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Enhanced fetal growth in sheep administered progesterone during the first three days of pregnancy.

Two experiments were conducted to determine whether administration of progesterone during early pregnancy affects fetal growth in sheep and if any effect is specific to the days of treatment. In the first experiment, Merino ewes were randomly allocated to four treatment groups and inseminated at a synchronized oestrus. Three groups received progesterone on days 1-3, 3-6 or 1-6 of pregnancy while the fourth group was untreated. Concentrations of progesterone in peripheral plasma increased (P < 0.05) in all treatment groups. Fetal growth (to day 74) was greater in all treatment groups than in the control group (P < 0.001) and was greatest when treatments started on day 1. Pregnancy rate was not affected by progesterone treatment on days 3-6, but was reduced (P < 0.05) when treatment began on day 1. In the second experiment, embryos that had been exposed to either a normal (control) or a high concentration of progesterone on days 1-3 were randomly transferred, within groups, to recipient ewes that had or had not been treated with progesterone on days 1-3. In another group, embryos were exposed to a high concentration of progesterone on days 1-3 and the oviducts of the ewe were ligated. An increase in fetal mass was observed in the recipient group that had been treated with progesterone (P < 0.01) but was not observed in the initial group treated with progesterone. A greater fetal mass was also obtained when embryos that had been ligated in the oviducts of ewes treated with progesterone (P < 0.05) were transferred.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

Growth and development of bovine fetuses and neonates representing three genotypes.

Growth was examined in bovine fetuses and neonates that typically differ in mature size and postnatal developmental pattern. Pregnancies were established from matings expected to produce early (E), late (L), and intermediate (I) maturing postnatal growth patterns. Tissues were collected at 100 and 200 d of gestation and 30 d postnatal. Muscle:body weight ratios were lower at 100 and 200 d for the E maturity type than for the L maturity type (P < .05). This differs from observations of muscle:body weight ratios made at 30 d postnatal, at which time ratios for E were either greater than (triceps brachii, P < .05) or similar to those for L. Few differences due to maturity type were observed at 100 d for bone weight:body weight ratios; however, at 200 d of gestation E bone weight:body weight ratios were generally lower (P < .05) than those for L. The genotypic relationship for bone weight:body weight ratio at 30 d postnatal was similar to that observed at 200 d of gestation. Observations of organ weight:body weight ratios revealed no clear patterns due to maturity type. The genotypic relationship for total muscle DNA content was similar to that observed for muscle weight. These results indicate that fetal muscle development differs in cattle that have different postnatal growth patterns by as early as 100 d of gestation and that differences in fetal muscle growth are related to differences in muscle hyperplasia.

Animals↗

Histogenesis of the reticular groove of the buffalo (Bubalus bubalis) stomach.

Histogenesis of the reticular groove (sulcus reticuli) of the buffalo (Bubalus bubalis) was observed from primordial stage to birth. The epithelium of the reticular groove was considered early embryonic until a crown-rump (CR) length of 2.2 cm, and was uniformly distributed at CR 2.2 cm; superficial and basal zones developed by CR 3.2. cm. At CR 10.5 cm, the basal zone in the floor evaginated and formed longitudinal folds. At CR 25.5 cm, the basal zone in the lipids evaginated and formed papillae. The core of the longitudinal folds and papillae was formed by the lamina propria, muscularis mucosae, and submucosa. Keratinization was seen at CR 50.5 cm, and the epithelium was stratified squamous epithelium with keratinization, similar to that of the adult buffalo. The floor and lip had a single layer of muscle. A small oblique muscle layer was also found in the concavity of the lip. The correlation between structure and function of the reticular groove is discussed.

Animals↗

Fine structure and myelination of the developing human vagus nerve.

The development of the cervical part of the vagus nerve was studied by electron microscopy in 17 human embryos and fetuses from 18 to 220 mm crown-rump (CR) length, approximately 7--23 postovulatory weeks old. By the end of the embryonic period proper, processes of neurolemmocytes are beginning to invade the nerve bundles of the vagus. Early in the fetal period, the nerve fibres become more regularly arranged, the lemmocyte/axon ratio is diminishing, the neurolemmocytes are dividing, and the connective tissue elements are becoming differentiated. By 14 postovulatory weeks (120 mm CR), examples of a 1:1 lemmocyte/axon ratio are observed, and the spiral development characteristic of myelination is beginning. By 17 weeks, myelinated fibres at varying phases of myelinogenesis are apparent, and desmosome-like junctions in the opposed plasma membranes are seen where lemmocyte processes form a mesaxon. By 23 postovulatory weeks, the diameter of the axons varies from 0.2 to 3.5 micrometer, and the vagus shows its mature structure, although nerve fibres at the beginning of myelin formation are still visible.

