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Influence of drinking water -- tap versus purified -- on embryo and fetal development in mice.

Pregnant CD-1 mice drank either chlorinated tap water obtained at NIEHS from the City of Durham, North Carolina municipal water supply or this same water passed in sequence through an organic removal cartridge and a demineralizer, followed by glass distillation. No significant overall differences in the reproductive status of pregnant mice were noted when the two groups were compared. Similarly, no significant overall influence on the incidence of malformed fetuses could be traced to the purity of drinking water. Month by month comparisons indicated that there were three statistically significant differences; all of which indicated improved performance for the mice that drank tap water. When the results for both groups were combined and a month by month comparison was made there was a significant difference in the pregnancy rate for February (68%) as compared with an overall pregnancy rate of 80% and a 79-93% spread for the other months, but the decrease was due to the low incidence of pregnancy in the group that drank the purified water.

Abnormalities, Drug-Induced↗

Influence of formaldehyde and Sonacide (potentiated acid glutaraldehyde) on embryo and fetal development in mice.

Pregnant outbred albino mice were given formaldehyde or Sonacide (potentiated acid glutaraldehyde) by gavage on days 6--15 of gestation. The mice were killed on day 18, the general health and reproductive status of the dam evaluated, and the fetuses examined and processed in order to characterize external, visceral, and skeletal malformations. Although formaldehyde (stock solution containing 12--15% methanol as a preservative) was lethal to 22 of 34 dams treated with 185 mg/kg/day, and one of 35 dams treated with 148 mg/kg/day, these doses did not produce statistically significant (two-sided p < 0.05 versus controls) teratogenic effects in the fetuses of the surviving dams. Sonacide was also judged not to be teratogenic to the mice employed in this study, in spite of the fact that relatively high doses were employed. The highest doses of Sonacide studied (5.0 ml/kg/day, which is equivalent to 100 mg/kg/day of glutaraldehyde) killed 19 of 35 dams and caused a significant reduction in the mean weight gain of the surviving mothers. In addition, this dose produced a significant increase in the number of stunted fetuses.

Abnormalities, Drug-Induced↗

Acute effects of cadmium on the pregnant rat and embryo-fetal development.

In rats, of the Wistar-Porton strain, a single intravenous injection of 1.25 mg Cd2+ between days 9 and 15 of gestation results in a high incidence (80% of hydrocephalus, together with other malformations in the fetuses, examined on day 20. This dose is critical, since 1.1 mg Cd2+/kg is not teratogenic, while 1.35 mg Cd2+/kg kills all the embryos. Intravenous injection of Cd2+ to the pregnant rat on day 12 causes a dose-dependent inhibition of placental Zn2+ transport. At the teratogenic dose, Zn2+ transport is inhibited by about 75% at 4 hr. Thereafter, inhibition decreases with time but is still significant at 48 hr. At 20 hr after administration of Cd2+ the embryonic concentration of Zn2+ is depressed by 33%. In the whole embryo the activity of the Zn2+-dependent thymidine kinase is inhibited by about 60% at 4 hr and at 20 hr the DNA concentration is reduced significantly. Placental transport of 14C-leucine and 14C-uridine, as well as the embryonic incorporation of these precursors into protein and RNA is unaffected at least at short times after the administration of Cd2+. It is possible therefore, that the teratogenic effects of Cd2+ may be related to the inhibition of DNA synthesis in the embryo.

Abnormalities, Drug-Induced↗

Morphogenesis of the small intestine during fetal development.

During the last five days ('last trimester') of the 22-day gestation period of the rat the mucosa of the small intestine changes from undifferentiated stratified epithelium without villi to a mucosa with villi covered with simple columnar epithelium. During this process many secondary lumina form in the primitive stratified epithelium; these lumina enlarge and eventually fuse with the main intestinal lumen as degenerating superficial epithelial cells are exfoliated and as upward growth of mesenchyme towards the main lumen takes place. Proliferation of intestinal epithelial cells occurs along the entire length of the newly formed villi until one or two days before birth, when proliferating epithelial cells become confined to incompletely formed crypts at the base of the villi. In contrast, differentiation of the small intestinal mucosa in human fetuses begins much earlier in gestation. Villi form at 9 to 10 weeks and crypts are well developed by 12 weeks (first trimester). By 17 weeks, all epithelial cells types seen in intestinal crypts of adults are present. Absorptive cells on villi have a prominent apical tubular system, large meconium-filled lysosomes and abundant glycogen between 10 and 22 weeks' gestation. Whereas there is uptake of the macromolecular marker, ferritin, into the apical tubular system after eight or more minutes of in vitro exposure, there is no evidence of transport of ferritin across the absorptive cells after up to 40 minutes of exposure between 11 and 12 weeks' gestation.

