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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↗

PubMed1988

Horseshoe kidney: a new theory on its embryogenesis based on the study of a 16-mm human embryo.

We studied a human embryo of 16 mm crown-rump (CR) length in excellent condition with a horseshoe kidney malformation. An exhaustive study of this specimen and a review of published material on the human embryo brings us to propose a new theory on the embryogenesis of this malformation. The most commonly accepted theory consists of a mechanical interpretation based on the relation between the metanephroi and the umbilical arteries during the development of the latter. Nevertheless, in those cases where renal parenchyma constitutes the isthmic region, we believe that these arise from nephrogenic cells that have migrated across the primitive streak in the final phase of gastrulation and thus arise from the posterior nephrogenic area of the epiblast.

Embryonic and Fetal Development↗

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↗

PubMed1987

Gestational changes of thyroid hormone action in the developing fetal bovine epiphysis.

Thyroid hormones are essential for cartilage growth and maturation. In order to assess their actions during different periods of skeletal development, [125I]-triiodothyronine (T3) binding capacity in epiphyseal cartilage and triiodothyronine concentrations in serum were quantitated in bovine fetuses of the second and third trimesters of gestation (equivalent to fetal sizes of 10-90 cm crown-rump (CR) length), and related to the alkaline phosphatase activities in the same cartilaginous tissues. Nuclear T3 binding levels, which were initially low during 10-30 cm CR, rose to a peak value (1.7 pmol/mg DNA) at the end of the second trimester (40-50 cm CR). Then, following a sharp decline at 50-60 cm CR, T3 binding rose to a moderate level in the later gestational period (60-90 cm CR). Serum total triiodothyronine rose transiently in fetuses of 30-50 cm CR to a peak level (34 ng/100 ml), and subsequently increased continuously in the later period (60-90 cm CR). Alkaline phosphatase activities measured in epiphyseal chondrocytes rose significantly in fetuses of 60-90 cm CR. The coincident rise of cartilage triiodothyronine binding capacity and serum circulating triiodothyronine levels in the late second trimester suggests that this thyroid hormone induces its own binding sites in bovine epiphyseal cartilage; the dramatic increase in the level of serum triiodothyronine during the third trimester of gestation is temporally related to the increase in alkaline phosphatase activity of chondrocytes, as well as other recognized developmental changes in the fetal bovine skeletal tissues.

Alkaline Phosphatase↗

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↗

PubMed1988

Effects of a natural versus artificial environment on the tempo of maturation in female rhesus monkeys.

To identify factors that regulate the tempo of growth and puberty, the present study examined how the environment influenced the timing of menarche and first ovulation in rhesus monkeys and how these events were related to differential rates of growth. Spring-born females were raised from 12 months of age under natural outdoor conditions (OH; n = 6) or indoors (IH; n = 9) under a controlled photoperiod (12h of light, 12h of darkness) and temperature (20-23 C). Ages at the initial increases in serum bioactive LH levels (27.7 +/- 0.7 vs. 31.4 +/- 1.0 months), menarche (26.0 +/- 0.7 vs. 32.5 +/- 0.9 months), and first ovulation (33.9 +/- 1.4 vs. 43.5 +/- 0.3 months) were significantly advanced in IH compared to OH females. First ovulation for the OH females occurred exclusively in October and November of the fourth year, whereas the distribution of first ovulation of IH females was biomodal, with seven of nine occurring in November or December at 31.8 +/- 0.5 months, and two of nine ovulating in September or October at 41.2 +/- 0.5 months. Serum levels of PRL varied seasonally in OH females throughout development, with peaks in July and nadirs in October. A similar rhythm was observed for IH females during the first 12 months of indoor housing, after which point the period decreased from 11.9 +/- 0.5 to 9.3 +/- 0.6 months. Overall increments in body weight did not differ between groups. An acceleration of growth in both crown-rump and tibial lengths occurred just before menarche in both groups, and this occurred at about 26 months for IH and about 32 months for OH females. Skeletal maturity was significantly advanced at 27 months in IH females and at every chronological age thereafter. Serum concentrations of somatomedin-C and GH paralleled group differences in bone maturation. Both hormones were significantly elevated by 16-18 months of age in IH animals compared to OH females and remained so until 34-36 months of age. Although a distinct seasonal rhythm in both GH and somatomedin-C was evident in OH animals, no such pattern was observed in IH females. These data suggest that exposure to an outdoor environment moderates the tempo of both sexual and skeletal maturation. The acceleration in reproductive development in animals exposed to a constant environment was associated with an acceleration in bone maturation, suggesting that common factors may be responsible for the initiation of both events.

Aging↗

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↗

PubMed1988

[Reproduction studies of carboplatin (II)--Intravenous administration to rats during the period of fetal organogenesis].

