In less severe cases of cerebellar hypoplasia, larger parts of the vermis and of the hemispheres are present. In other cases the malformed cerebellum shows only slight, uniform or irregular reduction in size of individual lobes and folia. Most cases of BVDV-induced cerebellar hypoplasia are associated with alterations of the cerebrum, i. Teratogenic lesions associated with intrauterine infection with bovine virus diarrhea virus BVDV in cattle.
The lesions are representative also for other teratogenic viruses infecting cattle. There are only small irregular parts of the developing cerebellum black asterisk. Posterior to the cerebellar tissue, the 4th ventricle is visible which is covered by congested choroid plexus tissue white asterisk.
The posterior and dorsal parts of the cerebral hemispheres are collapsed, partially ruptured and covered by thin membranes consisting of congested leptomeningeal tissue. The cerebellum is severely hypoplastic and reduced to a small, narrow mass of tissue arrows.
Between the posterior parts of the collapsed cerebral hemispheres and the hypoplastic cerebellum the rostral and caudal colliculi asterisks of the quadrigeminal plate are visible. There is marked bilateral thinning of the grey and white matters of the cerebral brain tissue surrounding the extremely dilated lateral ventricles. The dorsal parts of the cerebral hemispheres are partially covered by thin, partly translucent leptomeninges.
Beneath the meninges the brain tissue is focally absent arrow. Transverse brain section at the level of the optic chiasm. There is slight dilation of both lateral ventricles asterisks.
In the cerebral white matter bilateral porencephalic cysts are present arrows. Cut surfaces of cerebellar tissue reveal the presence of variable-sized cystic cavities affecting the cerebellar hemispheres and the vermis arrows. In hydranencephaly, the cerebral hemispheres are transformed into large sac-like fluid-filled cavities, which are covered by thin, partly translucent leptomeninges Fig. In such cases, upon severing the head from the vertebral column and also during opening the skull, clear, watery cerebrospinal fluid drain off from the vertebral canal and from the sac-like cavities.
The cerebral lesions most severely affect the posterior and dorsal parts of the hemispheres Fig. Transverse sections of hydranencephalic brains reveal severely dilated lateral ventricles and presence of remnants of atrophic cerebral brain tissue Fig. In cases of hydrocephalus, the lateral ventricles are slightly or markedly dilated with accumulation of clear cerebrospinal fluid Fig.
Macroscopically, depending on the degree of ventricular enlargement, the hydrocephalus can be associated with the presence of an enlarged and dome-shaped calvarium Fig. Microencephaly, characterized by subnormally-sized cerebral hemispheres occurs less frequently [ 21 , 23 ]. Porencephaly is characterized by the presence of circumscribed variable-sized cystic cavities, which may occur in the cerebral hemispheres or in the cerebellum Fig. Porencephalic cysts in brains of BVDV infected calves are located in the white matter alone or both in the grey matter cortex and white matter and, depending on their size, are macroscopically visible or can be found at microscopical examination [ 21 , 23 ].
In brains with hydrocephalus, cavitating lesions may also be present in the periventricular brain parenchyma porencephaly Fig. This suggests that the dilation of the ventricles represents hydrocephalus ex vacuo , i. Both in spontaneous and experimental cases of bovine BVDV infection, hypomyelination of brain and spinal cord white matter has been described [ 24 — 28 ]. In case of hypomyelination, macroscopic abnormalities are absent and detection requires histological examination and confirmation of deficiency of stainable myelin by special staining e.
Luxol fast blue stain of CNS tissue. Congenital ocular lesions after spontaneous or experimental BVDV infection of bovine foetuses are commonly associated with cerebellar hypoplasia known as oculo-cerebellar syndrome [ 13 , 14 , 18 , 19 ]. These lesions can occur either as single entities or can be associated with CNS or ocular lesions.
Schmallenberg virus is a member of the genus Orthobunyavirus , characterized by three genomic ssRNA segments, and has been classified within the species Sathuperi virus of the Simbu serogroup [ 30 ]. SBV was discovered in as a novel and emerging pathogen in ruminants in north-western Europe and appeared as the first orthobunyavirus on this continent [ 31 ]. Several orthobunyaviruses of the Simbu serogroup show teratogenic properties in ruminants and transplacental orthobunyaviral infections, resulting in congenital malformations, have been reported in Asia, Australia, Africa and the Middle East [ 32 — 34 ].