Animals↗

Expression of the epidermal growth factor receptor in developing fetal mouse palates: an immunohistochemical study.

Epidermal growth factor (EGF) stimulates the growth of various tissues and, therefore, EGF receptor expression in fetal tissues may play a key role in organogenesis. We have examined immunohistochemically the ontogeny and localization of the EGF receptor in the fetal mouse palate during in vivo and in vitro palatogenesis using the anti-human EGF receptor rabbit antibody. Immunoreactive products against the EGF receptor were observed in the palatal tissue examined on days 12, 13, and 14 of gestation. On days 12 and 13, the immunoreactive products were predominantly positive on the oral and medial edge epithelia but were minimal on the epithelium of the vertical shelf. The EGF receptor immunoreactivity was less intense in the posterior palate as compared with the midpalatal region. In the fusing palate of day 14 fetuses, the cells forming the midline epithelial seam were continuously positive for EGF-R immunoreactivity. The mesenchyme of palatal shelves also showed regional heterogeneity and temporal sequence in EGF receptor expression. The localization of the EGF receptor in fetal mouse palates cultured in a serumless medium generally simulated that observed in vivo.

Animals↗

Studies on the fetal development of the gubernaculum in cetacea.

BACKGROUND: Adult cetacean males, like non-mammalian vertebrates and other testicond mammals, have intra-abdominal testes. There is no evidence of a processus vaginalis in them. Testicondia in cetaceans is considered secondary as they are judged, evolutionarily, the descendants of terrestrial mammals (ungulates) with testis descent. A possible argument in support of the latter contention would be that cetacean fetuses develop gubernacula which are the primordia of the processus vaginalis and other structures associated with testis descent in other placental mammals. The present study intended to analyse cetacean fetuses in this respect. METHODS: Serial sections of 25 fetuses (total body length between 39.5 and 160 mm) of 4 cetacean species (Delphinus delphis, Phocoena phocoena, Eschrichtius robustus, Physeter catodon) were examined with special attention to the presence or absence of structures homologous to the gubernaculum of other placental mammals (rats and humans). RESULTS: Gubernacular primordia were observed in fetuses from about the time of onset of sexual differentiation. Their shape and anatomical relationship with the surrounding structures were similar as those in mammals with testis descent. The gubernaculum in males developed into a large mass of dense connective tissue in the ventral-caudal abdominal region at the site of the insertion of the mesonephric inguinal ligament and associated to the tip of the internal abdominal oblique muscle. No (or only very little) development of a processus vaginalis was noticed. CONCLUSIONS: The results demonstrate initial emergence of mammalian-like gubernacular primordia in cetacean fetuses without their further development to elaborate structures required for testis descent. The findings support the view that cetaceans are secondarily testicond. It is suggested that (1) absence of the pelvic girdle together with (2) the development of structures in and beyond the caudal abdominal region, particularly the caudal hypaxial musculature, precludes the outgrowth, into caudal direction, of hollow organs (such as the processus vaginalis) from the abdominal cavity.

Animals↗

Organization of human hypothalamus in fetal development.

The organization of the human hypothalamus was studied in 33 brains aged from 9 weeks of gestation (w.g.) to newborn, using immunohistochemistry for parvalbumin, calbindin, calretinin, neuropeptide Y, neurophysin, growth-associated protein (GAP)-43, synaptophysin, and the glycoconjugate 3-fucosyl- N-acetyl-lactosamine. Developmental stages are described in relation to obstetric trimesters. The first trimester (morphogenetic periods 9-10 w.g. and 11-14 w.g.) is characterized by differentiating structures of the lateral hypothalamic zone, which give rise to the lateral hypothalamus (LH) and posterior hypothalamus. The PeF differentiates at 18 w.g. from LH neurons, which remain anchored in the perifornical position, whereas most of the LH cells are displaced laterally. A transient supramamillary nucleus was apparent at 14 w.g. but not after 16 w.g. As the ventromedial nucleus differentiated at 13-16 w.g., three principal parts, the ventrolateral part, the dorsomedial part, and the shell, were revealed by distribution of calbindin, calretinin, and GAP43 immunoreactivity. The second trimester (morphogenetic periods 15-17 w.g., 18-23 w.g., and 24-33 w.g.) is characterized by differentiation of the hypothalamic core, in which calbindin- positive neurons revealed the medial preoptic nucleus at 16 w.g. abutted laterally by the intermediate nucleus. The dorsomedial nucleus was clearly defined at 10 w.g. and consisted of compact and diffuse parts, an organization that was lost after 15 w.g. Differentiation of the medial mamillary body into lateral and medial was seen at 13-16 w.g. Late second trimester was marked by differentiation of periventricular zone structures, including suprachiasmatic, arcuate, and paraventricular nuclei. The subnuclear differentiation of these nuclei extends into the third trimester. The use of chemoarchitecture in the human fetus permitted the identification of interspecies nuclei homologies, which otherwise remain concealed in the cytoarchitecture.