Desmosomes↗

The role of cartilage in osteogenesis in the human fetal vertebral body.

The cartilage canals of the thoracic and lumbar vertebrae of fetuses ranging in crown-rump (C.R.) length from 33 to 180 mm were examined under light microscopy. The activity of the cells within these canals contributed to the anterolateral growth of the vertebral body. Bone formation was seen to commence in the center of the vertebral body. The cells of the connective tissue contained within the cartilage canals appeared to participate in the process of osteogenesis in multiple, discrete foci. In five-month-old fetuses, periosteal bone was noted on the anterior and posterior surfaces of the vertebral body, and calcification in the walls of the cartilage canals gave the histologic appearance of bone spicules.

Cartilage↗

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↗

Comparison of dexamethasone-induced embryotoxicity in vitro in mouse and rat embryos.

Previous work demonstrated that rat embryos were more susceptible to the growth retardation effect of the synthetic glucocorticoid dexamethasone (DEX) in vivo than were mouse embryos. The purpose of this study was to examine this species difference using an in vitro system. Embryos of CD rats and CD-1 mice were cultured in a whole embryo culture system with concentrations of DEX from 5 to 250 micrograms/ml. Rat embryos were explanted on day 9 of gestation (GD 9: plug day = GD 0), while mouse embryos were removed on GD 8. After 48 h in culture, each viable embryo was evaluated for morphological score, and the number of somite pairs, crown-rump, and head lengths, as well as DNA and protein concentrations were determined. A reduced morphological score was observed for mouse embryos at 5 micrograms DEX/ml, but a significant decrease in this parameter was only observed at DEX concentrations of > or = 100 micrograms/ml in rat embryos. Significant reductions in the number of somite pairs were observed at 25 micrograms/ml for mouse embryos and 100 micrograms/ml for rat embryos. Crown-rump and head lengths as well as DNA and protein concentrations were significantly decreased at 100 micrograms/ml in mouse embryos and 150 micrograms/ml in rat embryos. Therefore, in vitro mouse embryos were adversely affected by lower concentrations of DEX than were rat embryos for each of the six end points examined in this study. This species sensitivity in vitro could be due to inherent genetic differences or to the slightly different developmental stages evaluated using the culture system.(ABSTRACT TRUNCATED AT 250 WORDS)

Abnormalities, Drug-Induced↗

The foetal thyroid of the dromedary: its relation to body weight and dimensions and to the weight of the Dam's thyroid.

Growth and iodine content of the thyroid glands in relation to body weight, length [total (BCVRT), crown-rump (CR), and curved crown-rump (CVR)], chest circumference (CC), and age were investigated in 83 camel foetuses from 70 to 355 days of gestation (mean gestation length 390 days). Weight and iodine content of the dam's thyroid were also studied. Highly significant (P less than 0.01) correlations of 0.883, 0.797, 0.798, 0.792, and 0.813 were obtained between foetal thyroid weights on the one hand and body weight, BCVRT, CR, CVR, and CC on the other hand. A significant (P less than 0.05) correlation of 0.345 was obtained between weights of the foetal thyroid and dam's thyroid. The relative weight of the foetal thyroid to body weight was 0.045% at 70-99 days of gestation, but decreased to 0.028 (0.023 to 0.036%) in the subsequent stages. Iodine trapping by the foetal thyroid was first detected at 100-129 days of gestation. Total iodine then increased until 310 days, but decreased thereafter. The foetal thyroid has 4 to 25 times higher avidity to iodine accumulation than that of the dam.

Animals↗

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↗

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↗

Protection of rat embryos in culture against the embryotoxicity of acrolein using exogenous glutathione.

