Nonpregnant Rabbits Research Articles

Fetal Loss in Pregnant Rabbits Infected with Genotype 3 Hepatitis E Virus Is Associated with Altered Inflammatory Responses, Enhanced Virus Replication, and Extrahepatic Virus Dissemination with Positive Correlations with Increased Estradiol Level.

Hepatitis E virus (HEV) causes adverse clinical outcomes in pregnant women, but the underlying mechanisms remain poorly understood. To delineate the mechanisms of pregnancy-associated adverse effects during HEV infection, we utilized a genotype 3 HEV from rabbit (HEV-3ra) and its cognate host (rabbits) to systematically investigate the clinical consequences, viral replication dynamics, and host immune and hormonal responses of HEV infection during pregnancy. We found a significant fetal loss of 23% in HEV-infected pregnant rabbits, indicating an early-stage miscarriage. HEV infection in pregnant rabbits was characterized by higher viral loads in feces, intestinal contents, liver, and spleen tissues, as well as a longer and earlier onset of viremia than in infected nonpregnant rabbits. HEV infection altered the pattern of cytokine gene expressions in the liver of pregnant rabbits and caused a transient increase of serum interferon gamma (IFN-γ) shortly after a notable increase in viral replication, which may contribute to early fetal loss. Histological lesions in the spleen were more pronounced in infected pregnant rabbits, although moderate liver lesions were seen in both infected pregnant and nonpregnant rabbits. Total bilirubin was elevated in infected pregnant rabbits. The serum levels of estradiol (E2) in HEV-infected pregnant rabbits were significantly higher than those in mock-infected pregnant rabbits at 14 days postinoculation (dpi) and correlated positively with higher viral loads in feces, liver, and spleen tissues at 28 dpi, suggesting that it may play a role in extrahepatic virus dissemination. The results have important implications for understanding the severe diseases associated with HEV infection during pregnancy. IMPORTANCE HEV causes adverse pregnancy outcomes, with a mortality rate of >30% in pregnant women, but the underlying mechanisms are poorly understood. In this study, we utilized HEV-3ra and its cognate host (pregnant rabbit) to delineate the potential underlying mechanisms of pregnancy-associated adverse outcomes during HEV infection. We found that infected pregnant rabbits had a fetal loss of 23%, which coincided with enhanced viral replication and an elevated systemic IFN-γ response, followed by longer viremia duration and extrahepatic viral dissemination. Estradiol levels were increased in infected pregnant rabbits and correlated positively with higher fecal viral shedding and higher viral loads in liver and spleen tissues. Infected pregnant rabbits had more pronounced splenic lesions, higher serum total bilirubin, and an altered cytokine gene expression profile in the liver. The results will contribute to our understanding of the mechanisms of HEV-associated adverse pregnancy outcomes.

Histological Feature of Uterus and Uterine Tube During Late Period of Pregnancy in Rabbits

Current work was conducted to investigate the histological architecture of the uterine tube and uterus during the period of late pregnancy in rabbits. Twelve adult local breed rabbits were used. The samples from different parts of the uterine tube were prepared for histological study after staining with H&E, Masson’s trichrome and combine Alcian blue (pH2.5)-PAS. The pre ampulla was a narrow tube and its tunica mucosa had slightly long simple mucosal folds lined by pseudostratified columnar epithelium, the ampulla had a wide lumen and its tunica mucosa displayed several highly tall branched mucosal folds with few short simple folds while the isthmus was the narrowest region and its tunica mucosa displayed few of tall and short simple mucosal folds. The mucosa of three parts of the uterine tube was lined by pseudostratified columnar epithelium which is composed of three types of cells: mucous secretory cells, non-secretory cells and basal cells, the mucous secretory cells were the predominant type and revealed secretory activities. The lamina propria-submucosa of the uterine tube was composed of cellular connective tissue and tunica muscularis. The uterus had a very thick wall with well-recognized endometrium and myometrium, the endometrium was composed of many-branched and simple endometrial folds that were covered by multinucleated syncytial cells and simple cuboidal epithelial cells. Lamina propria was composed of loose connective tissue had scattered groups of well growing simple uterine glands that showed secretory activities. The current result showed that the uterus during the late period of pregnancy was differed from those of non-pregnant rabbits, while the uterine tube at late pregnancy has a structure that appeared prepared for the next physiological period.

