is enhanced by ACTH pretreatment of the fetus in vivo and for the utilization of circulating A in the fetus as a precursor for estrogen in both fetal and maternal compartments.

Adrenal Glands↗
PubMed1989

Hormone ontogeny in the ovine fetus and neonatal lamb. XX. Effect of age, breeding season, and twinning on the growth hormone (GH) response to GH-releasing factor: evidence for a homeostatic role of fetal GH.

The ovine GH (oGH) response to GRF (1-44 amide) was evaluated in 74 chronically catheterized fetal and neonatal lambs. After a 1-h control period, GRF was administered iv, and the oGH response was studied during the next 60 min. The following variables were analyzed: GRF dose, fetal or neonatal age, breeding season, and singleton or multiple pregnancy. One and 10 micrograms/kg GRF elicited a similar oGH response, which was greater (P less than 0.001) than the response to 0.1 microgram/kg GRF. GRF-stimulated oGH release was strikingly age dependent. The mean peak incremental oGH response in fetuses of 89-122 days gestation (294 +/- 55 ng/ml) was higher (P less than 0.05) than that in fetuses of 127-145 days gestation (136 +/- 19 ng/ml); the fetal response was much greater (P less than 0.005) than the mean peak increment in neonatal lambs (46 +/- 7 ng/ml). A remarkable difference in basal and GRF-induced oGH secretion was observed in both fetuses and lambs of ewes bred in the normal breeding season (on-season) and those bred out of season (off-season). In the neonatal lamb, the mean basal oGH concentration was higher (P less than 0.005) in the on-season (12 +/- 2 ng/ml) than in the off-season (7 +/- 0.5 ng/ml) neonatal lambs, as was the mean peak incremental oGH response to GRF (70 +/- 12 vs. 33 +/- 7 ng/ml; P less than 0.01). In contrast, in singleton, late gestational fetuses (127-145 days), the mean basal oGH concentration was lower (P less than 0.03) in the on-season (74 +/- 9 ng/ml) than in the off-season (124 +/- 18 ng/ml) fetuses, as was the mean peak incremental oGH response to GRF (136 +/- 9 vs. 292 +/- 41 ng/ml; P less than 0.005). Further, compared to the on-season, late gestational singletons, on-season twin fetuses had higher (P less than 0.0001) basal oGH levels (199 +/- 19 ng/ml) and peak incremental oGH responses (248 +/- 11 ng/ml). Moreover, off-season twin fetuses had the highest basal GH concentrations and the most striking increment in GH concentration after GRF treatment of any of the groups. The strikingly age-dependent pattern of the GRF-induced oGH response in fetal and neonatal lambs is compatible with the concept that the inhibitory influences or their effects on the somatotrope increase gradually during late gestation and sharply at birth.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed1989

Effect of estrogen on pituitary peptide-induced dehydroepiandrosterone secretion in the baboon fetus at midgestation.

We have previously shown that ACTH and PRL stimulate baboon fetal adrenal dehydroepiandrosterone (DHA) production both in vitro and in vivo and that estrogen diminishes the responsivity of the adrenal to tropic peptides in vitro. In the present study we determined the effects of increasing placental estrogen production by the administration of androstenedione at midgestation on DHA production by the baboon fetus in vivo. Pregnant baboons were untreated (n = 8) or treated (n = 9) with increasing numbers of androstenedione implants inserted in the mother at 8-day intervals between days 70-100 of gestation (term = day 184). On day 100, the fetuses were exteriorized, and a constant infusion of saline (0.1 ml/min) was initiated via a catheter inserted into a femoral vein of the fetus. At 40 min, a bolus injection of either 30 nmol ACTH or 40 nmol ovine PRL was administered to fetuses. ACTH or PRL (0.2 nmol/min.0.1 ml saline) were then infused for an additional 25 min. The concentrations of serum estradiol (E2) in the uterine vein (20.2 +/- 1.5 ng/ml; mean +/- SE) and estrone (E1) in umbilical vein (11.9 +/- 3.1 ng/ml) of androstenedione-treated baboons were 2-fold greater (P less than 0.05) than respective values in untreated baboons. Baseline concentrations of DHA in the femoral vein of the fetus were similar in all treatment groups (overall mean, 120 +/- 20 ng/ml) and greater (P less than 0.05) than values (27 +/- 3) in the mother. In untreated control baboons, basal DHA concentrations in the fetus were increased (P less than 0.05) by 69 +/- 17% and 94 +/- 29% after fetal injection of ACTH (n = 4) or PRL (n = 4), respectively. In contrast, neither PRL (n = 5) nor ACTH (n = 4) had any effect on serum DHA when injected into androstenedione-treated baboons. Regardless of treatment, injection of ACTH or PRL into the fetus had no effect on DHA concentrations in the mother. Collectively, these findings indicate that the ability of the fetal adrenal to increase DHA production in response to an acute infusion of ACTH or PRL was abolished in baboons in which placental estrogen production was increased prematurely at midgestation. Therefore, we suggest that during the second half of gestation in the baboon a regulatory system may exist in utero, in which there is feedback control of the placental product estrogen on the formation of the fetal adrenal precursor DHA.

