Articular damages in multi-generational female offspring due to prenatal caffeine exposure correlates with H3K9 deacetylation of TGF beta signaling pathway
TOXICOLOGY
Authors: Zhao, Zhe; Qin, Jun; Pei, Linguo; He, Zheng; Luo, Hanwen; Magdalou, Jacques; Chen, Liaobin; Wang, Hui
Abstract
Adverse environment during pregnancy could lead to maternal glucocorticoid overexposure in utero, and then induce the intrauterine growth retardation (IUGR) and the programmed change in cartilage development. The transforming growth factor beta (TGF beta) signaling pathway plays a crucial role in the process of chondrogenesis, cartilage growth, development, maturation, and phenotype maintenance. Our previous results had shown that prenatal caffeine exposure (PCE) could result in the damaged articular cartilage in offspring rats. However, whether this change could transmit to multiple generations was still unknown. In this study, pregnant Wistar rats received either saline or caffeine (120 mg/kg, i.g.) once daily from gestational day 9-20 (GD9-20). The female offspring mated with normal male rats to generate the following generations. We obtained the articular cartilages in subsequent F1 to F3 female offspring. The H3K9 acetylation and expression of the TGF beta signaling pathway were detected; the content of the cartilage matrix was detected. The results showed that PCE reduced the H3K9 acetylation and the expression of the TGF beta signaling pathway, then reduced the extracellular matrix in F1, F2, and F3 generations. in vitro, corticosterone could induce the H3K9 deacetylation of the TGF beta signaling pathway, thus inhibiting the expression of the TGF beta signaling pathway and extracellular matrix. The overall results revealed that PCE induced a multi-generational damaged articular cartilage in female offspring rats, which was partially related to the maternal high glucocorticoid-induced H3K9 hypoacetylation of TGF beta signaling pathway.
Transgenerational reproductive effects of two serotonin reuptake inhibitors after acute exposure in Daphnia magna embryos
COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
Authors: Heyland, Andreas; Bastien, Trysta; Halliwushka, Kelsey
Abstract
The release of pharmaceuticals and personal care products (PPCPs) into aquatic environments has been a major concern for the health of ecosystems. Transgenerational plasticity is a potential mechanism for organisms to respond to changing environmental conditions, including climate change and environmental contaminants. The purpose of the present study was to determine the long-term transgenerational effects of an abundant freshwater zooplankton, Daphnia magna, to acute embryonic exposures of serotonin re-uptake inhibitors (SSRI - fluoxetine and sertraline). Both SSRIs have been used extensively to treat depression and anxiety disorders for decades and persist in freshwater ecosystems at physiologically relevant concentrations. Our results revealed that even short (72 h) embryonic exposures of D. magna embryos had long lasting consequences on life history and expression of 5HT related genes in the unexposed generation (F3). Moreover, we identified direct effects of SSRIs on heart rate and swimming behavior in the first generation that carried over from embryonic exposure. We also found that SSRI exposure resulted in a transient increase of ephippia formation in the F1 and F2 . Our results suggest that SSRI exposure has transgenerational consequences to the unexposed generation and potentially beyond, even at low concentration (10-100 x lower than what can be found in natural ecosystems) and as a result of embryonic exposure. Because of the short reproductive period of D. magna and their integral role in aquatic food webs, these findings have population-level implications and deserve further investigation.