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PubMed1997

Cancer mortality among atomic bomb survivors exposed in utero or as young children, October 1950-May 1992.

Cancer mortality for the period from October 1950 through May 1992 was analyzed in atomic bomb survivors exposed in utero. Risk estimates for this group were also compared to those for survivors who were less than 6 years old at the time of exposure. The cohorts studied include 807 in utero survivors and 5,545 persons exposed during childhood with all members of both groups having estimated doses of at least 0.01 Sv. The comparison group includes 10,453 persons with little (<0.01 Sv) or no exposure. Analyses were limited mainly to cancer deaths occurring between the ages of 17 and 46. Only 10 cancer deaths were observed among persons exposed in utero. However, there is a significant dose response with an estimate of excess relative risk per sievert (ERR/Sv) of 2.1 (90% confidence interval of 0.2 to 6.0). This estimate does not differ significantly from that for survivors exposed during the first 5 years of life. The cancer deaths among those exposed in utero involved leukemia (2), female-specific organs (3) and digestive organs (5). Nine deaths occurred in females, where the excess risk for all solid cancers has a 90% confidence interval on the ERR/Sv of 1.6 to 17. Significant risks were found for cancers of the digestive system [90% confidence interval (CI) on the ERR/Sv of 0.7 to 20] and for female-specific cancers (90% CI on the ERR/Sv of 0.7 to 42). These risks do not differ significantly from those seen in females exposed as children. There were no deaths from solid cancer in men exposed in utero. The ERR/Sv has an upper 95% confidence bound of 2.5 which does not differ from that for exposed children, where the upper 95% confidence bound is 1.5. The sexes differ even when female-specific cancers are excluded from the comparison. Although there were only two leukemia deaths among those exposed in utero, the leukemia death rate for this group is higher than that in the comparison group (P = 0.054) with an exposure effect that is about half the magnitude and not significantly different from that seen after childhood exposure (P = 0.103). However, there is no evidence of a dose response among those exposed in utero because no high-dose leukemia deaths were observed, a result that differs considerably from that for those exposed as children. There is a need for caution in the interpretation of these data. First, the number of cancer deaths is small; second, there is unexplained significant difference in the mortality from solid cancer between the sexes; and third, the excess of leukemia in those exposed in utero is not reflected in an increasing dose response.

Adult↗

PubMed1997

Understanding utero-placental blood flow in normal and hypertensive pregnancy through a mathematical model.

Normal development of utero-placental circulation is crucial not only for the survival and growth of the fetus in utero, but also for maternal well-being. Any disturbance or abnormality may reflect underlying pathology. Geometric conversion of a pre-pregnant spiral vessel into a divergent low-resistance vessel is believed to be responsible for the increased utero-placental blood flow in normal pregnancy. Known biomedical investigative techniques have failed to explain many such underlying haemodynamic changes taking place in the utero-placental system. Therefore, proper understanding of the system using a mathematical model has been found to be useful. The physiological fluid dynamic study is the first in this branch of physiology. Abnormal pressure gradient, axial velocity, volume flow and shear rate are obtained for various slowly changing geometries such as, tapering, divergence, local constrictions and sinusoidal tube for low Womersley parameters. The model can explain many enhanced patho-physiological changes, such as persistence or the appearance of local constriction in the utero-placental vessels. Such pathological changes are considered to be responsible for very high utero-placental resistance, leading to blood flow insufficiency in pre-eclampsia or intra-uterine growth retardations. It is believed that these changes may be caused by low shear rate on the pre-existing deranged or abnormal endothelium. Furthermore, this derangement is caused by an abnormal proliferation of either spiral vessels or the invading non-villous trophoblasts. Doppler flow study can explain and validate some of the theoretically derived flow velocity results. The study opens up a new area of research into utero-placental physiological fluid dynamics.