Early pregnancy diagnosis of rabbits: A non-invasive approach using Vis-NIR spatially resolved spectroscopy

Pregnancy diagnosis is essential for rabbit's reproductive management. The early identification of non-pregnant rabbits allows for earlier re-insemination, increases the service rate, and reduces the laboring interval in commercial operations. The objective of this study was to establish the feasibility of using a Vis-NIR spatially resolved spectroscopy for diagnosing pregnancy in female rabbits. A total of 141 female rabbits, including 67 pregnant female rabbits (PRs) and 74 non-pregnant female rabbits (NPRs), were measured spectrally between 350 and 1000 nm with different source-detector distances (SDD). Different preprocessing methods were used to transform and enhance the spectral signal. A partial least squares-discriminant analysis (PLS-DA) classification model of the original and preprocessed spectra was established. The highest accuracy of the calibration set and prediction set was 91.75% and 86.05%, respectively. Competitive adaptive reweighted sampling (CARS) and successive projection algorithm (SPA) were used to select characteristic wavelengths from the variables of VIP > 1 (Variable importance in projection),and four classification models were established based on selected wavelengths, including PLS-DA, support vector machine (SVM), K-Nearest Neighbor (KNN) and Naïve Bayes. SPA-SVM was the optimal classification model, the sensitivity, specificity, and accuracy of the validation set and prediction set were 93.18%, 94.44%, 93.88%, 86.96%, 90.00%, 90.69% respectively. The results showed that Vis-NIR spatially resolved spectroscopy combined with classification models could discriminate the PRs and NPRs.

Effect of season and pregnancy on minerals serum variations of local rabbits in Tiaret, Algeria

Abstract The present study aimed to assess the season and pregnancy influence on minerals serum of local rabbits raised in semi-arid climate type. Fifty-nine multiparous does was used in this study during 2019. The semi-intensive rhythm of reproduction was used. All pregnant does were at the late stage of pregnancy at the sampling date. Serum samples were collected in two seasons: winter and summer. In this study, biochemical parameters concentrations of pregnant rabbits were significantly higher (p<0,05) compared with non-pregnant rabbit. The value of biochemical parameters total protein, albumin, triglyceride, cholesterol, calcium, and phosphorusus changed significantly. In this study, most parameters were influenced by pregnancy.

Effects of Induced Haemorrahge on Thermoregulation, Blood Constituents and Serum Biochemical Parameters in Pregnant and Non-Pregnant Rabbits (Oryctolagus cuniculus)

Background and Objectives: Haemorrhage is a leading cause of mortality and morbidity of mother and foetus. Pregnancy is associated with changes which may influence responses to bleeding. This study was designed to examine the influence of controlled haemorrhage and compare thermoregulation and haematological and biochemical parameters in pregnant and nonpregnant rabbits.
 Materials and Methods: Twelve pregnant and nonpregnant rabbits, 6 in each group, were used in the studies. Both groups of animals were subjected to 20% haemorrhage of total blood volume on gestation day 21. The rectal temperature (Tr), respiratory rate (RR) and heart rate (HR) were monitored for 2 days following bleeding. Blood samples were collected at 24 hrs before induction of bleeding and then after bleeding at 30 min, 24 hrs and 48 hrs. The samples were used for measurements of haematological parameters; coagulation profile, arterial blood gases and serum electrolytes.
 Results: The general trend indicates lower Tr values in pregnant rabbits at 30 min post-haemorrhage. The values of RR and HR were significantly (P ≤ 0.01) higher in pregnant and nonpregnant animals at 24 hrs post-haemorrhage. The pregnant rabbits showed significant (P<0.05) decrease in platelets count at 24 hrs post-haemorrhage compared to the nonpregnant values. In pregnant rabbits, haemorrhage was associated with significant increase in PT. The activated partial thromboplastin time (APTT) was significantly (P≤ 0.01) prolonged at 24 hrs post-haemorrhage in pregnant and nonpregnant rabbits. The partial pressure of arterial oxygen (PaO2) in pregnant and nonpregnant rabbits was significantly (P≤ 0.01) increased at 24hrs and 48 hrs post-haemorrhage. The partial pressure of arterial carbon dioxide (PaCO2) decreased significantly (P≤0.01) at 30 min post-haemorrhage in pregnant rabbits. There was a slight increase in Na and Ca levels in pregnant rabbits’ post-haemorrhage. Haemorrhage in rabbits was associated with significant decreases in plasma osmolality in pregnant rabbits.
 Conclusion: Pregnancy induces modifications in some physiological responses to haemorrhage. The information generated could be used in monitoring maternal health during pregnancy and risks of changes associated with haemorrhage in mammals.

