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PubMed2001

Spatial and temporal distribution of nerves, ganglia, and smooth muscle during the early pseudoglandular stage of fetal mouse lung development.

Neural tissue and smooth muscle appear early in the developing fetal lung, but little is known of their origin and subsequent distribution. To investigate the spatial and temporal distribution of nerves, ganglia, and airway smooth muscle during the early pseudoglandular stage, fetal mouse lungs at embryonic days (E) 11 to 14 were immunostained as whole-mounts and imaged by confocal microscopy. At E11, the primordial lung consisted of the future trachea and two budding epithelial tubules that were covered in smooth muscle to the base of the growing buds. The vagus and processes entering the lung were positive for the neural markers PGP 9.5 (protein gene product 9.5) and synapsin but no neurons were stained at this stage. An antibody to p75NTR revealed neural crest cells on the future trachea as well as in the vagus and in processes extending from the vagus to the lung. This finding indicates that even though neuronal precursors are already present at this stage, they are still migrating into the lung. By E12, neural tissue was abundant in the proximal part of the lung and nerves followed the smooth muscle-covered tubules to the base of the growing buds. At E13 and E14, a neural network of interconnected ganglia, innervated by the vagus, covered the trachea. The postganglionic nerves mainly followed the smooth muscle-covered tubules, but some extended out into the mesenchyme beyond the epithelial buds. Furthermore, we show in a model of cultured lung explants that neural tissue and smooth muscle persist and continue to grow and differentiate in vitro. By using fluorescent markers and confocal microscopy, we present the developing lung as a dynamic structure with smooth muscle and neural tissue in a prime position to influence growth and development.

Actins↗
PubMed1981

Insulin gene expression during development of the fetal bovine pancreas.

Poly(A+) RNA was isolated from the bovine pancreas at three stages of fetal development. Approximately 1% of the total RNA from first, second, and third trimester fetuses was polyadenylated, and the mean chain length of each RNA population was 1350 nucleotides. In cell-free protein synthesis experiments the concentration of insulin-immunoreactive translation products was 10.2%, 11.3%, and 9.7% for first, second, and third trimesters, respectively. Insulin mRNA sequences were estimated by transcription of insulin mRNA to [3H]cDNA and hybridization of cDNA with plasmid pI19 DNA containing rat proinsulin I sequences. Hybridization experiments gave insulin mRNA concentrations of 7.6%, 12.9%, and 3.9% for first, second, and third trimesters, respectively. These results show that insulin mRNA levels vary during development and become proportionally lower in third trimester, when the exocrine tissue is rapidly increasing in mass.

Animals↗
PubMed2004

PI3K-AKT pathway mediates growth and survival signals during development of fetal mouse lung.

We examined the roles of the PI3K-AKT signalling pathway in fetal lung development. By Western blotting, phosphorylated AKT (pAKT) was highly expressed in fetal days 12 and 14 with decreased expression thereafter. By immunohistochemistry, pAKT was expressed mainly in the respiratory epithelium of early fetal days. We examined the effects of fibroblast growth factor 1 (FGF1), PI3K inhibitors (LY294002 and wortmannin), MAPK inhibitor (PD98059) and both of FGF1 and each inhibitor on lung morphogenesis, BrdU incorporation and apoptosis. In the FGF1-treated explants, the number of terminal buds and BrdU-labelled cells increased significantly, while the LY294002-, wortmannin-, PD98059-treated explants demonstrated obvious decreases. The effects by FGF1 were inhibited by LY294002, wortmannin and PD98059. Regardless of the presence of FGF1, the LY294002-, wortmannin- and PD98059-treated explants increased apoptosis revealed by terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay in the mesenchyme of the explants. At the same time, the effect of LY294002, wortmannin, PD98059 on expression of surfactant apoprotein C (SPC) were also studied. The LY294002 and wortmannin treatments showed decreased expression of SPC. These findings suggest that the PI3K-AKT signalling pathway plays a pivotal role in mouse lung development through various biological processes.

Androstadienes↗
PubMed2005

Expression of androgen receptor associated protein 55 (ARA55) in the developing human fetal prostate.