Adrenocorticotropic Hormone↗
PubMed2006

Endocrine regulation of human fetal growth: the role of the mother, placenta, and fetus.

The environment in which the fetus develops is critical for its survival and long-term health. The regulation of normal human fetal growth involves many multidirectional interactions between the mother, placenta, and fetus. The mother supplies nutrients and oxygen to the fetus via the placenta. The fetus influences the provision of maternal nutrients via the placental production of hormones that regulate maternal metabolism. The placenta is the site of exchange between mother and fetus and regulates fetal growth via the production and metabolism of growth-regulating hormones such as IGFs and glucocorticoids. Adequate trophoblast invasion in early pregnancy and increased uteroplacental blood flow ensure sufficient growth of the uterus, placenta, and fetus. The placenta may respond to fetal endocrine signals to increase transport of maternal nutrients by growth of the placenta, by activation of transport systems, and by production of placental hormones to influence maternal physiology and even behavior. There are consequences of poor fetal growth both in the short term and long term, in the form of increased mortality and morbidity. Endocrine regulation of fetal growth involves interactions between the mother, placenta, and fetus, and these effects may program long-term physiology.

11-beta-Hydroxysteroid Dehydrogenases↗
PubMed1989

Development of an ultrasonic system for three-dimensional reconstruction of the fetus.

The ultrasonic diagnostic devices available at present can only represent one section of the fetus. We have developed a system for three-dimensional reconstruction of the ultrasonic fetal image in order to facilitate the understanding of the 3-D structure of the fetus and also to make 3-D recordings of this image. Either a real-time linear array probe or a convex array probe of the ultrasonic scanner was mounted on a position sensing arm of a manual compound scanner in order to detect the position of the probe. A microcomputer was used to convert the positional information to a recording of a visual image of videotape. This image was superimposed onto the ultrasonic tomographic image simultaneously using a superimposer and was recorded on the video tape, thereafter, being recalled by the image processing minicomputer. The minicomputer VAX11/780 (DEC) system was used for 3-D reconstruction and 3-D display. In the memory system the image of the anterior uterine wall was identified and subsequently excluded in order to visualise the fetus more clearly. The threshold of brightness was set to a high level so that the fetus could be separated from the amniotic fluid. The fetus was displayed three-dimensionally using computer graphics. Using this system, we have made it possible to observe the whole image of the fetus in utero non-invasively. This system offers a method for easier understanding of the 3-D structure of the fetus in utero and also makes 3-D recording possible. In the future, we confidently expect that this system will be used for screening for fetal anomalies and abnormalities of fetal growth.

Equipment Design↗
PubMed1996

Morphology of active sleep--quiet sleep transitions in normal human term fetuses.

