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PubMed1988

Influence of nicotine and caffeine on rat embryonic development.

The influence on embryonic development of nicotine and caffeine at dose levels approximating human consumption was investigated in Sprague-Dawley rats. One group of animals received nicotine administered subcutaneously by an Alzet mini-osmotic pump from gestational day 6 through 12 (25 mg over 7 days; rate 149 micrograms/hr). Control animals received physiological saline in a similar manner. A second group received a single intravenous injection of caffeine (25 mg/kg) on gestational day 6. Control animals were treated with physiological saline. A further group received both nicotine and caffeine on gestational day 6 as described for the two previous groups. There were no significant differences among any of the groups with respect to maternal weight gain, litter size, embryolethality, fetal weight, or crown-rump length. The offspring of nicotine treated animals showed a significantly higher incidence of hydrocephaly when compared to the controls, but in the combined treatment group no malformed fetuses were observed. Light microscopic examination of maternal liver, kidney and placentas revealed changes in the hepatic sinusoids, glomeruli and intervillous spaces after nicotine and combined treatment. In addition, the decidua basalis was poorly developed compared to the controls. Chorionic villi and fetal kidney appeared normal in all groups. A coteratogenic effect is not evident from these findings.

Animals↗

PubMed1978

Peptidergic (VIP) innervation of the esophagus.

Nerves displaying vasoactive intestinal polypeptide (VIP) immunoreactivity were demonstrated in the esophagus of rats, cats, and pigs. Furthermore, electron microscopy revealed the presence of nerve terminals displaying the features of peptidergic nerves. VIP nerves were abundant within the smooth muscle layer of the lower esophagus of cat and pig. Immunoreactive nerve fibers and nerve cell bodies were found in the plexuses of the esophageal wall. In pig fetuses VIP immunoreactive nerve cell bodies were observed already at crown-rump length of 4 cm. VIP nerves were also observed in human fetal esophagus. For recording of the motor effects of VIP, segments were taken from cat esophagus close to the esophagogastric junction. VIP induced a dose-dependent relaxation upon contraction by carbamylcholine.

Animals↗

PubMed1979

Changes in axonal numbers in developing human trochlear nerve.

Complete axonal counts have been made in the intracranial parts of trochlear nerves from human fetuses of 9.2, 10 and 24 cm crown-rump length. A count was also made in the intraorbital part of the nerve from the 10 cm specimen. Schwann cell nuclei were also counted in typical cross sections, but do not necessarily reflect very accurately the schwann cell contents of the nerves. Axonal numbers conform to the propositions (1) that they do not all grow out at once, (2) do not all survive and (3) that degeneration may occur before or after myelination has begun. It seems inevitable that some loss of Schwann cells occurs in relation to the degeneration of myelinated axons, but there is no evidence for or against such a loss in relation to the degeneration of unmyelinated axons. Overall, however, Schwann cell numbers tend to increase as the number of myelinated axons increases.

Axons↗

PubMed1979

Muscular development of the bladder neck in the human fetus.

We conducted a histologic study of the muscular development of the bladder neck in human fetuses of 5 to 23 cm crown-rump length (CRL) and in neonates in special reference to the middle circular layer of the posterior wall of the bladder neck (posterior circular muscle of the bladder neck) and the deep trigonal muscle. Our attempt was to determine the anatomic relationship between and the origins of the two musculatures. The posterior circular muscle had begun to differentiate in the fetus of 8.3 cm CRL in which the trigonal musculature was indistinguishable. Differentiation of the deep trigonal musculature was evident in the fetus of 17 cm CRL; a complete growth in which the muscle was connected to the posterior circular muscle of the bladder neck was evident only in the largest fetus (23 cm CRL). We conclude that the deep trigonal muscle and the posterior circular muscle of the bladder neck are of different origins.

Gestational Age↗

PubMed1978

Palatal shelf elevation in the Wistar rat fetus.

