Artificially extended photoperiod administered to pre-partum mares via blue light to a single eye: Observations on gestation length, foal birth weight and foal hair coat at birth.

In seasonally breeding animals, photoperiod perception is crucial for timing of important physiological events. In the horse, long day photoperiod influences the onset of ovulation and cyclicity, shedding of the heavier winter coat and the timing of parturition. In this compilation of studies, conducted across three breeding seasons and two countries, the impact of artificially extended day length was investigated on gestation length, foal birth weight and foal hair coat at birth. The light therapy was administered to pre-partum mares via mobile head worn masks which provided short wavelength blue light to a single eye. In Study 1, reductions in gestation lengths were observed following administration of artificially extended day length (124.8 ± 15.11 days) in the final months of pregnancy to a group of Thoroughbred mares compared to controls (P < 0.05; 339.7 ± 9.56 days vs 350.6 ± 9.13). Study 2 revealed that pre-partum exposure to artificially extended day length (104.6 ± 9.89 days) increased foal birth weight compared to controls (47.13 ± 2.93 kg vs 43.51 ± 6.14 kg; P < 0.05) in mares bred early in the year. In Study 3, artificially extended day length (87.53 ± 19.6 days) administered to pre-partum mares affected the coat condition of foals at birth with respect to hair weight (P < 0.0001) and hair length (P < 0.0001) compared to controls (0.34 ± 0.20 µg vs 0.59 ± 0.12 µg and 1.93 ± 0.56 cm vs 2.56 ± 0.32 cm, respectively). Collectively, these studies serve to highlight the influential role of the circa-annual changes in photoperiod length on the pre-partum mare for normal foetal development during the natural breeding season. It also emphasizes the potential that exists to improve breeding efficiency parameters by artificially simulating this important environmental cue in the latter stages of gestation against the backdrop of an economically driven early breeding season.

Maternal mobile phone exposure adversely affects the electrophysiological properties of Purkinje neurons in rat offspring.

Electromagnetic field (EMF) radiations emitted from mobile phones may cause structural damage to neurons. With the increased usage of mobile phones worldwide, concerns about their possible effects on the nervous system are rising. In the present study, we aimed to elucidate the possible effects of prenatal EMF exposure on the cerebellum of offspring Wistar rats. Rats in the EMF group were exposed to 900-MHz pulse-EMF irradiation for 6h per day during all gestation period. Ten offspring per each group were evaluated for behavioral and electrophysiological evaluations. Cerebellum-related behavioral dysfunctions were analyzed using motor learning and cerebellum-dependent functional tasks (Accelerated Rotarod, Hanging and Open field tests). Whole-cell patch clamp recordings were used for electrophysiological evaluations. The results of the present study failed to show any behavioral abnormalities in rats exposed to chronic EMF radiation. However, whole-cell patch clamp recordings revealed decreased neuronal excitability of Purkinje cells in rats exposed to EMF. The most prominent changes included afterhyperpolarization amplitude, spike frequency, half width and first spike latency. In conclusion, the results of the present study show that prenatal EMF exposure results in altered electrophysiological properties of Purkinje neurons. However, these changes may not be severe enough to alter the cerebellum-dependent functional tasks.