Biomarkers↗

Fetal development of primate chemosensory corpuscles. II. Synaptic relationships in early gestation.

Fungiform papillae contained well-developed chemosensory corpuscles in macaque monkey fetuses with crown-rump lengths of 5.0-9.0 cm. These fetuses corresponded to stages from the last part of the first and beginning of the second trimester of gestation. Chemosensory cells extended from the epithelial basal lamina to the taste pore anlage at the apex of the corpuscle and had typical afferent synaptic contacts with presumptive gustatory axons. Apical secretory granules, the distinctive cytologic feature of sustentacular cells, were absent. Cells with cytologic characteristics intermediate between chemosensory cells and basal extragemmal cells were considered to be differentiating chemosensory (DC) cells and appeared to arise from existing basal cells as well as undifferentiated postmitotic cells. Although extragemmal cells were extensively coupled by gap junctions which are apparent in electron micrographs of thin sections, similar junctions were absent from chemosensory and DC cells. While having minimal structural requirements for transduction and transmission of sapid stimuli (i.e., an intraoral surface and afferent synaptic contacts) chemosensory cells lacked efferent synapses and subsurface cisternae, which can be observed at later stages of gestation. Axoaxonic synapses, present between gustatory axons in the intragemmal and extragemmal epithelium and in the subgemmal connective tissue, were observed with greater frequency than at later stages of gestation. We conclude that the differentiation of chemosensory cells precedes the differentiation of sustentacular cells by several weeks. This fact lends support to the concept that chemosensory cells are a unique identifiable cells type in all chemosensory corpuscles.

Animals↗

Human fetal development between 90 and 170 days postmenses.

Linear measurements, total weights, and organ weights of 133 fresh human fetuses were obtained after therapeutic abortion between 90 and 170 days postmenses. Great apparent variation was observed in fetuses of given ages, especially in organ weights. There was no evidence of sex or parity differences.

Anthropometry↗

Histochemical and immunohistochemical distribution of glycosaminoglycans, type II collagen, and fibronectin in developing fetal cartilage of congenital osteochondrodysplasia rat (ocd/ocd).

The osteochondrodysplasia rat (ocd/ocd) is a lethal dwarfism. The ocd/ocd shows histological abnormalities of the epiphysis, characterized by a decrease in amount of glycosaminoglycans (GAGs) in the extracellular matrix (ECM). The present study describes histochemical and immunohistochemical distributions of GAGs, type II collagen, and fibronectin (FN) in abnormal humeral cartilage of the ocd/ocd fetuses on days 16-21 of gestation. A wide-spread region with severe necrosis was observed in the cartilage on days 20 and 21. The affected cartilage has small amounts of ECM, irregular columnizations, thinner hypertrophic zones, and expanded and pyknotic chondrocytes on days 16-21 of gestation. The severely expanded chondrocytes did not have cytoplasmic glycogens on days 19-21. Reactions for chondroitin sulfate (CS) and hyaluronic acid (HA) in the ECM were consistently lower in ocd/ocd than in +/+ during the entire period of observation, although there were granules immunoreactive to CS within the chondrocytes of ocd/ocd. The distribution of type II collagen seemed normal in relatively normal regions in the affected cartilage. Strong reactions for CS, HA, type II collagen, and FN were present in the necrotic region on days 20 and 21 of gestation. These findings suggest that the affected chondrocyte may have some defects in releasing ECM substances, which may be released by the process of cell rupture. We hypothesize that some defects in releasing processes inherent to the ocd/ocd cartilage may relate to cellular differentiation and cell death.

Animals↗