Palatogenesis in the Wistar rat fetus was studied macroscopically, microscopically, ultrastructurally and experimentally between days 13 and 19. The developmental ages of the fetuses were calculated from the smear age of the litter adjusted for individual variations in crown-rump lengths. Palatal shelf elevation occurs at day 16.4 +/- 0.1. Experimentally induced shelf elevation in freshly delivered fetuses was sluggish at day 14, but by day 16.3 it occurred in less than 1 second. Both shelf elevation and shelf fusion begin anteriorly where the shelves show a marked convexity of their margins, and proceed posteriorly. The extreme posterior part of each shelf (future soft palate) is horizontal from the beginning. The matrix of the shelf mesenchyme (especially in the region of the anterior convexities) shows an increasing accumulation of mucopolysaccharides from day 14 to day 16.3 and becomes increasingly oedematous. The shelf attachment to the main maxillary process is progressively undercut by epithelial invagination, producing a fulcrum for shelf elevation. The maxillary and palatine osteogenic blastemata are present at the base of the shelf prior to elevation and rapidly invade the shelves after the event. The elevated palatal shelves fuse with the nasal septum anteriorly, but posteriorly the palate is not attached to the septum. The posterior septum at first has a free lower edge, but then it develops lateral flanges which fuse with corresponding bulges on the lateral nasal walls. In this way two sphenoethmoidal recesses are formed above the fused flanges, while a common nasal passage is formed above the palate, roofed anteriorly by the septal flanges and posteriorly by the cranial base. The space needed to create (simultaneous with shelf elevation) the common nasal passage is made available by flattening of the tongue and protrusion of its tip out of the oral cavity--this protrusion being facilitated by the sloping bulge of the primary palate and nasal septum. Many existing theories of shelf elevation are inconsistent with these observations. It was concluded that shelf elevation occurs very rapidly at a rather precise developmental stage and that turgor (due to binding of water to mucopolysaccharides) is the intrinsic force which elevates the shelves, a force which at 16.4 days reaches a threshold level enabling the shelves to force their way up and over the intervening tongue.

Animals↗

PubMed1976

Milk protein quantity and quality in low-birthweight infants: I. Metabolic responses and effects on growth.

The optimal quantity and quality of protein for low-birthweight infants is undefined. In this study, 106 well, appropriate-for-gestational age, low-birthweight infants weighing 2,100 gm or less were grouped in three gestational age categories: T1 = 28 to 30 weeks; T2 = 31 to 33 weeks; T3 = 34 to 36 weeks. Each group was assigned randomly to either banked human milk (BM) or to one of four isocaloric formulas varying in quantity and quality of protein but not in mineral content or in fat content: formula 1 = 1.5 gm of protein per 100 ml, 60 parts bovine whey proteins to 40 parts bovine caseins; formula 2 = 3.0 gm of protein per 100 ml, 60:40; formula 3 = 1.5 gm of protein per 100 ml, 18:82; formula 4 = 3.0 gm of protein per 100 ml, 18:82. Caloric intake was 117 kcal/150 ml/kg/day for the formulas. Human milk was fed at 170 ml/kg/day in order to attain a caloric intake approximately equal to that of the formulas. No significant differences were found in the rate of growth in crown-rump length, in femoral length, in head circumference, or in rate of gain in weight from time of regaining birthweight to time of discharge at 2,400 gm. Blood urea nitrogen, urine osmolarity, total serum protein, serum albumin, and serum globulin varied directly with the quantity of protein in the diet: F2, F4 greater than F1, F3 greater than BM. Blood ammonia concentration varied with both quantity and quality of protein in the diet: F2, F3, F4 greater than F1, BM. Metabolic acidosis was more frequent, more severe, and more prolonged in the infants fed the casein-predominant formulas (F3,F4) than in those fed the whey protein-predominant formulas (F1, F2).

Ammonia↗

PubMed1977

[The effect of glucocorticosteroids on sex differentiation in rats].

The influence of two glucocorticoids (hydrocortisone and dexamethasone) on the somatic sex differentiation of female rats was investigated. During the time of sexual differentiation of their foetuses, pregnant rats were given dexamethasone (0.1-0.3 mg/day) or hydrocortisone (20-200 mg). Both compounds interfere with foetal development by virtue of their strong growth-inhibitory activity which manifests itself in reduction of the body weight, the crown-rump length, the length of the genital folds and the genital cord. The inhibition of growth seems to be reversible. Only hydrocortisone acts teratogenically as it causes a shift of the differentiation of the female genital tract into male direction. This virilisation consists of partial stabilisation of the Wolffian ducts, the suppression of mammary nipple development and a male-type differentiation of the urogenital sinus. The relevance of these findings for human beings is briefly discussed.