2.45 GHz microwave irradiation-induced oxidative stress affects implantation or pregnancy in mice, Mus musculus.

The present experiment was designed to study the 2.45 GHz low-level microwave (MW) irradiation-induced stress response and its effect on implantation or pregnancy in female mice. Twelve-week-old mice were exposed to MW radiation (continuous wave for 2 h/day for 45 days, frequency 2.45 GHz, power density=0.033549 mW/cm(2), and specific absorption rate=0.023023 W/kg). At the end of a total of 45 days of exposure, mice were sacrificed, implantation sites were monitored, blood was processed to study stress parameters (hemoglobin, RBC and WBC count, and neutrophil/lymphocyte (N/L) ratio), the brain was processed for comet assay, and plasma was used for nitric oxide (NO), progesterone and estradiol estimation. Reactive oxygen species (ROS) and the activities of ROS-scavenging enzymes- superoxide dismutase, catalase, and glutathione peroxidase-were determined in the liver, kidney and ovary. We observed that implantation sites were affected significantly in MW-irradiated mice as compared to control. Further, in addition to a significant increase in ROS, hemoglobin (p<0.001), RBC and WBC counts (p<0.001), N/L ratio (p<0.01), DNA damage (p<0.001) in brain cells, and plasma estradiol concentration (p<0.05), a significant decrease was observed in NO level (p<0.05) and antioxidant enzyme activities of MW-exposed mice. Our findings led us to conclude that a low level of MW irradiation-induced oxidative stress not only suppresses implantation, but it may also lead to deformity of the embryo in case pregnancy continues. We also suggest that MW radiation-induced oxidative stress by increasing ROS production in the body may lead to DNA strand breakage in the brain cells and implantation failure/resorption or abnormal pregnancy in mice.

Effects of [123I]ADAM, a serotonin transporter radiopharmaceutical, on pregnant Sprague-Dawley rats.

Serotonin transport abnormalities are implicated in neuropsychiatric disorders. [(123)I]ADAM ([(123)I]-2-([2-({dimethylamino}methyl)phenyl]thio)-5-iodophenylamine) is a novel radiotracer that targets serotonin transporters. We assessed the toxicity of [(123)I]ADAM (18.5 MBq) administered in early- and late-phases (8 and 14 day postfertilization, respectively) of pregnancy. The mortality, clinical status, and gross necropsy were measured in pregnant rats, and the fertility index was measured in rat offspring (weight, clinical observations). We found no dosing-related clinical signs. In conclusion, [(123)I]ADAM was not toxic in an animal pregnancy model.

Proliferation and differentiation of neural stem cells irradiated with X-rays in logarithmic growth phase.

Exposure of the fetal brain to ionizing radiation causes congenital brain abnormalities. Normal brain formation requires regionally and temporally appropriate proliferation and differentiation of neural stem cells (NSCs) into neurons and glia. Here, we investigated the effects of X-irradiation on proliferating homogenous NSCs prepared from mouse ES cells. Cells irradiated with X-rays at a dose of 1Gy maintained the capabilities for proliferation and differentiation but stopped proliferation temporarily. In contrast, the cells ceased proliferation following irradiation at a dose of >5Gy. These results suggest that irradiation of the fetal brain at relatively low doses may cause congenital brain abnormalities as with relatively high doses.

The effect of radiofrequency radiation on DNA and lipid damage in non-pregnant and pregnant rabbits and their newborns.

The concerns of people on possible adverse health effects of radiofrequency radiation (RFR) generated from mobile phones as well as their supporting transmitters (base stations) have increased markedly. RFR effect on oversensitive people, such as pregnant women and their developing fetuses, and older people is another source of concern that should be considered. In this study, oxidative DNA damage and lipid peroxidation levels in the brain tissue of pregnant and non-pregnant New Zealand White rabbits and their newborns exposed to RFR were investigated. Thirteen-month-old rabbits were studied in four groups as non-pregnant-control, non-pregnant-RFR exposed, pregnant-control and pregnant-RFR exposed. They were exposed to RFR (1800 MHz GSM; 14 V/m as reference level) for 15 min/day during 7 days. Malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels were analyzed. MDA and 8-OHdG levels of non-pregnant and pregnant-RFR exposed animals significantly increased with respect to controls (p < 0.001, Mann-Whitney test). No difference was found in the newborns (p > 0.05, Mann-Whitney). There exist very few experimental studies on the effects of RFR during pregnancy. It would be beneficial to increase the number of these studies in order to establish international standards for the protection of pregnant women from RFR.

Effects of gestational exposure to 1.95-GHz W-CDMA signals for IMT-2000 cellular phones: Lack of embryotoxicity and teratogenicity in rats.