PURPOSE: Development and differentiation of the human fetal prostate are androgen dependent and follow a specific pattern of solid bud-ductal morphogenesis, which involves stromal-epithelial interactions. Androgen receptor associated protein 55 (ARA55) an androgen receptor coactivator localized in stromal cells, binds to androgen receptor (AR) and regulates androgen receptor translocation and transcriptional activity. We investigated whether ARA55 has a role in human prostate development. MATERIALS AND METHODS: ARA55 expression was examined in 25 human prostates from fetuses at gestational ages 10 to 40 weeks and compared to the expression of 34betaE12 (a basal cell marker), smooth muscle actin, desmin (a smooth muscle marker), vimentin (a mesenchymal marker) and Ki-67 (a proliferation marker) by immunohistochemistry. RESULTS: Prostatic epithelium appeared as solid epithelial buds from the urogenital sinus. It underwent arborization and ductal differentiation from the center to the periphery. ARA55 was expressed in stromal cells with a zonal pattern, primarily in the peripheral zone surrounding the noncanalized acini. Most cells in solid buds were positive for 34betaE12, while only basal layer cells in the centrally located epithelial ducts stained with 34betaE12. Solid buds also had a higher proliferation index than ducts. In addition, ARA55 expressing stromal cells but not ARA55 negative stromal cells showed smooth muscle differentiation. CONCLUSIONS: The intimate relationship between ARA55 expressing stromal cells and mitotically active, noncanalized acini suggests that ARA55 has a role in the stromal-epithelial interaction involved in fetal prostate development.

Cell Differentiation↗
PubMed1995

Effect of zidovudine on human fetal lung development.

Zidovudine (AZT) is currently used to treat human immunodeficiency virus (HIV)-positive women during pregnancy to prevent the prenatal transmission of HIV type 1 (HIV-1). However, AZT not only inhibits HIV replication but also affects the DNA polymerases of human cells; hence AZT is not recommended during the first trimester of pregnancy. The lung is a unique organ because it continues to grow and develop throughout fetal life. Using a human fetal lung organ culture system, we sought to determine the effect of AZT on morphogenesis and epithelial cytodifferentiation of developing alveoli. Lung tissues from three fetuses, 14-15 weeks gestational age, were grown in culture for 24 hours (day 0). AZT at a concentration of either 0.4, 4.0, 8.0, or 40.0 mumol/L was added on days 1, 5, and 10 of growth. The cultures were interrupted on days 6 and 15 and examined by light and electron microscopy for alveolar saccular development, interstitial thinning, and epithelial cell differentiation. On day 6 of growth the treated cultures demonstrated fewer alveolar saccules and a thicker, more cellular interstitium compared to the controls. After 15 days of growth the cultures treated with 0.4 mumol/L of AZT appeared structurally similar to the controls. The cultures treated with AZT concentrations of 4.0 to 40.0 mumol/L appeared unchanged from day 6, implying arrested maturation of the culture. However, epithelial cell differentiation was unaffected. We conclude that AZT at concentrations of 4.0 mumol/L and greater affects the structural development of the human fetal lung in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)

Cell Differentiation↗
PubMed1996

[Significance of middle cerebral artery doppler velocimetry based on behavioral states in intrauterine growth retarded fetuses--prediction of development of fetal distress].

Middle cerebral artery resistance indices (MCARI) based on fetal behavioral states were calculated in 60 normal and 20 intrauterine growth retarded (IUGR) fetuses between 33 and 40 weeks of gestational age. Fetal behavioral states were determined by recording fetal actocardiograms. The results obtained were as follows: 1. MCARI was significantly lower in the active phase than in the resting phase in normal fetuses. 2. Of the 20 IUGR fetuses, 9 subsequently developed fetal distress. Seven of 11 fetuses who did not develop fetal distress had abnormally low MCARI (less than M-2.0 SD) in the active phase. On the other hand, seven of the fetuses that subsequently developed fetal distress had abnormal MCARI not only in the active phase but also in the resting phase. The fetuses that did not develop fetal distress had different MCARIs in the two phase, but the fetuses that developed fetal distress exhibited no such difference. 3. The sensitivity and specificity in predicting the development of fetal distress in IUGR fetuses with abnormal MCARI in the resting phase were 77.8% and 81.8%, respectively. This study showed that in normal fetuses MCARI differs according to the behavioral state, and that resting phase MCARI is useful for predicting fetal distress in IUGR fetuses.

