Long-term effects of diagnostic ultrasound during fetal period on postnatal development and adult behavior of mouse

Pregnant Swiss albino mice were exposed to diagnostic levels of ultrasound (3.5 MHz, intensity 65 mW, I(SPTP) = 1 W/cm(2), I(SATA) = 240 W/cm(2)) for 10, 20 and 30 minutes on day 14 of gestation. Sham exposed controls were maintained for comparison. Fifteen pregnant mice were exposed for each group. Exposed as well as control animals were left to complete gestation and parturition. Ultrasound induced changes in maternal vaginal temperature was recorded. The changes in the physiological reflexes and postnatal mortality up to 6 weeks of age were recorded. The litters were subjected to behavioral tests for locomotor activity, learning and memory at 4 month and 1 year of age. Neither the physiological reflexes nor the postnatal mortality was affected by ultrasound exposure. However, there was a noticeable impairment in both locomotor and learning behavior even after a 10 min exposure, which further increased with increases in exposure time. Thus the present study demonstrates the neurotoxicity of diagnostic ultrasound and the high susceptibility of early fetal brain to induction of lasting detrimental changes by ultrasound exposure.     

The embryotoxic effects of ultrasound exposure in pregnant ICR mice

The embryotoxicity of ultrasound exposure during pregnancy was investigated in DUB:(ICR) mice. On day 0 of gestation (day of plug), pregnant mice were assigned to one of five groups: cage control, sham exposed (0 W/cm2), 0.05 W/cm2, 0.50 W/cm2. or 1.00 W/cm2. Females were anesthetized on day 8 of gestation and their abdomens were shaved to assure good acoustic coupling. The animals were strapped on a lucite board and placed vertically into a distilled degassed water bath (30 degrees C) so that the abdomen was fully submerged and centered in the axis of the ultrasonic beam. Insonation was carried out using a PZT transducer with a radius of 1.27 cm and a frequency of 1 MHz under continuous wave conditions. Each animal was placed at a distance of 25 cm from the transducer and exposed to the appropriate intensity for 120 seconds. On day 17 of gestation, the maternal animals were killed, the uterine contents were examined, and live fetuses were weighed and then shipped in cold lactated Ringer's solution from Maryland to Arkansas. Fetuses were examined on the day following maternal sacrifice for external and visceral defects and skeletons were prepared and examined subsequently. Slight but significant differences were detected between the cage control and sham-exposed groups. No statistically significant changes were seen that could be attributed to ultrasound exposure, although there was a slight increase in the incidence of malformed fetuses and the occurrence of multiple malformations in individual fetuses as intensity of the ultrasonic exposure increased.     

Effects of gestational exposure to ethane dimethanesulfonate in CD-1 mice: microtia and preliminary hearing tests

BACKGROUND: Microtia is a reduction in pinna size, usually seen in humans in conjunction with other medical conditions. We report microtia in CD‐1 mice after gestational exposure to ethane dimethanesulfonate (EDS), an alkylating agent and adult rat Leydig cell toxicant. METHODS: Time‐pregnant CD‐1 mice were administered 0, 80, or 160 mg EDS/kg on gestation days (GD) 11–17, or 0 or 160 mg EDS/kg on GD 11–13, GD 13–15 or GD 15–17. Pinnae were measured on postnatal days (PND) 4, 8, 18, and 28; and were observed for detachment from birth through PND 8. Branchial‐arch derived skeletal structures and histology of the pinna was examined on PND 4 and 24. Brainstem auditory evoked response (BAER) tests were carried out at approximately PND 160 to determine possible effects on hearing. RESULTS: All offspring of EDS‐treated dams exhibited bilateral, dose‐related decreases in pinna size. Gestational exposure during GD 11–13 produced smaller ears than during GD 13–15 or 15–17, but not as small as the GD 11–17 regimen. Ossification of other pharyngeal arch derivatives was delayed whereas histology was unremarkable. BAER analysis showed a decrease in the proportion of adult offspring producing a quantifiable response to varied auditory stimuli among EDS‐treated litters. CONCLUSIONS: Gestational exposure to EDS affects pinna development in the mouse, with a broad period of sensitivity during the second half of gestation. Microtia induced by EDS may be associated with hearing deficits, suggesting functional importance of pinna size or additional effects of EDS on ear development not detected by morphological examination. Birth Defects Res B68:383–390, 2003. © 2003 Wiley‐Liss, Inc.     