The present study was designed to evaluate whether gestational exposure to an EMF targeting the head region, similar to that from cellular phones, might affect embryogenesis in rats. A 1.95-GHz wide-band code division multiple access (W-CDMA) signal, which is one applied for the International Mobile Telecommunication 2000 (IMT-2000) system and used for the freedom of mobile multimedia access (FOMA), was employed for exposure to the heads of four groups of pregnant CD(SD) IGS rats (20 per group) for gestational days 7-17. The exposure was performed for 90 min/day in the morning. The spatial average specific absorption rate (SAR) for individual brains was designed to be 0.67 and 2.0 W/kg with peak brain SARs of 3.1 and 7.0 W/kg for low (group 3) and high (group 4) exposures, respectively, and a whole-body average SAR less than 0.4 W/kg so as not to cause thermal effects due to temperature elevation. Control and sham exposure groups were also included. At gestational day 20, all dams were killed and fetuses were taken out by cesarean section. There were no differences in maternal body weight gain. No adverse effects of EMF exposure were observed on any reproductive and embryotoxic parameters such as number of live (243-271 fetuses), dead or resorbed embryos, placental weights, sex ratios, weights or external, visceral or skeletal abnormalities of live fetuses.

Altered blood chemistry and hippocampal histomorphology in adult rats following prenatal exposure to physiologically-patterned, weak (50-500 nanoTesla range) magnetic fields.

PURPOSE: To discern changes in blood chemistry, cerebral sizes, and hippocampal cytomorphology in adult male and female albino Wistar rats that had been exposed during their entire prenatal development to one of two patterns of magnetic fields and one of four intensities: Very low 5 - 20 nT; low 30 - 50 nT; medium 90 - 580 nT; and high 590 nT to 1.2 microT. MATERIALS AND METHODS: A total of 48 pregnant females were exposed to either a repetitive frequency-modulated magnetic field or to a complex sequence of 50, 200-msec physiologically-patterned fields. As adults blood, cerebral, and histomorphological data were obtained from the 137 rats that had been exposed to one of these eight conditions. RESULTS: Compared to other groups, adult rats that had been exposed prenatally to the physiologically-patterned magnetic fields at the low (30 - 50 nT) and medium (90 - 580 nT) intensities exhibited peak elevations of aminotransaminase, glucose, and uric acid. Numbers of cytometric anomalies were also significantly elevated within regions of the hippocampus known for neuronal neogenesis in adults. CONCLUSIONS: The results suggest that a common factor in cellular adhesion or plasticity might be permanently altered by prenatal exposure to a narrow intensity of a series of physiologically-patterned magnetic fields.

Exposure of pregnant dairy heifer to magnetic fields at 60 Hz and 30 microT.

Thirty-two pregnant Holstein heifers weighing 499 +/- 45 kg, at 3.1 +/- .7 months of gestation and 21 +/- 2.0 months of age were confined and exposed to 30 microT magnetic fields (MFs) and a 12 h light/12 h dark light cycle. The heifers were divided into two replicates of 16 animals. Each replicate was divided into two groups of eight animals each, one group the non-exposed and the second, the exposed group. The animals were subjected to the different treatments for 4 weeks. After 4 weeks, the animals switched treatment, the exposed group becoming the non-exposed group and vice versa. Then the treatment continued for 4 more weeks. Catheters were inserted into the jugular vein, and blood samples were collected twice a week to estimate the concentration of progesterone (P4), melatonin (MLT), prolactin (PRL), and insulin-like growth factor 1 (IGF-1). Feed consumption was measured daily. The results indicated that exposure of pregnant heifers to MF similar to those encountered underneath a 735 kV high tension electrical power line for 20 h/day during a period of 4 weeks produces slight effects. This is evidenced by statistically significant higher body weight (1.2%), higher weekly body weight gain (30%), and decreases in the concentration of PRL (15%) and IGF-1 (4%) in blood serum. The absence of abnormal clinical signs and the absolute magnitude of the significant changes detected during MF exposure, make it plausible to preclude any major animal health hazard.

Effects of sub-acute exposure to static magnetic field on hematologic and biochemical parameters in pregnant rats.

