Radiation risks to germline cells (sperm and ova) include reduced fertility, and hereditary risks of increased mutation rate. These effects are dependent on the radiation dose: (males) [0.15-0.5 Gy] reduced sperm count, [0.5-6 Gy] temporary sterility, [greater 6 Gy] permanent sterility, and (females) [2-12 Gy depending on age] causes permanent sterility. Hereditary risks of increased mutations have been demonstrated in animal models but data with humans in insufficient.
After conception there are different radiation risks which vary greatly based on the gestational stage of development with the most common being : pre-implantation (pre-natal death), organogensis (microcephaly) and fetal (mental retardation).
In this post we will cover each of these major topics so that you understand the potential dangers of radiation impacts and we conclude by discussing diagnostic imaging doses in regards to these risk.
- Fertility and Hereditary Risks (Radiation Risks for Germline Cells)
- Categories of Genetic Mutations
- Animal Experiments
- Human Risk Assessment
- Gestational Radiation Risk Overview
- Simplified Gestational Timeline
- Risks from radiation exposure at different stages
- Summary of Gestational Risks
- Context of Diagnostic Imaging
Fertility and Hereditary Risks (Radiation Risks for Germline Cells)
Radiation to the germline cells (sperm and ova) can lead to temporary or permanent sterility depending on radiation dose. Male fertility: reduced sperm count (0.15-0.5 Gy), temporary sterility (0.5-6 Gy), permanent sterility (~6 Gy). Female permanent sterility: 12 Gy (before puberty) and 2 Gy (near menopause).
|Temporary sterility||(0.15-0.5 Gy) reduced sperm count, (0.5-6 Gy) temporary sterility||NA|
|Permanent sterility||Greater ~6 Gy||2 Gy (near menopause) 12 Gy (before puberty)|
|Hormone Changes||None||Similar to menopause|
Stereotypes & Reality For Germline damage
In science fiction there are often wild tales of mutations wherein strange new anatomies occur, and sometimes even special powers are granted. However, in reality this is not the case for mutations which occur due to radiation. The mutations which can occur due to radiation are the same mutations which occur in the regular popular. The difference is that high levels of radiation, especially in animal models, have been shown to cause an increase in the incidence of mutations.
Rad Take Home Point: There are not any new mutations which can occur due to radiation. The mutations have been shown in animals to occur at a higher rate in a population that has had high levels of radiation to the germline cells (sperm/ova).
Hereditary effects, i.e. increased chance of mutations can occur when germline cells (either the ovum or the sperm cells) receive significant levels of radiation dose.
If the dose is relatively large, radiation can cause fertility issues as well. In men, if the radiation dose is around 6 Gy, it can cause permanent loss of fertility (i.e. sterility). In the case of dose levels from 0.5 Gy, up to 6 Gy, there will be a period of temporary sterility. The temporary sterility will be delayed from the time when the radiation dose is received, as sperm cells are constantly being regenerated. The delay is about 6 weeks between the moment when dose is given and when sterile period occurs. It then can take from ~10 months – 20 months for the sperm count to return to its highest level (which may be lower than before the radiation).
At lower radiation doses (0.15 Gy – 0.5 Gy) there can be a reduction in the sperm count. In this case there is not full sterility but there can be a reduction in fertility due to the lower sperm count.
In men the hormones and libido are unaffected by radiation as the hormones do not originate from the same location as the sperm cells. the case of radiation but this is different in case of females because hormones are based around of ovum.
Unfortunately, much of the information on radiation effects for spermatogenesis (sperm generation) came from a University of Washington study during the years 1963-1968 where 200 inmates at the Washington State Penitentiary received relatively high levels of radiation without medical benefit. This type of study would not be approved today and is often used in modern ethics trainings materials.
Unlike men where the germline cells are produced throught-out their life females have all of their ovum just a few days after they are born. Since, just a few days after birth, all of the ova are present there is no potential for temporary sterility.
If the radiation exposure occurs to a rather young female, it can take up to 12 Gy to cause the sterility. However, for older women who are close to menopause radiation dose of 2 Gy can lead to permanent sterility.