Computer Simulation↗

PubMed1996

Exogenous prostaglandin F2 alpha stimulates utero-ovarian release of prostaglandin F2 alpha in sheep: a possible component of the luteolytic mechanism of action of exogenous prostaglandin F2 alpha.

Exogenous prostaglandin F2 alpha (PGF2 alpha) is luteolytic in sheep, but its mechanism of action is not completely understood. We hypothesized that exogenous PGF2 alpha stimulates the uterine and(or) ovarian secretion of PGF2 alpha and that, when intramuscular doses of PGF2 alpha are minimal, the utero-ovarian unit is a component of the luteolytic mechanism of action of exogenous PGF2 alpha. Thus, this study was conducted to determine whether exogenous PGF2 alpha stimulates the utero-ovarian release of PGF2 alpha. Catheters were positioned in the vena cava at points cranial and caudal to the entry of utero-ovarian blood, and ewes were either hysterectomized and ovariectomized (H/OX) or left intact (Intact). Treatments were in a 2 x 2 factorial arrangement (i.e., H/OX and PGF2 alpha were the main effects), and there were five ewes per treatment group. In Experiment 1, on Day 9 after the onset of estrus, either saline or PGF2 alpha (15 mg) was injected intramuscularly in the neck, and vena caval blood samples were collected frequently for 120 min, then less frequently for 48 hr. In Experiment 2, on Day 9 after estrus or H/OX, either saline of PGF2 alpha (5 mg, then 5 mg 3 hr later) was injected intramuscularly in the neck, and vena caval blood samples were collected frequently for 150 min after each injection. In both experiments, exogenous PGF2 alpha induced immediate and significant increases in the utero-ovarian release of PGF2 alpha. The increases in PGF2 alpha concentrations were considerably more pronounced in vena caval blood samples collected cranial than in those collected caudal to the entry of utero-ovarian blood, and the increase was significantly greater in Intact than in H/OX ewes treated with PGF2 alpha. Vena caval concentrations of 13,14-dihydro-15-keto-PGF2 alpha (PGFM) increased after exogenous PGF2 alpha, but the changes in PGFM were not suitable representations of the changes in vena caval concentrations of PGF2 alpha. Changes in progesterone concentrations indicated that both PGF2 alpha injection regimens were luteolytic. The results from this study indicate that exogenous PGF2 alpha stimulates the utero-ovarian production of PGF2 alpha, and we believe that the utero-ovarian unit is a component of the luteolytic mechanism of action of exogenous PGF2 alpha.

Abortifacient Agents, Nonsteroidal↗

PubMedDate not supplied

Evolution of viviparity in sceloporine lizards: in utero PO2 as a developmental constraint during egg retention.

Reptilian viviparity evolves through selection for increasingly prolonged egg retention within the oviduct. In the majority of sceloporine lizard species, however, egg retention past the normal time of oviposition results in retarded or arrested embryonic development. In this study, we tested the hypothesis that the amount of embryonic development normally attained in utero is directly related to in utero oxygen partial pressure (PO(2)). The three species of sceloporine lizards we used are characterized by developmental arrest (Urosaurus ornatus), retarded development (Sceloporus virgatus), and normal development (Sceloporus scalaris) when eggs are retained. We incubated eggs of these species for 10 d under conditions that simulated retention in the oviduct at a range of experimental oxygen partial pressures (PO(2)). We estimated in utero PO(2) from a standard curve generated from the stage and dry mass of experimental embryos incubated for 10 d at known PO(2). The standard curve was then used to predict the PO(2) associated with the observed rate of development of embryos retained in utero. The results of this study showed that the degree of embryonic development attained in utero during egg retention was positively associated with in utero PO(2). The results indicate that oxygen availability in utero is associated with interspecific differences in the capacity to support intrauterine development in sceloporine lizards.

Animals↗

PubMed2005

Risk factors for in utero and intrapartum transmission of HIV.