Maternal LPS Exposure during Pregnancy Impairs Testicular Development,Steroidogenesis and Spermatogenesis in Male Offspring

Lipopolysaccharide (LPS) is associated with adverse developmental outcomes including embryonic resorption, fetal death, congenital teratogenesis and fetal growth retardation. Here, we explored the effects of maternal LPS exposure during pregnancy on testicular development, steroidogenesis and spermatogenesis in male offspring. The pregnant mice were intraperitoneally injected with LPS (50 µg/kg) daily from gestational day (GD) 13 to GD 17. At fetal period, a significant decrease in body weight and abnormal Leydig cell aggregations were observed in males whose mothers were exposed to LPS during pregnancy. At postnatal day (PND) 26, anogenital distance (AGD), a sensitive index of altered androgen action, was markedly reduced in male pups whose mothers were exposed to LPS daily from GD13 to GD 17. At PND35, the weight of testes, prostates and seminal vesicles, and serum testosterone (T) level were significantly decreased in LPS-treated male pups. At adulthood, the number of sperm was significantly decreased in male offspring whose mothers were exposed to LPS on GD 13–17. Maternal LPS exposure during gestation obviously diminished the percent of seminiferous tubules in stages I–VI, increased the percent of seminiferous tubules in stages IX–XII, and caused massive sloughing of germ cells in seminiferous tubules in mouse testes. Moreover, maternal LPS exposure significantly reduced serum T level in male mice whose mothers were exposed to LPS challenge during pregnancy. Taken together, these results suggest that maternal LPS exposure during pregnancy disrupts T production. The decreased T synthesis might be associated with LPS-induced impairments for spermatogenesis in male offspring.     

Effect of nonionizing radiation on the purkinje cells of the rat cerebellum

In one experiment, Sprague Dawley rats (16–21 days of gestation) and their offspring were exposed to 100-MHz (CW) electromagnetic radiation at 46 mW/cm² (SAR 2.77 mW/g) for 4 h/day for 97 days. In another experiment, the pregnant rats were irradiated daily from 17 to 21 days of gestation with 2450-MHz (CW) microwaves at 10 mW/cm² (SAR 2 mW/g) for 21 h/day. In a third experiment, 6-day-old rat pups were irradiated 7 h/day for five days with 2450-MHz radiation at 10 mW/cm². Equal numbers of animals were sham irradiated in each group. Quantitative studies of Purkinje cells showed a significant and irreversible decrease in rats irradiated during fetal or fetal and early postnatal life. In animals exposed postnatally, and euthanized immediately after irradiation, significant decrease in the relative number of Purkinje cells was apparent. However, restoration apparently occurred after forty days of recovery.     

妊娠期和哺乳期双酚A暴露对幼年子代小鼠焦虑和抑郁行为的影响

双酚A(bisphenol-A,BPA)对脑和行为发育的低剂量效应已引起广泛关注。本研究分别于妊娠最后2周和分娩后前2周母鼠灌胃BPA(0.4和4 mg/kg.d),然后以旷场、高架十字迷宫、明暗箱、镜子迷宫、强迫游泳和被动回避箱等模型,分别测试幼年期(生后21～28 d)子代小鼠的行为,探讨围生期不同阶段的BPA暴露对幼年仔鼠自发活动、探究、焦虑、抑郁和被动回避记忆等行为的影响。结果表明,围生期不同阶段的BPA暴露对这些行为的影响不同,主要表现为:妊娠期BPA暴露促进幼年仔鼠的活动性,减弱其焦虑状态,提高雄性仔鼠的探究能力,促进雌性仔鼠的被动回避记忆;哺乳期BPA暴露减少幼年仔鼠的活动性,但对其焦虑行为的影响相对较弱,不影响仔鼠的探究能力和被动回避记忆;而妊娠期和哺乳期BPA暴露均加剧幼年仔鼠的抑郁行为。以上结果提示,妊娠期和哺乳期BPA暴露均可影响幼年仔鼠的焦虑、抑郁、被动回避记忆等多种行为,而妊娠期可能是BPA影响的更敏感时期。     

