Expression of Trophoblast Cell-Specific Pregnancy-Related Genes in Somatic Cell-Cloned Bovine Pregnancies1

Patel, Osman V.; Kizaki, Keiichiro; Takahashi, Toshio; Imai, Kyoichi; Takahashi, Seiya; Izaike, Yoshiaki; Schuler, Linda A.; Takezawa, Toshiaki; Hashizume, Kazuyoshi

doi:10.1095/biolreprod.103.020198

Cited by 24 publications

(18 citation statements)

References 46 publications

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“…In this study, expression of PAG-9 mRNA was detected in day 17 AI embryos, but was undetectable in SCNT embryos. This concurs with reports that expression of PAG-1 and PAG-9 is lower in day 30 placental tissues of SCNT embryos compared to AI embryos (Patel et al 2004b). The present study suggests that, in day 17 SCNT embryos, either no TGC are present or the TGC that are present are not functioning normally in terms to PAG-9 production.…”

Section: Discussionsupporting

confidence: 93%

“…Even though these results are in conflict, they clearly indicate that trophoblast development in SCNT embryos is altered. In addition, the mRNA and protein levels for gene associated with TGC function such as PL and PAG vary between naturally derived and SCNT placentas (Hashizume et al 2002, Patel et al 2004b, Ravelich et al 2004b, Hoffert et al 2005. Given the morphological variation and consequent dysfunction of TGC in placentas from SCNT embryos, it is of considerable interest to explore the expression of factors involved in bovine trophoblast differentiation during the early stages of placental formation.…”

Section: Introductionmentioning

confidence: 99%

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Somatic cell nuclear transfer alters peri-implantation trophoblast differentiation in bovine embryos

Arnold¹,

Bordignon²,

Lefebvre³

et al. 2006

Reproduction

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Abnormal placental development limits success in ruminant pregnancies derived from somatic cell nuclear transfer (SCNT), due to reduction in placentome number and consequently, maternal/fetal exchange. In the primary stages of an epithelial-chorial association, the maternal/fetal interface is characterized by progressive endometrial invasion by specialized trophoblast binucleate/giant cells (TGC). We hypothesized that dysfunctional placentation in SCNT pregnancies results from aberration in expression of genes known to be necessary for trophoblast proliferation (Mash2), differentiation (Hand1), and function (IFN-t and PAG-9). We, therefore, compared the expression of these factors in trophoblast from bovine embryos derived from artificial insemination (AI), in vitro fertilization (IVF), and SCNT prior to (day 17) and following (day 40 of gestation) implantation, as well as TGC densities and function. In preimplantation embryos, Mash2 mRNA was more abundant in SCNT embryos compared to AI, while Hand1 was highest in AI and IVF relative to SCNT embryos. IFN-t mRNA abundance did not differ among groups. PAG-9 mRNA was undetectable in SCNT embryos, present in IVF embryos and highest in AI embryos. In postimplantation pregnancies, SCNT fetal cotyledons displayed higher Mash2 and Hand1 than AI and IVF tissues. Allelic expression of Mash2 was not different among the groups, which suggests that elevated mRNA expression was not due to altered imprinting status of Mash2. The day 40 SCNT cotyledons had the fewest number of TGC compared to IVF and AI controls. Thus, expression of genes critical to normal placental development is altered in SCNT bovine embryos, and this is expected to cause abnormal trophoblast differentiation and contribute to pregnancy loss.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Somatic cell nuclear transfer alters peri-implantation trophoblast differentiation in bovine embryos

Arnold¹,

Bordignon²,

Lefebvre³

et al. 2006

Reproduction

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“…Placental BC products, such as bPL, bPSPB and bPAG-1, have been suggested as useful markers for embryonic or placental health, pregnancy normalcy and embryonic mortality, and for the prediction of abnormal conceptus development and postpartum pathological events (Patel et al 1997, Szenci et al 1998, Tefera et al 2001. Such BC products or the relative abundances of their placental transcripts have already been used in an attempt to detect or predict conceptus abnormalities after in vitro embryo manipulations (Vasquez et al 1995, Schmidt et al 1996, Hill et al 2000, Hashizume et al 2002, Heyman et al 2002, Ishiwata et al 2003, Patel et al 2004a, Ravelich et al 2004, and results from these studies have increasingly contributed to the understanding of those abnormalities.…”

Section: Discussionmentioning

confidence: 99%

Expression profile and protein levels of placental products as indirect measures of placental function in in vitro-derived bovine pregnancies