Adult↗
PubMed2004

How early are fetal cerebral sulci visible at prenatal ultrasound and what is the normal pattern of early fetal sulcal development?

OBJECTIVES: To evaluate the time of appearance and pattern of development of fetal cerebral sulci at prenatal ultrasound. METHODS: We studied 50 normal fetuses for visibility of cerebral sulci, especially sulci which appear early in anatomical studies, namely the parieto-occipital fissure, calcarine sulcus, cingulate sulcus, convexity sulci and insula/Sylvian fissure. The gestational ages of the fetuses studied ranged from 15.6 to 29.6 weeks. RESULTS: Sulci could be seen by transabdominal ultrasound as early as 18.5 weeks. Medial hemispheric sulci and the insula were visible earlier and more confidently than convexity sulci. The earliest gestational ages at which specific sulci could be seen in any fetus were as follows: parieto-occipital fissure 18.5 weeks, calcarine sulcus 18.5 weeks, cingulate sulcus 23.2 weeks and convexity sulci 23.2 weeks. In the present series, the gestational ages at which these sulci were always visible were as follows: parieto-occipital fissure >20.5 weeks, calcarine sulcus >21.9 weeks, cingulate sulcus >24.3 weeks and convexity sulci >27.9 weeks. The insula and its margin (the circular sulcus) and the overgrowing opercula undergo characteristic maturation. The circular sulcus at the margin of the insula was initially smooth but started becoming angular after about 17 weeks as it started to be overgrown by the parietal and temporal lobe opercula. Initially the insula/operculum angle was obtuse. An acute angle was first evident at 23.2 weeks and in all fetuses older than 24.5 weeks. Our ultrasound data were consistent with anatomical studies and fetal magnetic resonance imaging findings. CONCLUSIONS: Some cerebral sulci can be seen at prenatal ultrasound as early as 18.5 weeks. Familiarity with the normal pattern of sulcal development and the discriminating gestational ages for the appearance of different sulci may allow early suspicion of lissencephaly.

Cerebral Cortex↗
PubMed1977

Retarded development of fetal renal alkaline phosphatase in mice given 2,4,5-trichlorophenoxyacetic acid.

Histologic study of the fetal offspring of maternal mice given 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) suggested that the previously reported fetal "cystic kidneys" were due to a retardation in fetal renal development and downgrowth of the renal papilla into the pelvis. To determine a possible retardation in renal alkaline phosphatase or functional development, maternal mice received by gavage 60-120 mg/kg, 2,4,5-T on days 6-14 of pregnancy. At necropsy on day 17, the fetal kidneys were excised and fixed 24 hr in cold 65% ethanol. Paraffin sections stained by Gomori's method revealed alkaline phosphatase mainly in tubules in the inner renal cortex. Fetal kidneys showing diminished or no alkaline phosphatase were designated subnormal. There was a statistically significant greater incidence of subnormal fetal kidneys in the 2,4,5-T-treated mice than in the untreated controls. In three experiments, some mice were also sacrificed on day 18, and the incidence of subnormal fetal kidneys was significantly lower than on day 17. This retardation in renal alkaline phosphatase development indicates a retardation in renal functional development and indirectly supports the view that 2,4,5-T also retards the morphological development of the fetal kidney and is not a renal teratogen in mice. It also illustrates that selected histochemical studies may be helpful in a teratologic investigation.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1990

The development of fetal heart rate patterns during normal pregnancy.

Characteristics of the fetal heart rate (FHR) were studied longitudinally throughout the second and third trimesters in 43 low-risk singleton fetuses. The second trimester was characterized by an FHR pattern showing minimal differences between quiet and active intervals of fetal behavior. Few movements were accompanied by accelerations of small magnitude. Brief decelerations of variable magnitude exceeded the number of accelerations, and their frequency declined with advancing maturity. The percentage of body movements accompanied by FHR acceleration, the amplitude of these accelerations, and the rate of rise in heart rate increased with gestational age. Up to 30 weeks, the characteristics of the baseline FHR were similar in both periods of fetal rest and activity, with the baseline variability becoming significantly greater with advancing gestation. However, during quiet cycles of fetal behavior after 30 weeks, the baseline variability became progressively narrower, so that in late pregnancy different behavioral states could be determined reliably from characteristics of the baseline FHR alone.