Periods of no coincidence (PsNC) among state variables appear to be more predictive of neurobehavioral outcome than the amount of time spent in any particular behavioral state. It has recently been suggested that analysis of the ordering of state variables during a state transition may provide results equivalent to full state analysis. If this were the case, then there ought to be a relationship between the duration of PsNC and fetal heart rate (FHR)-fetal eye movement (FEM) sequencing at the time of a state change. To test this hypothesis, we compared full state analysis with analysis of individual state transitions for 52 normal human fetuses between 38 and 42 weeks of gestation. For the study population as a whole, FHR was the first variable to change in 62 (77%) of 81 1F-->2F transitions and FEM was the first variable to change in 50 (63%) of 79 2F-->1F transitions (chi 2 = 67.9, p < 0.001). Ordering of FHR and FEM at the time of a state change was reversed in 8 (67%) of 12 fetuses with PsNC > or = 15% and is only 6 (15%) of 40 fetuses with PsNC < 15% (chi 2 = 12.5, p < 0.001). We conclude that fetuses who exhibit poor state organization more often display a FHR-FEM sequence at the time of a state transition which is opposite that of fetuses with considerably better state control. However, since only one-third of fetuses with reversed FHR-FEM sequencing actually exhibited more than one such episode, it is unlikely that isolated analysis of state transitions will provide a reliable measure of behavioral state organization in the individual fetus.

Eye Movements↗
PubMed1992

Spacing of fetuses and local competition in strains of mice with large, medium and small litters.

The tendency for fetuses to be evenly spaced along the uterine horn and the relationship of this to local competition between fetuses was examined in three strains of mice which characteristically produce large, medium and small litters. Local competition was assessed by correlating, within each uterine horn, the weight of each fetus or placenta with the mean distance to its immediate neighbours. Weights and distances were measured on day 19 of gestation, on the day before expected parturition and distances only on day 7. Average litter sizes (live fetuses) were 16.3 +/- 0.9, 11.7 +/- 0.6 and 7.2 +/- 0.5 (mean +/- SEM) in the large, medium and small litter strains, respectively (n = 7, 7 and 10, respectively). On day 19, the mean distance between fetuses was significantly less (P < 0.05) in the large strain (10.1 +/- 1.0 mm) than in the medium (14.0 +/- 1.2 mm) or small (13.5 +/- 1.0 mm) strains. Evenness of spacing, expressed as the standard deviation of distances between fetuses divided by the mean distance, improved from day 7 to day 19 of gestation in all three strains and effectively prevented local competition between fetuses in the medium litter (r = 0.04) and small litter strains (r = 0.17), but not in the large litter strain (r = 0.45, P < 0.01). Thus, local crowding does not seem to be detrimental to fetal growth in mice, except in strains specifically bred for large litters.

Animals↗
PubMedDate not supplied

[Assess flow velocity in the ductus venosus and inferior vena cava in fetuses in isoimmunized pregnancies].

OBJECTIVE: Ductus venosus and inferior vena cava flow velocity was assessed in fetuses in isoimmunized pregnancies. METHODS: Examination of 61 fetuses aged 27 to 35 weeks from Rh-erythrocyte antigen isoimmunized women was carried out from June 1999 to June 2004. All fetuses were submitted to the examination of ductus venosus and inferior vena cava flow velocity. Blood samples were collected to determine hemoglobin values and hemoglobin concentration deficits. Accordingly, fetuses were grouped as follows: non-anemic; mildly anemic; moderately anemic and severely anemic fetuses. Comparison of the variation of average flow velocity in the inferior vena cava and ductus venosus across the four groups was carried out using the chi-square test. RESULTS: Inferior vena cava flow velocity was found to be altered in 3.8% of non-anemic fetuses; in 3.1% of the mildly anemic, in 40.0% of those moderately anemic; and in 76.0% of the severely anemic ones. Alteration in ductus venosus flow velocity, in turn, was identified in 7.7% of non-anemic fetuses; 3.1% of mildly anemic; 32.5% of moderately anemic and 68.0% of those severely anemic. Results were statistically significant with p < 0.001. CONCLUSION: The study shows that alteration of flow velocity in the inferior vena cava and ductus venosus increased with the severity of anemia.

Adult↗
PubMed2004

Abnormal vomer development in human fetuses with isolated cleft palate.

