Dwarfism and Insulin Resistance as Consequence of Gestational Hypertension Treatment

Gestational hypertension is a common and serious complication, which can have severe consequences for mother and unborn child if left untreated. Unfortunately, many medications such as ACE inhibitors cannot be used, as they increase the risk of fetal deformation or are not sufficiently assessed for safety in pregnant women. Consequently, treatment options are limited, and according to respective national guidelines, alpha/beta-blockers such as labetalol or alpha1-adrenergic blockers such as prazosin may also be used.

An interdisciplinary research team of the Center of Brain, Behavior and Metabolism (CBBM), University of Lübeck, now revealed that an alpha1-adrenergic blockade during pregnancy can lead to impaired growth and diabetes in the adult offspring mice. Interestingly, this phenotype was only observed in the male offspring, according to the study published online 1st of July 2017 in “Molecular Metabolism”.

“One possible explanation for the observed problems could be a reduced secretion of hepatic IGF-1 in the male offspring”, reports Dr. Rebecca Ölkrug, first-author of the study. The secretion of IGF-1 is regulated by the growth hormone receptor, which was strongly reduced in the male offspring due to altered epigenetic programming. “Epigenetic regulation of gene expression is an exciting new research area, focused on how environmental factors for instance can permanently alter the activity of certain genes without altering the genetic information itself”, explains Dr. Henriette Kirchner, co-author of the study and PI of the “Epigenetics & Metabolism” group at the CBBM.

“The observed gender specific differences are typical for epigenetic alterations that can occur during pregnancy”, adds Prof. Jens Mittag, senior author of the study. “However, our study is just the first step; now it will be important to conduct retrospective epidemiological studies to reveal whether a same connection between alpha-blockers during pregnancy and dwarfism or insulin resistance in offspring can also be observed in humans.”

The study was a collaborative effort of the CBBM groups of “Molecular Endocrinology”, “Epigenetics and Metabolism”, “Neurobiology/Chronophysiology” and from the Department of Internal Medicine I of the USKH. The study was supported from the Deutsche Forschungsgemeinschaft Graduiertenkolleg 1957, Emmy-Noether- and Heisenberg-Program and the DFG-Schwerpunktprogramm „ThyroidTransAct“.

 

Publication:
Rebecca Oelkrug, Beate Herrmann, Cathleen Geissler, Lisbeth Harder, Christiane Koch, Hendrik Lehnert, Henrik Oster, Henriette Kirchner, Jens Mittag:Dwarfism and insulin resistance in male offspring caused by α1-adrenergic antagonism during pregnancy. Molecular Metabolism. Published online 1 July 2017.
PII: S2212-8778(17)30367-8. DOI: 10.1016/j.molmet.2017.06.016