Like most orthobunyaviruses, SBV is transmitted by Culicoides spp. Although the origin of SBV has not been elucidated, the virus was introduced in the region of the German-Dutch borders [ 41 ]. Within 2 years, SBV disseminated into 27 European countries, indicating a very efficient transmission through the arthropod vector [ 35 , 41 ].
Infection during the gestation period may lead to transplacental infection of the foetus, however, the rate of vertical transmission seems low [ 44 ]. Teratogenic effects depend on the foetal developmental stage at the time of infection and as neuronal cells in the developing CNS are the target cells [ 45 ], infection results in a syndrome of congenital hydranencephaly and arthrogryposis.
Furthermore, the foetal bovine immune system, being developed between approximately GDs 40 and , is capable to react with a CNS inflammatory response [ 46 ]. The severity of lesions in the brain and spinal cord depends on a complex interaction between foetal neurogenesis and immunocompetency and virulence of the strain [ 46 ].
SBV infection during early gestational stages results in severe dysplastic CNS lesions, whereas late gestational infections lead to encephalomyelitis [ 49 ]. Like most viral infections, transplacental transmission of SBV does not elicit placentitis and most malformed calves are stillborn at term. The weight of malformed calves is significantly less than normal with a correlation between the body mass deficit, the severity of the malformations and the amount of skeletal muscles [ 50 ].
Malformations of the vertebral column and arthrogryposis, which are regarded secondary to dysplastic CNS lesions, are the most conspicuous exterior gross lesions in affected calves Fig. Thoracic vertebral column malformations are often associated with a flattened ribcage. Scoliosis, kyphoscoliosis and kyphosis without torticollis appear less frequently and lordosis of the thoracolumbar part is observed sporadically.
Congenital arthrogryposis of all four limbs arthrogryposis multiplex congenita appears in various degrees with bilaterally symmetric arthrogryposis in both fore- and hindlimbs as the most frequently observed malformation of the extremities.
Sometimes, arthrogryposis is only present in both forelimbs or, rarely, only in both hindlimbs. Occasionally, unilateral arthrogryposis occurs, again mainly, if present, in the forelimbs. In most malformed calves congenital arthrogryposis is accompanied with vertebral column malformations, whereas vertebral column malformations without arthrogryposis are only observed sporadically [ 49 , 50 ].
Teratogenic lesions associated with intrauterine infection with Schmallenberg virus SBV in cattle. Parasagittal section through the head exposing the severely dilated right lateral ventricle asterisk. The axial and appendicular bones are normally founded and the vertebral malformations and arthrogryposis develop due to imbalance in foetal muscular activity flexor vs.
In the brain and spinal cord, neuron loss is reflected in both the loss of descending tracts in the ventral spinal cord white matter and in the loss of ventral horn motor neurons in the spinal cord grey matter and in deficient ventral spinal nerve roots. Loss of spinal cord tissue, grossly visible in severely affected cases as a small dorsoventral flattened spinal cord micromyelia , accounts for failure of normal skeletal muscle development due to denervation of the axial and appendicular musculature and hence to vertebral column malformation and arthrogryposis, respectively.
Skeletal muscle tissue of arthrogrypotic limbs is hypoplastic, reflecting the extent of spinal cord dysplasia in the cervical and lumbar intumescences [ 49 , 50 ]. Occasionally, a flattened skull and brachygnathia inferior are found.
Deformation of the skull is assessed in combination with brain malformations. Neuroparenchymal loss in the brain may be visible by more or less severe defects in the grey and white matter of the cerebrum, cerebellum, midbrain, brainstem and medulla. Cerebral defects range from microencephaly, porencephaly in combination hydrocephalus and lack of gyri lissencephaly to hydranencephaly with only a small rim of cortical tissue left Fig.