Bertolini¹,

Wallace²,

Anderson³

2006

Reproduction

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Bovine conceptus development and its association with placental proteins present in maternal, foetal and neonatal plasma and foetal (amniotic and allantoic) fluids were investigated in in vivo-and in vitro-produced (IVP) concepti and newborn calves. Females were superovulated to obtain control embryos, whereas IVP embryos were derived from established in vitro procedures. Pregnant animals were slaughtered on days 90 or 180 of gestation or allowed to develop to term for the assessment of physical traits. Foetal, maternal and neonatal blood and foetal fluids were collected for the determination of bovine placental lactogen (bPL) and bovine pregnancy-specific protein B (bPSPB) concentrations. Placental transcripts for bPL and bPSPB, determined by quantitative RT-PCR, were elevated in IVP placentomes. No major physical differences were observed between groups on day 90, but concentrations of bPL and bPSPB were higher in foetal plasma and allantoic fluid of IVP concepti in day 180 pregnancies, which were correlated with larger uterine and conceptus traits. Maternal concentrations of bPL in IVP pregnancies were lower than controls during the last 8 weeks of gestation, to become similar as parturition approached. Newborn IVP calves and foetal membranes were larger and displayed higher concentrations of plasma bPL than controls (10 and 60 min after birth). Our results indicated that differential patterns of secretion of bPL and bPSPB into the maternal and foetal systems occurred at distinct stages of gestation, and these were associated with altered conceptus development after in vitro embryo manipulations, indirectly demonstrating deviations in placental function in IVP pregnancies. Reproduction (2006) 131 163-173 IntroductionWith the onset of the trophoblast apposition to the endometrium during the process of bovine placenta formation and development, large granulated cells, the trophoblast binucleate cells (BCs), migrate from the trophectoderm to fuse with uterine epithelial cells (Wooding 1992), forming short-lived trinucleate cells. This phenomenon occurs throughout pregnancy in cattle, but the number and period of existence of trinucleate cells decline towards the end of gestation (Wooding 1992, Green et al. 2000. Binucleate cells comprise about 20% of the trophoblast cells and are responsible for hormones and bioactive products important for the regulation of foetal growth and development (Anthony et al. 1995, Green et al. 2000, Schlafer et al. 2000. The contents of the membranebounded secretory granules of BCs are released by exocytosis towards the maternal capillary bed, reaching the maternal blood system (Wooding 1992). Many proteins are produced by the BCs, including placental lactogen (PL) and a range of glycoproteins (Wooding 1992), such as pregnancy-specific protein B (PSPB) (Butler et al. 1982).PL lactogen is a member of the growth hormone (GH)/prolactin (PRL) gene family synthesized and stored in secretory granules of the trophoblast BCs (Byatt et al. 1992a, Wooding 1992, Gootwine 2004. Although ...

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“…Bovine NT embryos were produced from cumulus cells as described previously [19]. Control pregnancies were derived by artificial insemination (AI) of Japanese black cows (day 0=day of insemination).…”

Section: Nt and Control Animalsmentioning

confidence: 99%

DNA Methylation Profiles of Donor Nuclei Cells and Tissues of Cloned Bovine Fetuses

Kremenskoy

Kremenska

Suzuki

et al. 2006

Journal of Reproduction and Development

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Abstract. Methylation of DNA in CpG islands plays an important role during fetal development and differentiation because CpG islands are preferentially located in upstream regions of mammalian genomic DNA, including the transcription start site of housekeeping genes and are also associated with tissue-specific genes. Somatic nuclear transfer (NT) technology has been used to generate live clones in numerous mammalian species, but only a low percentage of nuclear transferred animals develop to term. Abnormal epigenetic changes in the CpG islands of donor nuclei after nuclear transfer could contribute to a high rate of abortion during early gestation and increase perinatal death. These changes have yet to be explored. Thus, we investigated the genome-wide DNA methylation profiles of CpG islands in nuclei donor cells and NT animals. Using Restriction Landmark Genomic Scanning (RLGS), we showed, for the first time, the epigenetic profile formation of tissues from NT bovine fetuses produced from cumulus cells. From approximately 2600 unmethylated NotI sites visualized on the RLGS profile, at least 35 NotI sites showed different methylation statuses. Moreover, we proved that fetal and placental tissues from artificially inseminated and cloned cattle have tissuespecific differences in the genome-wide methylation profiles of the CpG islands. We also found that possible abnormalities occurred in the fetal brain and placental tissues of cloned animals.

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Expression of Trophoblast Cell-Specific Pregnancy-Related Genes in Somatic Cell-Cloned Bovine Pregnancies1

Cited by 24 publications

References 46 publications

Somatic cell nuclear transfer alters peri-implantation trophoblast differentiation in bovine embryos

Somatic cell nuclear transfer alters peri-implantation trophoblast differentiation in bovine embryos

Expression profile and protein levels of placental products as indirect measures of placental function in in vitro-derived bovine pregnancies

DNA Methylation Profiles of Donor Nuclei Cells and Tissues of Cloned Bovine Fetuses

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