Days Of Intrauterine Life Research Articles

Janus kinase-signal transducer and activator of transcription signaling pathway in the ocular cells of rat fetuses exposed to maternal saturated fat ingestion.

The aim of this study was to analyze possible alterations (morphological and inflammatory) in the ocular cells of fetuses from mothers with insulin resistance exposed to saturated fatty acids through the period of pregnancy. Wistar female rats were induced to develop insulin resistance before pregnancy. Fetuses' skulls were collected on the 20th day of intrauterine life. The rats were separated on the first day of management into two groups according to the diet applied: control group (C): diet containing soybean oil as a source of fat; and saturated fatty acid group (S): diet containing butter as a source of fat. Histological and immunohistochemical analyses have been conducted. The immunohistochemical analyses of interleukin 6, suppressor of cytokine signaling, 3 and signal transducer and activator of transcription 3 did not demonstrate alterations in the expression of proteins in the fetuses of mothers fed with a saturated fatty diet. Moreover, no histopathological changes were noticed between groups. The saturated fatty diet does not induce tissue changes or activate the Janus kinase/signal transducer and activator of transcription signaling pathway during eye development in the fetuses of mothers with insulin resistance.

Proinflammatory State in the Odontogenesis of Fetuses Exposed to Different Types of Fatty Acids during Pregnancy

Objectives: The aim of the present study was to analyze the possible changes caused by the maternal ingestion of different types of fatty acids during pregnancy in the proinflammatory state in the odontogenesis of the fetuses. Subject and Methods: Twenty-four jaws (n = 6 per group) of Wistar rats were collected on the 20th day of intrauterine life. Mothers were separated on the first day of pregnancy into 4 groups according to diet, as described below: control group (C) – diet with soy oil as a source of fat; saturated fatty acid group (S) – diet with lard in saturated fatty acids; trans-fatty acid group (T) – diet with vegetable fat, rich in trans-saturated fatty acids; and polyunsaturated fatty acid (PUFA) group – diet with fish oil, rich in PUFAs. Results: Microscopic analysis showed no alterations in tissue development of the teeth between the groups with different lipid diets (T, S, and PUFA) when compared to the control group (C); immunohistochemical analysis for the expression of JAK2, STAT3, P-STAT3, SOCS3, and IL-6 showed no statistically significant difference (p > 0.05) compared to the control group. However, there were changes (p < 0.05) between the T group and the PUFA group in the expression of JAK2. Conclusion: Thus, lipid consumption in the maternal diet remains a topic to be explored in embryonic development, despite not causing morphological changes to the tooth germ of rats.

Evidence of Dental Lamina Preservation in the Development of Mice First Molars

The aim of this work was to analyse the behaviour of the dental lamina during the development process of first molar teeth. The offspring of female mice were analysed at the 16th day of intra-uterine life and since birth till 17 days old with the aim to evaluate the dental lamina evolution of upper and lower first molars. The animals were sacrificed, and the heads embedded in paraffin in order to get frontal or sagittal sections whose were stained by hematoxylin and eosin method. The results showed a very clear presence of the dental lamina in all periods under analysis, without the occurrence of its disorganization, in other words, it was permanently connecting the developing tooth germ to the oral epithelium until advanced dental eruption.

Non-random distribution of deleterious mutations in the DNA and protein-binding domains of IRF6 are associated with Van Der Woude syndrome.