This study investigated the effects of a static magnetic field (SMF) on hematopoiesis and biochemical parameters in female rats. Pregnant rats were exposed to SMF (128 mT-1 hour/day from day 6 to day 19 of pregnancy). At 25 degrees C, the exposure of rats 1 hour/day for 13 consecutive days to SMF induced an increase in hematocrit (Ht) level (+6%, p < 0.05), hemoglobin (Hb) concentration (+12%, p < 0.05) and LDH levels (67%, p < 0.05 ), suggesting an hypoxia-like state. Moreover, exposure to SMF increased blood glucose and decreased insulin release, leading to a diabetic-like state in pregnant rats.

Influence of a 60 Hz, 3 microT, electromagnetic field on the reflex maturation of Wistar rats offspring from mothers fed a regional basic diet during pregnancy.

The aim of the present study was to observe how the exposition of the pregnant rats to the electromagnetic field (EMF), with frequency of 60 Hz, magnetic field of 3 microT for 2 h per day and/or using the so-called regional basic diet (RBD) influenced the reflex maturation in their offspring. Four groups were formed: Group A (casein), B (casein and EMF), C (RBD) and D (RBD and EMF). The diet manipulation occurred during the pregnancy. The reflexes--assessed daily between 12:00 and 14:00--were: palm grasp (PG), righting reflex (RR), cliff avoidance (CA), vibrissae placing (VP), negative geotaxis (NG), auditory startle (AS) and free-fall righting (FFR). The association between EMF and deficient diet caused a delay in all reflexes when compared with Group A. When the diets were compared with both groups exposed to EMF, the delay occurred in the RR, VP, NG and CA in Group D. In the Groups C and A, the delay was observed in RR, CA, VP, NG, AS and PG. In relation to the EMF, Group B differed from Group A in CA, AS, FFR and PG and Group D differed from C in the PG. In conclusion, all the reflexes studied in this research were delayed by the association of the EMF with undernutrition during pregnancy.

Radioadaptive response for protection against radiation-induced teratogenesis.

To clarify the characteristics of the radioadaptive response in mice, we compared the incidence of radiation-induced malformations in ICR mice. Pregnant ICR mice were exposed to a priming dose of 2 cGy (667 muGy/min) on day 9.5 of gestation and to a challenging dose of 2 Gy (1.04 Gy/min) 4 h later and were killed on day 18.5 of gestation. The incidence of malformations and prenatal death and fetal body weights were studied. The incidence of external malformations was significantly lower (by approximately 10%) in the primed (2 cGy + 2 Gy) mice compared to the unprimed (2 Gy alone) mice. However, there were no differences in the incidence of prenatal death or the skeletal malformations or the body weights between primed and unprimed mice. These results suggest that primary conditioning with low doses of radiation suppresses radiation-induced teratogenesis.

Effect of 10 kV, 30 microT, 60 Hz electric and magnetic fields on milk production and feed intake in nonpregnant dairy cattle.

Milk production is the main agricultural income in the province of Québec, and the electrical distribution network traverses the rural dairy production region. This study evaluates the hypothesis that electric and magnetic fields may affect dairy production. Sixteen multiparous nonpregnant lactating Holstein cows (weighing 662 +/- 65 kg and with 150.4 +/- 40 days of lactation) were confined to wooden metabolic crates during the experiment with a 12:12 h light:dark cycle. The cows were divided into two replicates of eight cows each and exposed to a vertical EF of 10 kV/m and an uniform horizontal MF of 30 microT at 60 Hz. Replicate one was exposed for three periods. Each period was represented by an estrous cycle ranging from 24 to 27 days. During the first period, the electric and magnetic fields (E&MF) were off; during the second period they were on; and during the final period, they were off. The second replicate was exposed for three periods also, but the exposure protocol was reversed (first period, on; second period, off; last period, on). Exposure to E&MF (on) resulted in an average decrease of 4.97, 13.78, and 16.39% in milk yield, fat corrected milk yield, and milk fat, respectively; and an increase of 4.75% in dry matter intake.

