Circadian Health and Fertility

Factors Related to Circadian Rhythm, Such as Melatonin, May Play Out in Fertility – and Child Health

“Fertility Problems: Why Artificial Light Harms Chance of Pregnancy For Middle-Aged Women”

Posted on Medical Daily .com, Aug 25, 2015, By Lizette Borreli  LINK

The study was done using mice. The article gives more background and discusses further considerations about melatonin and circadian factors regarding fertility and the health of the fetus and the mother.

“The findings revealed altering the body clock of mice had no effect on young mice, but pregnancy rates decreased in middle-aged mice. Within the cohort of lab mice, 71 percent of the older mice with normal body clocks got pregnant compared to about 10 percent of those whose circadian rhythm had been disrupted. The researchers concluded optimal circadian periods help protect female mice from the effects of age-related fertility. ”

” “The ability to rescue reproductive function by altering the light schedule in a rodent model suggests that improvements in ‘circadian hygiene’ — for example, reductions in evening illumination, more regular meal timing, or avoiding rotating shiftwork or schedules that lead to irregular sleep — may all be important remedies for reproductive difficulty,” Block said.”

I was particularly struck by these statements:

• “In women who are already pregnant, interference with melatonin levels can affect the health of the unborn child.
• If the fetus doesn’t get the right amount of melatonin from their mother, their biological clock can become confused.
• A lack of adequate melatonin levels has been linked to behavioral problems such as attention deficit hyperactivity disorder (ADHD) or autism in young children.”

From looking in PubMed, researchers are actively examining these topics. I’m not sure how firmly these effects have been established to occur in people, and how much this is extrapolation from animal findings, but for sure we’ll be seeing more research publications on these topics appearing soon. See further on this below.

References:

Thanks to Bill Lagakos, who is a leading tweeter and blogger on many things, including all things circadian, for heads-up on this article: @CaloriesProper, caloriesproper.com

Takasu NN, Nakamura TJ, Tokuda IT et al. Recovery from Age-Related Infertility under Environmental Light-Dark Cycles Adjusted to the Intrinsic Circadian Period. Cell Reports. 2015.   LINK

Reiter RJ, Tamura H, Tan DX et al. Melatonin and the circadian system: contributions to successful female reproduction. Fertility and Sterility. 2014. LINK to abstract

• “The cyclic levels of melatonin in the blood pass through the placenta and aid in the organization of the fetal SCN. In the absence of this synchronizing effect, the offspring may exhibit neurobehavioral deficits. Also, melatonin protects the developing fetus from oxidative stress. Melatonin produced in the placenta likewise may preserve the optimal function of this organ.”

Hum Reprod Update. 2014 Mar-Apr;20(2):293-307. doi: 10.1093/humupd/dmt054. Melatonin and stable circadian rhythms optimize maternal, placental and fetal physiology.
Reiter RJ1, Tan DX, Korkmaz A, Rosales-Corral SA.  Free Full Text  LINK

A partial list of the topics covered at length in this review article (quotes):

• Melatonin is produced in both the ovary and in the placenta where it protects against molecular mutilation and cellular dysfunction arising from oxidative/nitrosative stress.
• The placenta, in particular, is often a site of excessive free radical generation due to less than optimal adhesion to the uterine wall, which leads to either persistent hypoxia or intermittent hypoxia and reoxygenation, processes that cause massive free radical generation and organ dysfunction.
• This may contribute to pre-eclampsia and other disorders which often complicate pregnancy.
• Melatonin has ameliorated free radical damage to the placenta and to the fetus in experiments using non-human mammals.
• Likewise, the maintenance of a regular maternal light/dark and sleep/wake cycle is important to stabilize circadian rhythms generated by the maternal central circadian pacemaker, the suprachiasmatic nuclei.
• Optimal circadian rhythmicity in the mother is important since her circadian clock, either directly or indirectly via the melatonin rhythm, programs the developing master oscillator of the fetus.
• Experimental studies have shown that disturbed maternal circadian rhythms, referred to as chronodisruption, and perturbed melatonin cycles have negative consequences for the maturing fetal oscillators, which may lead to psychological and behavioral problems in the newborn.
• To optimize regular circadian rhythms and prevent disturbances of the melatonin cycle during pregnancy, shift work and bright light exposure at night should be avoided, especially during the last trimester of pregnancy.

Of the many sections in this review, one is “Programming fetal circadian rhythmicity”. Of that section, a small portion is this:

“There is now general agreement that maternal circadian rhythms are influential in the entrainment and programming of fetal and newborn circadian rhythms (Fig. 5), but what rhythms are affected may be species specific. While information in this field is still rudimentary, evidence has shown that disturbances of the fetal circadian system, regardless of the cause of those perturbations, have long-term consequences in the offspring. As an example, women who engage in shift work during pregnancy have an increased incidence of spontaneous abortions, premature deliveries and low birthweight infants (Zhu et al., 2004). Shift work greatly alters the melatonin cycle, the sleep/wake rhythm and feeding times which also could be instrumental in contributing to these complications. Exposure of rats to simulated shift work caused increased hyperleptinemia and adiposity of the offspring at 3 months after birth and altered glucose tolerance and insulin resistance, reminiscent of that seen in metabolic syndrome, when the offspring were 1 year of age (Varcoe et al., 2011). Clearly, the impact of a disturbed light:dark cycle in late pregnancy and during the perinatal period may have major effects on subsequent behavioral and metabolic functions (Ferreira et al., 2012). Given the remarkable rise in the diagnosis of metabolic syndrome, obesity, attention deficit-hyperactivity disorder, autism spectrum disorders, etc., it may be worthwhile to be more attentive to the light:dark environment during pregnancy (Hardeland et al., 2012). This is especially true since the frequency of these conditions has run in parallel with excessive use of light at night, a change that is difficult to avoid in current societies.

Offspring that are delivered prematurely are not exposed to a normal maternal melatonin rhythm that they would be if they were still in utero and they do not generate a melatonin rhythm on their own (Kennaway et al., 1992). Thus, preterm infants are deprived of exposure to the melatonin cycle during a critical interval of their development. How or whether the lack of exposure to this rhythm in these premature infants has consequences on any aspect of development remains unexamined. This problem could be potentially partially rectified if premature infants would be breast fed since a melatonin rhythm normally exists in human breast milk, with higher levels at night than during the day (Illnerova et al., 1993). This still would require, however, that the mother be in darkness for several hours before and at the time of night-time breast feeding and also the much lower levels of melatonin in the breast milk (relative to those in the blood) may render these concentrations insignificant in terms of programming the SCN of the newborn.”

Clearly, as the above authors say, “information in this field is still rudimentary”. The implications all this are staggering, more attention to these topics is urgently needed.

If the health concerns raised by these findings and speculations are confirmed, maybe we will need family members of 3 successive generations to “splint” their circadian and metabolic functioning to turn this around? (“Splint” = take intentional measures to impose order on their circadian rhythm and metabolic functions – like splinting a sprained ankle.)

For related content:

• click on tags in the side column for related topics, such as sleep, light, etc.
• see the page Sleep, Light, Circadian
• see post Pre-teen and Teen Metabolic Health