BackgroundThe development of the face occurs during the early days of intrauterine life by the formation of facial processes from the first Pharyngeal arch. Derangement in these well‐organized fusion events results in Orofacial clefts (OFC). Van der Woude syndrome (VWS) is one of the most common causes of syndromic cleft lip and/or palate accounting for 2% of all cases. Mutations in the IRF6 gene account for 70% of cases with the majority of these mutations located in the DNA‐binding (exon 3, 4) or protein‐binding domains (exon 7–9). The current study was designed to update the list of IRF6 variants reported for VWS by compiling all the published mutations from 2013 to date as well as including the previously unreported VWS cases from Africa and Puerto Rico.MethodsWe used PubMed with the search terms; "Van der Woude syndrome," “Popliteal pterygium syndrome,” "IRF6," and "Orofacial cleft" to identify eligible studies. We compiled the CADD score for all the mutations to determine the percentage of deleterious variants.ResultsTwenty‐one new mutations were identified from nine papers. The majority of these mutations were in exon 4. Mutations in exon 3 and 4 had CADD scores between 20 and 30 and mutations in exon 7–9 had CADD scores between 30 and 40. The presence of higher CADD scores in the protein‐binding domain (exon 7–9) further confirms the crucial role played by this domain in the function of IRF6. In the new cases, we identified five IRF6 mutations, three novel missense mutations (p.Phe36Tyr, p.Lys109Thr, and p.Gln438Leu), and two previously reported nonsense mutations (p.Ser424*and p.Arg250*).ConclusionMutations in the protein and DNA‐binding domains of IRF6 ranked among the top 0.1% and 1% most deleterious genetic mutations, respectively. Overall, these findings expand the range of VWS mutations and are important for diagnostic and counseling purposes.

Expression of the matrix metalloproteinases 2 and 9 in the rat small intestine during intrauterine and postnatal life.

The expressions of matrix metalloproteinases 2 and 9 have been described during the development, as an example in heart and tooth but not in the small intestine yet. In this context, this study aimed to evaluate the expressions of MMP-2 and MMP-9 in the small intestine of Wistar rats during intrauterine (IU) and postnatal (PN) life. Expressions were determined on the 15th and 18th days of IU life and the 3rd, 10th, 17th, 25th, and 32nd days of PN life. Intestinal samples obtained from six animals were submitted to zymography, immunohistochemistry, and staining with Masson's trichrome. The results showed that MMP-2 and MMP-9 were not expressed during IU life; however, after birth, MMP-9 was immunolocalized in the goblet and mast cells. In conclusion, our results showed that MMP-2 and MMP-9 were not expressed in absorptive epithelial cells during the IU period of the small intestine but after birth, MMP-9 was expressed in the goblet cells, and mast cells present in the lamina propria.

POMME: The New Cohort to Evaluate Long-Term Effects After Prenatal Medicine Exposure.

The POMME (PrescriptiOn Médicaments Mères Enfants) cohort has been implemented for the evaluation of the long-term consequences of medicine prenatal exposure. It holds anonymous medical information as well as information on medicine and healthcare reimbursement to the children, from the first day of intra-uterine life until childhood. This article provides a description of the cohort regarding its structure and content and presents an outlook of the studies that could be performed with this new data source. Data sources include (1) the French Health Insurance Database (medicines and medical care prescriptions and reimbursements to children and mothers during pregnancy) and (2) the Mother and Child Protection Centre Database (child health certificates at birth, 9months of age and 24months of age). Children born in Haute-Garonne (south-west France), over a period of 1year (from 1 July to 30 June), are registered in POMME every 5years. The cohort began on 1 July, 2010. To date, 8372 children have been recorded in POMME. They have reached 7years of age now. Among them, 4249 (50.8%) are boys, 286 (3.4%) were from multiple pregnancies and 519 (6.2%) were born prematurely. They were prenatally exposed to 9.8 ± 6.1 medications. After birth, drug exposure was greatest in children aged 0-2years. Children were mostly exposed to paracetamol, anti-infective agents and respiratory system drugs; 908 (10.8%) children presented with at least two signs of psychomotor development disorders. POMME provides an observatory study on drug exposure and medical care use in children. This innovative cohort would make it possible to assess the risk of the long-term consequences of prenatal medicine exposure.