Carboplatin, an oncostatic drug, was administered intravenously to pregnant Crj: CD (Sprague-Dawley) rats from day 7 through 17 of gestation at dose levels of 1, 2 and 4 mg/kg/day. The summarized results obtained are as follows: 1. Carboplatin 4 mg/kg suppressed the maternal body weight gains from day 13 through 20 of gestation. 2. Uterine weights were reduced in F0 dams at term at carboplatin 4 mg/kg. 3. Carboplatin 4 mg/kg brought the inhibition of fetal growth accompanied by the lowered values in fetal weights, crown-rump distances and tail lengths. Furthermore, the elevated incidences of unossified 5th and 6th sternum , as well as retarded ossification of sacrococcygeal vertebrae were also noted in this dose level. 4. The birth rate was reduced in neonates (F1) at carboplatin 4 mg/kg. 5. Body weight gains in male F1 rats were suppressed at carboplatin 4 mg/kg from 4 to 8 weeks of age. 6. Carboplatin 4 mg/kg decreased the brain weights on an absolute basis in female F1 rats, but failed to affect their postnatal differentiations, early behavioral developments, learning ability, motor activity or emotional development. 7. Reproductive ability in F1 rats of both sexes were not affected by carboplatin. 8. Influences on prenatal development were not apparently observed for F2 fetuses derived from F1 rats whose dams had ever received carboplatin during the organogenetic period. Based on these results, the no-effect dose level of carboplatin under the present experimental condition was estimated to be 2 mg/kg/day against dams and their offspring.

Animals↗

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↗

PubMed1987

Temporal relationship between fetal bovine skeletal growth and circulating hormonal levels.

Skeletal growth and serum hormonal levels in bovine fetuses were studied cross-sectionally from late first trimester to late third trimester of gestation (corresponding approximately to 75-275 days of age, and a crown-rump (CR) 5-105 cm/in size). Measurements of tibial and femoral lengths showed that bone growth proceeds at a 30% faster rate in fetuses of 50-105 cm CR, coincident with the appearance and exponential growth (y = 0.000207 e 0.12522 x; y, dried weights of ossification in grams and x, CR in cm) of a secondary center of ossification in the epiphysis. During this period there is an increase in the proportion of [3H]-thymidine-labeled nuclei (measured by autoradiography) in the proliferative zone of the epiphyseal growth plate and a progressive hypertrophy of chondrocytes in the epiphysis; in serum there is a rise in alkaline phosphatase activity, a rise in the calcium, and a decrease in the phosphorus concentrations. Cellularity (nuclei/area) and the proportion of [3H]-thymidine labeled nuclei in epiphyseal cartilage decline during the period of 15-105 cm CR, except at 25-45 cm CR when both parameters of chondrocyte growth have transiently stabilized. [35S]-Sulfate and [3H]-proline incorporation (cpm/100 micrograms DNA) in epiphyseal cartilage also decline initially during 10-25 cm CR, then attain a stable level during 25-50 cm CR; subsequently, [35S]-sulfate incorporation gradually increases and [3H]-proline incorporation remains at a constant level. The proportion of [3H]-thymidine-labeled nuclei in the epiphyseal growth plate also declines in early gestation, then becomes stabilized at 20-50 cm CR. The whole growth plate thickness varies during gestation and is maximal during 20-50 cm CR. The proliferative zone attains maximal thickness at 20-50 cm CR while the hypertrophied and degenerative zone has maximal thickness at 40-80 cm CR. Gestational changes of hormone levels were quantitated in fetal serum. Glucocorticoids and thyroxine were measured by radioimmunoassay; somatomedinlike bioactivity was measured as the capacity of a serum sample to stimulate [3H]-thymidine incorporation in chondrocytes compared to that of a control serum. Temporally related to the changes occurring in the skeletal tissues, there is a high serum level of glucocorticoids at 10-20 cm CR when the cartilaginous activities are declining, a peak level of serum somatomedinlike bioactivity at 20-50 cm CR when cartilage growth and metabolism become stabilized, and a rise of thyroxine level after 45 cm CR during which time there is an increasing rate of bone formation.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1975

[Normal prenatal growth of the golden hamster (author's transl)].

In the golden hamster (Mesocricetus auratus) the gestation period and the loculus size of the gravid uterus from day 6 to day 15.5 (parturition) of gestation as well as the weight, width (umbilcus-black) and lenght (crown-rump) of the embryos from day 9 to the parturition were measured. The results obtained were as follows: 1. The gestation period of the golden hamster was 15 days and 15 +/- 3 hours post coitum. 2. The average values of the length (in the direction of uterine long axis) and width (mesome-trial-antimesometrial axis) in the loculus of the gravid uterus were 0.39 cm and 0.56 cm at 6 days, and 2.42 cm and 1.74 cm at 15.5 days (partiurition), respectively. 3. The average values of the crown-rump measurements, width (umblicus-back) and weight in the hamster embryos were 0.42 cm, 0.24 cm and 0.026 g at 9 days, and 2.40 cm, 1.39 cm and 2.272 g at 15.5 days (parturition), respectively. 4. The loculus size of the gravid uterus, the crown-rump measurements and width (umblicus-back) of the embryos in the period from day 13 to day 14 of gestation were markedly increased in comparison with any other period, and the weight increase of the embryos occurred rapidly from day 13 of gestation. 5. The shape of the loculus during the gestation was ovoid (mesometrial-antimesometrial axis) until the end of 10 days converged to the spherical form and thereafter changed gradually to the ovoid from in the direction of uterine long axis contraly to the previous days.

Animals↗