Browsing by Author "Wooldridge, Lydia K."

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    Cytokines That Serve as Embryokines in Cattle
    Ealy, Alan D.; Speckhart, Savannah L.; Wooldridge, Lydia K. (MDPI, 2021-08-05)
    The term “embryokine” has been used to denote molecules produced by the endometrium, oviduct, or by embryo itself that will influence embryo development. Several cytokines have been identified as embryokines in cattle and other mammals. This review will describe how these cytokines function as embryokines, with special emphasis being placed on their actions on in vitro produced (IVP) bovine embryos. Embryokines are being explored for their ability to overcome the poor development rates of IVP embryos and to limit post-transfer pregnancy retention efficiencies that exist in IVP embryos. This review will focus on describing two of the best-characterized cytokines, colony-stimulating factor 2 and interleukin 6, for their ability to modify bovine embryo quality and confirmation, promote normal fetal development, and generate healthy calves. Additional cytokines will also be discussed for their potential to serve as embryokines.
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    Interleukin-6 increases inner cell mass numbers in bovine embryos
    Wooldridge, Lydia K.; Ealy, Alan D. (2019-02-01)
    Background Work in other species suggests that interleukin-6 (IL6) promotes early embryo development. It was unclear whether IL6 serves as an embryokine in cultured bovine embryos. This work was undertaken to elucidate the role of IL6 during in vitro bovine embryo production. Results Transcripts for IL6 and its two cognate receptor subunits (IL6R, IL6ST) were confirmed in bovine embryos from the 1-cell to blastocyst stages. Supplementing 100 ng/ml recombinant bovine IL6 to in vitro-produced bovine embryos at day 1, 3 or 5 increased (P < 0.05) inner cell mass (ICM) cell number and the ICM:trophectoderm (TE) ratio but not TE cell number. No increase in ICM or TE cell number was observed after supplementation of 1 or 10 ng/ml IL6 beginning at either day 1 or 5. Sequential supplementation with 100 ng/ml IL6 at both day 1 and 5 (for a total of 200 ng/ml IL6) increased (P < 0.05) ICM cell number to a greater extent than supplementing IL6 at a single time period in one study but not a second study. Additionally, providing 200 ng/ml IL6 beginning at day 1 or 5 yielded no further increase on ICM cell numbers when compared to supplementing with 100 ng/ml IL6. IL6 treatment had no effect on cleavage or blastocyst formation in group culture. However, IL6 supplementation increased cleavage and day 8 blastocyst formation when bovine embryos were cultured individually. Conclusions These results implicate IL6 as an embryokine that specifically increases ICM cell numbers in bovine embryos and facilitates bovine blastocyst development in embryos cultured individually.
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    Interleukin-6 promotes primitive endoderm development in bovine blastocysts
    Wooldridge, Lydia K.; Ealy, Alan D. (2021-01-12)
    Background Interleukin-6 (IL6) was recently identified as an embryotrophic factor in bovine embryos, where it acts primarily to mediate inner cell mass (ICM) size. This work explored whether IL6 affects epiblast (EPI) and primitive endoderm (PE) development, the two embryonic lineages generated from the ICM after its formation. Nuclear markers for EPI (NANOG) and PE (GATA6) were used to differentiate the two cell types. Results Increases (P < 0.05) in total ICM cell numbers and PE cell numbers were detected in bovine blastocysts at day 8 and 9 post-fertilization after exposure to 100 ng/ml recombinant bovine IL6. Also, IL6 increased (P < 0.05) the number of undifferentiated ICM cells (cells containing both PE and EPI markers). The effects of IL6 on EPI cell numbers were inconsistent. Studies were also completed to explore the importance of Janus kinase 2 (JAK2)-dependent signaling in bovine PE cells. Definitive activation of STAT3, a downstream target for JAK2, was observed in PE cells. Also, pharmacological inhibition of JAK2 decreased (P < 0.05) PE cell numbers. Conclusions To conclude, IL6 manipulates ICM development after EPI/PE cell fates are established. The PE cells are the target for IL6, where a JAK-dependent signal is used to regulate PE numbers.