Complete Pentalogy of Cantrell: A case report and a review of literature

Pentalogy of Cantrell is a rare congenital malformation syndrome involving specific combination of ventral midline defects with ectopia cordis', as the most severe malformation. The complete form consists of five anatomical defects. We report a case of a one hour old female neonate delivered to a 27 year old primipara who presented with the complete form of the syndrome. She had surgery on the 4 th day of life, however died 36 hours 1 It is also known as Cantrell-Haller-Ravitch syndrome named after the initial authors. 2 The cardinal features of the syndrome were anterior abdominal defect (omphalocele) in association with ectopia cordis (EC) (evisceration of the heart). Toyama (1972) subsequently described the full spectrum of the Cantrell's syndrome to consist of ectopia cordis, a defect in the diaphragmatic pericardium, a deficiency of the anterior diaphragm, lower sternal defect, a midline supraumbilical abdominal wall defects, various structural congenital intracardial anomalies. 3 The precise cause of Pentalogy of Cantrell has remained elusive. One hypothesis that has enjoyed wide acceptance is that it results from a developmental failure of a segment of the lateral mesoderm at about the 14 th to 18 th days of intrauterine life, with subsequent failure in the development of the transverse septum of the diaphragm and the failure in the ventromedial migration of the paired mesodermal folds of the upper abdomen.

Diagnosis and Management of Velopharyngeal Insufficiency Associated with Chromosomal Syndromes

All congenital structural defects in the body are the result of an error in morphogenesis. Morphogenesis takes place around 25 to 29 days of intrauterine life. Chromosomal syndromes involve a phenotypically significant structural and/or numerical chromosomal abnormality. An insufficient function of the velopharyngeal sphincter induces excessive nasal resonance during speech. This abnormal resonance is called hypernasality. A deficient seal of the velopharyngeal sphincter creates an airflow leaking into the rhinopharynx, resulting in abnormal air turbulence through the nasal cavities which can be easily perceived and is called nasal emission. Hypernasality and nasal emission are the clinical signs of velopharyngeal insufficiency (VPI). In other words, VPI is the velopharyngeal inability to create an efficient seal during speech. Most chromosomal syndromes cause VPI as a consequence of a cleft palate. However, when patients with a chromosomal abnormality and VPI are being clinically assessed, it is essential to keep in mind that an apparently and morphologically intact uvula and velum do not rule out the possibility of a sub mucous cleft palate. Several chromosomal syndromes can be associated with VPI, including: 22q11.2 deletion syndrome (22q11.2DS) or velocardiofacial syndrome among other names, Opitz G/BBB syndrome (OS), Kabuki syndrome (KS) and Jacobsen syndrome (JS). Pierre – Robin sequence (PRS) can be associated with some chromosomal syndromes. In these ncases, PRS is referred as syndromic PRS. In this paper, the diagnosis and management of VPI in the most common chromosomal syndromes is discussed.

Undernutrition upregulates fumarate hydratase in the rat nucleus accumbens

Previous comparative studies of fumarate hydratase (FH) protein density revealed that the enzyme was overexpressed in the striatum of rodents that are less influenced by rewarding stimuli, from cocaine to food. Therefore, we recently proposed FH as a potential striatal biomarker of brain reward deficiency and addiction vulnerability. This work has been focused to investigate FH activity in the Nucleus Accumbens (NAc) of undernourished rats, taking into account that malnutrition has been related to increased responsiveness to food and drug reward. To this end, we have studied adult female Wistar rats severely food restricted from the 16th day of intrauterine life until adulthood. Animals were sacrificed to dissect the NAc and obtain mitochondrial and cytosolic fractions after homogenisation and centrifugation. FH activity was measured by conversion of malate to fumarate, and protein levels were compared by Western blot analysis when fractions showed differences in activity. Undernutrition did not change cytosolic FH activity but led to a marked increase of mitochondrial FH activity (72%) and protein content (50%) in the NAc. This change was in the opposite direction that one would predict if it was related to addiction vulnerability of some kind, but strongly suggests that mitochondrial FH needs to be at some optimal level for normal reward responsiveness.