The aldehyde acrolein is embryotoxic in vivo and in vitro. Since acrolein is reactive towards thiols, glutathione was evaluated for its protective effects against the in vitro embryotoxicity of acrolein. Day 10 rat embryos were cultured in the presence of acrolein and glutathione, either concurrently or sequentially, and evaluated for embryo deaths, malformations, growth retardation, and content of glutathione and protein. Acrolein, added alone at the initiation of the culture period, was embryolethal to 64 and 100% of the embryos at 120 and 160 microM respectively. At acrolein concentrations of 80 and 120 microM, 50 and 100%, respectively, of the surviving embryos were malformed. In addition, both of these concentrations of acrolein produced growth retardation manifested by significant decreases in the yolk sac diameter, crown-rump and head lengths, number of somites, and morphological score. Concurrent exposure to 100 or 500 microM glutathione markedly protected embryos against all of these effects. To study the mechanism of the protective effect of glutathione against the embryotoxicity of acrolein, the effects of sequential addition of acrolein and glutathione were determined. When rat embryos were cultured in the presence of acrolein for 2 hr prior to exposure to glutathione, even 500 microM glutathione could not offer any protection against the embryolethality, teratogenicity, and growth retardation induced by acrolein. However, a 6-hr preincubation with 500 microM glutathione, prior to exposure to acrolein (in the absence of exogenous glutathione), significantly decreased the incidence of embryo deaths at 160 microM acrolein and brought the number of deaths and malformations among embryos exposed to 120 microM acrolein down to a level not significantly different from control; unlike the embryos exposed concurrently to acrolein and glutathione, however, the sequential treatment with glutathione and acrolein did not protect against growth retardation. While there were some changes in the total glutathione and protein content of embryos and yolk sacs with acrolein exposure, none of the treatments had any overall effect on the glutathione concentration per mg protein. Thus, exogenous glutathione can protect against the in vitro embryotoxicity of acrolein. We propose that this protection is mediated in part by a direct interaction between glutathione and acrolein, added concurrently to the serum medium, and in part by an indirect effect on the embryo of glutathione added prior to acrolein.

Abnormalities, Drug-Induced↗

Studies of marginal zinc deprivation in rhesus monkeys. IV. Growth of infants in the first year.

Growth was evaluated in rhesus monkey infants that were the offspring of females given a marginally zinc-deficient diet (4 micrograms/g zinc) from the beginning of pregnancy and through 12 months of postnatal life. These zinc-deficient (ZD) infants were compared to controls whose mothers were fed a complete diet, either ad libitum or pair-fed to zinc-deficient dams, throughout gestation and lactation. Male ZD infants had evidence of growth retardation at birth. In contrast, growth retardation in female ZD infants was not observed until 1 month of age. From 3 to 9 months of age (late lactation and subsequent to weaning) ZD infants attained weights similar to those of the control group. However, analysis of crown-rump and femur length indicated that ZD infants' growth was less than optimal throughout the entire 1st yr of observation. In addition, skinfold thickness was markedly higher in ZD than in control infants in the postweaning period. In the juvenile period (9-12 months of age) both male and female ZD animals fell behind controls in body weight. ZD juveniles were also hypogeusic, as determined by a quinine acceptance test. Low weight ZD infants had reduced somatic growth as reflected in sitting height, long bone growth, head circumference, and limb circumference. Regression analysis indicated that impaired growth rates from 9 to 12 months were associated with both lower food intake and reduced food use efficiency. Plasma zinc concentration was, in general, inversely related to weight gain in both groups during the 1st yr.

Animals↗

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↗

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↗

Androstenedione metabolism in the indifferent stage of bovine gonad development.

Suspensions of cells obtained from genital ridges and gonads of bovine embryos of 1.0-3.4 cm in crown-rump (C-R) length were used for studies of the metabolism of radiolabeled exogenous steroid precursor. Tritiated androstenedione was employed as precursor and the final products of their metabolism were evaluated after separation by thin-layer chromatography. Genetic sex was determined by the karyotype of hepatocytes from the same embryos. The extent of conversion of tritiated androstenedione was higher in cells from male embryos than cells from female embryos. Furthermore, androstenedione was metabolized mainly to testosterone in male embryos. By contrast, cells obtained from female embryos transformed androstenedione to estrone and 17 beta-estradiol. The onset of this activity was observed at 1.8 cm in C-R length in males and at 2.2 cm in C-R length in females. In all cases, after the onset, the metabolic activity increased in relation to the age of the embryos. These data show that in the bovine embryo gonad, the activity of aromatase and 17 beta-hydroxysteroid dehydrogenase are present when the morphological differentiation of the gonadal sex has not yet been established.

Androstenedione↗

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↗

[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↗