Biology subjects

Frambourg, A.

Publications and source records attributed to Frambourg, A..

3 recordsLinked to original sources

bioRxiv2025

The effect of environmental enrichment on immune cell DNA methylation profiles depends on the parity of sows.

The aim of this study was to identify epigenetic markers that reflected positive affective states in multiparous pregnant sows. The animals were housed during gestation in either a conventional (C) environment (2.4 m{superscript 2} per sow), featuring a concrete slatted floor and minimal enrichment, or in an enriched (E) environment (3.5 m{superscript 2} per sow) with deep straw bedding. Peripheral blood mononuclear cells (PBMCs) were isolated at day 98 of gestation (G98) and day 12 of lactation (L12) for genomic DNA extraction and reduced representation bisulfite sequencing (RRBS). Significant effects of individual class of parity (low-parity (LP) versus high-parity (HP)) were observed with the identification of 1,358 and 680 differentially methylated cytosines (DMCs) at G98 and L12, respectively. Interestingly, some of them are organized into differentially methylated regions (DMRs). Some DMRs colocalized with or near a gene and displayed a continuous methylation distribution (44 at G98 and 15 at L12 including 4 in common): 5 targeted genes are related to epigenetic regulation (DNMT3A, KDM8, HDAC4, SIRT2 and U2) and 12 to immune function (CD2, CD5, CAMK4, SECTM1, URODL1, CMIP, SEC14L1, SKI, TNFRSF1B, CCND3, SGK1, PACS1). These results suggested a true epigenetic impact of parity class on individual immunity. Considering the two parity classes separately, a minor effect of environmental enrichment was observed (at G98: 60 and 42 DMCs; at L12: 35 and 81 DMCs, in the LP and HP groups, respectively). Remarkably, some DMC-associated genes had previously been linked to affective states in humans. In conclusion, unexpected DNA methylation changes associated with parity class were identified, suggesting a genome adaptation during reproductive life and modifying the response to housing conditions. Furthermore, specific CpG sites emerged as potential biomarkers of positive affective states in pigs. HighlightsO_LIThis study revealed a substantial impact of the genetic background of sows on DNA methylation patterns, emphasizing the need to account for genetic factors when analysing epigenetic data. C_LIO_LIParity, which was confounded with the age of the sows in this study, significantly influenced DNA methylation, even among multiparous sows, highlighting the importance of this factor in modulating epigenetic mechanisms in immune cells. C_LIO_LIWe observed minor differences in the effects of environmental enrichment on DNA methylation profiles, which differed depending on the parity group. C_LIO_LIWe suggest a short list of possible biomarkers with biological meaning responding to environmental enrichment. C_LI

genomics↗

bioRxiv2025

Short-term exposure to Cook, Vitrolife, and KSOM media shapes early calcium oscillations in ICSI-fertilized mouse oocytes and impacts adult phenotype

PurposeThe influence of culture media used during in vitro fertilization (IVF) on offspring phenotype remains controversial. However, specific effects of short exposure time after fertilization remain underexplored. By evaluating Ca2+ oscillations as a readout of the first response of eggs to their microenvironment, we aim to investigate if early differences correlate with later adult phenotypes. MethodsOocytes fertilized by ICSI were cultured for four hours in three different media (Cook and Vitrolife, used in human IVF, and KSOM, used for mouse embryos). They were either measured for Ca2+ oscillations or transferred into pseudo-pregnant females. After birth, growth curves of pups were measured up to adulthood and various organs weighed. ResultsCulture media significantly modulate Ca2+ oscillations during oocyte activation. ICSI-fertilized oocytes cultured in Cook and Vitrolife exhibited fewer oscillations, lower frequency, and reduced variability compared to KSOM. These early differences correlated with long-term developmental outcomes: females from Cook and Vitrolife cultures were heavier throughout growth and had larger adult organ sizes compared to those from KSOM. ConclusionsBrief exposure to media immediately after ICSI shapes Ca2+ dynamics and adult phenotypes. Optimizing embryo culture protocols in assisted reproductive technologies may improve IVF outcomes by modulating metabolic pathways linked to development.

developmental biology↗

bioRxiv2023

DMRT1 is a Testis Determining Gene in Rabbits and is Also Essential for Female Fertility

DMRT1 is the testis-determining factor in several species of vertebrates, but its involvement in mammalian testes differentiation, where SRY is the testis-determining gene, remains ambiguous. So far, DMRT1 loss of function has been described in two mammalian species and induces different phenotypes: disorders of sex development (46, XY DSD) in men and male infertility in mice. We thus abolished DMRT1 expression by CRISPR/Cas9 in a third species of mammal, the rabbit. First, we observed that gonads from XY DMRT1-/- rabbit fetuses differentiated like ovaries, highlighting that DMRT1 is involved in testis determination. In addition to SRY, DMRT1 is required in the supporting cells to increase the expression of the SOX9 gene, which heads the testicular genetic cascade. Second, we highlighted another function of DMRT1 in the germline since XX and XY DMRT1-/- ovaries did not undergo meiosis and folliculogenesis. XX DMRT1-/- adult females were sterile, showing that DMRT1 is also crucial for female fertility. To conclude, these phenotypes indicate an evolutionary continuum between non-mammalian vertebrates such as birds and non-rodent mammals. Furthermore, our data support the potential involvement of DMRT1 mutations in different human pathologies, such as 46, XY DSD as well as male and female infertility.

developmental biology↗