OBJECTIVE: To identify predictors of in utero and intrapartum HIV-1 transmission in infants born in the Women and Infants Transmission Study between 1990 and 2000. METHODS: In utero HIV-1 infection was defined as an infant with the first positive HIV-1 peripheral blood mononuclear cell culture and/or DNA polymerase chain reaction assay at 7 days of age or younger; intrapartum infection was defined as having a negative HIV-1 culture and/or DNA polymerase chain reaction assay at 7 days of age or younger and the first positive assay after 7 days of age. RESULTS: Of 1709 first-born singleton children with defined HIV-1 infection status, 166 (9.7%) were found to be HIV-1 infected; transmission decreased from 18.1% in 1990-1992 to 1.6% in 1999-2000. Presumed in utero infection was observed in 34% of infected children, and presumed intrapartum infection, in 66%. Among infected children, the proportion with in utero infection increased over time from 27% in 1990-1992 to 80% (4 of 5) in 1999-2000 (P = 0.072). Maternal antenatal viral load and antiretroviral therapy were associated with risk of both in utero and intrapartum transmission. Controlling for maternal antenatal viral load and antiretroviral therapy, low birth weight was significantly associated with in utero transmission, while age, antenatal CD4 cell percentage, year, birth weight, and duration of membrane rupture were associated with intrapartum transmission. CONCLUSION: Although there have been significant declines in perinatal HIV-1 infection over time, there has been an increase in the proportion of infections transmitted in utero.

Age Factors↗

PubMed2007

In utero nicotine exposure alters fetal rat lung alveolar type II cell proliferation, differentiation, and metabolism.

We recently suggested that alveolar interstitial fibroblast-to-myofibroblast transdifferentiation may be a key mechanism underlying in utero nicotine-induced lung injury. However, the effects of in utero nicotine exposure on fetal alveolar type II (ATII) cells have not been fully determined. Placebo, nicotine (1 mg/kg), or nicotine (1 mg/kg) + the peroxisome proliferator-activated receptor (PPAR)-gamma agonist prostaglandin J(2) (PGJ(2), 0.3 mg/kg) was administered intraperitoneally once daily to time-mated pregnant Sprague-Dawley rats from embryonic day 6 until their death on embryonic day 20. Fetal ATII cells were isolated, and ATII cell proliferation, differentiation (surfactant synthesis), and metabolism (metabolic profiling with the stable isotope [1,2-(13)C(2)]-d-glucose) were determined after nicotine exposure in utero or in vitro. In utero nicotine exposure significantly stimulated ATII cell proliferation, differentiation, and metabolism. Although the effects on ATII cell proliferation and metabolism were almost completely prevented by concomitant treatment with PGJ(2), the effects on surfactant synthesis were not. On the basis of in utero and in vitro data, we conclude that surfactant synthesis is stimulated by nicotine's direct effect on ATII cells, whereas cell proliferation and metabolism are affected via a paracrine mechanism(s) secondary to its effects on the adepithelial fibroblasts. These data provide evidence for direct and indirect effects of in utero nicotine exposure on fetal ATII cells that could permanently alter the "developmental program" of the developing lung. More importantly, concomitant administration of PPAR-gamma agonists can effectively attenuate many of the effects of in utero exposure to nicotine on ATII cells.

Animals↗

PubMed2000

Effects of in utero and environmental tobacco smoke exposure on lung function in boys and girls with and without asthma.

