Gestational Chronodisruption Impairs Circadian Physiology in Rat Male Offspring, Increasing the Risk of Chronic Disease

Abstract

Chronic exposure to light at night, as in shift work, alters biological clocks (chronodisruption), negatively impacting pregnancy outcome in humans. Actually the interaction of maternal and fetal circadian systems could be a key factor determining a fitting health in adults. We propose that chronic photoperiod shift (CPS) during pregnancy alter maternal circadian rhythms and impair circadian physiology in the adult offspring, increasing health risks. Pregnant rats were exposed to normal photoperiod (12 h light, 12 h dark) or to CPS until 85% of gestation. The effects of gestational CPS were evaluated on the mother and adult offspring. In the mother we measured rhythms of heart rate, body temperature, and activity through gestation and daily rhythms of plasma variables (melatonin, corticosterone, aldosterone, and markers of renal function) at 18 days of gestation. In adult offspring, we measured rhythms of the clock gene expression in the suprachiasmatic nucleus (SCN), locomotor activity, body temperature, heart rate, blood pressure, plasma variables, glucose tolerance, and corticosterone response to ACTH. CPS altered all maternal circadian rhythms, lengthened gestation, and increased newborn weight. The adult CPS offspring presented normal rhythms of clock gene expression in the SCN, locomotor activity, and body temperature. However, the daily rhythm of plasma melatonin was absent, and corticosterone, aldosterone, renal markers, blood pressure, and heart rate rhythms were altered. Moreover, CPS offspring presented decreased glucose tolerance and an abnormal corticosterone response to ACTH. Altogether these data show that gestational CPS induced long-term effects on the offspring circadian system, wherein a normal SCN coexists with altered endocrine, cardiovascular, and metabolic function.

Perinatal light imprinting of circadian clocks and systems (PLICCS): A signature of photoperiod around birth on circadian system stability and association with cancer

“…Taken together, these studies suggest that the light/ dark cycling itself may have an important role in development compared to constant conditions. Mendez et al (2016) report profound effects on maternal rat dams following chronic phase shift exposure during pregnancy, similar to those reported by Varoce and colleagues (Mendez et al, 2016;Varcoe et al, 2013Varcoe et al, , 2011. These include changes to the temporal organisation of physiology, endocrinology, and metabolism in offspring raised to 90 days in 12:12 LD.…”

“…Metabolic changes include no observable circadian rhythm for creatinine, BUN, urea, or ureic acid, increased plasma glucose, and impaired glucose regulation. These changes were observed despite no difference in SCN Per2 or Bmal1 expression suggesting a working SCN (Mendez et al, 2016) -evidence of PLICCS with specific relevance to the peripheral clocks and systems.…”

“…Whilst melatonin secretion was normal, the phases of corticosterone, leptin, glucose, insulin, free fatty acids, triglycerides, and cholesterol were disrupted. These perturbations likely contribute to the metabolic derangement observed in young offspring (Varcoe et al, 2013) and adult offspring (Mendez et al, 2016).…”

The role of melatonin in the neurodevelopmental etiology of schizophrenia: A study in human olfactory neuronal precursors

“…Although melatonin is synthesized in human placenta since the first weeks and prevails during the whole pregnancy, maternal pineal melatonin, which readily crosses the placental barrier, seems to be the most important supply of this indoleamine for the fetus and has an important role in its development . In human fetal brain, melatonin receptors are widespread expressed at around 15 weeks of gestation, and nocturnal melatonin in the maternal serum reaches a peak during the third trimester of pregnancy .…”

Simulated shift work disrupts maternal circadian rhythms and metabolism, and increases gestation length in sheep

“…These effects appear to be established in the first third (7 weeks) of pregnancy because differences were seen between CON and combined SSW groups. Maternal circadian disruption throughout pregnancy similarly increased the gestation length of rats by 12 h in the one rodent study to report precise timing of delivery (Mendez et al 2016). Interestingly, a study utilizing the National Danish Birth Cohort found that fixed night work increased the risk of post term birth (>41 weeks of gestation) in singleton human pregnancies (Zhu et al 2004b).…”