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Mouse fetuses generated by in vitro embryo culture and embryo transfer exhibit impaired lung development, altered composition of pulmonary epithelial cells associated with downregulation of several genes involved in lung development and toll-like receptor (TLR) signaling pathway. The aims of the present study were to determine the expression of all TLRs and to examine if the expression of TLRs, along with genes involved in TLR signaling pathway, is altered in the lung tissue of mouse fetuses generated through embryo culture and embryo transfer. Two experimental (EGs) and one control (CG) group were included in the study. Embryos cultured at 5% CO2-95% air for 95 h or less than 24 h were transferred to pseudo-pregnant females to obtain fetuses comprising EGin vitro (n = 18) and EGin vivo (n = 18), respectively. Fetuses obtained from naturally ovulating females on day 18 of pregnancy served as the CG (n = 18). Western blot and immunohistochemistry were used to determine the expression of TLR proteins. The expression of transcripts encoding TLRs, and the genes involved in TLR signaling pathway (Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos), was determined using qRT-PCR. While all TLRs were expressed by cells lining the bronchial/bronchiolar epithelium of lung tissues in all groups, some of the TLRs were expressed in a specific pattern. When compared to CG, the expression of transcripts encoding TLR-2, -3, -4, -5, -7, -8, -9, -12, -13, Lbp, Pik3r1, Pik3cb, Nfkbia, and Fos was significantly downregulated in both EGs. It appears that stress imposed on embryos at preimplantation stages of development is associated with downregulation of TLRs, along with some of the genes involved in TLR signaling pathway, in the lung tissue during the perinatal period. It remains to be determined if downregulation of TLRs, along with the genes involved in TLR signaling pathway, has any functional consequences in the adult lung tissue.

DOGAN, GOKSEL/0000-0002-4583-3140; CINAR KUL, Bengi/0000-0002-8955-0097, WOS: 000510017700006, PubMed: 31504752, In vitro culture under atmospheric oxygen puts embryos under oxidative stress and impairs preimplantation development. However, to what extent this process alters the redox balance in the perinatal period remains largely unknown. the aim of the present study was to examine if the redox balance is altered in the lung tissue of fetuses generated through transfer of mouse embryos exposed to atmospheric oxygen at different stages of development and to determine if this has any effect on lung morphogenesis and gene expression. Two experimental groups (EGs) were generated by transferring in vitro- and in vivo-derived blastocysts to pseudo-pregnant females. in vivo-developed fetuses served as control. Enzymatic/nonenzymatic antioxidants, malondialdehyde (MDA) levels, total antioxidant capacity, stage of lung development and gene expression were evaluated on day 18 of pregnancy. Weight of fetuses was significantly less in both experimental cohorts (ANOVA, P < 0.001 versus control), associated with delayed lung development, higher amounts of MDA (ANOVA, P < 0.001 versus control) and altered expression of several genes in oxidative stress/damage pathways. Evidence gathered in the present study indicates that pre-implantation stress caused by culture under atmospheric oxygen, even for a short period of time, leads to fetal growth restriction, impaired lung development and redox balance along with dysregulation of several genes in oxidative stress response. Absence of an EG in which in vitro embryo culture was performed at 5% oxygen and the use of genetically heterogeneous F2 fetuses are the limitations of the study. in any case, the long-term impact of such dramatic changes in the developmental programming of resulting fetuses warrants further investigations., Scientific and Technological Research Council of Turkey (TUB.ITAK)Turkiye Bilimsel ve Teknolojik Arastirma Kurumu (TUBITAK) [112O259], This work was funded by the Scientific and Technological Research Council of Turkey (TUB.ITAK, Project no: 112O259).