Cerebellar hypoplasia is mainly observed in combination with cerebral defects, which also accounts for dysplasia of the midbrain, brainstem and medulla [ 49 , 50 ]. Bluetongue virus, the causative agent of the disease bluetongue BT in ruminants, is a member of the genus Orbivirus within the Reoviridae family, with a genome, consisting of 10 dsRNA segments.
Currently, 26 serotypes are distinguished, determined by variations of the outer-capsid protein VP2, which induces specific virus-neutralising antibodies [ 51 ]. The global distribution of BTV in temperate and sub tropical zones coincides with the presence of Culicoides spp. The regional presence of the various BTV serotypes is associated with particular Culicoides spp.
BT most commonly occurs in sheep, whereas cattle, acting as reservoir, sporadically develop clinical signs. The clinical outcome of a BTV infection varies with virulence and transmission potential of the infecting strain phenotype and depends on host species, breed, age, immune status , vector and environmental factors [ 4 , 53 ].
After infection of a susceptible host, BTV disseminates via the regional lymphnode to various organs, especially the lung and spleen. Subsequently, BTV replicates in mononuclear leukocytes and endothelial cells, organizing vascular injury, coagulopathy and hypovolemic shock [ 52 ]. Seasonal outbreaks of BT due to BTV serotypes 1, 2, 4, 9 and 16 have appeared since in the Mediterranean Basin at the boundaries of the temperate zone [ 52 ].
However, in BTV serotype 8 BTV-8 emerged unexpectedly in north-western Europe, far beyond the previously known geographic area of BT and being an unknown serotype within Europe [ 54 — 56 ]. Initially, the morbidity and mortality rate in sheep and cattle appeared moderate, compared with other BTV-serotypes, but the severity and impact increased in the following 2 years [ 57 , 58 ]. Clinical signs, also obvious in cattle, included fever, salivation, facial oedema, lesions on lips and nostrils, ulcerations in the oral and nasal mucosa, including tongue and gingiva, and coronitis [ 54 ].
Yet, in addition, BTV-8 exhibited an ability to cross the ruminant placenta, an unusual and unprecedented property of wild-type BTV, causing congenital brain malformations [ 59 — 65 ]. Experimental infections with various BTV-serotypes, using direct inoculation in bovine foetuses, have demonstrated that infection early in gestation, i.
Infection during this time window causes hydranencephaly, occasionally combined with cerebellar defects, or leads to porencephaly and hydrocephalus [ 1 ]. As immunocompetency develops, foetal infection during the second half of gestation, i. However, acute infection at the final stage of gestation could lead to a seronegative PCR-positive offspring [ 63 ].
A seronegative PCR-positive calf could also indicate the existence of immunotolerance and hence persistently infected calves, though to date no convincing evidence has been presented for this phenomenon [ 56 ]. Follow-up of 37 seemingly healthy PCR-positive calves up to 5 months after birth showed that BTV-8 was not detectable any longer by PCR at the end of the sampling period [ 68 ].
Apparently, seemingly healthy PCR-positive calves may be the outcome of foetal infection during the second half of gestation whereas foetuses with cerebral defects, infected during the vulnerable time window of CNS development at the first half of gestation, are also able to survive an intrauterine BTV-8 infection. Pathological changes in these cases, up to many months after birth, are confined to hydranencephaly, reflecting the predominant involvement of the cerebral cortex in interpretation of stimuli and behavioural patterns, and the function of intact remains of the brain, performing vital functions and locomotion [ 69 ].
Teratogenic BTV affects neuronal and glial precursor cells in the brain. Furthermore, vascular injury and infarction in the cerebrum may contribute to cerebral defects [ 69 , 70 ]. Foetuses infected at later stages of gestation show encephalitis but no brain malformations [ 70 — 72 ]. Lesions in aborted or stillborn bovine foetuses associated with spontaneous foetal BTV-8 infections mainly consist of hydranencephaly, while porencephaly is observed less frequent.
This probably reflects the foetal gestational age at the time of infection as seen in experimental infections [ 1 ]. Both lesions may be accompanied by cerebellar hypoplasia, which vary in severity from mild to almost complete lack of cerebellum. A slightly domed calvarium is present in some cases of hydranencephaly [ 59 ]. In liveborn intrauterine BTV-8 infected calves, surviving for up to several months, the dominating lesion is hydranencephaly Fig. Hydranencephaly associated with intrauterine infection with bluetongue virus BTV in cattle.