Woman will experience all the same symptoms of going through menopause as the ovaries produce the hormones oestrogen and progesterone. As mentioned above this is in contrast to men where the hormone levels will not be affected by the radiation.
Categories of Genetic Mutations
There are different categories of mutations with varying levels of complexity. In this table we outline the terminology for the different types of mutations.
Simple mutations (Mendelian) happen in one known area of chromosome of the germ cell. Chromosomal mutations affect the entire chromosome. The last category is multifactorial cases that involved a number of separate factors.
|Mendelian||A mutation that occurs on a single gene. The most direct mutations to track.||Dominant gene |
|Huntington’s chorea |
|Chromosomal||A mutation to a single chromosome||Chromosome number |
|Down’s syndrome |
|Multifactorial||A mutation that involve a number of separate factors. |
No simple relationship between a single mutation and disease.
|Birth abnormalities |
Adult onset diseases
|cleft palate |
Mendelian is a simple mutation that occurs at one single gene. It could be that it occurs on a dominant gene, recessive gene or sex-linked gene, and those all have different processes.
Mendelian mutations are the most direct to tract with Tay-Sachs and sex linked color blindness being examples.
Chromosomal mutations occurs just on a single chromosome, or even change the number of chromosomes. For example, Down syndrome or chromosome aberrations are problems with the chromosomes themselves.
Multifactorial mutations happen as a result of multiple factors. Some examples of these include cleft palate and diabetes.
Many animal experiments have been done to define important parameter for hereditary effects called doubling dose. This is a radiation dose needed to double the likelihood of a given mutation to happen in animals irradiated animals compared with whole population.
The first experiments of hereditary effects were done in fruit flies. Hermann Muller received the nobel prize in 1946 for the discovery of mutations due to radiation. The experiments were done relatively easily because of large number of fruit flies that can be studied and their relatively short lifespan.
Different mutations that occurred were eye color changes from red to white and the doubling dose was 0.05 Gy to 1.5 Gy depending on the situation.
William and Liane Russel were pivotal in carrying out the so-called “mouse house” studies where roughly a quarter million mice were included in a given study and 7 million mice over all of the studies from 1947-2009.
In mutant mice different colors appeared at a higher rate when exposed to radiation. The doubling dose for mice was about 1 Gy (there was a dependence on the dose rate, i.e how quickly the dose was given and 1 Gy was for the relatively lower dose rate conditions).
Human Risk Assessment
There is not sufficient data to determine if there are hereditary risks at the low radiation doses of diagnostic x-ray and CT scanning. A quotation from the BEIR-VII (Biological Effects of Ionizing Radiation) summary on this, “However, there is no
direct evidence of increased risk of non-cancer diseases at low doses, and data are inadequate to quantify this risk if it exists.”
An additional quote from the full text of an earlier version, BEIR-V is “Due to lack of increase in human heritable effects resulting from radiation exposure the estimates of genetic risks in humans are based primarily on experimental data obtained with laboratory animals.”
A hybrid model has been used in practice to attempt to estimate the potential hereditary risk. This model takes as assumptions the mutation rate in the regular population, and uses experimental data from animal models to estimate the impact of radiation via the doubling dose data (doubling dose 1Gy from mouse data).
If you are interested in more reading on the topic. The UNSCEAR 2001 report on Hereditary Effects on Radiation (United Nations Scientific Committee on the Effects of Atomic Radiation) has detailed estimates of hereditary diseases in humans including individual model calculations for different mutations.
Rad Take Points:
- Doses of radiation have impact on sterility in males and females
- There is possibility of aberration and different mutations at gene, chromosomal level, or they can be multifactorial.
- No demonstration of hereditary effects have been demonstrated directly in humans, but models have been made using animal data.
Gestational Radiation Risk Overview
Radiation risks arise after conception are characterized separately from the hereditary or genetic radiation risks that occur when germ cells receive radiation. Here we will focus on the radiation risks from conception through birth.
