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PubMed1991

Computer simulation model of swine production systems: II. Modeling body composition and weight of female pigs, fetal development, milk production, and growth of suckling pigs.

Theoretical concepts and relationships used to develop a deterministic computer simulation model of female pigs during their reproductive life are described. The model predicts, in a continuous form, body composition and weight of female pigs, fetal development, sow milk yield, and growth of suckling pigs according to genotype, diet, and management conditions. The model simulates growth of adult female pigs. Dietary nutrients are used first for maintenance and second for fetal growth or milk production. Any surplus is retained in the body. Energy and protein body reserves are mobilized when a nutrient deficit occurs during gestation or lactation. However, the rates of body protein and fat accretion as well as the fat/protein ratio are limited by boundaries, the values of which depend on the nutritional and physiological status of the pig. The model's ability to simulate sow body weight changes and composition, fetal growth, milk production, and suckling pig's growth is illustrated.

Animals↗

PubMed1994

Human red cell Aquaporin CHIP. II. Expression during normal fetal development and in a novel form of congenital dyserythropoietic anemia.

Channel-forming integral protein (CHIP) is the archetypal member of the Aquaporin family of water channels. Delayed CHIP expression was shown recently in perinatal rat (Smith, B. L., R. Baumgarten, S. Nielsen, D. Raben, M. L. Zeidel, and P. Agre. 1993. J. Clin. Invest. 92:2035-2041); here we delineate the human patterns. Compared with adult, second and third trimester human fetal red cells had lower CHIP/spectrin ratios (0.72 +/- 0.12, 0.94 +/- 0.22 vs 1.18 +/- 0.11) and reduced osmotic water permeability (0.029, 0.026 vs 0.037 cm/s); CHIP was already present in human renal tubules by the second trimester. A patient with a novel form of congenital dyserythropoietic anemia (CDA) with persistent embryonic and fetal globins and absent red cell CD44 protein was studied because of reduced CHIP-associated Colton antigens. Novel CDA red cells contained < 10% of the normal level of CHIP and had remarkably low osmotic water permeability (< 0.01 cm/s), but no mutation was identified in Aquaporin-1, the gene encoding CHIP. These studies demonstrate: (a) unlike rat, human CHIP expression occurs early in fetal development; (b) red cell water channels are greatly reduced in a rare phenotype; and (c) disrupted expression of red cell CHIP and CD44 suggests an approach to the molecular defect in a novel form of CDA.

Adult↗

PubMed1995

Maternal dietary carbohydrate restriction and mild-to-moderate exercise during pregnancy modify aspects of fetal development in rats.

To determine whether acute bouts of exercise during pregnancy would predispose the fetus to increased risk if maternal dietary carbohydrate were restricted, untrained pregnant rats were randomly assigned to a 0% (low), 12% (moderate) or 60% (high) glucose diet, and either rested or exercised daily for 20 min from d 16 to term on a rodent treadmill at a mild (15.5 m/min) or moderate (24.3 m/min) intensity. A 3 x 3 nested factorial model with and without food intake as a covariate was employed. Both greater exercise intensity and the lower levels of dietary carbohydrate independently decreased term maternal liver and plantaris glycogen concentrations and increased plasma lactate concentrations. However, significant differences due to exercise disappeared (except for plasma lactate) with food intake controlled for in the model, indicating that energy deficits modulated these exercise effects. In contrast, for the offspring, when food intake was controlled for, a restricted level of maternal dietary carbohydrate significantly lowered fetal weight, plasma glucose and insulin concentrations and liver glycogen concentrations measured at term. Exercise alone did not reduce mean fetal weight if nested weights within a litter were used in the statistical analysis. Mild to moderate maternal exercise lowered only fetal plasma glucose concentrations and only if maternal food intake was not controlled for. These results indicate that acute exercise during pregnancy can have detrimental effects on fetal development only if dietary glucose is severely restricted. Otherwise, adequate glucose and energy in the maternal diet in untrained pregnant rats during repeated bouts of acute exercise seem to protect the fetus.

Amniotic Fluid↗

PubMed1987

Endocrine and body growth traits in heifers exposed to testosterone-propionate during early fetal development.