Effects of prenatal X-irradiation on the 14th-18th days of gestation on postnatal growth and development in the rat

Thirty-nine pregnant adult Wistar strain rats were randomly assigned to one of three exposure groups: 0, 0.75, or 1.50 Gy X-radiation total exposure. Animals were exposed from the 14th to the 18th days of gestation at 0, 0.15, or 0.30 Gy per day. At term, 15 rats were killed and morphologic analyses were completed. Twenty-four rats were allowed to deliver their offspring. On the first day of postnatal life, litters were reduced to a maximum of eight pups per litter, with equal numbers of male and female offspring wherever possible. A total of 187 pups were observed for the age of acquisition of five reflexes (air righting, surface righting, visual placing, negative geotaxis, auditory startle) and the appearance of four physiologic markers (pinna detachment, eye opening, vaginal opening, testes descent). There was significant dose-related weight reduction in term fetuses and offspring throughout the 86-day postnatal period. Postnatal growth rate (g gained/day) was unaffected. Adult offspring brain and gonadal weight and organ weight:body weight ratios were reduced. Using the PAC50 methodology, dose-related alterations occurred in the acquisition of several reflexes. All physiologic markers exhibited a dose-related delay in appearance. These results indicate that fractionated exposure to X-radiation during the fetal period in the rat results in dose-dependent alterations in postnatal growth and physiologic development. These studies are important for our understanding of the long-range effects of prenatal exposure to ionizing radiation late in gestation.     

Influence of low-intensity ultrasonic irradiation on prenatal development of two inbred mouse strains.

Effects of low-intensity ultrasonic irradiation on prenatal development of DHS and A/HeMk mice were studied. On day 8 of gestation (VP day = 0) pregnant females were exposed to ultrasonic waves with a frequency of 2.25 MHz and power of 40 mW/cm2 for 5 h. A low frequency of severe cranial and facial anomalies occurred that was attributable to the irradiation in both strains. The difference in frequency of malformed fetuses was marked between irradiated and untreated control A/HeMk mice, but not DHS mice. Fetal growth inhibition and death were also produced in both strains, although the possible effect of binding the pregnant mice for irradiation cannot be discounted.     

Influence of pre- and postnatal exposure of rats to 2.45-GHz microwave radiation on neurobehavioral function

Rats exposed to microwaves prenatally (2,450 MHz, 10 mW/cm2, 3 h/day, days 5-20 of gestation) or perinatally (same as above plus days 2-20 postnatally) were examined by a neurobehavioral test battery on postnatal days 30 and 100. Body mass, locomotor activity, startle to acoustic and air-puff stimuli, fore- and hindlimb grip strength, negative geotaxis, reaction to thermal stimulation, and swimming endurance were assessed. The prenatally and the perinatally exposed rats (male and female) weighted more than sham-exposed rats at 30, but not at 100, days of age. In addition, the perinatally exposed animals had less swimming endurance at 30, but not at 100, days of age relative to sham-exposed rats. For the other measures, only the air-puff startle response was altered and was limited to the prenatally exposed female pups; ie, at postnatal day 30, the startle response was increased in magnitude, and at postnatal day 100, the response was decreased. No other reliable effects were observed. In a second experiment, rats treated as described above were examined for alterations in body mass, locomotor activity, reaction to air-puff stimuli, reaction to thermal stimulation, and swimming endurance at postnatal days 30-36. Again, perinatally exposed rats were larger in body mass and had less swimming endurance compared with sham-exposed rats. The latency to the air-puff startle response was longer in female pups exposed prenatally. These data indicate that altered endurance and gross motor activity result from perinatal exposure to microwave irradiation.     