Morphological Analysis of the Enamel Organ in Rats Treated with Fluoxetine

PURPOSE:Previous studies have evaluated the presence of serotonin in the dental epithelia and mesenchyme during odontogenesis, suggesting its participation in tooth development.MATERIALS AND METHODS:Here, we used fluoxetine, a selective serotonin re-uptake inhibitor, at a dose of 10 mg/kg, administered for 20 days during pregnancy in 12 Wistar rats to examine the influence of this drug on the development of the enamel organ of the upper first molars of rat fetuses at 17 days of intra-uterine life (i.u.l.), and at one, five and ten days postpartum. The pregnant rats were anesthetized with xylazine at 10 mg/kg and ketamine at 25 mg/kg. The fetuses were removed and beheaded; their jaws were removed, and the upper jaws were exposed. The tissues were fixed in Bouin’s fixative, decalcified in 5% nitric acid for 4 – 12 h, conventionally processed for microscopy, and embedded in paraffin. Serial sections of approximately 5 μm were obtained and stained with hematoxylin and eosin, as well as periodic acid-Schiff.RESULTS AND CONCLUSION:Morphological analysis showed no structural changes in the experimental group compared to the controls, suggesting that, at the dose used, fluoxetine does not interfere with serotonin-mediated development of the enamel organ or the process of amelogenesis.

The hypothalamic magnocellular neurosecretory system in developing rats.

Studies concerning the development of the magnocellular system are scarce and discordant in literature. We carried out an immunohistochemical study on supraotic and paraventricular hypothalamic nuclei using antivasopressin and antioxytocin antibodies in developing rats between the 15th day of intrauterine life and the 6th day of postnatal life. In addition, we performed RT-PCR experiments to establish the stage at which these hormones appear and neurosecretory activity commences. The results showed that supraoptic and paraventricular nuclei appear, respectively, on the 16th and the 18th day of intrauterine life and both immediately synthetize vasopressin neurohormone. By contrast, synthesis of oxytocin takes place from the 2nd day after birth. Probably, these nuclei synthetize oxytocin in conjunction with the decline of placental maternal oxytocin.

Histomorphogenesis and immunohistochemical study of the bovine pineal gland (Bos taurus) during prenatal development (160 days of gestation to birth).

The ontogenesis of the pineal gland of 20 bovine embryos (Bos taurus) has been analysed from 160 days of gestation to birth by means of optical microscopy and immunohistochemical techniques. For this study, the specimens were grouped into two stage in accordance with the most relevant histological characteristics: Stage 1 (160 to 200 days of prenatal development) and Stage 2 (220 days of prenatal development to birth). At 160 days of gestation some rounded structures with a central lumen, which we refer to as glandular rosettes, begin differentiation from the epithelium of the pineal recess, experiencing an extraordinary increase in number and size at 200 days of intrauterine life. In the interior of the pineal parenchyma we observed some morphologically rounded cells with oval euchromatic nuclei and a well-differentiated nucleolus that we refer to as the pinealoblasts. We also observed other cells characterised by the presence of low cytoplasm and rounded and highly stained nuclei that we refer to as the interstitial cells. The glandular stroma is formed from the capsular, trabecular, and perivascular connective tissue as well as from the reticular network that comes from the cellular processes of the interstitial cells. The blood vessels, at 240 of gestation, show well-formed walls where the endothelial cells stand out. At 160 days of gestation we witnessed some cells with small, dense, oval nuclei, positive to the glial fibrillary acidic protein (GFAP). At this age NPY positive fibres were detected, distributed around the blood vessels and among the pinealoblasts. We conclude by clarifying that the changes detected in the morphology as well as in the number and size of glandular rosettes appear to be related to the functional activity of the pineal gland during embryonic development.

Embryonic development of the bovine pineal gland (Bos taurus) during prenatal life (30 to 135 days of gestation).