This study was conducted to determine the effects of testosterone-propionate exposure during fetal development on sexual differentiation and growth rates in heifers. Ten pregnant cows were given subcutaneous injections of testosterone-propionate (250 mg/injection) every other day during d 40 to 60 of gestation. Four cows aborted after the end of testosterone treatment, while four heifers (androgenized females) and two bulls (androgenized males) were produced from the six remaining pregnant, testosterone-propionate treated cows. Calves from cows that did not receive exogenous hormone treatment were used as controls. At 8 mo of age, the androgenized heifers and control heifers and control steers were challenged with 1 mg estradiol-17 beta to induce a preovulatory luteinizing hormone (LH) surge. Two weeks later, pituitary responsiveness to exogenous luteinizing hormone releasing hormone (LHRH; 75 micrograms) was evaluated in androgenized heifers and in control heifers and control steers. To monitor growth rates, all animals were weighed at 28-d intervals from birth to 380 d of age. Androgenized females exhibited a partially masculinized phenotype as well as internal male reproductive structures. Treatment with estradiol-17 beta first depressed (P less than .05) serum LH concentrations in all animals, then induced (P less than .05) a preovulatory-like LH surge in control and androgenized females. Control steers did not (P greater than .05) exhibit a preovulatory-like LH surge following administration of estradiol-17 beta. Exogenous LHRH treatment stimulated peak LH concentrations (P less than .05) to a greater extent in control and androgenized females than in control steers.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Phenolsulphotransferase: localization in kidney during human embryonic and fetal development.

The aim of our study was to localize phenolsulphotransferase (PST) in the developing mesonephric and metanephric kidneys of the human embryo and fetus using immunohistochemical methods with an antibody preparation recognizing members of the human phenolsulphotransferase enzyme family. In embryonic and early fetal development of the metanephric kidney, PST is located primarily in derivatives of the ureteric bud such as the ureter, pelvis, calyces and collecting ducts. This predominance declines by mid-fetal life: first, as nephrons evolve and develop they become increasingly PST-immunoreactive such that in mature metanephric kidney, the proximal tubules are highly PST-reactive, with other elements of the nephron also immunopositive (albeit at lower reactivities) and secondly, with the formation of an immunonegative transitional epithelium in ureter, pelvis and calyces, the reactivity retained in collecting ducts is only a small proportion of the total. The distribution of PST immunoreactivity is relatively uniform in proximal tubular cells throughout development, in contrast to collecting ducts, where, in fetal life, this reactivity is displaced to apices and bases by intracellular glycogen deposits. Mesonephric kidney tubules and the mesonephric duct are PST-immunoreactive and although mesonephric immunopositivity overlaps with that in the developing metanephric kidney the renal contribution to sulphation is absent or low at a time when the developing conceptus is most vulnerable to the potential toxic effects of teratogens.

Adult↗

PubMed1995

Utrophin expression during human fetal development.

Utrophin, a protein encoded by chromosome 6 is highly homologous to the cysteine-rich domain and most of the C-terminal domain of dystrophin. In order to clarify its functional role we analyzed its expression during human fetal development. We carried out immunohistochemical analysis on muscle from normal human fetuses at different ages of gestation using an antibody directed against a specific COOH-terminal sequence of the protein. In addition, we stained serial sections with antibodies against dystrophin and alpha-bungarotoxin FITC-BTX. Our findings show that, at week 9 of gestation, utrophin is diffusely expressed in the cytoplasm. From week 12 to 22 the immunostaining is still cytoplasmic, though the reaction intensity progressively decreases. Moreover we observed a strong reaction in fetal nerve at week 18 and 22. There was no correlation between utrophin expression and progressive dystrophin membrane localization.

Amino Acid Sequence↗

PubMed2003

Ammonium induces aberrant blastocyst differentiation, metabolism, pH regulation, gene expression and subsequently alters fetal development in the mouse.