Before going into the details of the different stages in the gestational timeline we provide a highlights table with links to the information on gestational stages down below.
|Stage||Time||Animal Experiments||Atomic Bomb Survivors|
|Pre-implantation||week 1||pre-natal death||assumed pre-natal death|
|Organogenesis||week 2-6||abnormalities, neo-natal death||microcephaly|
|fetal period||week 6-birth||permanent growth retardation||mental retardation (8-12 wk high risk)|
risk of cancer up 6% / Gy
The effects of radiation exposure range from: mortality to malformations (such as microcephaly) to mental retardation, growth changes and increased risk of cancer. The risk of different consequences is HIGHLY dependent on the developmental stage at the time of irradiation. Therefore, we will first discuss briefly the gestational timeline.
Simplified Gestational Timeline
We consider three stages of development in this simplified gestational timeline. By breaking the development up into these different components, it is possible to map the studies done in animals to the human equivalent as the overall time of gestation can vary widely for different animals.
In first phase, the pre-implantation stage, the embryo is formed and it is less than a few days old. The embryo has not yet been implanted into the uterus. As seen in this figure the pre-implantation stage is about one week.
The next phase in the gestational timeline is referred to as organogenesis where the undifferentiated cells from pre-implantation now start to become differentiated. The organ systems begin to be formed during this phase. In the organogenesis phase cells start to become differentiated and start to have a destiny as to which specific type of organ they will become.
The third period, from approximately six weeks to the birth, is called the fetal period. After the organogenesis phase the organs are formed. During the fetal period there is significant development and growth.
Risks from radiation exposure at different stages
In this phase an embryo has been formed but the cells are not yet differentiated, and therefore radiation damage cannot affect specific organs (as the cells are all the same, and not organ specific yet).
When radiation exposure occurs, it will cause either death of the embryo or no damage at all. This is a very binary event with radically different outcomes. Therefore, in the pre-implantation stage there are no specific side effects that can be observed.
During this stage, organs are actively being developed and this phase is relatively radiosensitive. During organogenesis radiation exposure can cause birth abnormalities or even neonatal death.
In animal experiments the relative likelihood of abnormalities increases with radiation dose, until the dose level at which there are abnormalities observed in 100% of the population. In experiments in mice this occurred with radiation doses of 2 Gy.
Microcephaly or small head size and reduced growth have been observed among atomic bomb survivors who received the radiation during this critical gestational phase.
In this phase, organs are formed and the risk of abnormalities caused by radiation exposure are lower than during organogenesis. Experiments on mice showed that there are risks of permanents growth retardation from exposure during the fetal period.
Growth retardation and higher risks of mental retardation have also been documented among atomic bomb survivors where the surviving baby was in the fetal phase during the radiation exposure.
There is also an estimated cancer induction risk that is 6% higher per Gray of radiation exposure.
Given all of these risks, after a pregnancy is declared, the radiation dose which is allowable is only 0.5 millisieverts (mSv) per month.
Summary of Gestational Risks
We would like to summarize once again the the different stages of gestation and the risks that have been identified in animal experiments and in atomic bomb survivors.
In the pre-implantation stage, animal experiments showed that radiation doses might cause prenatal death. In atomic bomb survivors, it’s assumed that there was prenatal death because the individual never would have known that there was an embryo that had not yet implanted.
During the organogenesis phase, animal experiments indicated increase rates of neonatal death and abnormalities. While the risks are lower during the fetal period there is still the of potential of growth and mental retardation.
Context of Diagnostic Imaging
There have been a number of thoughtful works presented by Cynthia McCollough’s CT group at Mayo on this topic.
In this educational paper a good summary is provided in one of the references from the American College of Committee of Obstetricians and Gynecologists (Guidelines for diagnostic imaging during pregnancy. ACOG Committee opinion no. 299, September 2004):
“Women should be counseled that the x-ray exposure from a single diagnostic procedure does not result in harmful fetal effects, specifically exposure to less than 5 rad or 50 milligray has not been associated with an increase in fetal abnormalities or pregnancy loss.”
As with all diagnostic exams the doses should be kept as low as reasonably achievable and for certain clinical indications alternative diagnostic modalities may be considered such as ultrasound, but the value of the clinical information gained from x-ray or CT can be significant to confirm or rule out a given diagnosis.