Animals↗

PubMed1976

Experimental amniocentesis and teratogenesis. 1. Evaluation of the intra-amniotic route of treatment in teratological studies.

Experiments were designed to evaluate the usefulness of the intra-amniotic route of administration of test-substances in teratological studies. Particular attention was given to the differences in fetal parameters of growth and development and the incidence of fetal mortality between treated and untreated offspring which might be induced as a result of the treatment. Amniocentesis on gestational days 14, 15 or 16 produced a high incidence of fetal mortality and a significant reduction in the weights and crown-rump lengths of treated offspring. With increasing gestational age at the time of treatment and by reducing the volume of solvent injected, fetal mortality was decreased.

Amnion↗

PubMed1990

Growth of linear parameters in trisomy 18 fetuses.

Linear growth in fetuses with trisomy 18 has not been systematically described. We studied the relationship between long-bone, crown-rump, and foot length and gestational age in 17 postmortem fetal specimens with this syndrome. Long-bone and crown-rump lengths were compared with normal regression lines and foot length was compared with gestational age determined on the basis of menstrual dates. Correlation between foot length and menstrual dates was weak in trisomy 18. Gestational age predicted by crown-rump length was significantly lower than gestational age by menstrual dates. All long bones were significantly shortened and fell below normal regression lines for gestational age. The fetal femur/foot length ratio was reduced. Thus no endogenous measure of gestational age appears to exist in this aneuploidy, forcing reliance on menstrual dates. The observed pattern of growth alterations will likely preclude the development of a gestational age-dependent biometric screen for the prenatal detection of this syndrome.

Bone and Bones↗

PubMed1991

Measurements of the auricle in the human fetus.

The auricular length, auricular base length and auricular width were measured in 94 human fetuses with crown-rump (CR) lengths ranging from 49 mm (approximately 11 weeks of gestational age) to 250 mm (approximately 31 weeks of gestational age). The three measurement values showed linear increases as the CR length increased, suggesting that they are useful parameters to indicate intrauterine growth. The measurement values also suggested that the mandibular and hyoid derivatives did not grow independently, but did grow with maintaining a certain relationship.

Anthropometry↗

PubMed1978

Electron microscopy of the early embryonic development of the human corneal epithelium.

The eyes of a human embryo in the 6th week, 11 mm crown-rump (C.R.) length, and of a human embryo in the 7th week, 19 mm C.R. length, were examined. In the embryo of 11 mm C.R. length, the lens vesicle had just detached from the surface ectoderm, the presumptive corneal epithelium. The acellular primary corneal stroma appeared between the lens vesicle and the overlying ectoderm. The fine structure of the ectodermal cells, of their basal lamina, and of the primary stroma is described. In the embryo of 19 mm C.R. length, mesenchymal cells had moved from the periphery into the space between the ectoderm and the lens. There were remarkable changes in the structure of the corneal epithelial cells, in their basal lamina, and in the underlying substances of the primary stroma.

Cornea↗

PubMed1975

Estimating the age of the human foetus from crown-rump measurements.

When data from various sources were compared, it was found that estimates of foetal age based upon crown-rump measurements varied considerably. These variations are probably related to the positions in which the foetuses were measured. Tables relating foetal age to foetal length should therefore specify the precise posture in which the foetus was placed for measurement. A standard readily reproducible position is proposed for the foetus when recording its length and it is suggested that crown-rump length should be related to "conceptual" age instead of the more conventional "menstrual" age.

Anthropometry↗

PubMed1987

In vitro embryotoxic effects of ethylene glycol in rats.

Rat embryos of the CD strain were treated in a whole embryo culture system with either 30 or 40 microliters of ethylene glycol (EG) per milliliter of culture medium for the first 8 (0-8 hr) or second 8 (8-16 hr) hr of a 48-hr culture period. The compound was not embryolethal under these conditions but did alter growth and development. EG at 40 microliters/ml of culture medium at 8-16 hr decreased morphological score, somite number, crown-rump and head lengths, as well as DNA and protein contents. The most frequent abnormality induced by the compound was absence of yolk sac circulation; absent hindlimb bud, hypoplastic telencephalon, and lack of development of the otic and optic systems were also seen in EG-exposed embryos. Since it has been reported that rodent embryos cultured in vitro lack alcohol and aldehyde dehydrogenases that metabolize EG, present results suggest that the parent compound is capable of altering normal embryonic development when administered during a brief period or organogenesis.

