Biology subjects

Behura, S. K.

Publications and source records attributed to Behura, S. K..

4 recordsLinked to original sources

bioRxiv2022

Can blood at adult age predict epigenetic changes of the brain during fetal stages?

Correspondence in DNA methylation between blood and brain is known in humans. If this pattern is present in pig has not been examined. In this study, we profiled DNA methylation of blood from pigs at adult ages, and compared those with the methylation profiles of fetal brain. Neural network regression modeling showed specific methylations in the adult blood that can reliably predict methylation of the fetal brain. Genes associated with these predictive methylations included markers of specific cell types of blood and brain, in particular, markers of bone marrow hematopoietic progenitors, and glial cells primarily the ependymal and Schwann cells of brain. The results of this study show that developmental methylation changes of the brain during fetal stages are maintained as an epigenetic memory in the blood in adult life. Thus, pig models may be harnessed to uncover potential roles of epigenetic memory in brain health and diseases.

genomics↗

bioRxiv2022

Role of Caveolin 1 in metabolic programming of fetal brain

Caveolin-1 (Cav1) encodes a major protein of the lipid rafts, called caveolae, which are plasma membrane invaginations found in most cells of mammals. Cav1-null mice, at an early adult age, exhibit symptoms that are hallmarks of Alzheimers disease, and show brain aging similar to that of one and half year old wildtype mice. In the present study, integrative analysis of metabolomics, transcriptomics, epigenetics and single cell data was performed to test the hypothesis that metabolic deregulation of fetal brain due to lack of Cav1 influenced brain aging in these mice. The results of this study show that lack of Cav1 deregulated lipid and amino acid metabolism in the fetal brain. Genes associated with the deregulated metabolites were significantly altered in specific glial cells of the fetal brain, and epigenetically altered in a coordinated manner with specific genes of mouse epigenetic clock. The interaction between metabolic and epigenetic changes in the fetal brain altered gene expression of the brain at old age. Together, these results suggested that metabolic deregulation in the fetal life elicited an epigenetic memory that altered brain programming for aging in Cav1-null mice.

genomics↗

bioRxiv2022

Fetal origin of sex-bias brain aging

DNA methylation plays crucial roles during fetal development as well as aging. Whether the aging of the brain is programmed at the fetal stage remains untested. To test this hypothesis, mouse epigenetic clock (epiclock) was profiled in fetal (gestation day 15), postnatal (day 5), and aging (week 70) brain of male and female C57BL/6J inbred mice. Data analysis showed that on week 70 the female brain was epigenetically younger than the male brain. Predictive modeling by neural network identified specific methylations in the brain at the developing stages that were predictive of epigenetic state of the brain during aging. Transcriptomic analysis showed coordinated changes in expression of epiclock genes in the fetal brain relative to placenta. Whole-genome bisulfite sequencing identified sites that were methylated both in the placenta and fetal brain in a sex-specific manner. Epiclock genes and genes associated with specific signaling pathways, primarily the gonadotropin-releasing hormone receptor (GnRHR) pathway, were associated with these sex-bias methylations in the placenta as well as fetal brain. Transcriptional crosstalk among the epiclock and GnRHR pathway genes was evident in the placenta that was maintained in the brain during development as well as aging. Collectively, these findings suggest that sex differences in the aging of brain are of fetal origin and epigenetically linked to the placenta.

genomics↗

bioRxiv2022

Sperm exposure to accessory gland secretions alters the transcriptomic response of the endometrium in cattle

In a recent study from our group, mating to intact, but not vasectomised, bulls modified the endometrial transcriptome, suggesting an important role of sperm in the modulation of the uterine environment in this species. However, it is not clear whether these changes are driven by intrinsic sperm factors, or by factors of accessory gland (AG) origin that bind to sperm at ejaculation. Thus, the aim of the present study was to determine whether ejaculated sperm, which are suspended in the secretions of the AGs, elicit a different endometrial transcriptomic response than epididymal sperm, which have never been exposed to AG factors. To this end, bovine endometrial explants collected from heifers in oestrus were incubated alone (control), or with epididymal or ejaculated sperm. RNA-sequencing revealed 1912 differentially expressed genes (DEGs) between in endometrial explants exposed to epididymal sperm compared with control explants, whereas 115 DEGs genes detected between endometrial explants exposed to ejaculated sperm in comparison to control explants. In both cases, the top pathways associated with these genes included T cell regulation and NF-KB and IL17 signalling. To confirm whether AG factors were directly responsible for the dampening of the endometrial response elicited by ejaculated sperm, endometrial explants were incubated with epididymal sperm previously exposed, or not, to seminal plasma (SP). Exposure to SP abrogated the downregulation of SQSTM1 by epididymal sperm, and partially inhibited the upregulation of MYL4 and CHRM3 and downregulation of SCRIB. These data indicate that factors of AG origin modulate the interaction between sperm and the endometrium in cattle.

genomics↗