January 21, 2022

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Father’s circadian disorder will be passed on and affect health of offspring

Science: Father’s circadian disorder will be passed on to offspring and affect the health of offspring

Father’s circadian disorder will be passed on and affect health of offspring.  The circadian rhythm of the parent may control the metabolism of the offspring by changing the developmental environment in the uterus, thereby affecting the health of the offspring.

Our life is based on a 24-hour cycle, including light and dark phases. Organisms have a circadian rhythm, which combines sleep-wake and fast-eating cycles with light-dark cycles, allowing the body to predict daily environmental changes and coordinate physiological activities.

In mammals, the circadian rhythm is achieved by the biological clock.

We live in a “24-hour society”, with light and food available around the clock, schedules are getting tighter, and pressure is getting heavier, which will interfere with our normal rhythm and cause a certain degree of circadian rhythm disorder. Epidemiological studies and model biological control studies have shown that circadian rhythm disorders are related to increased risks of complex diseases such as metabolism, mentality, and tumors.

Although more and more evidence shows that the mother’s circadian rhythm disorder, whether before or during pregnancy, will change the phenotype of the offspring, leading to sub-health of the offspring. But little is known about the role of the father’s circadian rhythm on the health of the offspring.

On May 26, 2021, the research team of the German Environmental Health Research Center published a research paper entitled: “Disruption of paternal circadian rhythm affects metabolic health in male offspring via nongerm cell factors” in the Science Advances journal.

The research team found that the influence of the circadian rhythm of the parent mice will be transmitted to the offspring, and this effect is not transmitted through the germ cells, but through the corticosterone in the semen at conception that affects the transcriptional changes of the placenta and fetal tissues, which in turn affects the offspring’s health. These findings indicate that the father’s circadian health at conception is a new representative determinant.

Father’s circadian disorder will be passed on and affect health of offspring

First, the research team performed a 30-day night fast on male mice. The mice in this group developed hyperinsulinemia during the day, and corticosterone lost its classical peak at the beginning of the night phase, and profound transcriptional reprogramming of liver gene expression occurred, indicating that Thirty days of restricted diet is enough to disrupt the circadian rhythm of male mice.

Father’s circadian disorder will be passed on and affect health of offspring

The male offspring produced by mating this group of male mice with female mice that are not subject to dietary restrictions have overall hyperappetite, show a higher metabolic rate, hyperglycemia, and maintain glucose tolerance. Blood tests found that the offspring had hypercorticosteroneemia. These findings indicate that the disruption of the parent’s circadian rhythm can reprogram the feeding behavior and metabolic health of the male offspring.

Father’s circadian disorder will be passed on and affect health of offspring

According to the hypothesis of the developmental origin of health and disease, most individuals’ metabolic phenotypes are determined in the uterus. In order to understand whether the impact of parental circadian rhythm disorders on the health of offspring can affect the uterus, the research team established an independent F0 male cohort and mated them with the previously described age-matched and unexposed females.

At 18.5 days of embryonic day, placental RNA-seq showed changes in fetal growth-restricted gene expression patterns and glucocorticoid/glucocorticoid receptor (GC/GR) signals. Therefore, the disruption of the father’s circadian rhythm may lead to the changes in the GC/GR signal in the offspring and maternal uterus that are observed through fetal growth restriction.

Seminal plasma contains the nutritional factors of mature sperm and a series of cytokines, hormones and metabolites that are important for fertilization, implantation, placenta and pregnancy outcome. The research team measured the concentration of corticosterone in the seminal plasma of dietary restriction and control males under different light hours, and found that the 30-day night fasting severely inhibited the rhythm of corticosterone in the semen, and the peak during the day-to-night transition was significantly less obvious .

In order to test the hypothesis that the reduction of corticosterone in semen is important for the intergenerational consequences of paternal circadian rhythm disorders, the research team established a new method when corticosterone levels in seminal plasma were not significantly different between control and diet-restricted males. queue. The offspring of the cohort mice have hyperappetite and metabolic imbalance tending to normalize. It shows that the corticosterone signal at conception is very important for the influence of the parent’s circadian rhythm disturbance on the progeny.

In summary, the study used a validated environmental model in which night fasting of parents interfered with circadian rhythms, and showed that the circadian rhythm of the parents is important for the offspring’s eating behavior, glucose control, and hormone levels.

The 30-day restricted diet of the parents is sufficient to induce hyperphagia, hyperglycemia, and corticosterone rhythm disorders in male offspring who are fed with normal light-dark cycles and ad libitum.

The analysis of the placenta revealed the transcriptional characteristics of fetal growth restriction in the offspring of the parent’s circadian rhythm disorder.

Therefore, the circadian rhythm of the parent may control the metabolism of the offspring by changing the developmental environment in the uterus, thereby affecting the health of the offspring.

(source:internet, reference only)


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