OBJECTIVE: The aim of this study was to elucidate the prenatal human development of the vomer with emphasis on the vomeral footplate and to assess vomeral morphology in fetuses with isolated cleft palate. MATERIAL AND METHODS: Nine human fetuses of which four were normal (menstrual age [MA] 13 to 21 weeks) and five with isolated cleft palate (14 to 19 weeks MA) were studied. Midaxial cranial tissue blocks from the fetuses were cut frontally in 4microm serial sections. Sections were stained with toluidine blue in 30% ethanol. RESULTS: From 16 weeks MA, the vomeral footplate of normal fetuses was formed from bilateral ossifications located below a U-shaped vomeral body. Later in development, an osseous connection was found between the footplate and the vomeral body. Neither bilateral areas of ossification below the vomer nor a vomeral footplate was observed in isolated cleft palate fetuses. CONCLUSIONS: In normal fetuses, the base or footplate of the vomeral bone appears from 16 weeks MA in frontal sections. In fetuses with isolated cleft palates, with no connection between the nasal septum and the maxillary processes, this vomeral footplate does not develop in the period observed (14 to 19 weeks MA).

Case-Control Studies↗
PubMed1992

Bioactive and immunoreactive FSH and immunoreactive inhibin concentrations in the ovine fetus.

The bioactive (B) and immunoreactive (I) pituitary contents/concentrations of FSH, together with the plasma concentrations of B-FSH, I-FSH and I-inhibin were determined in ovine fetuses at days 55, 75, 90 and 135 of gestation (day 145 = term). The pituitary contents and concentrations of B-FSH and I-FSH increased in both sexes with gestational age. The female fetuses had significantly (P < 0.01) higher pituitary contents/concentrations of B-FSH and I-FSH than the male fetuses at days 75 and 135. The pituitary B/I ratios of FSH were not significantly different with age or sex. The plasma concentrations of B-FSH remained relatively constant from days 75 to 135, with no significant differences between sexes or with age. In contrast, the plasma concentrations of I-FSH reached a peak at day 90 and then declined towards term in both sexes. At all gestational ages except day 55, the female fetuses had significantly (P < 0.05) higher plasma concentrations of I-FSH than the males. In both sexes, the plasma B/I ratios of FSH were lowest at day 90 and had increased again by day 135, with the male fetuses having significantly (P < 0.05) higher B/I ratios compared with the female group at days 75 and 135 but not at day 90. At all gestational ages, the plasma concentrations of I-inhibin declined throughout gestation in the female fetuses, whereas in the males they reached a nadir at day 75 and then increased towards term. The concentrations of I-inhibin were significantly (P < 0.01) higher in the male fetuses compared with the females.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1996

Median charge of gonadotrophin isoforms in the pituitary gland and in the circulation of sheep fetuses from mid- to late gestation.

The heterogeneity of LH and FSH in the sheep fetus was studied by determining the median charge of pituitary and circulating isoforms. Pituitary extracts from male and female fetuses at days 75, 95, 120 and 135 of gestation were subjected to agarose suspension electrophoresis. For all fetuses except the day 75 age group, the median mobility of the gonadotrophin isoforms in matching serum samples from the individual fetuses were also determined. LH and FSH in extracts, peripheral samples and column eluates were measured using sensitive and specific sandwich fluoroimmunoassays for ovine gonadotrophins. The median charge of pituitary LH became more basic (P < 0.001) with gestational age, whereas for pituitary FSH more acidic forms (P < 0.001) were present in the older groups. The female fetuses had more basic pituitary isoforms of LH than the males (P < 0.01) between days 95 and 135, and for FSH at day 75 (P < 0.05). In the matching serum samples, the median charge of the LH (P < 0.001) and FSH (P < 0.05) isoforms were more acidic than those in the pituitary gland. No significant effects of age or sex were detected in the median charge of the gonadotrophin isoforms in serum, but in a number of instances the median charge could not be determined due to low serum concentrations which affected the group sizes. These data show that in the sheep fetus LH and FSH are differentially regulated in qualitative as well as quantitative terms, and that the charge of fetal gonadotrophin isoforms changes according to the age and sex of the fetus.

Animals↗
PubMed1996

Pulsatile and diurnal secretion of GH and IGF-I in the chronically catheterized pig fetus.