Specimen of the right half of the brain of a 4-days-old calf, born 2 weeks before term with nervous symptoms and blindness. The dorsal part of the cerebral hemisphere is ruptured and collapsed asterisk while the midbrain, brainstem, cerebellum and medulla oblongata are not affected.
Spontaneous foetal infection with BTV. Intrauterine BTV-8 infections do not cause significant lesions to the brainstem, medulla and spinal cord and hence are not associated with musculoskeletal disorders such as arthrogryposis and vertebral column malformations.
Their principal vectors are Culicoides spp. AKAV was first suspected of causing congenital abnormalities in in Japan, with the distinct syndromes of hydranencephaly and arthrogryposis, sometimes accompanied by other abnormalities including abortion, stillbirth, polioencephalomyelitis and possibly microencephaly, frequently observed in parts of Australia [ 73 — 75 ].
AV is related to AKAV and has been occasionally associated with hydranencephaly and arthrogryposis in Australia but is antigenetically and biologically distinct [ 76 ], as is the closely related Chuzan virus [ 77 ].
AKAV is widely distributed in tropical and subtropical regions of Australia where it regularly infects young female cattle prior to gestation. AKAV is also suspected of causing abortion, premature births, stillbirths and possibly other congenital abnormalities of the CNS, including porencephaly and microencephaly [ 78 ].
The hemispheres are partly collapsed due to severe hydranencephaly. Fluid is oozing out the brain cavities due to damage to the vulnerable remnants of the cerebrum during opening of the skull and surrounds the brain. Notice the normal sized cerebellum. Hydranencephaly usually develops in foetuses infected with AKAV between days 79 and in gestation.
An investigation of a bovine epizootic of congenital hydranencephaly and arthrogryposis in New South Wales NSW , Australia resulted in the identification of five groups of foetal abnormalities, corresponding to the gestational age of infection, from late group 1 to early group 5 [ 73 ]. Common symptoms include fever, cough, loss of taste or smell and shortness of breath and more serious symptoms include breathing difficulties, chest pain and loss of mobility.
On Aug. In December , this vaccine became the first to be approved after a large clinical trial, according to Nature. According to WHO , the disease infected camels before passing into humans and can trigger a fever, coughing and shortness of breath in infected people.
There is no vaccine available to prevent this disease, according to the NHS. The best way to reduce the chances of infection is to wash hands regularly, avoid contact with camels and not consume products containing raw animal milk. Live Science. See all comments Don't said:. Meh said:. Comment on rabies fatality rate. Although all warm-blooded animals are thought to be susceptible to rabies, there are strains of the rabies virus multiple bat stains strains are maintained in particular reservoir host s , with some cross over especially in the US between raccoons and skunks.
Although a strain can cause rabies in other species, the virus usually dies out during serial passage in species to which it is not adapted, and non-carnivores cows, horses, deer, groundhogs, beavers AND CATS, like small rodents, are dead-end hosts.
The CDC estimates in the US, 1 million dollars per potential life saved is spent by post-exposure prophylaxis in cases of exposure to animals other than bats, canines, fox, raccoon, skunks. Hundreds of unvaccinated cats are infected with, and die or are euthanized of rabies each year -no way every human exposure to "the kitten in the park " is tracked down. Certainly, many farmers and ranchers are unknowingly exposed. Yet almost all of the people diagnosed in the US yearly, knew they were bitten by a dog when outside the US or handled a bat.
And there have been several incidences since , where people got rabies secondary to solid organ transplants. Species vary in susceptibility to various strains, humans are 'most' susceptible to canine rabies and, in the US, the silver-haired bat strain. This is a solitary bat with infrequent human interaction, whereas we have much more exposure to big and little brown bats and Mexican free-tailed bats.
Only a small percentage of any of these have rabies, -it kills them too! The virus needs to get to a nerve, so if a bite is not deep enough, or a small viral load is deposited, or the 'victim' immune system responds - an infection will never be established. Mercury exposure most commonly happens through eating contaminated fish and getting amalgam mercury dental fillings. If you need dental work done while pregnant, talk to your dentist about using non-mercury filling material.