Activation of cortical and striatal regions during the expression of a naturalistic compulsive-like behavior in the rabbit

Nest building behavior in the pregnant rabbit (Oryctolagus cuniculus) can serve as a model for compulsions in obsessive compulsive disorder (OCD). Previous work showed that the “straw carrying” phase of nest building (during which the rabbit repeatedly collects straw in its mouth, carries it into the nest box and deposits it there, and then returns to collect more) is associated with increased c-FOS expression (a marker of neuronal activity) in the orbitofrontal, anterior cingulate, and piriform cortices. In the present study, we quantified c-FOS expression in the caudate and putamen, as well as in the primary motor, somatosensory, and prefrontal cortices of: (1) pregnant rabbits given straw (PREG + STRAW); pregnant rabbits not given straw (PREG); (3) estrous rabbits given straw (ESTROUS + STRAW); and (4) estrous rabbits not given straw (ESTROUS). We found that straw carrying was associated with increased c-FOS expression in the dorsal putamen, ventral caudate, primary motor cortex, and somatosensory cortex. Additionally, a correlational analysis of PREG + STRAW animals revealed that these regions, along with the premotor and prelimbic cortices, were significantly intercorrelated with respect to c-FOS expression, suggesting their “coactivation” during repetitive straw carrying. By contrast, behavioral interactions of non-pregnant (ESTROUS) rabbits with straw (e.g., sniffing, nibbling it) were associated with a distinct pattern of c-FOS expression that included the medial and ventral putamen. c-FOS expression in PREG + STRAW rabbits is similar to patterns of regional brain activity in OCD patients exposed to obsession-provoking stimuli, as well as to those observed in healthy human mothers responding to infant-associated stimuli.

Pregnancy affects the pharmacokinetics of sildenafil and its metabolite in the rabbit

1. There is growing interest in the use of sildenafil during pregnancy for various maternal and fetal conditions. This study aims to investigate the effect of pregnancy on the maternal pharmacokinetics (PK) of sildenafil and its main metabolite desmethylsildenafil in rabbits. Using NONMEM, population PK modeling was performed based on plasma samples from 31 rabbits of whom 15 were pregnant and 16 were not. All received a single subcutaneous sildenafil dose of 10 mg/kg. One sample was obtained per rabbit at either 30, 60, 120, 360, 720 or 1320 min after sildenafil administration.2. A two- and one-compartment PK-model best described the data for sildenafil and desmethylsildenafil, respectively. Compared to non-pregnant rabbits, the central and peripheral volume of distribution and inter-compartmental clearance of sildenafil were lower in pregnant rabbits [32.1 versus 12.2 L, 110 versus 44.4 L and 25.5 versus 12.1 L/h; all p < 0.05]. The formation clearance from sildenafil to desmethylsildenafil was also reduced during pregnancy [13.3 versus 7.8 L/h; p < 0.05].3. In contrast, the elimination clearance of desmethylsildenafil, was higher in pregnancy [73.5 versus 116. 9; p < 0.05]. In rabbits, pregnancy impacts PK parameters of sildenafil and its metabolite, leading to an increased peak concentration and 24 h exposure for sildenafil and a decreased 24 h exposure for desmethylsildenafil.

Co-relation of estrous cycle phases with uterine bacterial and fungal flora in non-pregnant female laboratory rabbits.