Animals↗

PubMed1991

Lack of attenuation of valproic acid-induced effects by folinic acid in rat embryos in vitro.

The anticonvulsant drug valproic acid (VPA) is suspected to be a developmental toxicant in humans, inducing primarily neural tube defects. The mechanism for this effect is unknown, but it has been suggested that the drug may act via a deficiency of the vitamin folic acid. We examined this possibility by concurrent treatment of rat embryos in a whole embryo culture system with VPA and folinic acid (FA), a folic acid derivative. Groups of CD rat embryos were treated with various concentrations of VPA, various concentrations of FA, or a combination of a teratogenic dose of VPA plus various levels of FA. At the end of the 44 hour culture period, each embryo was evaluated for viability (presence of a heartbeat), yolk sac circulation, presence of any malformations, morphological score, crown-rump and head lengths, as well as DNA and protein contents. The anticonvulsant did not decrease viability but did decrease yolk sac circulation and all growth and developmental endpoints in a dose-responsive manner. There was also a dose-related increase in the incidence of open neural tubes. The addition of FA alone had no significant effect on growth and development. When various concentrations of FA were added simultaneously with a teratogenic dose of VPA, there was no decrease in the incidence of open neural tubes. Growth and developmental endpoints were altered in a somewhat random fashion but were never increased to the control level. The lack of attenuation by FA was not due to instability of the compound in the culture system, nor was there a difference in the amount of FA present in the exocoelomic fluid of VPA-treated and control embryos.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1975

Early intrauterine development: I. The rate of growth of Caucasian embryos and fetuses between the 6th and 20th weeks of gestation.

Liberalization of abortion laws in various countries and states of Europe and America has offered an opportunity for the study of the correlations between menstrual age and the rate of bodily development of human embryos and fetuses. In several institutions where local bylaws mandated the consent of the patients requesting therapeutic abortion to pathological investigation of the products of conception, various parameters of growth were measured systematically. These included crown-rump and foot lengths and body weight. The analysis of the data indicated that in the embryosic stages of development the rate of growth is substantially slower than it had been assumed previously. In the more advanced fetal stages of development the findings supported the validity of the long-established standard of Streeter. Since the current study has been based on apparently normal gestations of healthy women, whereas earlier data had rested, to a great extent, on spontaneously aborted and extopic embryon and fetuses, it seems evident that pathological specimens are not suitable for the purpose of establishing reliable standards of normal intrauterine growth rate. The present data support the suggestion, based on various experimental and clinical observations, that pathological gestations often result from abnormal ovulations that occur at times other than the mid-cycle and that such conceptions are frequently followed by a bleeding episode that simulates menstruation. It is likely that the inclusion of a high number of such cases biased the results of earlier investigations concerning embryonic growth rate on account of the frequent incidence of erroneous menstrual histories. The material available did not permit the extension of the investigation beyond the 20th week of gestation. It appears, however, that the average growth rate in the mid-trimester may be slower than the data adopted by the American Academy of Pediatrics would indicate. The possible causes of some phenomena observed in the course of the investigation, such as unexplained scatter of growth-rate patterns at all developmental stages and discrepancies among various literary data, have been discussed in some detail. While a tentative attempt has been made to correlate the investigated parameters of fetal growth with biparietal diameters of the head, a measurement accessible to direct assessment by sonography during pregnancy, the necessity of improving these standards through a prospective study has been emphasized.

Abortion, Therapeutic↗

PubMed1978

Development of the omasum in sheep.

Data are presented on the histogenesis of the omasal mucosa in sheep from the 2.5 cm crown-rump (c-r) length fetus to the adult. 11 stages of fetal development, and 4 post-natal stages, were studies. The distribution of glycogen in the omasal epithelium was also studied. During fetal life the omasal epithelium was initially stratified cuboidal in type, but the superficial layers of cells became flattened in later stages of gestation. This epithelium became extremely thick by the late stages of fetal life, reaching a maximum of 358 micron, and consisting of greater than 20 layers of cells, in the 45 cm c-r fetus (approximatelay 140 days). After birth the epithelium became markedly reduced in thickness, being approximately 77 micron in the adult, and had differentiated into a cornified stratified squamous epithelium of the adult type by 12 weeks after birth. Glycogen was extremely abundant in the omasal epithelium of the 2.5 cm fetus, and declined gradually thereafter to be almost completely absent in post-natal specimens. 4 orders of laminae were present in the adult omasum, distributed in the seqeunce 1-4-3-4-2-4-3-4-1. The 1st order was already present in fetuses of 2.5 cm c-r length, with the 2nd, 3rd and 4th appearing by the 3.5, 5.5 and 11.0 cm stages, respectively. Initial stages in the development of conical papillae were first seen in 15.0 cm fetuses, but the development of these papillae was not completed until after birth.