The ontogenesis of the pineal gland of 30 bovine embryos (Bos taurus) has been analysed from 30 until 135 days of gestation by means of optical microscopy and immunohistochemical techniques. For this study, the specimens were grouped into three stages in accordance with the most relevant histological characteristics: Stage 1 (30 to 64 days of prenatal development); Stage 2 (70 to 90 days) and Stage 3 (106 to 135 days). In the cow, it is from 30 days of gestation that the first glandular outline becomes differentiated from the diencephalic ependyma of the third ventricle. This differentiation includes the phenomena of proliferation and multiplication of the ependymal cells that form the epithelium of the pineal outline in development. At 82 days of intrauterine life, in the interior of the pineal parenchyma, we witnessed some incipient pseudoglandular structures that at 135 days were well differentiated. The pineal parenchyma displays a cytology made up of two cellular types of structurally distinct characteristics: pinealoblasts and interstitial cells. Both cellular types begin differentiation at 70 days of embryonic development, the pinealoblasts being greater in number than the interstitial cells. The glandular stroma is formed from the capsular, trabecular and the perivascular connective tissue, filling the interparenchymal space. A dense network of capillaries, which drive across the trabecular connective tissue towards the central glandular zone where their density increases and their calibre is reduced, complete the glandular structure. GFAP positive cells were observed in the embryonic pineal parenchyma in stage 3. At 135 days of gestation, NPY positive fibers entered the pineal gland through the pineal capsule occupying a perivascular localization. Morphological studies of this nature are vital for future use as parameters, indicative of the functional activity of the bovine pineal gland during embryonic development.

Morphometric and immunohistochemical study of the reticulum of red deer during prenatal development.

Iberian red deer need to be conserved for their economic role and for their genetic importance as an important component of the ecosystem. Modifications currently being made to traditional management systems require a better understanding of the structure, function and development of their alimentary system. Here we describe a histomorphometric and immunohistochemical analysis of the stomach of 25 red deer embryos and fetuses from 30 days of gestation until birth (235 days). Differentiation of the reticular compartment from the primitive gastric tube begins at 67 days, forming a three-layered structure: epithelium, pluripotential blastemal tissue and serosa. The primitive reticular cells are initiated as small epithelial evaginations (primary ribs) at 117 days. At 142 days, lateral growths appear from the primary reticular ribs, forming the corneum papillae. The secondary reticular ribs form at 142 days as growths from the primary ribs. The uneven height of primary and secondary reticular ribs leads to the formation of cells of varying size. Growth of the reticular ribs involves the lamina propria but not the submucosa, so clear separation of these layers is maintained during histodifferentiation. Formation of the tunica muscularis from the pluripotential blastemal tissue begins at 67 days of intrauterine life, as two layers of longitudinally and circularly arranged myoblasts. Differentiation of the muscularis from the mucosa occurs at approximately 205 days, as longitudinal projections of the internal bundles of the tunica muscularis form the musculature of the primary ribs. The secretion of neutral and acid mucopolysaccharides by the reticular epithelial layer begins at 67 days, establishing the gradual adaptation of the mucosa to its protective function in postnatal life. Neuroendocrine (non-neuron enolase) and glial cells (glial fibrillary acidic protein and vimentin) were detected by immunohistochemistry, in a similar localization and intensity to that reported in the rumen. The neuropeptides vasoactive intestinal peptide and neuropeptide Y showed a positive immunoreaction in the reticular epithelium from 142 days of prenatal life, again earlier than reported for the rumen. In comparison with domestic ruminants, deer were shown to be less precocious with regard to development of gastric tube, in their capacity to secrete neutral mucopolysaccharides, and in their neuroendocrine nature, as determined by the detection of positive neuroendocrine and/or glial cells.