This study was designed to investigate the relationship between the estrous cycle phases with uterine bacterial and fungal flora in non-pregnant female rabbits. Thirty laboratory mature multiparous rabbits were used for this purpose. Samples from uterine lavage for culture of bacteria and fungi were collected at different stages of estrous cycle (based on vaginal cytology), and histopathological observations were evaluated based on the scoring system used for defining the infection of the uterus. Various types of bacteria and fungi were isolated from rabbits at all stages of estrous cycle. The widest variety of bacteria and fungi was isolated at Di-estrous stage and the lowest variety was detected at estrous stage. Klebsiella oxytoca as well as yeast have been isolated at all stages of estrous cycle. This study showed that infection with K. oxytoca and yeast had no relationship with different stages of estrous cycle but other bacteria and fungus were associated with one or more stages of the estrous cycle in rabbits.

Experimental infection of pregnant rabbits with hepatitis E virus demonstrating high mortality and vertical transmission.

A high mortality rate of approximately 20% in pregnant women with hepatitis E has been reported in previous studies. However, other studies showed no difference between pregnant and nonpregnant women in the severity of hepatitis E. To determine the effects of HEV infection on pregnancy, we successfully established HEV infection in six pregnant rabbits (PR) and six nonpregnant rabbits (NPR) with a rabbit HEV isolate, taking three PR and one NPR without HEV infection as controls. Tests for HEV RNA by RT-PCR, anti-HEV antibodies by ELISA and HEV antigen via immunohistochemistry and histopathology were carried out. Two of six infected PR miscarried and three of the remaining four PR died which may be attributed to severe liver necrosis caused by HEV infection. Moreover, vertical transmission was found to be associated with the replication of HEV in placenta, indicated by the presence of HEV RNA and antigen in placenta from the infected PR. Our findings strongly suggest that HEV infection could lead to adverse outcomes in pregnancy and vertical transmission, suggesting the necessity for pregnant women at risk of HEV infection to be vaccinated.

Evaluation the effect of placenta on some clinical biochemical parameters during different reproductive periods in New Zealand white female rabbits

The current study was conducted to evaluate the effect of different reproductive periods on some biochemical parameters (ALP, ALT, AST and GGT) in New Zealand white female rabbits. The study was carried out in the animal house of the college of veterinary medicine in Al- Qadisyia university on 21 female New Zealand white rabbits, the animals were divided to 3 groups each group contain 7 rabbits: group A as control non-pregnant rabbits, group B were pregnant rabbits and final group C were lactating female rabbits. Fresh blood samples (4 ml) were collected and centrifuged to obtained serum, then Reflotron apparatus was used for estimation of some enzymes (ALP,ALT, AST and GGT) in all groups of the experiment. The results of group A revealed that the means of (ALP, ALT, AST and GGT) were (44.54, 45.52, 20.74 and 6.08) U/L respectively, while the means of enzyme levels in group B were (105.9, 48.08, 22.68 and 6.8) U/L respectively, and the means of enzyme levels in group C were (49.9, 46.21, 21.84 and 6.72) U/L respectively. The levels of ALP in group B showed a significant increase (P&lt;0.01) as compared with A and C groups, while there no significant increment among sera of three groups levels of (ALT, AST, and GGT).

Serotonin regulates contractile activity of the uterus in non-pregnant rabbits

Serotonin (5-HT) can stimulate the cholinergic system of the uterus by indirect actions on the modulation of reflexes and a direct action on smooth muscles. We investigated the role of 5-HT in the regulation of the cholinergic activity in the uterine parts of non-pregnant rabbits. The right vagus or pelvic nerve and the left sympathetic trunk were stimulated by an electrical field, and the uterine contractile activity was evaluated by measuring the amplitude and frequency of slow wave electromyogram (EMG), with the surface of microelectrodes applied to the uterus bottom, body, and cervix, respectively. Double stimulation of the vagus or pelvic nerve and the sympathetic trunk increased the frequency and the amplitude of the slow wave EMG in all the uterine parts. Furthermore, the administration of exogenous 5-HT increased the vagus or pelvic induced EMG activity in all parts of the uterus. Overall our results demonstrate that 5-HT enhances the vagus contractile activity with a magnitude of the effect decreasing from the bottom to the cervix, whereas 5-HT enhances the pelvic nerve contractile functions with a magnitude of the response increasing from the bottom to the cervix. The administration of droperidol, a 5-HT3 and 4 receptor inhibitor, and spiperone, a 5-HT2 receptor antagonist, inhibited the effect of the serotoninergic fibers of the sympathetic trunk to increase the vagus and pelvic nerve EMG activity. These data suggest that 5-HT stimulation of the parasympathetic nerves results in the induction of uterine contraction via the activation of 5-HT2, 3, and 4 receptor subfamilies.

