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Effects of hyperphenylalaninemia in the fetal stage on the postnatal development of fetal rat brain.

The effect of exposure at different prenatal stages to maternal hyperphenylalaninemia (HyPhe) on the somatic and neurological development of fetuses in rats was studied, with special respect to the change of relevant enzyme activities in the brain. While evident somatic damage was found only in the fetuses exposed to maternal HyPhe at a last stage of gestation, distinct mental retardation seemingly due to some irreversible damage to the brain was observed in all the treated fetuses regardless of the timing of exposure, and a significantly reduced activity of 2', 3'-cyclic nucleotide 3'-phosphohydrolase (CNPase), a marker enzyme of myelin, was confirmed in the mantle region of the brain.

2',3'-Cyclic Nucleotide 3'-Phosphodiesterase↗

Zygote donor nitrogen metabolism and in vitro embryo culture perturbs in utero development and IGF2R expression in ovine fetal tissues.

Tests were made of the effects of altering nitrogen metabolism in zygote donor ewes on fetal development and expression of the gene encoding the type II insulin-like growth factor receptor (IGF2R) following the transfer of ovine embryos cultured from these zygotes, either in the absence or presence of serum. Zygotes, recovered from superovulated ewes (32 on a urea supplemented (30 g urea/kg) diet (high N) and 32 on a control diet (low N)) 36 h after intrauterine AI using semen from a single sire, were cultured for 5 days in synthetic oviductal fluid (SOF) media either with BSA and amino acids (SOF-) or with 10% (v/v) steer serum (SOF+). In total, 166 embryos, including 30 in vivo controls, were transferred singly at day 6 post-AI to synchronous recipients and the products of conception recovered at day 125 of gestation. Elevated plasma urea concentrations in zygote donors were associated with accelerated early embryo development, low pregnancy rates (16%) for embryos from the high N, SOF+ treatment, and significantly influenced fetal development and the expression of IGF2R in the fetal heart at day 125 of gestation. Importantly, the culture of sheep zygotes under serum-free conditions led to a high incidence of aberrant conceptus development and IGF2R expression. Consequently, maternal nitrogen metabolism prior to zygote recovery and in vitro culture can influence fetal development and the expression of an imprinted gene following embryo transfer, and these data support the notion that environmental effects on the follicle-enclosed oocyte may contribute to the etiology of the Large Offspring Syndrome.

Animals↗

Expression of differentiation markers during fetal skin development in humans: immunohistochemical studies on the precursor proteins forming the cornified cell envelope.

The cornified cell envelope is formed during the terminal differentiation of epidermis through cross-linking of specific proteins by transglutaminases. The specific arrangement of individual protein in the cornified cell envelope and participation of individual protein in the cornified cell envelope at different regions of skin, i.e., palm, foreskin, lips, etc. are not clearly understood. In order to understand the pattern and expression schedule of each individual precursor protein during the differentiation and formation of cornified cell envelope, the expression of precursor proteins in developing human fetal skins from the first to the third trimester were examined by immunohistochemical studies. Involucrin was found in the periderm and intermediate layer from 14 wk estimated gestational age, while loricrin and small proline-rich protein 1 were found in the periderm from 16 wk estimated gestational age. Filaggrin and trichohyalin that are absent in the adult cornified cell envelope were found in the granular and horny layers from 24 wk estimated gestational age. The precursor proteins except trichohyalin did not change their patterns after the onset of initial expression during development. Trichohyalin was transiently expressed in the granular and horny layers of the epidermis from 24 wk estimated gestational age with peak expression at 27 wk estimated gestational age, but was not detected in adult skin. In hair follicles, trichohyalin expression was stable without change from 20 wk estimated gestational age. These findings suggest that fetal skin may have different sets of barriers from the second trimester; the immature cornified cell envelope is formed in the early second trimester and the mature cornified cell envelope is formed in the late second or early third trimester when filaggrin and trichohyalin appear.

Adult↗

The development of stomach during the fetal period.

The objective of this study was to explore the fetal development of the stomach, its morphology and relationship with neighboring structures. The study is carried out in 2003 using 160 human embryos and fetuses (81 males and 79 females) aged between 9 and 40 weeks of gestation. None of the cases had any external pathology or anomaly. Its topographical localization and relationship with surrounding structures were revealed with anatomical dissections. Width and height of the stomach, lengths of the greater and lesser curvatures, the angle between horizontal and vertical axes of the stomach and types of stomach were established. During the fetal life stomach was most commonly located above the transverse axis passing through the umbilicus, in left and right hypochondrium (81%). There were significant differences among trimester groups with respect to the localization of the stomach in the quadrants (P < 0.001). There were no significant sex differences in parameters. After the second trimester, the height of the stomach increased more than the width of the stomach and anterior abdominal height. The angle of stomach decreased from 100 degrees to 50 degrees throughout the fetal period. During the fetal period, wide angles stomach was more common in the first(f) and second trimesters while acute-angled stomach was more common in the third trimester and term fetuses. Diagnosis and treatment of fetal anomalies and pathologies of the stomach requires knowledge of fetal anatomy of the stomach. Data acquired in this study are believed to contribute to the studies of obstetrics, perinatology, forensic medicine and fetal pathology on fetal development of the stomach, and diagnosis and treatment of its anomalies, pathologies, and variations.

