Comparison of Gene Expression in Male and Female Mouse Blastocysts Revealed Imprinting of the X-Linked Gene, Rhox5/Pem, at Preimplantation Stages

Research Institute for Microbial Diseases, Osaka University, 3-1 Yamadaoka, Suita, Osaka 565-0871, Japan.
Current Biology (Impact Factor: 9.57). 02/2006; 16(2):166-72. DOI: 10.1016/j.cub.2005.11.071
Source: PubMed


Mammalian male preimplantation embryos develop more quickly than females . Using enhanced green fluorescent protein (EGFP)-tagged X chromosomes to identify the sex of the embryos, we compared gene expression patterns between male and female mouse blastocysts by DNA microarray. We detected nearly 600 genes with statistically significant sex-linked expression; most differed by 2-fold or less. Of 11 genes showing greater than 2.5-fold differences, four were expressed exclusively or nearly exclusively sex dependently. Two genes (Dby and Eif2s3y) were mapped to the Y chromosome and were expressed in male blastocysts. The remaining two (Rhox5/Pem and Xist) were mapped to the X chromosome and were predominantly expressed in female blastocysts. Moreover, Rhox5/Pem was expressed predominantly from the paternally inherited X chromosome, indicating sex differences in early epigenetic gene regulation.

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    • "ene - dosage compensa - tion , which results in the phenotypic sexual dimorphism associated with DNA and RNA content . As mentioned above , a males ' faster growth was first described in mam - malsÀ Àyet this phylum utilizes the opposite heteromorphic sex chromosome pattern , and vast of majority of genes show higher expression in female embryos ( Kobayashi et al . , 2006 ) ."
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    ABSTRACT: Studies of dioecious animals suggest that sex-specific development occurs from the onset of embryogenesis. This must be accounted for when addressing issues involving sex-ratio regulation in domestic animals and conservation biology. We investigated the occurrence of growth-rate sexual dimorphism in 84 chicken embryos incubated for 30 hr and nucleic-acid abundance in 99 embryos incubated for 4 hr. Comparative expression of the genes engaged in cell-cycle regulation (16 genes), embryo growth (10 genes), metabolic activity (2 genes), and epigenetic regulation (4 genes) in 4-hr male and female embryos were further analyzed by reverse-trancriptase quantitative PCR. At the stage when somite structure commences, males are growing faster than females. DNA and RNA yields at 4 hr are elevated in males compared to females, and most cell-proliferation-promoting genes are overexpressed in males. Expression of key metabolic genes (G6PD and HPRT) and the principal genes responsible for DNA methylation (DNMTs), however, does not differ between the sexes. These data suggest that the faster growth of early male embryos is conserved among mammalian and bird phyla, and may have an evolutionary importance. Mol. Reprod. Dev. 2015. © 2015 Wiley Periodicals, Inc. © 2015 Wiley Periodicals, Inc.
    Molecular Reproduction and Development 02/2015; 82(5). DOI:10.1002/mrd.22476 · 2.53 Impact Factor
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    • "It has been suggested that Rhox5 plays a vital role in the differentiation of embryonic stem cells. Rhox genes are abundant in E9.5 trophoblasts and Rhox5, which is localized in the X chromosome, is expressed predominantly in female mouse blastocysts rather than male blastocysts [30]. Embryonic stem cells with constitutively expressing Rhox5 (Pem) are not differentiated into the primitive endoderm nor embryonic ectoderm, but embryonic stem cells with constitutively expressing Rhox5 (Pem) developed into the teratoma containing only undifferentiated embryonic carcinoma-like cells. "
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    ABSTRACT: Homeobox genes play essential roles in embryonic development and reproduction. Recently, a large cluster of homeobox genes, reproductive homeobox genes on the X chromosome (Rhox) genes, was discovered as three gene clusters, α, β, and γ in mice. It was found that Rhox genes were selectively expressed in reproduction-associated tissues, such as those of the testes, epididymis, ovaries, and placenta. Hence, it was proposed that Rhox genes are important for regulating various reproductive features, especially gametogenesis in male as well as in female mammals. It was first determined that 12 Rhox genes are clustered into α (Rhox1-4), β (Rhox5-9), and γ (Rhox10-12) subclusters, and recently Rhox13 has also been found. At present, 33 Rhox genes have been identified in the mouse genome, 11 in the rat, and three in the human. Rhox genes are also responsible for embryonic development, with considerable amounts of Rhox expression in trophoblasts, placenta tissue, embryonic stem cells, and primordial germ cells. In this article we summarized the current understanding of Rhox family genes involved in reproduction and embryonic development and elucidated a previously unreported cell-specific expression in ovarian cells.
    Clinical and Experimental Reproductive Medicine 09/2013; 40(3):107-114. DOI:10.5653/cerm.2013.40.3.107
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    • "Thus, the double X-chromosome dosage in females and the presence of a Y-chromosome in males not only determine the transcriptional level of sex chromosome-encoded genes, but can also influence the transcription of genes present in autosomal chromosomes (Bermejo-Alvarez et al. 2010; Wijchers and Festenstein 2011). The use of sexing technologies, such as transgenesis and sex-sorted spermatozoa, in combination with microarray analysis of gene expression has uncovered nearly 600 differentially expressed genes between male and female mouse blastocysts (Kobayashi et al. 2006) and 3000 in the bovine model (Bermejo-Alvarez et al. 2010). These results confirm differences reported previously for some genes in male and female bovine blastocysts (Gutiérrez-Adán et al. 2000; Morton et al. 2007). "
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    ABSTRACT: Preimplantation developmental plasticity has evolved in order to offer the best chances of survival under changing environments. Conversely, environmental conditions experienced in early life can dramatically influence neonatal and adult biology, which may result in detrimental long-term effects. Several studies have shown that small size at birth, which is associated with a greater risk of metabolic syndrome, is largely determined before the formation of the blastocysts because 70%-80% of variation in bodyweight at birth has neither a genetic nor environmental component. In addition, it has been reported that adult bodyweight is programmed by energy-dependent process during the pronuclear stage in the mouse. Although the early embryo has a high developmental plasticity and adapts and survives to adverse environmental conditions, this adaptation may have adverse consequences and there is strong evidence that in vitro culture can be a risk factor for abnormal fetal outcomes in animals systems, with growing data suggesting that a similar link may be apparent for humans. In this context, male and female preimplantation embryos display sex-specific transcriptional and epigenetic regulation, which, in the case of bovine blastocysts, expands to one-third of the transcripts detected through microarray analysis. This sex-specific bias may convert the otherwise buffered stochastic variability in developmental networks in a sex-determined response to the environmental hazard. It has been widely reported that environment can affect preimplantation development in a sex-specific manner, resulting in either a short-term sex ratio adjustment or in long-term sex-specific effects on adult health. The present article reviews current knowledge about the natural phenotypic variation caused by epigenetic mechanisms and the mechanisms modulating sex-specific changes in phenotype during early embryo development resulting in sex ratio adjustments or detrimental sex-specific consequences for adult health. Understanding the natural embryo sexual dimorphism for programming trajectories will help understand the early mechanisms of response to environmental insults.
    Reproduction Fertility and Development 12/2012; 25(1):38-47. DOI:10.1071/RD12262 · 2.40 Impact Factor
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