Morphometry of megakaryocytes in the liver of New Zealand White rabbits during intrauterine and postnatal development

The hepatic megakaryocytic cells of New Zealand White rabbit in the intrauterine phase and in the immediate postnatal period were studied. Statistical analysis of the data concerning the cytoplasm and nucleus of those cells, i.e., area, perimeter, maximum diameter, minimum diameter, volume and shape factor, presented significant differences (p&lt;0.01) for F values concerning the life phases studied on15th, 22nd and 29th day of intrauterine life and 10th day of postnatal life, and for F values for animal within each phase. The Tukey’s test showed that most of the parameters studied in the cytoplasm and nucleus of these megakaryocytic cells presented the lowest values on the 15th day of intrauterine life and the highest on the 22nd day of the same phase.

Plasma Leptin Levels in Rat Mother and Offspring during Pregnancy and Lactation

The profiles of plasma leptin levels in pregnant and lactating rats and their offspring were determined. The plasma leptin levels increased on days 12 and 20 of gestation and declined on day 21 of gestation, remaining at this level during lactation. These changes were similar for lumbar adipose tissue weight, and a significant correlation was found when both variables were plotted with individual values. During the last 2 days of intrauterine life, the plasma leptin levels in the fetuses were in the same range as in their mothers, declining from day 20 to day 21. On the 1st day of life, the leptin levels increased to decline in suckling newborns after 4 days, remaining stable until day 20 of life. The enhancement in maternal white adipose tissue mass that takes place during pregnancy and its decline around parturition and lactation are proposed to contribute actively to the changes in the plasma leptin profile detected at these stages. Besides the contribution of placental leptin for the fetus and milk leptin for the suckling newborn, it is proposed that brown adipose tissue, which is the first form of adipose tissue that appears during development in the rat, is responsible for most of the changes in plasma leptin levels seen around birth, whereas its later decline could be mediated by the hormonal changes occurring after birth.

Developmental Changes in Apolipoprotein B Gene Expression in the Liver of Fetal Calves

Changes in apolipoprotein (apo B) gene expression in the liver were determined in fetal calves from 90 to 260 days of intrauterine life. Results were compared with those obtained from the livers of 1-month-old calves and adult cows. By Western blot analysis using a rabbit antiserum to bovine apo B, apo B100 was detected from 90 days of intrauterine life. Apo B100 was shown to be the only form of apo B detected in the liver of fetal calves whatever the gestational age indicating the lack of editing process during the prenatal period. Hepatic apo B contents were stable during intrauterine life and comparable to those of calves and lower than those of cows. Hepatic contents of apo B mRNA increased with the gestational age similarly to total RNA. Values of apo B mRNA at 260 days of intrauterine life were comparable to those in the liver of 1-month-old calves and adult cows. These results suggested that hepatic synthesis of calf apo B during fetal development is specifically regulated at a posttranscriptional level, either by a decrease in the rate of translation and/or by an increase in the rate of intracellular apo B degradation.

Perinatal estrogen exposure: Later repercussion on the fertility of rats

The aim of the present study was to investigate the effects of perinatal estrogen exposure in the fertility of rats. Thus, rats were treated with estrogen on the 21st or 22nd day of intra-uterine life or treated with estrogen immediately after birth. It was observed that the testicular descent of males and beginning of puberty of females were advanced in all estrogen-treated groups. The females from estrogen-treated groups showed reduced frequency of estrous in 15 consecutive days of study, and there was an increase in estrous duration. Their fertility also were impaired and a reduction in the number of alive fetuses, as well as enhancement of pre-and postimplantation loss, mainly in the group treated with estrogen on the 21st day of intra-uterine life. However, the alterations observed in the fertility of estrogen-treated male rats were slighter and only females mated with male rats from the group treated with estrogen immediately after birth showed enhanced preimplantation loss. We suggest that the reproductive function is impaired by exposure to estrogen in the perinatal life of rats, and that the mechanisms involved in this effect are distinct for males and females.