Preeclampsia is caused by continuous sympathetic center excitation due to an enlarged pregnant uterus

To deduce the origin of preeclampsia characterized by hypertension and proteinuraia on the basis of results from animal studies and its therapeutic strategies. Sympathetic and parasympathetic zones of female non-pregnant rabbit brain were stimulated electrically with Kurotu's electrodes. Systolic blood pressure, urine volume, and proteinuria were evaluated before and after the stimulation of autonomic zones. Excitation, hypertension, urine reduction, cloudy urine, and proteinuria were observed following stimulation of the sympathetic zone. A stable state, low blood pressure, increased urine volume, and no proteinuria were observed following stimulation of the parasympathetic zone. Hypertension and proteinuria in preeclampsia are caused by continuous stimulation of the sympathetic nervous center in the hypothalamus through the innervation between the enlarged uterus and hypothalamus in the latter stages of pregnancy or in a complete hydatidiform mole. Future studies are needed to address the potential of pharmacological suppression of an overactive sympathetic nerve system.

Systemic infection induced by intranasal inoculation of Bovine herpesvirus 1.1 in pregnant and non-pregnant rabbits

Bovine herpesvirus (BoHV) type 1.1 (BoHV-1.1) causes repeated outbreaks of upper respiratory disease and abortion in cattle. The systemic effects of BoHV-1.1 in rabbits, using intranasal inoculation are reported. Female rabbits were divided into four groups and inoculated with the virus 10days before mating, and at 15 or 22days of pregnancy. Studies of the clinical signs, antibody production, virus isolation, and DNA detection as well as histological and immunohistochemical studies were carried out on lungs, kidneys, spleen, placentas, uteri and foetal tissues. All virus-inoculated animals developed respiratory clinical signs and a humoral response. BoHV-1.1 was isolated from nasal swabs and plasma rich in leukocytes, and viral DNA was detected in blood, dead foetuses and placentas. Histopathological lesions were found in the respiratory tract and some placentas and foetuses were immunohistochemically positive. Intranasal inoculation might be useful to study the systemic effects of BoHV-1.1 infection in the rabbit model.

Impact of Pregnancy on Zonisamide Pharmacokinetics in Rabbits

Pregnancy is associated with various physiological changes which may lead to significant alterations in the pharmacokinetics of many drugs. The present study was aimed to investigate the potential effects of pregnancy on the pharmacokinetic profile of zonisamide (ZNM) in the rabbit. Seven female rabbits were used in this study. The pregnant and nonpregnant rabbits received ZNM orally at a dose of 10 mg/kg and blood samples were collected from the animals just before receiving the drug and then serially for up to 24 h. The plasma samples were analyzed using tandem mass spectrometric method. Following a single oral dose of ZNM to the rabbits, the mean values of ZNM plasma concentrations at different times were consistently low in pregnant compared to nonpregnant rabbits. The mean values of ZNM's C max and AUC0−∞ were significantly (P < 0.05) decreased, whereas the CL/F exhibited substantial increase (P < 0.05) in pregnant compared to nonpregnant rabbits. T max, t 1/2abs, t 1/2el, MRT, and Vd/F showed no significant differences between the two groups. The present study demonstrates that pregnancy decreased ZNM plasma concentrations in rabbits and that the decrease could be due to decreased extent of gastrointestinal absorption, induced hepatic metabolism, or enhanced renal elimination of the drug.