Hematologic and immunologic effects of pulsed microwaves in mice

Mice were exposed in the far field in an anechoic chamber to 2,880-MHz pulsed microwaves 3 to 7.5 h daily, 5 days/week for 60 to 360 h. Three experiments were performed at average power densities of 5 mW/cm2 and six at 10 mW/cm2, corresponding to averaged specific absorption rates (SARs) of 2.25 and 4.50 mW/g, respectively. Each experiment consisted of eight mice, with a concurrently sham-exposed group of eight. In two of three studies at 5 mW/cm2, there was a significant increase in bone marrow cellularity in the microwave-exposed groups compared to the sham-exposed groups. Significant differences were occasionally seen in erythrocyte, leukocyte, and platelet values from microwave-exposed groups, but were not consistently observed. In one of six groups exposed at 10 mW/cm2, mean bone marrow cellularity was reduced significantly in the microwave-exposed mice; in another group, the lymphocyte count was increased. In only one exposure (10 mW/cm2 for 360 h) was any significant effect noted on serum proteins: a reduction to 5.1 +/- 0.3 g/dl in the exposed versus 5.6 +/- 0.4 g/dl in the sham-exposed mice. This was due to a decrease in alpha and beta globulins, with no effect on albumin or gamma globulin concentrations. No effect on bone marrow granulocyte/macrophage colony-forming units (CFU) was revealed following exposure of mice to pulsed microwaves at 5 mW/cm2. In one of four exposures at 10 mW/cm2, there was a significant increase in CFU-agar colonies. No significant effects of exposures at 10 mW/cm2 were observed on in vivo and in vitro assays of cell-mediated immune functions. No exposure-related histopathologic lesions were found from examination of several tissues and organs. Results of these series of exposures of mice at SARs of 2.25 and 4.50 mW/g indicated no consistent effects on the hematologic, immunologic, or histopathologic variables examined.     

Effect of prenatal exposure to diagnostic ultrasound on the development of mice.

Pregnant Swiss albino mice were exposed to diagnostic ultrasound (3.5 MHz, approximately 65 mW) for 10 min on Day 3.5 (preimplantation period), 6.5 (early organogenesis period), or 11.5 (late organogenesis period) of gestation. Sham-exposed controls were maintained for comparison. Exposed as well as control fetuses were dissected out on the 18th day of gestation, and changes in total mortality, body weight, body length, head length, brain weight, sex ratio, and microphthalmia were recorded. Exposure on Day 3.5 of gestation resulted in a small increase in the resorption rate and a significant reduction in fetal body weight. A low fetal weight and an increase in the number of growth-retarded fetuses were produced by exposure on Day 6.5 postcoitus. A statistically nonsignificant increase in the incidence of microphthalmia was induced in fetuses exposed on Day 6.5 or Day 11.5 of gestation. These results indicate that ultrasound may have some adverse effects on the mouse embryos depending on the developmental stage at which the exposure occurred.     

Hormonal changes accompanying cigarette smoke-induced preterm births in a mouse model

