This 2018 French/Italian/Swiss rodent study was an extension of the work done by the group of researchers who performed Prenatal stress produces offspring who as adults have cognitive, emotional, and memory deficiencies and Treating prenatal stress-related disorders with an oxytocin receptor agonist:
“Reduction of maternal behavior [nursing behavior, grooming, licking, carrying pups] was predictive of behavioral disturbances in PRS [prenatally restraint stressed] rats as well as of the impairment of the oxytocin and its receptor gene expression.
Postpartum carbetocin [an oxytocin receptor agonist unavailable in the US] corrected the reduction of maternal behavior induced by gestational stress as well as the impaired oxytocinergic system in the PRS progeny, which was associated with reduced risk-taking behavior.
Moreover, postpartum carbetocin had an anti-stress effect on HPA [hypothalamic-pituitary-adrenal] axis activity in the adult PRS progeny and increased hippocampal mGlu5 [type 5 metabotropic glutamate] receptor expression in aging.
Early postpartum carbetocin administration to the dam enhances maternal behavior and prevents all the pathological outcomes of PRS throughout the entire lifespan of the progeny..proves that the defect in maternal care induced by gestational stress programs the development of the offspring.“
- Stress administered to the mothers three times daily every day during the second half of pregnancy up until delivery; and
- The effects on the mothers’ behavior of daily carbetocin administration during postpartum days 1 through 7.
The symbols denote which of these relationships had statistically significant effects:
- “* p [Pearson’s correlation coefficient] < 0.05 PRS-Saline vs. CONT-Saline;
- # p < 0.05 PRS-Carbetocin vs. the PRS-Saline group.”
There are many interesting aspects to this study. Ask the corresponding coauthor Dr. Sara Morley-Fletcher at firstname.lastname@example.org for a copy.
One place the paper referenced the researchers’ previous studies was in this context:
“Postpartum carbetocin administration reversed the same molecular and behavioral parameters in the hippocampus, as does adult chronic carbetocin treatment, i.e. it led to a correction of the HPA axis negative feedback mechanisms, stress and anti-stress gene expression, and synaptic glutamate release. The fact that postpartum carbetocin administration [to the stressed mothers in this study] had the same effect [on the PRS infants in this study] as adult carbetocin treatment [to the PRS offspring in the previous study] indicates a short-term effect of carbetocin when administered in adulthood and a reprogramming (long-term) effect lasting until an advanced age when administered in early development.”
This group’s research seems to be constrained to treatments of F0 and F1 generations. What intergenerational and transgenerational effects would they possibly find by extending research efforts to F2 and F3 generations?
As the study may apply to humans:
The study demonstrated that stresses during the second half of pregnancy had lifelong impacts on both the mothers’ and offsprings’ biology and behavior. Studies and reviews that attribute similar human biological and behavioral conditions to unknown causes, or shuffle them into the black box of individual differences, should be recognized as either disingenuous or insufficient etiological investigations.
The study showed that prevention of gestational stress was a viable strategy. The control group progeny’s biology and behavior wasn’t affected by carbetocin administration to their mothers because neither they nor their mothers had experience-dependent epigenetic deficiencies.
The study demonstrated a biological and behavioral cure for the PRS offspring by changing their stressed mothers’ behaviors during a critical period of their development. The above excerpt characterized improving the mothers’ behaviors as a long-term cure for the PRS descendants, as opposed to the short-term cure of administering carbetocin to the PRS children when they were adults.
What long-term therapies may be effective for humans who had their developmental trajectories altered by their mothers’ stresses during their gestation, or who didn’t get the parental care they needed when they needed it?
https://www.sciencedirect.com/science/article/pii/S0161813X18301062 “Reduced maternal behavior caused by gestational stress is predictive of life span changes in risk-taking behavior and gene expression due to altering of the stress/anti-stress balance” (not freely available)