The presence of ammonium in the culture medium has significant detrimental effects on the regulation of embryo physiology and genetics. Ammonium levels build up linearly over time in the culture medium when media containing amino acids are incubated at 37 degrees C. Ammonium in the culture media significantly reduces blastocyst cell number, decreases inner cell mass development, increases apoptosis, perturbs metabolism, impairs the ability of embryos to regulate intracellular pH, and alters the expression of the imprinted gene H19. In contrast, the rate of blastocyst development and blastocyst morphology appear to be normal. The transfer of blastocysts exposed to ammonium results in a significant reduction in the ability to establish a pregnancy. Furthermore, of those embryos that manage to implant, fetal growth is significantly impaired. Embryos exposed to 300 microM ammonium are retarded by 1.5 days developmentally at Day 15 of pregnancy. It is therefore essential that culture conditions for mammalian embryos are designed to minimize the buildup of ammonium to prevent abnormalities in embryo physiology, genetic regulation, pregnancy, and fetal development.

Animals↗

PubMed1993

The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas.

The differentiation of the predominant cell types of the mucosal epithelium of the mammalian gastrointestinal tract is characterized by increasing amounts of an intermediate-sized filament (IF) protein designated cytokeratin (CK) 20 which is a major cellular protein of mature enterocytes and goblet cells. Here we report the isolation of the human gene encoding CK 20, its complete nucleotide sequence and the amino acid sequence deduced therefrom that identifies this polypeptide (mol. wt. 48553) as a member of the type I-CK subfamily. Remarkable, however, is the comparably great sequence divergence of CK 20 from all other known type I-CKs, with only 58% identical amino acids in the conserved alpha-helical 'rod' domain of CK 20 and, e.g. CK 14. Using riboprobes corresponding to exon 6 of the gene in Northern blot and ribonuclease protection assays, we show that the approximately 1.75 kb mRNA encoding CK 20 is specifically produced in cells of the intestinal and gastric mucosa, including tumors and cell lines derived therefrom. The appearance of CK 20-positive cells in human embryonic and fetal development and in adult tissues has been studied using immunohistochemistry with CK 20-specific antibodies. CK 20 synthesis has first been recognized at embryonic week 8 in individual 'converted' simple epithelial cells of the developing intestinal mucosa. In later fetal stages, CK 20 synthesis extends over most goblet cells and a variable number of villus enterocytes. The distribution of CK 20-positive cells in the developing gastric and intestinal mucosa is similar to--but not identical with--the pattern in the adult intestine in which all enterocytes and goblet cells as well as certain 'low-differentiated' columnar cells contain CK 20, whereas the neuroendocrine ('enterochromaffin') and Paneth cells are negative. In gastrointestinal carcinomas similarly examined, CK 20 has been detected in almost all cases (50/52) of colorectal adenocarcinomas, including all grades of differentiation and malignancy and also metastatic tumors, whereas CK 20 immunostaining in gastric carcinomas has been found less consistent and more heterogeneous. The possible biological meaning of the specific expression of the CK 20 gene in certain cells of the gastrointestinal tract and carcinomas derived therefrom and the regulatory mechanisms involved in the integration of the protein in the IF cytoskeleton are discussed.

Adenocarcinoma↗

PubMed2001

The impact of ovarian stimulation on implantation and fetal development in mice.

The objective of this study was to evaluate, using an embryo donation model, whether impaired oocyte/embryo developmental competence and/or changes in uterine milieu are responsible for the previously observed adverse effects of superovulation with gonadotrophins on implantation and fetal development in mice. Embryos from superovulated and non-stimulated females were transferred to separate uterine horns within the same superovulated or non-stimulated pseudopregnant recipient mice. Embryo development was impaired as a significantly higher proportion of normal embryos from control donors (61%) were blastocysts on transfer day compared with superovulated donors (41%; P = 0.001). The implantation rate in control recipients was significantly reduced after transfer of embryos from superovulated donors (12%) compared with control donors (25%; P = 0.001). Uterine receptivity was impaired in superovulated recipients. The implantation rate of control embryos was significantly higher in control (25%) than in superovulated recipients (7%; P = 0.001). Transfer of embryos recovered from superovulated donors resulted in significantly higher post-implantation fetal mortality in superovulated recipients (69%) than in control recipients (36%; P = 0.01), and the mean weight of live fetuses was significantly lower for fetuses obtained from superovulated recipients (0.51 g) compared with that of fetuses obtained from control recipients (0.72 g; P = 0.006). Hence, ovarian stimulation appears to impair oocyte/embryo quality as well as uterine milieu.