Epidemiologic evidence indicates that maternal smoking increases the risk of preterm birth. While a number of plausible mechanisms for early delivery have been offered, the role of gestational hormones in this smoke-induced outcome is uncertain. Thus, a toxicologic study was performed to examine the effects and underlying hormonal mechanisms of mainstream cigarette smoke (MCS) exposure on gestational duration. Pregnant B6C3F1 mice were exposed by inhalation to MCS for 5 days/week (4 hrs/day) from Gestational Day (GD) 4 to parturition. Smoke-induced effects on gestational length, interpubic ligament length, maternal hormone secretion patterns (estradiol-17beta, progesterone, prolactin, and relaxin), body weight gain, postimplantation loss, litter size, and offspring sex ratio were examined. Dams exposed to MCS at a concentration equivalent to smoking less than one pack of cigarettes/day (carbon monoxide = 25 parts per million, total suspended particulates = 16 mg/m3) demonstrated a significant (P < 0.05) shortening of gestational duration (compared with pregnant, air-exposed mice). In addition, MCS-exposed mice sacrificed on GD 18 had significantly (P < 0.05) increased interpubic ligament length, elevated serum estrogen levels, and a reduced progesterone to estradiol-17beta ratio (compared with air-exposed controls); levels of progesterone and prolactin were only modestly decreased and increased, respectively, in the MCS-exposed mice. Smoke exposure had no significant effects on maternal relaxin levels, body weight gain, postimplantation loss, litter size, or sex ratio. Results of this study demonstrate that inhalation exposure of pregnant mice to a low dose of MCS shortens gestation and alters hormone secretory patterns, which are important for maintaining pregnancy and inducing parturition. These findings support the view that pregnant women who smoke (even modestly) may be at increased risk for preterm birth, and that early delivery may be related (at least partly) to MCS-induced.     

Prenatal exposure to antiandrogen flutamide affects androgen receptor (AR) expression in postnatal ovarian development in pig

The following study was undertaken to localize androgen receptors (ARs) in various structures of the porcine ovary after prenatal exposure to antiandrogen flutamide. In utero treatment by antiandrogens may have adverse effects on reproductive function in immature and adult animals. Flutamide was injected into pregnant swines between days 20 and 28 (GD20) or 80 to 88 (GD80) of gestation. The ovaries were collected from treated animals and from control ones (non-treated) at two different points of development: from immature and adult pigs. Immunoexpression of AR was determined for preantral and antral follicles and for stroma cells. Immunostaining showed that AR expression in immature animals was unaffected in the primary follicles, while in the preantral and antral follicles the AR level fluctuated depending on day of treatment as well as on analyzed tissue. In adult animals, the immunoexpression of AR slightly decreased in antral follicles independently on the day of flutamide treatment. Therefore, AR expression in postnatal life may be affected by in utero exposure to antiandrogen flutamide.     

Effect of continuous-wave and amplitude-modulated 2.45 GHz microwave radiation on the liver and brain aminoacyl-transfer RNA synthetases of in utero exposed mice

Investigations have been carried out concerning the effects of microwave (MW) exposure on the aminoacyl-transfer ribonucleic acid (tRNA) synthetase of the progeny of females that were exposed during their entire period of gestation (19 days). The changes caused by continuous-wave (CW) and amplitude-modulated (AM) MW radiation have been compared. CFLP mice were exposed to MW radiation for 100 min each day in an anechoic room. The MW frequency was 2.45 GHz, and the amplitude modulation had a 50 Hz rectangular waveform (on/off ratio, 50/50%). The average power density exposure was 3 mW/cm², and the whole body specific absorption rate (SAR) was 4.23 ± 0.63 W/kg. The weight and mortality of the progeny were followed until postnatal day 24. Aminoacyl-tRNA synthetase enzymes and tRNA from the brains and livers of the offspring (461 exposed, 487 control) were isolated. The aminoacyl-tRNA synthetase activities were determined. The postnatal increase of body weight and organ weight was not influenced by the prenatal MW radiation. The activity of enzyme isolated from the brain showed a significant decrease after CW MW exposure, but the changes were not significant after 50 Hz AM MW exposure. The activity of the enzyme isolated from liver increased under CW and 50 Hz modulated MW. © 1996 Wiley-Liss, Inc.     

Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate

BACKGROUND: Gestational exposure to di-n-butyl phthalate (DBP), a ubiquitous environmental contaminant, has been shown to interfere with the development of the male reproductive tract by acting as an antiandrogen. This study was conducted to identify the critical days for the abnormal development of the male reproductive tract, specifically the testis and epididymis. METHODS: Timed-pregnant Sprague-Dawley rats were dosed with DBP at 500 mg/kg/day on gestation day (GD) 14 and 15, 15 and 16, 16 and 17, 17 and 18, 18 and 19, or 19 and 20 (GD 0=plug day). Anogenital distance (AGD) was measured on postnatal day (PND) 1 and 13, while areloa number was recorded on PND 13 only. After weaning, males were allowed to mature to PND 90 at which time they were necropsied. Areloa number and AGD were recorded and testes, epididymides, seminal vesicles, prostate gland, kidneys, and liver weighed. Blood serum was collected and assayed for total testosterone concentration. RESULTS: There were no observable effects on litter size, sex ratio, serum testosterone concentration, or mortality of pups. Statistically significant permanent reductions in AGD were seen in males exposed prenatally to DBP on GD 15 and 16 or GD 18 and 19. On PND 13, areola were present in males exposed to DBP on GD 15 and 16, 16 and 17, 17 and 18, and 19 and 20. However, permanent retention occurred only in males after DBP exposure on GD 16 and 17. Exposure to DBP on only GD 17 and 18 elicited a reduction in epididymal weights; while exposure on only GD 16 and 17 caused a significant increase in the weights of the testes due to edema. In this study, epididymal and testicular malformations were most prevalent after exposure to DBP on any gestational day. Epididymal malformations, characterized by agenesis of various regions and small or flaccid testes were significantly increased in DBP-exposed males only on GD 16 and 17. CONCLUSIONS: These findings suggest that 2-day DBP exposure is highly detrimental to the developing reproductive tract of the male fetus and the critical window for abnormal development is GD 16-18.     

Teratogenic, biochemical, and histological studies with mice prenatally exposed to 2.45-GHz microwave radiation

Pregnant CD-1 mice were exposed to 2.45-GHz continuous wave microwave radiation at an incident power density of 30 mW/cm2. The local specific absorption rate near the uterine area (deep colonic location), as determined from time-temperature profiles measured with a Vitek thermistor probe, was 40.2 mW/g. Groups of mice were exposed 8 hr per day through Days 1-6 or 6-15 of pregnancy. Other groups of animals were exposed to an elevated ambient temperature of 31 degrees C which increased the colonic temperature 2.3 degrees C, the same as that produced by the microwaves. Sham-irradiated groups of animals were treated exactly the same as the microwave-exposed animals. For the two conditions, temperature exposed and sham exposed, two groups of animals were used. One group was handled in the same manner as the microwave-irradiated group and the other group was not handled so as to evaluate the effects of stressing the animals by handling. Eleven groups of animals were used in the complete study: five groups for gestational Days 1-6, five groups for gestational Days 6-15, and one group of cage control animals. On Day 18 of gestation the dams of all experimental groups were sacrificed and their reproductive status was determined. The fetuses were examined for visceral and skeletal alterations. Brain cholinesterase activity and histology were evaluated in the groups exposed on Days 6-15. The results show that microwave radiation increases embryo lethality at the early stages of gestation (exposure Days 1-6). Fetal toxicity and teratogenicity were not significantly increased by exposure to microwaves on either Days 1-6 or 6-15 of gestation. Cholinesterase activity and histology of the brain of 18-day-old fetuses were not adversely affected.     