Limit mercury exposure by avoiding certain fish that have high concentrations of mercury. King mackerel, marlin, orange roughy, shark, swordfish, tilefish, tuna, and bigeye are all fish that are highest in mercury. Lead exposure can happen from contact with lead in the air, soil, water, and household dust. Paint used in homes before often contained lead, and many older water pipes are made of lead.
You can limit your exposure to household lead by keeping painted surfaces in good shape, cleaning lead dust with a wet paper towel, using only certified lead professionals for renovations, wiping or removing shoes before entering your home, and having lead water lines replaced. PCBs are found in fluorescent lights, fish caught in contaminated waters, older TVs and appliances, and soil around contaminated waste sites.
You can limit your exposure by not eating fish caught in contaminated water, updating older appliances, and staying out of the soil near contaminated waste sites. Some maternal health conditions pose teratogenic risks.
Chronic health conditions that can impact a developing fetus include:. Research suggests that maternal autoimmune disease may be associated with some birth defects, but not with most of them.
Risks associated with diabetes include birth defects of the spine, brain, limbs, and heart. PKU is a genetic disorder that is passed down from parents to children. It is managed through a special diet. Unmanaged during pregnancy, it can lead to low birth weight, intellectual disabilities, heart defects, and other birth defects.
If you have a pre-existing health condition, it is very important to maintain treatment to limit the teratogenic risk during pregnancy.
Talk to your healthcare provider about concerns you have about your health conditions and treatment options.
Avoid medications when you can and take the lowest dose possible of those you must take. If you need X-rays or other medical tests, be sure to inform your healthcare professional that you are pregnant. Controlling health conditions can help to limit the teratogenic risk.
The risk of teratogens to a developing fetus is often early in the pregnancy—usually the first trimester and often before implantation. Of course, the impact also depends on the level of exposure. If a teratogen has the ability to affect the development of the neural tube, the exposure would need to occur before the time the neural tube closes, which is around three to four weeks.
Some organ systems are susceptible throughout pregnancy, though. The central nervous system, for example, can be impacted throughout an entire pregnancy. Alcohol is an example of a teratogen that can impact a developing fetus at any time during pregnancy. It is important to avoid teratogens throughout your pregnancy, but the highest risk to a fetus is in the first trimester. Sometimes it can be difficult to avoid teratogens altogether, especially if you have a pre-existing health condition or require medication.
But, there are some things you can do to limit your exposure:. Nitroso guanidine, on the other hand, belongs among the most potent mutagens. Alkylating agents cause mispairing by attaching the functional group methyl-, ethyl- etc. Alkylating agents may induce all kinds of mutations and result ultimately in chromosomal aberrations and translocations. They act via oxidative deamination of aminogroup in adenine, guanine and cytosine as an example: nitrates and nitric acid. Amino- group is converted into keto- group.
Deamination alters the ability of bases to form hydrogene bonds. In general, hypoxanthin deaminated adenine pairs with cytosine, while uracil pairs with adenine. Nitric oxides are generated by combustion of fossil sources and by car exhausts. Nitrates, which are used in canning of smoked meat, are particularly dangerous towards gastrointestinal cells. May convert cytosin into hydroxy aminocytosine, which pairs with adenine forming CG:AT transition.
In the course of lysogenic cycle viruses may become incorporated into the DNA of the host. Incorporation of virus into the sequence of the gene affects substantially its function, the gene loses its function with subsequent consequences, such as chromosomal breaks, tumors.
Represent elements capable to transpose from one site of the genome to the other. Their shifts within a genome may have mutagenic effects. Most mutations negatively affect human health and, additionally, mutagenic compounds are often teratogenic and carcinogenic. Testing of the new compounds for their tentative mutagenic effect is a standard procedure within obligatory atests prior to the compounds is released on market.
Enables to disclose mutagenic activity, type of the mutations induced and test potential mutagens. For that purpose a special auxotrophic strain Salmonela typhimurium , capable to grow on medium containing histidine, was created.
Compounds be tested are added into the medium.
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