To investigate whether the effects of in utero exposure to maternal smoking and environmental tobacco smoke (ETS) exposure on lung function vary by sex or asthma status, we examined medical history and tobacco smoke exposure data for 5,263 participants in the Children's Health Study. At study enrollment, parents or guardians of each subject completed a questionnaire, and lung function was measured spirometrically with maximum forced expiratory flow-volume maneuvers. To assess the in utero effects of maternal smoking and ETS exposure on lung function, we used regression splines that accounted for the nonlinear relationship between pulmonary function, height, and age. In utero exposure to maternal smoking was independently associated with deficits in lung function that were larger for children with asthma. Boys and girls with a history of in utero exposure to maternal smoking showed deficits in maximum midexpiratory flow (MMEF) and a decrease in the FEV(1)/FVC ratio. As compared with children without asthma, boys with asthma had significantly larger deficits from in utero exposure in FVC, MMEF, and FEV(1)/FVC, and girls with asthma had larger decreases in FEV(1)/FVC. The effect of ETS exposure varied by children's gender and asthma status. Deficits in flows associated with current ETS exposure were present in children with and without asthma but were significant only among children without asthma. Past ETS exposure was associated with reduced FEV(1), MMEF, and FEV(1)/FVC among boys with asthma. In contrast, past ETS exposure was associated with decreased flow rates in girls without asthma. In summary, both in utero exposure to maternal smoking and ETS exposure were associated with persistent deficits in lung function. The effects of in utero exposure were greatest among children with asthma.

Adolescent↗

PubMed1993

Computer analysis of the human embryo growth curve: differences between published ultrasound findings on living embryos in utero and data on fixed specimens.

Accurate information on the normal growth rate of the human embryo is fundamental to a better understanding of the embryonic period of pregnancy. Crown-rump length measured previously in utero (N = 227) with vaginal ultrasound in 107 in vitro fertilization (IVF) or gamete intrafallopian transfer (GIFT) singleton pregnancies was compared to the greatest length of fixed human embryos from the Carnegie collection, of known developmental stage whose postovulatory ages were estimated from menstrual histories. Average crown-rump length in utero was 60% of the greatest length of the fixed specimens prior to postovulation day 33, but were equal after postovulation day 40. The growth rate of in utero embryos and fixed specimens, analyzed by computer using exponential equations, was compared to linear and polynomial equations used in previously published embryo growth tables. The exponential equation, length = exp(a + B/age), fit in utero measurements best, while the equation length = exp[a + b/exp(age)] fit the fixed specimens best. Differences between length in utero and in fixed specimens may be related to distortion of the fixed embryos resulting from the formalin fixation, to ultrasound distortion, to curling of the embryo, or to incorrectly estimated ages of the fixed specimens. Study of human embryos in utero is now practical with vaginal ultrasound.

Embryonic and Fetal Development↗

PubMed1993

The effects of in utero ethanol administration on the electrophysiological activity of rat nigrostriatal dopaminergic neurons.

Iontophoresis and single-unit extracellular recording techniques were utilized to study the effects of in utero ethanol administration on nigrostriatal dopaminergic (NSDA) neurons in adult rats. Pregnant Sprague-Dawley rats consumed an ethanol-containing liquid diet providing 0%, 17.5%, or 35% ethanol-derived calories (EDC) from gestation day 8 until parturition. A separate group was fed standard rat chow as an ad lib, diet control. The dose-response curves of intravenously administered apomorphine on the spontaneous activity of NSDA neurons were shifted to the right in animals exposed to a liquid diet containing 17.5% or 35% EDC compared to 0% EDC or ad lib. control groups. The responsiveness of NSDA neurons to microiontophoretic application of the D-2 DA receptor agonist, quinpirole, was not altered following in utero ethanol exposure. These results suggest that in utero ethanol exposure may produce a down-regulation in the function of DA receptors distinct from the somatodendritic impulse-regulating D-2 autoreceptors. The firing pattern of NSDA neurons was also found to be altered after in utero ethanol exposure. There was a dissociation between the firing rate and burst activity in neurons that displayed burst-firing patterns in animals with in utero ethanol exposure. These observations agree with biochemical and behavioral studies that in utero ethanol exposure produces a long-lasting effect on the development of electrophysiological and pharmacological characteristics of midbrain DA systems in adulthood.

Animals↗

PubMed1992

Cocaine in utero enhances the behavioral response to cocaine in adult rats.

