Exposure to synthetic progestin – a steroid hormone used to prevent premature birth in at risk women – has been linked to impaired cognitive function in a recent animal study co-authored by University at Albany Psychologist Christine K. Wagner.
The results of an animal study, recently published in the journal Endocrinology show that exposure to synthetic progestin (17 alpha-hydroxyprogesterone caproate/17-OHPC) during development could impair brain function later in life.
Wagner, along with Jari Willing, of the University of Illinois at Urbana-Champaign, note that there is little information regarding the potential effects of 17-OHPC on the developing brain, and yet the drug is prescribed during the late-second and third trimesters and can be detected in maternal and fetal plasma long after injection.
If a mother is prescribed 17-OHPC, developing infants may be exposed to the hormone during critical periods of cortical development. Willing and Wagner used a rodent model to test the effects of 17-OHPC during development on cognitive flexibility — the ability to change strategy in light of shifting environmental contingencies — a process which they point out is highly dependent on dopaminergic activity in the prefrontal cortex. Rats were trained to use a rule to find a food reward, and then the rule was changed, so the rats had to shift to the new rule to find the food reward again.
They found that the rats exposed to 17-OHPC during development had a harder time shifting to the new rule compared to their control counterparts, continuing to use the first rule longer than controls. What’s more, males seemed to have a harder time, suggesting that sex differences in exposure to the drug may exist.
The authors conclude that 17-OHPC exposure impaired cognitive flexibility and increased perseverative behavior in adulthood.
“The present findings reporting neurocognitive effects reminiscent of those often associated with developmental disorders such as ADHD and autism should highlight the need for additional research on the potential effects in children. Ultimately, they should also contribute to the assessment of the benefits versus the potential risks of synthetic progestin administration in pregnant women,” said Wagner.
To Wagner’s and Willing’s knowledge, the results from this study provide the first documentation of long-term consequences of 17-OHPC exposure during development on cognitive behavior and offer more insight into the potential role of progestins in neural development.
About this neurodeveoplment research
Source:University at Albany Image Source: The image is adapted from the University at Albany press release. Original Research:Abstract for “Exposure to the Synthetic Progestin, 17α-Hydroxyprogesterone Caproate During Development Impairs Cognitive Flexibility in Adulthood” by Jari Willing and Christine K. Wagner in Endocrinology. Published online November 10 2015 doi:10.1210/en.2015-1775
Exposure to the Synthetic Progestin, 17α-Hydroxyprogesterone Caproate During Development Impairs Cognitive Flexibility in Adulthood
The synthetic progestin, 17α-hydroxyprogesterone caproate, is increasingly used for the prevention of premature birth in at-risk women, despite little understanding of the potential effects on the developing brain. Rodent models suggest that many regions of the developing brain are sensitive to progestins, including the mesocortical dopamine pathway, a neural circuit important for complex cognitive behaviors later in life. Nuclear progesterone receptor is expressed during perinatal development in dopaminergic cells of the ventral tegmental area that project to the medial prefrontal cortex. Progesterone receptor is also expressed in the subplate and in pyramidal cell layers II/III of medial prefrontal cortex during periods of dopaminergic synaptogenesis. In the present study, exposure to 17α-hydroxyprogesterone caproate during development of the mesocortical dopamine pathway in rats altered dopaminergic innervation of the prelimbic prefrontal cortex and impaired cognitive flexibility with increased perseveration later in life, perhaps to a greater extent in males. These studies provide evidence for developmental neurobehavioral effects of a drug in widespread clinical use and highlight the need for a reevaluation of the benefits and potential outcomes of prophylactic progestin administration for the prevention of premature delivery.
“Exposure to the Synthetic Progestin, 17α-Hydroxyprogesterone Caproate During Development Impairs Cognitive Flexibility in Adulthood” by Jari Willing and Christine K. Wagner in Endocrinology. Published online November 10 2015 doi:10.1210/en.2015-1775