The Effects of Ascorbic Acid on the Estrogen/Progesteron Levels in the Isolated Rabbit Uterine Muscle

Background: The study was carried out to examine the effect of Ascorbic Acid (AsA) on estrogen/progesterone levels in the isolated non-pregnant rabbit uterine muscle. Methods: Twelve non-pregnant rabbits were randomized into two groups as the rabbits pretreated with AsA (n = 6) and the rabbits not pretreated with AsA (n = 6). After 30 mg/kg AsA was administered intraperitoneally, serum and tissue (uterine smooth muscle) levels of estrogen and progesterone were measured. Results: AsA at the above mentioned concentration caused a significant increase in tissue estrogen/progesterone ratio (P < 0.01), while did not induce any change in the hormone ratio in the serum. The increase in the tissue estrogen/progesterone ratio was resulted from both the decrease of the progesterone levels and the increase of estrogen levels (P < 0.001). Conclusion: In this context, the fact that the tissue levels of hormones and autacoids is more important than the serum concentrations should be concidered. The findings of this study indicate that in comparison to the control group, AsA causes decrease in the non-pregnant isolated uterine smooth muscle tissue levels of progesterone and increase in the non-pregnant isolated uterine smooth muscle tissue levels of estrogen while the serum levels keep constant. doi: http://dx.doi.org/10.4021/jcgo47w

The tissue distribution and metabolism of amidopyrine in the rat and pregnant and non-pregnant rabbit.

Abstract The tissue distribution of amidopyrine and its metabolites 4-amino-antipyrine and N-acetyl-4-amino-antipyrine has been determined at intervals following oral doses of 300 mg/kg of amidopyrine in pregnant, non-pregnant and foetal rabbits, and also in adult non-pregnant rats. Except in lung, their concentration was higher in the normal rabbit than the rat. In both species amidopyrine levels were maximal at 2 hr, but the metabolite levels varied with tissue, species and time interval. The dominant pathways were demethylation in the rabbit and acetylation in the rat. Plasma and tissue levels of amidopyrine were higher in non-pregnant than pregnant rabbits, whereas those of the metabolites varied. Studies indicate that 25-day, but not 14-day foetuses may metabolize amidopyrine.

Effect of Gestation and Season on the Haematological and Biochemical Parameters in Domestic Rabbit (Oryctolagus cuniculus)

The aim of this study was to investigate the effect of gestation and season on the haematological and biochemical parameters in domestic rabbit (Oryctolagus cuniculus) to improve the conditions of breeding and conservation in Saudi Arbia. For this study. 30 nonpregnant and 30 pregnant rabbits on day 24 to 26 of gestation were examined. The animals weighed between 2.6 and 3.6 kg and were 1.8-2.6 years old. Blood samples were collected from pregnant and non–pregnant rabbits in January (winter season), April (spring season), July (summer season) and October (autumn season) for analyzing hematological and biochemical parameters. It was revealed for the study that the value of hematological parameters i.e., erythrocyte, leukocyte, lymphocyte numbers and haemoglobin concentrations of pregnant rabbits were significantly (p<0.05) decreased compared with non-pregnant rabbit. Whereas, mean corpuscular volume was significantly (p<0.05) increased in pregnant rabbits compared with non-pregnant ones. The value of biochemical parameters i.e., total protein, albumin, triglyceride, cholesterol, calcium, and phosphorus were significantly (p<0.05) decreased in pregnant rabbits compared with non-pregnant. Whereas, glucose level was significantly (p<0.05) increased in pregnant rabbits compared with non-pregnant rabbits. Most of hematological parameters significantly (p<0.05) decreased in July. In contrast only few

Effect of the photoperiod on the glutamate level in the suprachiasmatic nucleus of pregnant and non-pregnant rabbits.