Embryonic and Fetal Development↗
PubMed1990

[Development of fetal semiology in North America].

A survey of the emergence of fetal semiology in the 17 editions of the Williams' Textbook of Obstetrics used by North-American medical students since 1900 was carried out. Three periods were identified: 1906-1950: the fetus, seen as a part of its mother, is ignored until birth and is of no interest to the obstetricians. From the fifties', the decrease in maternal mortality and progress in physiology and therapeutics permitted to study the fetus and a greater attention given to the care of the sick newborn. Since 1970, the availability of ultrasonography has contributed in making the fetus the second patient for obstetricians. It is now possible to study its growth, integrity, health, and well-being. Furthermore, the fetus is now accessible to establish a prenatal diagnosis.

Embryonic and Fetal Development↗
PubMed2006

Reevaluation of the fetal muscle development of the vesical trigone.

PURPOSE: Fetal development of the interureteral muscle, a precondition of a sufficient opposite anchoring of the ureterovesical junction, and the muscle architecture of the bladder neck was investigated using immunohistochemical analysis. MATERIALS AND METHODS: We investigated the ureterotrigonal units in 38 fetal specimens (16 females, 22 males) and 7 newborns (2 females, 5 males) at 9 to 40 weeks of gestation. Histology was based on serial consecutive sections of the bladder base. Anti-human alpha-smooth muscle actin immunostaining was used to demonstrate the time course of muscle development and arrangement. RESULTS: A much earlier developmental stage of the trigone muscle configuration during fetal life was noted than has been reported to date. The condensation of myoblasts located mainly in the dorsal wall of the trigone and at the bladder outlet was present beginning at 12 weeks of gestation. The trigone develops continuously as a single circular muscular layer corresponding to the posterior part of the vesical sphincter muscle. Muscle fibers forming the interureteral junction were demonstrable beginning at 14 weeks of gestation. CONCLUSIONS: There is a close connection between the trigonal smooth muscle layer and the vesical sphincter muscle forming the main part of the trigone by 12 weeks of gestation. Fetal development of the trigone, in particular the muscle architecture of the bladder neck, which consists of only a ring-shaped muscular layer, and the transverse oriented interureteral muscle results in a functional entity representing the anatomical basis for a competent ureterovesical junction.

Female↗
PubMed1996

Fetal neurobehavioral development.

The ontogeny of fetal autonomic, motoric, state, and interactive functioning was investigated longitudinally in a sample of 31 healthy fetuses from 20 weeks through term. Fetal heart rate and movement data were collected during 50 min of doppler-based fetal monitoring at 6 gestational ages. Measures of fetal heart rate and variability, activity level and vigor, behavioral state, and reactivity were derived from these digitized data. Weighted least squares analyses were conducted to model the developmental patterns and to examine the role of maternal and fetal covariates. With advancing gestation, fetuses displayed slower heart rate, increased heart rate variability, reduced but more vigorous motor behavior, coalescence of heart rate and movement patterns into distinct behavioral states, and increasing cardiac responsivity to stimulation. Male fetuses were more active than female fetuses, and greater maternal stress appraisal was associated with reduced fetal heart variability. An apparent period of neurobehavioral transition exists between 28 and 32 weeks. Fetal research methods are evaluated.

Adult↗
PubMed1991

Development of fetal rat ovaries responsiveness to LH during organ culture.

The responsiveness of fetal neonatal rat ovaries to LH was investigated in vitro using three complementary approaches. First, steroid production was assessed after culture. In control media, detectable levels of estrogens (estradiol and estrone) and progesterone were only observed from day 6 postpartum and during the second week of life respectively. In the presence of LH (100 ng/ml) ovaries produced both estrogens and progesterone from day 4 postpartum and the response to LH was enhanced with IBMX supplementation in the medium. Second, 3 beta-HSD activity was measured with either LH or (Bu)2 cAMP (1mM). Irrespective to the time-period studies (Bu)2 cAMP stimulated this enzyme whereas the stimulation with LH occurred only from day 5 postpartum Third, specific hCG binding was assessed and we found that it occurred only on days 7 and 10. However, when fetal ovaries were pretreated for 48 h with (Bu)2 cAMP, a specific hCG binding could be detected and progesterone production was enhanced in response to LH. An effect of the nucleotide via a stimulation of the neuraminidase activity did not seem to be involved. Lastly treatment of 18-day-old fetal ovaries with cholera toxin (10nM) or forskolin (1 microM) was found to stimulate progesterone production and VIP (0.1 to 1 microM) stimulated both the 3-HSD activity and the estradiol production. These data suggest that the absence of steroidogenic response to LH before day 4 postpartum could be explained by the absence of receptors, though the LH transmembrane signal-transduction system is functional in fetal ovaries.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1975

