Circadian Rhythm Disruptions Before Contraception May Have Transgenerational Impacts

Circadian Rhythm Disruptions Before Contraception May Have Transgenerational Impacts

On a trip to Capitol Reef National Park, I noticed, for one of the only times in my life, I could clearly see the Milky Way. The night was so dark I couldn’t see anything around me. Capitol Reef National Park received an International Dark Sky Designation from the International Dark Sky Association, the leading organization advocating action light pollution worldwide. Capitol Reef is one of the rare remaining places in the continental United States with natural darkness. To maintain a dark sky the National Park enforces strict policy on lights. The Park requires a cover for any light at night to keep the light waves going down toward the ground for their intended purpose and not toward the sky. I only slept for a few hours, but I woke up feeling more rested than I had in months. After digging into the differences unnatural night time light causes, I concluded that light pollution is a highly underrated issue.

Modern society adopted artificial light without regard to environment or human health. Nighttime illumination has spread globally and touches nearly every ecosystem on the planet, through countless items used by people every night. Even dim light at night is associated with a variety of psychological and physiological issues that disrupt circadian rhythms in mammals. The circadian rhythm has been shown to affect mate selectivity, immune system, and alter hormonal function. The benefits of using technology during the night, without restrictions, currently seem to outweigh the risks. Many people produce nighttime illumination through cell phones, televisions, night-lights, and even the light emanating from an alarm clock. This common assumption may be wrong. This study shows the potential implication that through light pollution and nighttime light, future generations may continuously become less ffective at fighting infections.

Ohio State Neuroscience graduate student, Yasmine Cisse, published Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity. The study used Siberian hamsters to test the hypothesis that “dLAN (dim light at night) has transgenerational influences on immune function,” (Cisse). The F1 generation of adult hamsters were only exposed to dark night and light days. Their parental generation was also only exposed to dark nights and light days. The F1 generation was selectively mated with only the female exposed to dLAN, only the male exposed to dLAN, both or neither exposed. All dLAN exposed rodents were subject to dLAN conditions, for nine week, before mating. Gestation (when the embryo or fetus is carried in the uterus in viviparous females) and offspring rearing were in dark night and light day environments.

Figure 1: visual representation of the mating method researchers used.
From: Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity

Researches evaluated immune function in several ways to determine how the exposure affected the offspring. They evaluated splenic methylation. Methylation is the process by which methyl groups are added to a DNA molecule. The addition of a methyl group can alter the activity of a DNA segment without changing the actual sequence of the DNA, which is called an epigenetic change. This can change the organism’s phenotype without changing the actual DNA sequence and can be passed to daughter cells. Methylation helps the body’s enzymes work more efficiency. An increase or decrease in methylation can be bad or good. This study aims to support or refute the hypothesis that certain epigenetic impacts related to methylation can also be passed onto daughter cells in sexual reproduction; and ultimately be passed onto the hamster’s children.

The first way the study tests transgenerational impact is Delayed Type Hypersensitivity (DTH). DTH is an “antigen specific T-cell mediated immune response.” (Cisse). It is considered an index of effector T cell function. The hamsters are subjected to the antigen that causes inflammation, from monocytes and lymphocytes, penetrating the skin to fight the agent. The amount of swelling serves as an indicator on how intense the immune system response was. All test groups displayed swelling. In maternal F1 dLAN exposure, male F2 offspring displayed less swelling (p<.05), and in F1 paternal and maternal dLAN exposure, female offspring displayed significantly less swelling (p<.05) too. This data supports reduced immune system response.

Figure 2 shows most swelling in offspring where both parents had dark nights and least swelling for offspring of two dLAN exposed parents. 

From: Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity

Researchers used Splenic Melatonin (MT1) to evaluate endocrine function. Melatonin is a hormone produced by various tissues in the body. It is released continuously at different levels to regulate sleep. “Melatonin is immediately diminished by exposure to light at night in both humans and rodents... The majority of immune cells and organs express melatonin receptors.” (Cisse). In the absence of light, melatonin is secreted. Peak melatonin levels should be secreted during the night and low levels during the day. Clear circadian rhythms regulate melatonin levels. “Melatonin is a potent immunomodulator and enhances immune responses by stimulating bone marrow proliferation, antigen presentation, and release of certain cytokines” (Cisse). Cytokines are small proteins that have an important cell signaling function and impact the behavior of cells around them. Their presence signals cells like white blood cells to come and help the body during times of infection. “Melatonin increases MT1 activity in the thymus and the spleen and enhances DTH response in Syrian hamsters.” (Cisse) Circadian rhythm plays a major role in both the immune system and endocrine system. The study found that paternal F1 dLAN produced F2 offspring with decreased melatonin in the spleen. When both parents were exposed there was also a decreased splenic methylation. MT1 was decreased significantly more in male offspring than in female offspring.  Researchers hypothesized that histone modification may play a role in offspring’s phenotype. They also suggesting sex played a role on the phenotypic inheritance. Offspring produced less than usual MT1 expressions when only the mothers were exposed to dLAN, in comparison to those who only had a father parent exposed. This might be because females have two copies of the X chromosome where many X-linked immune genes are while male offspring only have one copy allowing the females to express the altered phenotype in a less severe way than males.

The difference in effects between male and female offspring may be because of the X-chromosome contains more immune system-related genes than the Y chromosome (Bianchi). While a female mammal contains two copies of the X chromosome their male counterpart only contains one. A female receives twice the dosage of these immune system-related genes. After fertilization the cells undergoes a process where one of the two X chromosome genes is turned off, in a female called X-inactivation. The one inactivated chromosome is silenced. Every daughter cell produced from mitosis replicates the same one active and one inactivated gene as the parent cell. This occurs in the embryo’s early stages of development, and the few cells present don’t have to turn off the same gene. X-inactivation is random for each cell. While some female cells will have certain immune system genes silenced, those same genes may be expressed in other cells. Males who only have one copy of the X-chromosome are limited to that one X-chromosome’s immune genes in all of their cells. This unequal effect may also have a negative impact on a fitness and mating selection, in a species, in addition to a reduced immune system.

The data from this study supports that exposure to light at night; prior to conception does alter the offspring’s inherited immune system expression epigenetically. The effects of a completely normal part of modern life are very shocking. While some effects are only seen in the exposed generation such as increased body mass, others can be passed on. If light pollution or nighttime artificial light use can continue without any regard, generations will potentially become increasingly vulnerable to diseases and prone to conditions. Like with other, more publicized forms of pollution, light pollution should be considered serious. Simple lifestyle changes at home like turning off cell phones, televisions, and blacking out windows during night hours should be encouraged. Those changes in homes and in cities is for future generations as well as the present one.

Reference Study:

Cissé, Y. M. et al. Parental Exposure to Dim Light at Night Prior to Mating Alters Offspring Adaptive Immunity. Sci. Rep. 7, 45497; doi: 10.1038/srep45497 (2017).

Other references:

Brianchi, I, et al. The X chromosome and immune associated genes. Journal of Immunity, May 201, doi:10.1016/j.jaut.2011.11.012.

Morris, J., Hartl, D. L., & Knoll, A. H. (2016). Biology: how life works. New York, NY: Macmillian Education.