The Effect of Ethylmethylhydroxypyridine Succinate (Mexidol) on Oocyte Meiotic Maturation, Genome Integrity, and the Change in Gene Expression in Mouse Cumulus Cells under the Conditions of Systemic Immune Complex Damage
RUSSIAN JOURNAL OF DEVELOPMENTAL BIOLOGY
Authors: Kondratskaya, E. A.; Grushka, N. G.; Voznesenskaya, T. Yu.; Yanchii, R. I.
Abstract
The effect of ethylmethylhydroxypyridine succinate (HS, Mexidol) on oocyte meiotic maturation, level of DNA damage in follicular cells, and gene expression of gremlin 1 (Grem1), hyaluronan synthase 2 (HAS2), and cyclooxygenase 2 (COX2) in cumulus cells has been investigated using a model of experimental systemic immune complex damage induced by long-term immunization of CBA mice with bovine serum albumin (BSA). According to the literature data, these genes play a critical role in oogenesis and can characterize oocyte quality. The administration of HS exhibited a protective effect on the morphological and functional state of ovarian cells. The introduction of HS attenuated the genotoxic stress induced by BSA, which was reflected in a decrease in the number of cumulus cells with severe DNA damage. The following changes in gene expression have been observed: a 1.61-fold increase in the number of COX2 mRNA and a 1.47-fold increase in Grem1 mRNA. A 1.38-fold increase in the content of HAS2 gene transcripts has also been demonstrated, although this change was not statistically significant. The observed changes had a positive effect on oocyte meiotic maturation and were accompanied by a significant increase in the oocyte number during metaphase I and II. It is proposed that HS can be successfully used in the therapy of immune complex diseases.
Hyaluronan Rich Microenvironment in the Limbal Stem Cell Niche Regulates Limbal Stem Cell Differentiation
INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE
Authors: Gesteira, Tarsis F.; Sun, Mingxia; Coulson-Thomas, Yvette M.; Yamaguchi, Yu; Yeh, Lung-Kun; Hascall, Vincent; Coulson-Thomas, Vivien J.
Abstract
PURPOSE. Limbal epithelial stem cells (LSCs), located in the basal layer of the corneal epithelium in the corneal limbus, are vital for maintaining the corneal epithelium. LSCs have a high capacity of self-renewal with increased potential for error-free proliferation and poor differentiation. To date, limited research has focused on unveiling the composition of the limbal stem cell niche, and, more important, on the role the specific stem cell niche may have in LSC differentiation and function. Our work investigates the composition of the extracellular matrix in the LSC niche and how it regulates LSC differentiation and function. METHODS. Hyaluronan (HA) is naturally synthesized by hyaluronan synthases (HASs), and vertebrates have the following three types: HAS1, HAS2, and HAS3. Wild-type and HAS and TSG-6 knockout mice-HAS1(-/-); HAS3(-/-), HAS2(Delta/Delta CorEpi), TSG-6(-/-) -were used to determine the importance of the HA niche in LSC differentiation and specification. RESULTS. Our data demonstrate that the LSC niche is composed of a HA rich extracellular matrix. HAS1(-/-); HAS3(-/-), HAS2(Delta/Delta CorEpi), and TSG-6(-/-) mice have delayed wound healing and increased inflammation after injury. Interestingly, upon insult the HAS knock-out mice upregulate HA throughout the cornea through a compensatory mechanism, and in turn this alters LSC and epithelial cell specification. CONCLUSIONS. The LSC niche is composed of a specialized HA matrix that differs from that present in the rest of the corneal epithelium, and the disruption of this specific HA matrix within the LSC niche leads to compromised corneal epithelial regeneration. Finally, our findings suggest that HA has a major role in maintaining the LSC phenotype.