Light and electron microscopic studies of postcapillary venules in developing human fetal lymph nodes.

Developing lymph nodes from 30 human fetuses with crownrump lengths (CRL) of 38 mm (8.7 wk) to 245 mm (26 wk) were studied by light and electron microscopy. Blood vessels that appear to be postcapillary venules (PCV) are present in nodes of 47 mm CRL and older fetuses. These venules first appear in nodes whehn the nodal population of lymphocytes is sparse. In these early nodes PCV are distributed randomly and consist of a low endothelium, underlying basal lamina and incomplete pericyte sheath. Early nodal PCV are distinguised from other nodal blood vessels by the presence of lymphocyte diapedesis and several luminal lymphocytes. In the late stages of nodal development PCV are the more common non-capillary blood vessel and appear in the parenchyma near the periphery of the node. Late nodal PCV are generally characterized by a cuboidal endothelium that is rich in Golgi apparatus, lysosomes and Weibel-Palade bodies. The lumen and wall of late nodal PCV contain lymphocytes. The relationship between the development of the parenchyma of fetal nodes and the appearance and activity of PCV, the passage of lymphocytes through the PCV wall and the fine structure of developing PCV are described. It is suggested that the lymphocytes that first appear in developing nodes, and the majority of the lymphocytes found in late nodes, migrate to the node via the blood vascular system and enter the nodal parenchyma by passing across PCV endothelium.

Abortion, Spontaneous↗
PubMed1998

Fetal neurobehavioral development: associations with socioeconomic class and fetal sex.

This longitudinal study investigated neurobehavioral development in the human fetus from 24 to 36 weeks gestation. Subject (N=103) were stratified by socioeconomic class. Fetal data were collected for 50 min at three intervals, and included measures of heart rate, movement, and biobehavioral patterns. Repeated measures analysis of variance by fetal sex and maternal socioeconomic status was used to detect maturation effects and group differences. With advancing gestation, fetuses exhibited reduced heart rate, increased heart rate variability and coupling between movement and heart rate, increased movement vigor, and more biobehavioral concordance. Male fetuses displayed higher heart rate variability throughout gestation and somewhat earlier emergence of biobehavioral organization than females. Fetuses of women of lower socioeconomic status had reduced heart rate variability, moved less often and with less vigor, showed less coupling between movement and heart rate, and had fewer episodes of synchronous quiescence/activity. Results are discussed in terms of development of the central nervous system.

Brain↗
PubMed1989

Meclofenamate does not affect lung development in fetal sheep.

Prostaglandins may be involved in some aspects of fetal lung development, including surfactant metabolism, tracheal fluid production, and possibly lung growth. In the fetus, during the days before delivery, plasma PGE2 concentration increases and concurrently, tracheal fluid production decreases and surfactant production increases. To determine whether the increase in PGE2, specifically plasma PGE2 concentration, is responsible for these changes, we continuously infused the prostaglandin synthetase inhibitor, meclofenamate (0.7 mg/h per kg), into 8 fetal sheep for 5-13 days before delivery; 5 control fetuses received a continuous infusion of solvent for 5-11 days before delivery. Meclofenamate infusion significantly decreased plasma PGE2 concentrations until the day of delivery. However, meclofenamate did not affect tracheal fluid production or its decrease before delivery, fetal plasma cortisol concentration, surfactant content of tracheal fluid and lung tissue, organ weights, lung weights, or lung DNA and protein content. We conclude that the changes in lung development during the days before delivery are not dependent on the usual high fetal plasma concentration of PGE2 or its increase before delivery.

Animals↗