Fetal inoculation with donor cells in cardiac xenotransplantation

In utero fetal inoculation with allogeneic cells has produced subsequent tolerance to experimental cardiac allografts. We attempted to extend this observation to a model of xenogeneic cardiac transplantation. Lewis rat fetuses were inoculated with Golden Syrian hamster thymocytes (n = 5) or whole spleen cells (n = 5) on the tenth day of intrauterine life. Six weeks after the birth of pretreated fetuses, heterotopic cardiac transplantation using a hamster donor was performed. Three to 4 weeks after parturition, we performed heterotopic cardiac transplantation using hamster donors in the female Lewis rats whose fetuses had been treated in utero. Animals treated in utero with either thymocytes or whole spleen cells had graft survival of 3 days, not different from that in untreated Lewis rats (n = 5) (p = not significant). Maternal Lewis rats whose fetuses were treated with thymocytes (n = 5) or whole spleen cells (in = 4) had markedly reduced survival of xenogeneic cardiac grafts (range, 3 to 20 hours; mean, 15 hours; p < 0.01; and range, 5 to 15 minutes; mean, 10 minutes; p < 0.01, respectively). Female Lewis rats without intrauterine inoculation (n = 5) had expected xenograft survival time (3 days) (p = not significant). Immunohistochemical staining of hyperacutely rejected grafts showed deposits of immunoglobulin M as well as immunoglobulin G and complement. In normally rejected xenografts, no immunoglobulin M was detected. These studies reveal the surprising observation that fetal exposure to xenogeneic cells sensitizes the maternal rat without tolerizing the fetal rat as observed in an allograft model. In addition, whole spleen cells produce a more vigorous hyperacute rejection than thymocytes, suggesting that B cells or macrophages may be the sensitizing agents. The accelerated rejection observed has the characteristics of an immunoglobulin M antibody-mediated hyperacute rejection response with deposition of complement.

Developmental regulation of angiotensin converting enzyme and angiotensin type 1 receptor in the rat pulmonary circulation.

Factors that influence the development of the normal pulmonary vasculature are poorly understood. Since increased local production of angiotensin II (AII) by angiotensin converting enzyme (ACE) has been implicated in the medial hypertrophy of systemic and pulmonary hypertension, we questioned whether ACE and angiotensin receptor expression may influence the muscularization of the normal pulmonary vasculature during development. The approach employed measurement of lung ACE activity, assessment of local ACE expression by immunohistochemistry, and angiotensin type 1 receptor (AT1) expression by in situ hybridization in rat lungs ranging from 15 days of intrauterine life (term = 21 d) to adulthood. The temporal and spatial pattern of ACE expression was compared with that of the endothelial marker, von Willebrand factor (vWF), and the smooth muscle cell markers, alpha smooth muscle actin and smooth muscle myosin. ACE activity was first detected in lung homogenates on day 17 of gestation (1 +/- 0.2 mU/mg) and increased progressively to term (27.7 +/- 3.2 mU/mg). However, the greatest increase in lung ACE activity to adult levels (379 +/- 25.2 mU/mg) occurred between 2 and 4 wk of postnatal life. Immunohistochemistry demonstrated vWF expression by vascular endothelium throughout the lung as early as day 15 of gestation. In contrast, ACE expression was observed in the endothelium of only hilar pulmonary arteries on day 15 of gestation, and thereafter was noted to be expressed in endothelial cells of progressively more distal arteries, such that by term, endothelial cells of all muscularized arteries expressed ACE. Alveolar capillary ACE expression was not detected until day 20 of gestation, and increased dramatically after birth. Smooth muscle actin expression in lung arteries closely paralleled the expression of endothelial ACE. AT1 receptor mRNA was first expressed in the peripheral lung on day 17 of gestation by non-epithelial undifferentiated mesenchyme. In contrast, AT1 mRNA signal was much reduced in differentiated smooth muscle. We speculate that ACE expression in the fetal lung circulation may influence the muscularization of fetal pulmonary arteries by the interaction of locally produced angiotensin II with the AT1 receptor.