256 LINES OF PIGS SELECTED FOR COMPONENT TRAITS OF LITTER SIZE EXHIBIT DIFFERENTIAL GENE REGULATION AT THE ONSET OF EMBRYO (TROPHECTODERM) ELONGATION

2006 ◽  
Vol 18 (2) ◽  
pp. 235 ◽  
Author(s):  
J. R. Miles ◽  
L. A. Blomberg ◽  
B. A. Freking ◽  
K. A. Zuelke

Significant embryonic (<18%) loss occurs in the pig as the pre-implantation embryo undergoes a dramatic morphological change from ovoid (8-10 mm) at gestational Day 11 to a long, thin filament (<150 mm) by Day 12. Lines of pigs selected for increased uterine capacity have improved embryonic survival, whereas pigs selected for increased ovulation rate have decreased embryo survival. Alterations in the expression of genes that play key roles in embryo elongation and maternal recognition of pregnancy may reflect differences in embryo survival observed in these lines of pigs. The objective of the current study was to evaluate the expression level of transcripts involved in developmentally important processes, such as steroidogenesis, cellular differentiation, cell-cell interaction, and immune modulation, at the onset of porcine embryo elongation (gestational Day 11) in control animals and lines selected for increased ovulation rate or uterine capacity. Total RNA was isolated from Day 11 ovoid embryos, and gene expression was measured via real-time PCR. Data were analyzed for analysis of variance using GLM procedures. Expression of steroidogenic acute regulatory protein mRNA was decreased (P = 0.02) in embryos from the ovulation rate and uterine capacity lines compared with controls. Similarly, expression of cytochrome P450scc and aromatase mRNA were decreased (P < 0.003) in embryos from the ovulation rate and uterine capacity lines, compared with the control line. Interestingly, 17�-hydroxylase mRNA expression was decreased (P = 0.0004) only in embryos from the ovulation rate line compared with the control and uterine capacity lines. In contrast, expression of cytokeratin-8 and -18 mRNA were increased (P < 0.02) in embryos from the uterine capacity and ovulation rate lines, compared with controls. Expression of galectin 1 mRNA was increased (P = 0.02) in embryos from the uterine capacity line, compared with the ovulation rate line. Expression of interleukin-1 receptor type 1 mRNA was increased (P = 0.03) in embryos from the uterine capacity line, compared with both the control and the uterine capacity lines. Constitutive expression of 17�-hydroxysteroid dehydrogenase, stratifin, and interleukin-1� mRNA were observed in embryos from all lines. These results demonstrate altered gene expression in embryos from pigs selected for increased uterine capacity and ovulation rate compared with controls, and may contribute to differences observed in embryo survival between these lines of pigs.

Reproduction ◽  
2004 ◽  
Vol 127 (5) ◽  
pp. 587-592 ◽  
Author(s):  
M Holt ◽  
O Vangen ◽  
W Farstad

The aim of the present study was to evaluate how ovulation rate and survival rate through pregnancy had been affected by more than 110 generations of upwards selection on litter size in mice. The mean number of pups born alive was 22 in the high line (selected line) and 11 in the control line (an increase in 2.6 standard deviations). Selection on litter size increased ovulation rate by 4.6 standard deviations, and it is suggested that selection also increased embryonic mortality in late pregnancy. Embryo survival from ovulation until birth was 66% in the selected line and 69% in the control line, and the observed loss in litter size from day 16 of pregnancy until birth was possibly higher in the high line compared with the control line. Selection for higher litter size has significantly increased body weight in both males and females, as the mean weight at mating for the females was 46 g in the high line and 33 g in the control line respectively.


Author(s):  
J.P. Hanrahan

Variation in litter size in sheep is essentially attributable to variation in ovulation rate and embryo survival. Genetic variation in litter size, both among and within breeds, is largely attributable to variation in ovulation rate. While there is evidence for genetic differences among breeds in embryo survival the contribution of this component to within breed variation appears to be minor (Hanrahan, 1982). The impact of selection based on litter size on its component traits should reflect the relative contribution of these components to within breed variation. Data from two lines of Galway sheep, a Control line and one selected for increased prolificacy (Hanrahan and Timon, 1978), have been used to provide evidence on this point.Details relating to the selection experiment which provided the data for the present study are in Hanrahan (1984). Briefly a flock of Galway sheep was assembled from industry sources (both pedigree and non-pedigree) between 1963 and 1965.


1992 ◽  
Vol 283 (3) ◽  
pp. 705-712 ◽  
Author(s):  
N Kawamura ◽  
L Singer ◽  
R A Wetsel ◽  
H R Colten

The third component of complement (C3) is an important mediator of inflammation. Murine and human genomic cosmid clones were isolated, characterized and sequenced 5′ to the complement C3 gene transcriptional initiation sites to determine cis elements that participate in constitutive and regulated C3 gene expression. The murine and human 5′ flanking regions are 51% identical overall, with positions -36 to -1 and -146 to -68 showing 80% identity. Four TATA boxes were identified upstream of the murine transcriptional initiation site, but deletion and transfection analysis using reporter gene constructs in HepG2 cells indicated that only the TATA element at position -30, together with sequences -395 to -111, are essential for constitutive expression of murine C3 in hepatocytes. Deletion analysis also suggested that sequences between -1457 and -800 contain regulatory elements that are involved in suppressing basal expression. Sequences between -90 to -41 confer both enhancer activity and interleukin-1/-6 (IL-1/IL-6)-responsiveness. Mutation analyses showed that both sequences between -88 and -83 and -77 to -72 are essential for enhancer activity and responsiveness to IL-1, but only sequences between -88 and -83 are necessary for IL-6-responsiveness. A gel-retardation assay showed that several nucleoproteins, perhaps of the C/EBP family, from HepG2 cells bound to sequences between -88 to -83. Collectively, these results localize cis-acting elements involved in constitutive and IL-1/IL-6-regulated murine C3 gene expression and provide evidence for specific transacting factors.