Animals↗

PubMed1995

Differential localisation of UDP-glucuronosyltransferase in kidney during human embryonic and fetal development.

The aim of our study was to localise UDP-glucuronosyltransferase (UDPGT) in the developing mesonephric and metanephric kidneys of the human embryo and fetus, using immunohistochemical methods and an antibody preparation with broad specificity to the human isoforms. In embryonic and early fetal development of the metanephric kidney, UDPGT is located primarily in derivatives of the ureteric bud such as the ureter, pelvis, calyces and collecting ducts. This early predominance of UDPGT to ureteric bud derivatives declines by mid-fetal life: a) as nephrons evolve and develop they become increasingly UDPGT immunoreactive such that in mature metanephric kidney, the proximal tubules are highly UDPGT reactive, with other elements of the nephron also immunopositive (albeit at lower reactivities) and b) with the formation of an immunonegative transitional epithelium in ureter, pelvis and calyces, the reactivity retained in collecting ducts is only a small proportion of the total. The distribution of UDPGT immunoreactivity is relatively uniform in proximal tubular cells throughout development. This is in contrast to collecting ducts where, in fetal life, this reactivity is displaced to apices and bases by intracellular glycogen deposits. Parietal cells of Bowman's capsule are immunoreactive, but glomeruli are negative. In mesonephric kidney, as early as 32 days post-ovulation, tubules and the mesonephric duct are UDPGT immunoreactive and mesonephric immunopositivity overlaps with that in the developing metanephric kidney.

Embryonic and Fetal Development↗

PubMed1994

[Morphology of the neuroendocrine-immunologic network of connective tissue in rodent fetal development].

Multi-range neuro-endocrine-immunological function in regulation of body homeostasis gives reasons for establishment of peripheral morphological bonds. As a result from our study, the unit of trophic protection of pelvic connective tissue was identified in embryonal and fetal development of rodents. This unit connects blood vessels and their autonomic innervation with chromaffin cells, mast cells, and simple neurons. Nerve fibres of para-organ pelvic ganglions determine to complete. Author suggestion on integration of another connective tissue cells and erythroid cells with systemic network requires verification.

Animals↗

PubMed2006

Gene expression profiling identifies regulatory pathways involved in the late stage of rat fetal lung development.

Fetal lung development is a complex biological process that involves temporal and spatial regulations of many genes. To understand the molecular mechanisms of this process, we investigated gene expression profiles of fetal lungs on gestational days 18, 19, 20, and 21, as well as newborn and adult rat lungs. For this analysis, we used an in-house rat DNA microarray containing 6,000 known genes and 4,000 expressed sequence tags (ESTs). Of these, 1,512 genes passed the statistical significance analysis of microarray (SAM) test; an at least twofold change was shown for 583 genes (402 known genes and 181 ESTs) between at least two time points. K-means cluster analysis revealed seven major expression patterns. In one of the clusters, gene expression increased from day 18 to day 20 and then decreased. In this cluster, which contained 10 known genes and 5 ESTs, 8 genes are associated with development. These genes can be integrated into regulatory pathways, including growth factors, plasma membrane receptors, adhesion molecules, intracellular signaling molecules, and transcription factors. Real-time PCR analysis of these 10 genes showed an 88% consistency with the microarray data. The mRNA of LIM homeodomain protein 3a (Lhx3), a transcription factor, was enriched in fetal type II cells. In contrast, pleiotrophin, a growth factor, had a much higher expression in fetal lung tissues than in fetal type II cells. Immunohistochemistry revealed that Lhx3 was localized in fetal lung epithelial cells and pleiotrophin in the mesenchymal cells adjacent to the developing epithelium and blood vessel. Using GenMAPP, we identified four regulatory pathways: transforming growth factor-beta signaling, inflammatory response, cell cycle, and G protein signaling. We also identified two metabolic pathways: glycolysis-gluconeogenesis and proteasome degradation. Our results may provide new insights into the complex regulatory pathways that control fetal lung development.

Animals↗

PubMed2004

Metalloproteinase pregnancy-associated plasma protein A is a critical growth regulatory factor during fetal development.