Evaluation of the bioeffects of prenatal ultrasound exposure in the cynomolgus macaque (Macaca fascicularis): I. Neonatal/infant observations

The frequency of use of ultrasonography for evaluating the developing embryo/fetus has continued to rise although the possible risks from exposure still remain uncertain. The cynomolgus macaque (Macaca fascicularis) is currently being used in our laboratory as a model to assess these risks. In utero exposure was performed utilizing a commercial real-time mechanical sector scanner with a 7.5 MHz scanhead (ATL, MK 600). Maximum acoustic power output for this unit is as follows: I(SPTA) = 12.0 mW/cm2, I(SPPA) = 98 W/cm2, and Im = 137 W/cm2. Animals exposed to ultrasound (N = 16) were scanned five times weekly on gestational days (GD) 21-35 +/- 2 for 10 minutes/exam (m/e), three times weekly on GD 36-60 +/- 2 for 10 m/e, and once weekly on GD 61-150 +/- 2 for 20 m/e. Controls (N = 14) were "scanned" with the unit placed on standby. Assessment of simian Apgar scores at 1, 5, and 10 minutes of life revealed higher scores for treated animals at 10 minutes (P less than or equal to 0.045); greater scores in muscle tone (P less than or equal to 0.013) and color (P less than or equal to 0.016) were observed. Evaluation of morphometrics at birth including weight, biparietal diameter, occipitofrontal diameter, head circumference, hand and foot lengths, humerus and femur lengths, arm circumference, chest circumference, tail length, skinfold thickness, and crown-rump length (CRL) indicated a significant reduction in only two parameters, birth weight (P less than or equal to 0.027) and CRL (P less than or equal to 0.033). Hematologic analysis at 2 +/- 1, 9 +/- 1, and 16 +/- 1 days of life revealed a significant difference in white blood cell counts (WBCs). Treated animals displayed lower WBCs with reductions in numbers of segmented neutrophils and monocytes at all ages observed. Hematologic differences were not significant by 5-6 months of age. No abortions, gross malformations, or stillbirths were observed in the exposed animals.     

Teratological studies of prenatal exposure of mice to a 20 kHz sawtooth magnetic field

In order to evaluate the importance of gestational age in possible effects due to exposure to a 20 kHz sawtooth magnetic field, pregnant ICR mice at gestational 2.5-15.5 days post-coitus, which is the most sensitive stage for the induction of major congenital malformations, were exposed in a carrousel irradiator. The mice were exposed to a 20 kHz intermediate frequency (IF) sawtooth magnetic field had a 6.5 microT peak intensity for 8 h/day. The animals were sacrificed on the 18th day of gestation; and the fetuses were examined for mortality, growth retardation, changes in head size, and other morphological abnormalities. From the above conditions, it is concluded that the exposure to a 20 kHz sawtooth magnetic field with 6.5 microT peak intensity does not inflict any adverse effect on fetuses of pregnant mice.     

Immunity of Fetal Mice to Prenatal Administration of the Dopaminergic Neurotoxin 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine

Abstract: Subcutaneous injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) HC1 (25 mg/kg) in pregnant female mice at the 17th day of gestation markedly depleted striatal dopamine (DA) concentrations in the mothers 24 h later and at 24 h and 28 days after delivery. By contrast, in the offspring of the female mice exposed to MPTP during pregnancy, fetal brain DA concentrations at 24 h after injection and at 24 h after birth and striatal DA levels at 14 and 28 days postnatally were unaffected and identical to those in age-matched controls. The postnatal ontogenesis of striatal DA levels was identical in offspring of control vehicle- and MPTP-treated pregnant mice. Also, prenatal challenge with MPTP did not make nigrostriatal DA neurons more vulnerable to a second postnatal treatment with the toxin. Striatal DA depletions were identical in 6-week-old mice given MPTP, whether they were exposed to MPTP or to vehicle in utero. Monoamine oxidase (EC 1.4.3.4; MAO) type B activity was extremely low in the fetal brain and, relatively, much lower than that of MAO-A. Prenatal MPTP administration reduced maternal striatal and also embryonal brain MAO-B activity at 24 h post treatment but did not alter the normal postnatal development of striatal MAO-A and -B activities in the offspring. Study suggests that resistance of fetal DA neurons to the DA-depleting effect of MPTP may be due, at least in part, to an absence in the embryonal brain of adequately developed MAO-B activity required for the conversion of MPTP to its toxic metabolite, 1-methyl-4-phenylpyridinium ion.