Threshold effect for teratogenic risk of radiation depends on dose-rate and p53-dependent apoptosis.

PURPOSE: To obtain evidence that the p53 gene is indispensable for reduction of high teratogenic risk of radiation at a high dose-rate to zero risk by lowering the dose-rate. MATERIALS AND METHODS: Wild-type p53(+/+), heterozygous p53(+/-) and null p53(-/-) mice were exposed to gamma-rays at high or low dose-rates during days 9.5-10.5 of gestation. The incidence of malformations and prenatal deaths was studied. Frequencies of cells dying by apoptosis were measured during or after protracted irradiation. RESULTS: After irradiation with 2 Gy, the frequency of apoptotic cells increased to 20% for p53(+/+) mice and did not increase at all for p53(-/-) mice. For p53(+/+) mice, 2 Gy y-rays induced 70% malformations when given at 1.06 Gy/min, but no malformations above the control when given at 1.2 mGy/min. In contrast, after irradiation of p53(-/-) foetuses with 2 Gy at 1.2mGy/min, the incidence of malformations increased 12% above control levels. CONCLUSION: Foetal irradiation with 2 Gy at 1.2 mGy/min was not teratogenic for p53(+/+) mice but teratogenic for p53(-/-) mice. This indicates that the p53 gene is indispensable for a threshold effect in the risk of radiation at low doses or dose-rates.

In utero radiation-induced apoptosis and p53 gene expression in the developing rat brain.

PURPOSE: This study addressed the question of the role of the p53 gene in prenatal low-dose radiation-induced apoptosis in the neuroepithelium, in an effort to elucidate molecular mechanisms involved in the extreme radiosensitivity of the developing brain. MATERIALS AND METHODS: Pregnant Wistar rats were exposed to a single dose of 10, 20 or 40 cGy of X-rays on day 15 or 17 of gestation. Animals were sacrificed 4 or 24h after exposure. Apoptosis was studied by gel electrophoresis of isolated DNA and in situ by the TUNEL reaction. Expression of the p53 gene was studied by immunocytochemistry and Western analysis, as well as Northern analysis, for the detection of the protein and mRNA respectively. RESULTS: In utero low-dose irradiation led to apoptosis and an increase of p53 gene expression in the developing rat brain. Apoptotic as well as p53 immunopositive cells were detected among proliferating, migratory and post-mitotic neurones in the developing neuroepithelium following prenatal irradiation, even after only l0 cGy. In addition to the p53 protein, p53 mRNA brain levels were also increased following prenatal irradiation. CONCLUSIONS: Low-dose prenatal irradiation of the developing brain led to p53 induction and cell death by apoptosis.

In utero radiation-induced changes in growth factor levels in the developing rat brain.

PURPOSE: To investigate the role of growth factors in the compensatory response to radiation injury during development of the brain. Levels of gene expression in the embryonic rat brain were assessed for IGF-I, IGF-II, BDNF and NT-3. MATERIALS AND METHODS: Pregnant Wistar rats were exposed to a single dose of 10, 20 or 40 cGy X-rays on day 15 or 17 of gestation. Animals were sacrificed 4 or 24 h after exposure. IGF-I, BDNF and NT-3 proteins were detected by immunocytochemistry, while IGF-I and IGF-II mRNA by in situ hybridization, and Northern analysis respectively. RESULTS: In utero low dose X-irradiation led to a decrease in IGF-I gene expression and a compensatory increase in the expression of IGF-II, BDNF and NT-3 in the developing rat brain. IGF-I, BDNF and NT-3 immunopositive cells were detected among proliferating, migratory and post-mitotic neurones in the developing neuroepithelium. CONCLUSIONS: Low dose prenatal irradiation of the developing brain results in down-regulation of IGF-I, which could lead to cell death by apoptosis. On the other hand, IGF-II, BDNF and NT-3 gene expression is increased following irradiation, possibly as a compensatory mechanism.