2019 ◽  
Vol 44 (2) ◽  
pp. 77-87
Author(s):  
Koichi Ishida ◽  
Liyue Qin ◽  
Ting Wang ◽  
Ying Lei ◽  
Weiwei Hu ◽  
...  

Acupuncture manipulations are clinically important to traditional Chinese medicine, yet the biological mechanisms have not been fully understood. This study aimed to investigate continuous stimulation-induced gene expression changes at stimulated and non-stimulated adjacent acupoints in the same meridian. Catgut embedding into acupoint (CEP) was conducted at acupoint Yanglingquan (gall bladder meridian of foot-shaoyang 34, GB34) of Sprague Dawley rats once or continuously for eight weeks, and gene expression changes at GB34 were assessed by gene chip array analysis 72 h after the last CEP treatment. A total of 688 genes exhibited opposite changes in expression between the two treatments, and 1,336 genes were regulated only by the eight-week CEP treatment. Ingenuity Pathway Analysis revealed that among these differentially regulated genes by one-time and eight-week CEP treatment, insulin-like growth factor-1 pathway and integrin-linked kinase pathway, and Wnt/~ catenin signaling pathway match the observed gene changes to predicted up/down regulation patterns. Upstream analysis further predicted six molecules, namely, tumor necrosis factor, interleukin 1~, interleukin la, kallikrein-related peptidase 5, protein kinase Ca, and catenin ~1. On the other hand, continuous eight-week CEP stimulation at acupoint Xuanzhong (GB39) caused similar changes in the expression of 32 genes at acupoints GB34 and Fengshi (GB31) on the same meridian. Taken together, our results provide the first molecular evidence for the local acupoints' mechanisms for acupoint sensitization theory, and implicate the existence of signaling pathways, either direct or indirect, between acupoints within the meridian GB.


Cancers ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1761
Author(s):  
Luka Brcic ◽  
Alexander Mathilakathu ◽  
Robert F. H. Walter ◽  
Michael Wessolly ◽  
Elena Mairinger ◽  
...  

Malignant pleural mesothelioma (MPM) is an aggressive malignancy associated with asbestos exposure. Median survival ranges from 14 to 20 months after initial diagnosis. As of November 2020, the FDA approved a combination of immune checkpoint inhibitors after promising intermediate results. Nonetheless, responses remain unsatisfying. Adequate patient stratification to improve response rates is still lacking. This retrospective study analyzed formalin fixed paraffin embedded specimens from a cohort of 22 MPM. Twelve of those samples showed sarcomatoid, ten epithelioid differentiation. Complete follow-up, including radiological assessment of response by modRECIST and time to death, was available with reported deaths of all patients. RNA of all samples was isolated and subjected to digital gene expression pattern analysis. Our study revealed a notable difference between epithelioid and sarcomatoid mesothelioma, showing differential gene expression for 304/698 expressed genes. Whereas antigen processing and presentation to resident cytotoxic T cells as well as phagocytosis is highly affected in sarcomatoid mesothelioma, cell–cell interaction via cytokines seems to be of greater importance in epithelioid cases. Our work reveals the specific role of the immune system within the different histologic subtypes of MPM, providing a more detailed background of their immunogenic potential. This is of great interest regarding therapeutic strategies including immunotherapy in mesothelioma.


2020 ◽  
Vol 22 (1) ◽  
pp. 6
Author(s):  
Ievgeniia Gazo ◽  
Roman Franěk ◽  
Radek Šindelka ◽  
Ievgen Lebeda ◽  
Sahana Shivaramu ◽  
...  

DNA damage caused by exogenous or endogenous factors is a common challenge for developing fish embryos. DNA damage repair (DDR) pathways help organisms minimize adverse effects of DNA alterations. In terms of DNA repair mechanisms, sturgeons represent a particularly interesting model due to their exceptional genome plasticity. Sterlet (Acipenser ruthenus) is a relatively small species of sturgeon. The goal of this study was to assess the sensitivity of sterlet embryos to model genotoxicants (camptothecin, etoposide, and benzo[a]pyrene), and to assess DDR responses. We assessed the effects of genotoxicants on embryo survival, hatching rate, DNA fragmentation, gene expression, and phosphorylation of H2AX and ATM kinase. Exposure of sterlet embryos to 1 µM benzo[a]pyrene induced low levels of DNA damage accompanied by ATM phosphorylation and xpc gene expression. Conversely, 20 µM etoposide exposure induced DNA damage without activation of known DDR pathways. Effects of 10 nM camptothecin on embryo development were stage-specific, with early stages, before gastrulation, being most sensitive. Overall, this study provides foundational information for future investigation of sterlet DDR pathways.


1987 ◽  
Vol 80 (2) ◽  
pp. 430-436 ◽  
Author(s):  
T S Kupper ◽  
A O Chua ◽  
P Flood ◽  
J McGuire ◽  
U Gubler

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