Female↗

Synchronized rearrangement of T-cell gamma and beta chain genes in fetal thymocyte development.

Kinetics of mouse T-cell gamma gene rearrangements in ontogeny were determined as an approach to understanding the possible role of these genes in the development of fetal thymocytes. Two of these genes (C gamma 1 and C gamma 2) rearranged rapidly during days 14 to 17 of the gestational period in BALB/c mice. Moreover, these rearrangements seemed to be tightly synchronized with rearrangements of T-cell receptor beta chain genes in the same cells. It is suggested that the early transcriptional activity of gamma genes, which precedes that of beta chain genes, may not reflect the functional activation of these genes. Nevertheless, productive and therefore potentially functional gamma gene rearrangements precede surface expression of T-cell receptors in the thymus by 2 to 3 days, which is compatible with a role for gamma gene products in thymocyte development prior to antigen-specific stages.

Age Factors↗

Mouse major histocompatibility complex (H-2) and fetal lung development: implications for human pulmonary maturation.

Using C57/10Sn (B10, H-2b) and B10.A/SgSn (B10.A,H-2a) congenic mice, we measured 1) the level of endogenous pulmonary corticosterone during mouse development; 2) the degree of lung morphological maturation on gestation day 17, with or without corticosteroid treatment; and 3) the maternal influence on normal lung development and fetal response to corticosteroids. The results of our study indicate that there was a progressive increase in the level of endogenous hormone with time in fetal B10 (H-2b) and B10.A (H-2a) mice; throughout mid- to late gestation, the detectable amount of hormone was almost identical in lungs of both strains. Evaluating the degree of lung maturation by morphometry, B10.A mouse lungs were found to be less mature than B10 mouse lungs. Following corticosteroid treatment on day 12 of gestation, H-2a lungs were equal to or more mature than H-2b lungs. We also compared heterozygous mouse lungs from reciprocal crosses (B10.B10.A, b/a and B10.A.B10, a/b). Mice with a maternally derived H-2a haplotype had less mature lungs than those with a maternally derived H-2b haplotype, suggesting a maternal effect. When exogenous hormone was administered, all heterozygous mouse lungs increased in maturity regardless of the origin of the H-2a haplotype. The treated a/b or b/a lungs were more mature than homozygous b/b and less mature than homozygous a/a lungs. We conclude that progressive lung maturation is associated with a gene(s) at or near the H-2 complex, as is the ability to respond to corticosteroids.

Adrenal Cortex Hormones↗

Angiotensinogen in the developing rat fetal hindbrain and spinal cord from 18th to 20th day of gestation: an immunocytochemical study.

We have detected angiotensinogen immunoreactivity in the hindbrain and in the spinal cord of rat fetuses during the 18th to 20th day of gestation. In the 18th-day fetus, a few immunoreactive angiotensinogen cells are localized in precise brain areas. Their number sharply increase during the 19th and 20th day gestation period when there is an active cell differentiation and cell growth. These observations suggest a role of the renin-angiotensinogen system during cell growth and cell differentiation.

Angiotensinogen↗

Influence of endurance exercise and diet on human placental development and fetal growth.

The delivery of oxygen and substrate to the maternal-fetal interphase is the major maternal environmental stimulus which either up- or down-regulates feto-placental growth. During pregnancy, sustained exercise sessions cause an intermittent reduction in oxygen and substrate delivery to the interphase that may exceed 50% during the exercise but, it is probable that regular bouts of sustained exercise or exercise training may improve oxygen and substrate delivery at rest. The type of maternal carbohydrate intake (low- versus high-glycemic sources) and food intake frequency also influence substrate availability through their effects on maternal blood glucose levels and insulin sensitivity. As a result, different exercise regimens and/or different types of carbohydrate intake modify feto-placental growth. The magnitude and direction of the effect is determined by their average 24-h effect on oxygen and substrate availability at different time-points in pregnancy. In general, exercise in early and mid pregnancy stimulates placental growth while the relative amount of exercise in late pregnancy determines its effect on late fetal growth. Low-glycemic food sources in the diet decrease growth rate and size at birth while high-glycemic food sources increase it. Thus, it may be possible to improve pregnancy outcomes in both healthy, low-risk women and a variety of high-risk populaces by simply modifying maternal physical activity and dietary carbohydrate intake during pregnancy.