Microdialysis sampling was used to measure the glutamate level (GLU) contained in the suprachiasmatic nucleus (SCN) in 10 pregnant and 10 non-pregnant, subjected to either a 16:8 h light-dark cycle or a 12 h advanced photoperiod. Results revealed that GLU levels were significantly greater in samples taken for 2 h (15 min intervals), ?60, ?45 and ?30 min before parturition (P&lt;0.009, P&lt;0.04, P&lt;0.02), and +45 and +60 min after birth (P&lt;0.009, P&lt;0.05) respectively, in pregnant rabbits subjects to a 16:8 LD photoperiod (with light from 6:00-22:00 h). Parturition in these animals occurred at day 31 of gestation. Pregnant rabbits exposed to 12 h advanced photoperiod showed lower GLU levels in the SCN, and a longer gestation period and parturition process. In non-pregnant rabbits the GLU levels in the SCN were also significantly higher (P&lt;0.009, in all samples) in comparison with rabbits subjected to the 12 h shifted photoperiod. It is possible that the photoperiod may have influenced GLU levels, and consequently, the length of gestation, the number of young and the time of birth. However, further studies involving new biotechnologies and a greater number of animals are needed to confirm these results.

Effects of GSM-like radiofrequency on distortion product otoacoustic emissions in pregnant adult rabbits

To determine the effects of 1800 MHz GSM-like Radiofrequency (RFR) on the cochlear functions of pregnant adult rabbits by Distortion Product Otoacoustic Emissions (DPOAEs). Eighteen 13-month-old pregnant and eighteen 13-month-old non-pregnant New Zealand White rabbits were studied. They were randomly divided into four groups. Nine pregnant rabbits (Group 2) and nine non-pregnant rabbits (Group 4) were exposed to 1800 MHz GSM-like RFR 15 min daily for 7 days. Nine pregnant (Group 1) and nine non-pregnant rabbits (Group 3) were not exposed to GSM like RFR. Cochlear functions were assessed by DPOAEs at 1.0-8.0 kHz. In all pregnant groups except 2.0 kHz, DPOAE amplitudes were not different in Group 2 and Group1. In Group 4, DPOAE amplitudes at 1.0-4.0 kHz (-1.68 dB SPL at 1.0 kHz, 3.05 dB SPL at 1.5 kHz, 2.96 dB SPL at 2.0 kHz, 1.30 dB SPL at 3.0 kHz and 12.22 dB SPL at 4.0 kHz) were lower than Group 3 (8.67 dB SPL at 1.0 kHz, 17.67 dB SPL at 1.5 kHz, 26.10 dB SPL at 2.0 kHz, 18.10 dB SPL at 3.0 kHz and 35.13 dB SPL at 4.0 kHz) (P < 0.0125). In the pregnant group, harmful effects of GSM-like RFR were less than in the non-pregnant group. GSM-like RFR caused decreases in DPOAE amplitudes mainly in non-pregnant adult rabbits. Prolonged exposure may affect the DPOAE amplitude. Recommendations are given to prevent the potential hazardous effects of RF in humans.

The administration of an adenoviral thymidine kinase suicide gene to the uterine artery of rabbits does not affect fertility: a safety study of pregnant and nonpregnant rabbits and their offspring

Adenoviral gene therapy, based on herpes simplex virus thymidine kinase (AdvTK) is being developed for clinical use but no safety data are available with respect to the effects on female germ cells should the virus accidentally be released into systemic circulation. We studied the effects of AdvTK gene therapy on ovaries and germ cells in pregnant and nonpregnant rabbits and also the potential transmission of a transgene to offspring. To mimic the severest of conditions, gene transfer was made by direct catheter-mediated injection into the uterine artery of pregnant and nonpregnant rabbits. AdvTK or AdvLacZ at 1 x 10(10) pfu were used for gene transfer. Ganciclovir was administered to AdvTK-treated rabbits to induce gene therapy. The rabbits were mated 6 and 12 weeks following gene transfer and the surviving young (89 from a total of 114) were analysed. No change in fertility was observed in the two matings after the gene transfer. In addition, no change was observed in ovarian histology between the AdvTK group, the AdvLacZ group and the nontreated controls. Southern blotting analysis showed no genomic integration of the transgene. However, in PCR analysis, transgene DNA was found in 9.3% of the litter samples. This was not the case for results from the reverse transcription-PCR assay. Although AdvTK gene therapy may initially affect ovarian cells, the influence appears to be transient. However, after direct exposure of the ovarian cells in high concentration of adenoviruses, transmission of a transgene in the offspring cannot be excluded.