Pregnancy-associated plasma protein A (PAPPA) is a metzincin superfamily metalloproteinase in the insulin-like growth factor (IGF) system. PAPPA increases IGF bioavailability and mitogenic effectiveness in vitro through regulated cleavage of IGF-binding protein 4 (IGFBP4). To determine its function in vivo, we generated PAPPA-null mice by gene targeting. Mice homozygous for targeted disruption of the PAPPA gene were viable but 60% the size of wild-type littermates at birth. The impact of the mutation was exerted during the early embryonic period prior to organogenesis, resulting in proportional dwarfism. PAPPA, IGF2 and IGFBP4 transcripts co-localized in wild-type embryos, and expression of IGF2 and IGFBP4 mRNA was not altered in PAPPA-deficient embryos. However, IGFBP4 proteolytic activity was completely lacking in fibroblasts derived from PAPPA-deficient embryos, and IGFBP4 effectively inhibited IGF-stimulated mitogenesis in these cells. These results provide the first direct evidence that PAPPA is an essential growth regulatory factor in vivo, and suggest a novel mechanism for regulated IGF bioavailability during early fetal development.

Animals↗

PubMed2006

Choline: critical role during fetal development and dietary requirements in adults.

Choline is an essential nutrient needed for the structural integrity and signaling functions of cell membranes; for normal cholinergic neurotransmission; for normal muscle function; for lipid transport from liver; and it is the major source of methyl groups in the diet. Choline is critical during fetal development, when it influences stem cell proliferation and apoptosis, thereby altering brain and spinal cord structure and function and influencing risk for neural tube defects and lifelong memory function. Choline is derived not only from the diet, but from de novo synthesis as well. Though many foods contain choline, there is at least a twofold variation in dietary intake in humans. When deprived of dietary choline, most men and postmenopausal women developed signs of organ dysfunction (fatty liver or muscle damage), while less than half of premenopausal women developed such signs. Aside from gender differences, there is significant variation in the dietary requirement for choline that can be explained by very common genetic polymorphisms.

Brain↗

PubMed2002

Adrenocortical cytochrome b5 expression during fetal development of the rhesus macaque.

The developmental expressions of cytochrome b5 (b5), 17 alpha-hydroxylase/17,20-lyase cytochrome P450 (P450c17), and 3 beta-hydroxysteroid dehydrogenase were examined in primate fetal adrenals by immunocytochemistry from 50-160 d gestation. The expression of b5 was evident at 50 d in the developing fetal zone (FZ), but decreased markedly through midgestation, then increased again from 150 d to term. Similar changes in the temporal expression was observed for P450c17. Whereas P450c17 was induced largely in the transitional zone (TZ; outer-most FZ), b5 expression was strongest in FZ cells further from the capsule, although overlap between these regions involved a narrow band of cells beneath the TZ that may represent the developing zona reticularis. Thus, the induction of b5 in the FZ and of P450c17 in the TZ of the fetal adrenal late in gestation coincided temporally with the prepartum rise in dehydroepiandrosterone previously reported. These data are consistent with the proposed role of b5 in supporting 17,20-lyase activity of P450c17. However, the lack of cytochrome b5 and P450c17 expression in the FZ of the developing macaque adrenal cortex for much of the second and third trimesters distinguishes it from the mature zona reticularis seen in adult animals.

Adrenal Cortex↗

PubMed2004

Effects of short-term early gestational exposure to endophyte-infected tall fescue diets on plasma 3,4-dihydroxyphenyl acetic acid and fetal development in mares.