The effects of cocaine exposure in utero on cocaine-induced behaviors and dopamine (DA) transmission in the nigrostriatal and mesolimbic pathways were measured in adult rats. Pregnant rats received either saline or cocaine (1 or 3 mg/kg, IV) daily throughout gestation. When offspring were 3 months of age, locomotor and stereotypic behaviors were rated after an injection of either saline or cocaine (10 mg/kg, IP). Cocaine in utero increased the response to cocaine in adult offspring and increased basal locomotion in female offspring. Cocaine in utero increased amphetamine-stimulated release in female offspring but decreased release in males. On the other hand, male rats that had received cocaine in utero exhibited greater basal tritium release. One injection of cocaine increased amphetamine-stimulated [3H]DA release from striatal slices of male rats but not female rats. Neither cocaine in utero nor in vivo affected D2 DA receptor binding in striatum nor nucleus accumbens. Thus, cocaine in utero behaviorally sensitized animals to subsequent cocaine exposure and increased [3H]DA release from nigrostriatal endings, but the relationship of these two variables depended upon gender.

Animals↗

PubMed1990

Chronic utero-ovarian vein catheterization with subsequent occlusion prolongs the estrous cycle and changes electromyographic activity in the myometrium of ewes.

The objective of our study was to determine the effect of chronic utero-ovarian vein catheterization in ewes on estrous cycle length, plasma progesterone (P) concentration, and myometrial electromyographic activity. Cyclic ewes with inferior vena cava catheters were used as controls. Estrus was synchronized in ten ewes and 10 to 12 d following estrus, the ewes were anesthetized, fitted with myometrial electromyograph leads and with utero-ovarian vein (n = 5) or inferior vena cava (n = 5) catheters. After surgery, ewes returned to estrus as expected (16 to 18 d interestrus interval). The second cycle of four of five ewes with utero-ovarian vein catheters were prolonged (40 to 58 d). The inferior vena cava catheterized ewes had normal length second cycles. Plasma P concentrations reflected the estrous cycles: low (</= 0.01 ng/ml) at estrus and 2 to 3 ng/ml at midcycle. The inferior vena cava catheterized ewes had decreased plasma P concentrations after luteolysis (Days 13 to 14) while four of five utero-ovarian vein catheterized ewes maintained elevated plasma P concentrations for 20 to 58 d. Catheterization affected the myometrial electromyograph; short events (16 to 180 sec) were increased on Days 5 to 13 in utero-ovarian vein as compared with inferior vena cava catheterized ewes (P < 0.05); long events (180 to 900 sec) tended to decrease from Days 1 to 15 in utero-ovarian vein ewes, but this was not statistically significant (P > 0.05).

Journal Article↗

PubMed2004

Corroboration of in utero MRI using post-mortem MRI and autopsy in foetuses with CNS abnormalities.

AIMS: To corroborate the findings of in utero magnetic resonance imaging (MRI) with autopsy and post-mortem MRI in cases of known or suspected central nervous system (CNS) abnormalities on ultrasound and to compare the diagnostic accuracy of ante-natal ultrasound and in utero MRI. METHODS: Twelve pregnant women, whose foetuses had suspected central nervous system abnormalities underwent in utero MRI. The foetuses were imaged using MRi before autopsy. The data were used to evaluate the diagnostic accuracy of in utero MRI when compared with a reference standard of autopsy and post-mortem MRI in 10 cases and post-mortem MRI alone in two cases. RESULTS: The diagnostic accuracy of antenatal ultrasound and in utero MRI in correctly characterizing brain and spine abnormalities were 42 and 100%, respectively. CONCLUSION: In utero MRI provides a useful adjuvant to antenatal ultrasound when assessing CNS abnormalities by providing more accurate anatomical information. Post-mortem MRI assists the diagnosis of macroscopic structural abnormalities.

Adult↗

PubMed2004

[In utero transfer for preterm labor: experience of a regional perinatal hotline providing a 24-hour on call service].