Influence of gestational age at exposure on the prenatal effects of gamma-radiation.

The objective of this investigation was to evaluate the influence of gestational age at exposure on the prenatal effects of gamma-radiation. Pregnant ICR mice were exposed to a single dose of 2.0 Gy gamma-radiation at a gestational 2.5 to 15.5 days post-coitus (p.c.). The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, change in head size and any other morphological abnormalities. The only demonstrable effect of irradiation during the preimplantation period was an increase in prenatal mortality. Resorptions were maximal on post-exposure day 2.5 after conception. The pre-implantation irradiated embryos which survived did not show any major fetal abnormalities. Small head, growth retardation, cleft palate, dilatation of the cerebral ventricle, dilatation of the renal pelvis and abnormalities of the extremities and tail were prominent after exposure during the organogenesis period, especially on day 11.5 of gestation. Our results indicate that the late period of organogenesis in the mouse is a particularly sensitive phase in terms of the development of the brain, skull and extremities.

Influence of gestational age at exposure on the prenatal effects of gamma-radiation

The objective of this investigation was to evaluate the influence of gestational age at exposure on the prenatal effects of gamma-radiation. Pregnant ICR mice were exposed to a single dose of 2.0 Gy gamma-radiation at a gestational 2.5 to 15.5 days post-coitus (p.c.). The animals were sacrificed on day 18 of gestation and the fetuses were examined for mortality, growth retardation, change in head size and any other morphological abnormalities. The only demonstrable effect of irradiation during the preimplantation period was an increase in prenatal mortality. Resorptions were maximal on post-exposure day 2.5 after conception. The pre-implantation irradiated embryos which survived did not show any major fetal abnormalities. Small head, growth retardation, cleft palate, dilatation of the cerebral ventricle, dilatation of the renal pelvis and abnormalities of the extremities and tail were prominent after exposure during the organogenesis period, especially on day 11.5 of gestation. Our results indicate that the late period of organogenesis in the mouse is a particularly sensitive phase in terms of the development of the brain, skull and extremities.

Subchronic in vivo effects of a high static magnetic field (9.4 T) in rats.

The potential adverse biologic effects of sub chronic (cumulatively 10 weeks) exposure to a high magnetic field (9.4 T) were evaluated in young adult male and female Fischer rats as well as in their progeny. Biologic end points in adult rats included changes in daily clinical observations; spatial memory tests; weekly heart rates, body weights, food and water consumption, and the feed efficiency ratio; terminal hematologic, blood biochemical and urinary parameter changes; gross pathologic findings; and major organ weights. In offspring, biologic end points included the gestation period, number of live births, number of pups, ratio of male to female pups/litter; postnatal time period of eye opening; birth and weekly body weights, behavioral changes, central nervous system responses, as well as hematologic, blood biochemistry, and urinary parameter changes; and gross pathologic findings. Findings from this study showed that there were no adverse biologic effects in male and female adult rats or their progeny that could be attributed to 10-week exposure to a 9.4-T static magnetic field.

Biological effects of long-duration, high-field (4 T) MRI on growth and development in the mouse.

The effects of long-duration, high-field magnetic resonance imaging (MRI) on fetal growth and postnatal development in mice were studied. Seven experimental groups of pregnant ICR mice were exposed for 9 hours on day 9 and/or day 12 post coitus (pc) to magnetic fields (4 T static, 5 T/sec switched gradient, and 0.2 W/kg radiofrequency at 170 MHz) associated with MRI conditions. Two experimental groups (sham and exposure groups) were exposed to a combination of ultrasound (day 9 pc, 3.25 MHz, focused) and MRI-associated fields (day 12 pc). No statistically significant changes in fetal growth were observed in the animals exposed to only MRI or ultrasound fields. However, in the combined ultrasound and MRI-exposed group, the fetal weight and crown-rump length were reduced compared with the sham and cage controls. These results suggest that MRI and ultrasound exposure well in excess of current clinical conditions can exert biological effects if applied at sensitive stages of fetal development.