Consumption of wild-type (toxic) endophyte-infected tall fescue (E+) by horses during late gestation is known to adversely affect pregnancy outcome; however, little is known of the potential disruptive consequences of E+ consumption by mares during the critical phases of placentation and fetal development in early pregnancy. The objective of this study was to evaluate the detrimental effects of feeding E+ to mares during early gestation. Mares (n = 12) paired by stage of gestation (d 65 to 100) were assigned to diets (six per diet) consisting of endophyte-free (E-) or E+ tall fescue seed (50% E- or E+ tall fescue seed, 45% sweet feed, and 10% molasses fed at 1.0% of BW/d). Mares also had ad libitum access to E+ or E- annual ryegrass hay, and were fed diets for 10 d. Following removal from the tall fescue diet on d 11, mares were placed on common bermudagrass pasture and monitored until d 21. Morning and evening rectal temperatures were recorded and daily blood samples were collected for progesterone and prolactin (PRL) analyses, whereas samples for 3,4-dihydroxyphenyl acetic acid (a catecholamine metabolite) analysis were collected on alternate days. For clinical chemistry analysis, blood samples were collected on d 0, 5, 10 and 21. Daily urine samples were collected for ergot alkaloid analysis, and ultrasonography was performed for presence of echogenic material in fetal fluids. Rectal temperatures (E+ 37.76+/-0.03; E- 37.84+/-0.03 degrees C) and serum PRL concentrations (E+ 14.06< or =0.76; E- 12.11+/-0.76 ng/mL) did not differ (P = 0.96) between treatments. Measuring the change in basal serum concentration from d 0 over time, progesterone concentrations did not differ (-0.64 +/-1.49 and -0.55+/-1.47 ng/mL for E+ and E- mares, respectively). There was no negative pregnancy outcome, and ultrasonography indicated no increase in echogenic material in fetal fluids. Plasma 3,4-dihydroxyphenyl acetic acid concentrations decreased (P < 0.05) in E+ compared with E- mares (2.1+/-0.14 and 4.4+/0.43 ng/mL, respectively). Urinary ergot alkaloid concentration was greater (P < 0.01) in mares consuming E+ compared with E- (532.12+/- 52.51 and 13.36+/-2.67 ng/mg of creatinine, respectively). Although no fetal loss was observed during the current study, elevated concentrations of urinary ergot alkaloid were consistent with depressed endogenous catecholamine activity, suggestive of an endocrine disruptive effect of hypothalamic origin.

3,4-Dihydroxyphenylacetic Acid↗

PubMed1993

Effects of maternal bilateral ureteral ligation on fetal development of kidney in rats: morphometrical changes in glomerular components.

Development of the glomerulus in fetal kidney was studied morphometrically following ligation of both ureters of pregnant rats. The ligation was performed on days 17, 19, and 21 of gestation, and autopsy was done 24 hr after each operation. The percentage volumes of the five glomerular components (epithelial cells, capillary, mesangium, glomerular basement membrane, and Bowman's space) were determined by point counting, and the surface area of glomerular basement membrane per unit volume of glomerulus was calculated by intercept counting. On fetal days 18, 20, and 22, percentage volume of Bowman's space in the fetuses from the ligated mothers was significantly smaller than that in the fetuses from sham-ligated mothers. On fetal days 20 and 22, surface area of glomerular basement membrane and glomerular capillary length per unit volume of glomerulus and percentage of glomerular capillary volume in the fetuses from the ligated mothers were significantly larger than those in the fetuses from sham-ligated mothers. These results suggest that maternal bilateral ureteral ligation induces an increase in filtration area of glomerulus in fetal kidney when the fetal kidney is functional.

Animals↗

PubMed2001

Bi-iliac distance and iliac bone position compared to the vertebral column in normal fetal development.

Prenatal standards of bi-iliac width were not found in the literature based on autopsy investigations, nor was the caudo-cranial position of the ilia compared to the vertebral column. The first purpose of the present study was to establish normal standard values for the bi-iliac distance in fetal life, the second to evaluate the level of the iliac bones proportional to the ossified vertebral column. Whole body radiographs in antero-posterior projections from 98 human fetuses (36 female and 44 male fetuses, as well as 18 fetuses on which the sex had not been determined) were analyzed in the study. The fetuses derived from spontaneous or induced abortions and they were radiographed as part of the required autopsy procedure. The crown-rump-length (CRL) of the fetuses varied from 32 to 245 mm. The outer and inner bi-iliac distance was measured from the radiographs with a digital Helios slide caliper. The caudo-cranial position of the iliac bones was evaluated. The present study shows that in normal fetal development there is a continuous linear enlargement of the pelvic region in the transverse and vertical planes. The upper iliac contour stays at the level of the first sacral vertebral body, whereas the lower iliac line moves caudally. Significant differences between male and female fetuses were not found. The value of the present study is that the results can be used as reference standards in prenatal pathology.

Embryonic and Fetal Development↗