OBJECTIVE: Preterm labor is one of the major causes of concern for level I and II obstetricians. The purpose of this study was to determine the incidence of in utero transfer performed for preterm labor. We also aimed to evaluate the algorithm we used in case of call for preterm labor. This algorithm allowed us to study the rate of endovaginal sonography use prior to in utero transfer, to calculate its predictive value and to evaluate the risk of delivery during transfer. PATIENTS AND METHOD: We conducted an 8-months prospective study of all calls for preterm labor received at a regional call center in France (EU). All obstetrical data were entered in a computerized anonymous database. Three months after the first call midwives collected data from the receiving hospital. RESULTS: Calls for preterm labor account for 40% of calls for in utero transfer. Two hundred and sixty-five calls have been received for preterm labor; among them 50 cases were associated with a preterm rupture of membrane, a maternal or fetal pathology and 14 cases were lost for follow-up. Those 64 cases were excluded leaving 201 cases for analysis. Twenty-eight had a cervix dilated 4 cm, or more, while 173 had a cervix dilated less than 4 cm. Fifty percent of woman that had a cervical dilatation of 4 cm or more delivered more than 4 h after the call. Among the 173 patients that had a cervix dilated less than 4 cm, 71% had not delivered 7 days after the hotline call and 26% had an endovaginal ultrasonography performed before the transfer. None of the women that had a cervical length longer than 27 mm delivered in the 7 following days. None of the 176 women that were transferred delivered during the transfer. DISCUSSION AND CONCLUSION: In utero transfer for preterm labor is the leading cause of in utero transfer. Endovaginal ultrasonography prior to transfer should be performed in order to avoid unnecessary transfer. Women who have a preterm labor with a cervical dilatation of 4 cm or more are not an absolute contra-indication to in utero transfer. In those cases the transfer indication should be discussed on a case-to-case basis including the actual term and the distance between hospitals.

Female↗

PubMed2004

Successful in utero gene transfer using a gene gun in midgestational mouse fetuses.

BACKGROUND/PURPOSE: In utero gene therapy offers a number of potential advantages over postnatal gene therapy. A latest method of gene transfer to fetuses in utero uses a new tool called a gene gun. The gene gun is less invasive and simpler than other in utero methods. The current study was designed to determine whether the gene gun is an effective tool for transferring genes to mouse fetuses in utero. METHODS: Using a gene gun, we transferred plasmids that included enhanced green fluorescent protein (EGFP) genes and cytomegalo virus promoters to the abdominal skin of 40 A/J fetal mice at each of 3 gestational ages (13, 14, or 15 days). Four or 5 days after gene transfer, the number of surviving fetuses was counted, and a color image of EGFP in the skin was analyzed for gene transfer rates by fluorescence microscopy. Survival rates were analyzed using Fisher's Exact test. RESULTS: The mean survival rate was 89.2% (107 of 120) in gene transfer fetuses and 91.7% (55 of 60) in controls. There is no difference in survival rate between gene transfer fetus and control. The highest gene transfer rate was 100% (37 of 37) at the gestational age of 14 days. The rate was 97.1% (34 of 35) at gestational ages of 13 and 15 days. CONCLUSIONS: The results of this study show that in utero gene transfer by gene gun is a less-invasive technique, and the gene gun is an effective tool transferring genes to mouse fetuses in utero.

Animals↗

PubMed2004

Diabetes (db/db) mutation-induced female reproductive tract hypercytolipidemia: estrogenic restoration of utero-ovarian indices.