Adult↗

Antibody repertoire development in fetal and neonatal piglets. V. VDJ gene chimeras resembling gene conversion products are generated at high frequency by PCR in vitro.

The recovery of VDJ rearrangement is most often accomplished by PCR amplification of DNA extracted from mixtures of B-cells. Using this procedure in swine, VDJs containing chimeric V(H) genes that resemble gene-conversion products, are frequently encountered. To examine whether these chimeras could be the result of PCR artifacts, we used different combinations of swine VDJ templates, each having unique CDR1, CDR2 and D(H) segments, to generate >2600 clones. Using equal amounts of two templates and 30 cycles of PCR, up to 45% of the resultant clones were VDJ chimeras. The frequency of chimeras was independent of the specific VDJ template and the chimeras were generated regardless of whether Taq-, Pfu- or mixtures of Taq- and Pfu-polymerases were employed or whether PCR extension time was prolonged six-fold. The frequency of generating chimeras was dependent on the ratio of the two target DNAs although even ratios approximately 1:10 generated approximately 10% chimeric VDJs. Chimeras could be generated using only 10 cycles of PCR or using the initial template DNAs diluted as much as 1:10000. Of the 279 chimeric VDJs generated, 61% of the crossovers occurred in FR3, 21% in FR2 and 18% in both FR2 and FR3. We interpret these results to mean that in vivo gene conversion in this species can only be unambiguously proven when the VDJs from individual B-cells are bearing a single VDJ rearrangement amplified and sequenced or when VDJs are cloned without the use of PCR.

Animals↗

Biochemical and physiological development of fetal rhesus lung.

Study of 17 fetal rhesus monkeys (Macaca mulatta) revealed a sequential rise in lung phosphatidylcholine (PC) concentration due to elevations in both disaturated (DSPC) and unsaturated constituents. The % DSPC in lung tissue clinical abruptly at 145 days of gestation prior to significant increases in PC or DSPC concentration but in association with improved lung deflation stability (% V10). This suggests that the DSPC-to-PC ratio may be a sensitive biochemical indicator of surfactant phospholipid production in lung parenchyma. Phosphatidyl-glycerol content did not increase significantly until after 155 days gestation, which was coincident with maximizing pulmonary distensibility (V max). Declining levels of phosphatidylethanolamine and sphingomyelin in lung tissue at 162 days support the hypothesis that preferential synthesis of PC occurs during late gestation. A serial decline in lung glycogen content with advancing gestation may reflect glycogen utilization as a substrate for lung phospholipid production. Comparison of biochemical and physiological data confirms the impression that discordances occur among lung maturational events. Lastly, a relationship between rising fetal blood cortisol levels and indices of fetal lung development was not demonstrated.

Animals↗

Genomic analysis of neuroendocrine development of fetal brain-pituitary-adrenal axis in late gestation.

The present study was performed to identify the changes in genomic expression of critical components of the hypothalamus-pituitary-adrenal (HPA) axis in the second half of gestation in fetal sheep. We isolated mRNA from pituitary, hypothalamus, hippocampus, and brain stem in fetal sheep at 80, 100, 120, 130, and 145 days of gestation and 1 and 7 days after delivery (n = 4-5/group). Using real-time RT-PCR, we measured mRNA expression levels of glucocorticoid receptor (GR), mineralocorticoid receptor (MR), serum- and glucocorticoid-induced kinase-1 (sgk1), proopiomelanocortin (POMC), CRF, and arginine vasopressin (AVP). Both MR and GR were highly expressed in pituitary and hippocampus; in all tissues GR was more highly expressed than MR. AVP was more highly expressed than CRF in hypothalamus. MR, GR, and sgk1 expression were increased postnatally in brain stem, and sgk1 expression was increased postnatally in hypothalamus. GR expression was reduced in pituitary in term fetuses compared with younger ages. Hypothalamic CRF expression was increased at the end of gestation compared with younger ages, and AVP expression was increased in newborn lambs. Pituitary POMC was increased at 100 days of gestation compared with 80 days; hypothalamic POMC was increased at 120 days. Overall, the results demonstrate the expression of both MR and GR in brain regions important for control of the HPA axis. Decreases in expression of GR in pituitary at the end of gestation might contribute to the decreased corticosteroid negative feedback sensitivity at term in this species.

Adrenal Glands↗