The ontogeny of GH and IGF-I secretion was investigated in the fetal pig. Pulse studies were performed to describe the pattern of GH release. Twenty-four-hour profiles were recorded to examine possible diurnal variations in these hormones. (I) PULSE STUDIES: Blood samples were obtained at 15-min intervals for 2-h periods from 24 male and 20 female fetuses at various gestational ages (fetal day 89-113; term 113 +/- 1 S.D.). Fetuses revealed a pulsatile GH release. The GH pulse frequency did not vary with gestational age in either sex (0.95 +/- 0.19 pulses/h). In males the GH pulse amplitude decreased with increasing fetal age (r = -0.41; P < 0.02). In female fetuses no significant correlation could be calculated. Mean GH concentrations fell significantly in male fetuses 3 to 4 days before delivery (P < 0.05) and the same tendency was observed in females (P < 0.06). Between fetal days 94 and 98 GH pulse amplitude and GH and IGF-I concentrations were higher in males than in females (P < 0.01, P < 0.001 and P < 0.02 respectively). Fetal IGF-I secretion showed no ontogenetic changes in both sexes. However, maternal IGF-I concentrations increased with progressing gestation (r = 0.46; P < 0.001). (II) 24-H PROFILES: Eight male and four female late-gestational fetuses (fetal days 104-108) were studied. Blood samples were taken at 30-min intervals over 24 h. Dams and fetuses showed an episodic GH secretion over the 24-h period but no diurnal rhythm was observed. Whereas maternal IGF-I secretion was constant, fetal IGF-I release was characterized by marked fluctuations over the 24 h. In half of the fetuses (n = 6) the fluctuations appeared at regular intervals. Again no diurnal rhythm existed. These data demonstrated that: (1) porcine fetal GH secretion is pulsatile and decreases shortly before birth; (2) a sex difference in GH and IGF-I concentrations exists between fetal days 94 and 98, suggesting that IGF-I is at least partially under the control of GH before birth; (3) fetal GH and IGF-I secretion is episodic over 24 h, but does not vary diurnally; and (4) fetal and maternal GH and IGF-I secretion are regulated independently.

Animals↗
PubMed2000

The effect of intermittent umbilical cord occlusion on insulin-like growth factors and their binding proteins in preterm and near-term ovine fetuses.

Intermittent umbilical cord compression with resultant fetal hypoxia can have a negative impact on fetal growth and development. Insulin-like growth factors (IGFs) and their binding proteins (IGFBPs) are the most important regulators of fetal growth. In preterm (107-108 days of gestation) and near-term (128-131 days of gestation) ovine fetuses, we have determined the effect of intermittent umbilical cord occlusion (UCO) over a period of 4 days on the profile and expression of IGFs and IGFBPs. In experimental group animals (preterm n=7; near term n=7) UCOs were carried out by complete inflation of an occluder cuff (duration 90 s) every 30 min for 3-5 h each day, while control fetuses (preterm n=7; near term n=7) received no UCOs. Ewes were euthanized at the end of day 4, and fetal heart, lung, kidney, liver, skeletal muscle and placenta were collected. During UCOs, PO(2! ) fell (by approximately 13 mmHg), pH fell (by approximately 0.05) and PCO(2) increased (by approximately 7 mmHg), and changed to a similar extent in both preterm and near-term groups. In both preterm and near-term groups, there was no difference in fetal body or organ weight between UCO and control fetuses. No significant changes were observed in plasma IGF-I and -II concentrations or IGFBP-1, -2, -3 or -4 levels throughout the 4-day study at either gestational age. In the preterm group UCO fetuses, IGF-II mRNA (1.2-6.0 kb) levels were lower in fetal lung (33%, P<0.05), heart (54%, P<0.01) and skeletal muscle (29%, P<0.05), but there were no differences in IGF-I mRNA levels (7.3 kb); IGFBP-2 mRNA (1.5 kb) levels were lower in the right lobe of the liver (42%, P<0.05) and kidney (22%, P<0.01), but hig! her in the heart (72%, P<0.01), while IGFBP-4 (2.4 kb) levels were lower in skeletal muscle (21%, P<0.01). In the near-term group UCO fetuses, IGFBP-2 mRNA levels were greater in the placenta (39%, P<0.05). Thus, intermittent UCO as studied has a greater effect on the expression of genes encoding certain peptides of the fetal IGF system in selected tissues in preterm fetuses than that in near-term fetuses. Altered IGFBP-2 mRNA levels with reduced IGF-II mRNA levels in selected tissues may mediate changes in growth and/or differentiation that might become apparent if the length of the UCO study were extended.

Analysis of Variance↗