The diabetes (db/db) mutation (leptin-receptor defect) induces a hyperglycemic-hyperinsulinemic endometabolic environment that promotes hypercytolipidemic, utero-ovarian involution in C57BL/KsJ mice, resulting in reproductive sterility and eventual organoatrophy. The effectiveness of low-dose, 17-B-estradiol therapy (E2-HRx), initiated prior to the genetic expression of the overt diabetes-obesity syndrome (DOS) on preventing female reproductive tract involution was evaluated by analysis of cytochemical, endocrine and tissue lipo-metabolic indices relative to oil (O)-vehicle treated (HRx) control (+/?) and (db/db) groups. All HRx treatments started at 4 weeks of age (i.e., pre-overt DOS stage) and continued through 16 weeks of age (i.e., chronic DOS expression) when tissue parameters were evaluated. The DOS promoted a dramatic increase in phenotypic obesity, hyperglycemia and hyperinsulinemia in (db/db) groups, relative to (+/?) indices, throughout the experimental period. In contrast, utero-ovarian weights were dramatically reduced in (db/db) groups relative to (+/?). Chronic low-dose E2-HRx moderated these DOS-induced trends in (db/db) groups, maintaining lowered body weights and normoglycemic parameters while stimulating utero-ovarian weight indices. In addition, E2-HRx prevented the dramatic hypercytolipidemic condition which promotes utero-ovarian involution in (db/db) mice as evidenced by the maintenance of normal reproductive cytoarchitecture. The concurrent moderation of tissue lipase activity and stimulated glucose uptake rates by (db/db) utero-ovarian compartments, under persistent hyperinsulinemic influences, indicated that E2-HRx effectively reduced both the structural and endometabolic consequences of the DOS from promoting (db/db)-associated reproductive organoatrophy. These results indicate that the pathophysiological alterations induced by the (db/db) mutation may be ameliorated through low-dose steroidal therapy, the efficacy of which is suspected to occur via membrane metabolic cascade induction mechanisms or by direct nuclear transcription modulation in reproductive target cells. The subsequent re-establishment of insulin-coupled glucose utilization and suppressed caloric shunting towards lipogenesis promotes the normalization of utero-ovarian structural and metabolic homeostasis in C57BL/KsJ-db/db mutants.

Animals↗

PubMed1987

In utero ponderal index as a prognostic factor in the evaluation of intrauterine growth retardation.

The in utero ponderal index has become a method of estimating fetal growth. Several methods have been used in the formulation of the in utero ponderal index. In the present study, 1040 pregnant women underwent ultrasonic examination between 24 and 41 weeks of gestation, and the in utero ponderal index was determined by dividing the estimated fetal weight by the third power of the femur length, rendering a relatively constant value of 8.345 +/- 2.5 (2 SD). Fifty-one cases were defined as intrauterine growth retardation due to an estimated fetal weight lower than the tenth percentile for gestational age. The in utero ponderal index proved to be a valuable index in the prediction of fetal outcome in those cases of intrauterine growth retardation in which the in utero ponderal index was smaller than 1 SD from the average of 8.345. Fetal and neonatal well-being was clearly compromised when intrauterine growth retardation was associated with a low in utero ponderal index.

Birth Weight↗

PubMed1997

Metallothionein induction in fetal rat brain and neonatal primary astrocyte cultures by in utero exposure to elemental mercury vapor (Hg0).