Age Factors↗

PubMed1990

[Reproductive and developmental toxicity studies of buspirone hydrochloride (I)--Oral administration to rats during the period of fetal organogenesis].

Buspirone hydrochloride (buspirone), an anxiolytic drug, was administered orally to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 2, 12 and 75 mg/kg/day. The summarized results obtained are as follows: 1. Decreased activity was observed for F0 dams at buspirone 75 mg/kg. Further, the suppression of maternal body weight gains accompanied by the reduction of food consumption was shown during the administration period at the same dose level. 2. Liver weights were increased in F0 dams at term at buspirone 12 mg/kg and higher. Besides, brain, pituitary, adrenal and ovarian weights were increased in F0 dams at term at buspirone 75 mg/kg. 3. Buspirone 75 mg/kg brought the inhibition of fetal growth followed by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidence of skeletal abnormalities such as nodular and wavy ribs and unossified 5th and 6th sternum , as well as retarded ossification of cervical vertebrae, forelimbs and hindlimbs were also noted in this dose level. Also, the retarded ossification was observed at 12 mg/kg. 4. Buspirone failed to affect the parturition of F0 dams. 5. Buspirone did not function the viability of newborns (F1), and postnatal differentiations, learning ability, motility, motor activity or emotional development in F1 animals. 6. Body weight gains were depressed in female F1 rats from 4 to 9 weeks of age and food consumption was decreased in male F1 rats from 6 to 8 weeks of age at buspirone 75 mg/kg. 7. Buspirone 75 mg/kg produced suppressions of brain weights at 10 weeks of age in male and female F1 rats and lung weights at weaning in male F1 rats. Spleen weights were increased in female F1 rats at 10 weeks of age at the same dose level. However, buspirone failed to affect their reproductive ability. 8. F2 neonates derived from F1 rats whose dams had ever received buspirone during the period of fetal organogenesis showed no changes in observation items at birth. Based on these results, the no-effect dose level of oral buspirone under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Abnormalities, Drug-Induced↗

PubMed1979

Foot length--a new and potentially useful measurement in the neonate.

The foot length, occipito-frontal head circumference (OFC), crown-rump, and crown-heel length (CHL) of 123 neonates of gestational ages 26-42 weeks, were measured between 12 hours and 5 days. A gauge, designed and constructed at St Mary's Hospital, Manchester, was used to measure foot length. In term babies (37-42 weeks) who were of weights appropriate for gestational age (AGA) the scatter about the mean of foot length measurements was small (coefficient of variation = 4.5%) compared with birthweight (coefficient of variation = 12.0%). The wide range of foot length measurements in babies of different gestational ages prevented maturity being accurately estimated. The mean birthweight of term light-for-dates (LFD) babies was 30.9% lower than term AGA babies, whereas the mean foot length, OFC, and body length of LFD babies was reduced by only 4.2-8.8%. There was a positive linear correlation between foot length and other indices of body size in LFD and AGA babies of all gestational ages. However, in premature babies (less than 37 weeks) the correlation between foot length and birthweight (r = 0.95) and foot length and CHL (r = 0.96) was pronounced. The 95% confidence limits of the regression lines were +/- 327 g and +/- 2.3 cm respectively. Birthweight and CHL of premature babies can therefore be estimated from a measurement of foot length that is performed simply and rapidly. Measurements of foot length are valuable in premature babies who are too ill at birth for conventional anthropometric measurements to be made, and in whom such measurements cannot be carried out subsequently because of the encumbrance of the incubator and intensive care apparatus. Drug dosages and intravenous fluid requirements based on body weight or surface area can be indirectly calculated from a measurement of foot length.

Anthropometry↗