Brain metallothionein (MT) protein and mRNA levels were determined in the fetal rat following in utero (gestational days 7-21) exposure to elemental mercury vapor (Hg0; 300 microg Hg/m3; 4 h/day). Total RNA was probed on Northern blots with [alpha-32P]dCTP-labeled synthetic cDNA probes specific for rat MT isoform mRNAs. The probes for MT-I and MT-II mRNA hybridized to a single band of approximately 550 and 450 nucleotides, respectively. Expression of whole brain MT-I mRNA in full-term fetal rats (day 21) was significantly increased (P < 0.03) by in utero exposure to Hg0 compared to nonexposed controls. This corresponded to a 14-fold increase (P < 0.001) in fetal brain Hg concentration after in utero Hg0 exposure. In addition, astrocytes from both control and in utero Hg0-exposed fetuses were isolated, and neonatal primary astrocyte cultures were established and maintained in vitro for up to 3 weeks without additional experimental intervention. Astrocyte monolayers derived from in utero Hg0-exposed fetuses consistently expressed increased abundance of MT-I mRNA transcripts after 1, 2, and 3 weeks in culture (P < 0.03, P < 0.01, and P < 0.03, respectively) compared with controls. The abundance of astrocyte MT-II mRNA was unchanged at 1 and 2 weeks in culture, but was significantly increased at 3 weeks in cultures derived from brains of Hg0-exposed fetuses (P < 0.04). Consistent with the increase in MT mRNA, an increase in astrocytic levels of MT proteins was noted by Western blot analysis and MT-immunoreactivity. These studies suggest that in utero exposure to Hg0 induces brain MT gene expression, and that MT mRNAs and their respective proteins are useful quantitative biochemical markers of intrauterine exposure to Hg0, a potentially cytotoxic challenge to astrocytes in the developing brain. It is concluded that induction of MT by fetal/neonatal astrocytes represents an attempt by these glial cells to protect against Hg cytotoxicity in maintaining cerebral homeostasis.

Animals↗

PubMed2003

In utero infection with porcine reproductive and respiratory syndrome virus modulates leukocyte subpopulations in peripheral blood and bronchoalveolar fluid of surviving piglets.

It is well known that piglets congenitally infected with porcine reproductive and respiratory syndrome virus (PRRSV) can be viremic at birth, and that preweaning mortality due to secondary infections often increases during acute outbreaks of PRRS. Therefore, an immunosuppressive effect of in utero infection has been suggested. The aim of the present study was to characterise the changes of leukocyte populations in piglets surviving in utero infection with PRRSV. A total of 27 liveborn uninfected control piglets and 22 piglets infected transplacentally with a Danish strain of PRRSV were included. At 2 and 4 weeks of age, 21 of 22 (96%) and 7 of 14 (50%) examined infected piglets were still viremic, whereas PRRSV could not be detected in the six infected piglets examined at 6 weeks of age. Flow cytometry analysis was used to determine the phenotypic composition of leukocytes in peripheral blood and bronchoalveolar lavage fluid (BALF) of 2-, 4- and 6-week-old infected piglets and age-matched uninfected controls. The key observation in the present study is that high levels of CD8(+) cells constitute a dominant feature in peripheral blood and BALF of piglets surviving in utero infection with PRRSV. In BALF, the average high level of CD8(+) cells in 2-week-old infected piglets (33.4 +/- 12.6%) was followed by a decline to 7.3 +/- 3.0 and 11.1 +/- 3.0% at 4 and 6 weeks of age. BALF of control piglets contained 1.6 +/- 0.9, 2.3 +/- 1.8 and 1.9 +/- 0.5% CD8(+) cells, only. In peripheral blood, however, the average number of CD8(+) cells remained at high levels in the infected piglets throughout the post-natal experimental period (2.8 +/- 1.9, 2.9 +/- 1.8 and 3.2 +/- 1.7 x 10(6) CD8(+) cells/ml at 2, 4 and 6 weeks, respectively). In the controls, the average levels of CD8(+) cells were 0.9+/-0.2, 1.9 +/- 1.7 and 1.6 +/- 0.5 x 10(6)/ml, respectively. Furthermore, the numbers of CD2(+) , CD4(+)CD8(+) and SLA-classII(+) cells, respectively, in peripheral blood, together with the levels of CD2(+) and CD3(+) cells in BALF were increased in the infected piglets infected in utero compared to the uninfected controls. The kinetic analyses carried out in the present study reflect that in utero infection with PRRSV modulates immune cell populations in peripheral blood and BALF of surviving piglets. The observed changes are characterised by high levels of CD8(+) cells supporting an important role of these cells in PRRSV infection. The present results, however, do not support the existence of post-natal immunosuppression following in utero infection with PRRSV.

Aging↗