Differential sensitivity of male and female mouse embryos to oxidative induced heat-stress is mediated by glucose-6-phosphate dehydrogenase gene expression

Pérez-Crespo, Míriam; Ramírez, Miguel Ángel; Fernández‐González, Raúl; Rizos, Dimitrios; Lonergan, Patrick; Pintado, Belén; Gutiérrez-Adán, A.

doi:10.1002/mrd.20366

Cited by 87 publications

(66 citation statements)

References 42 publications

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“…Because the proportion of males at birth was low only among women in the placebo group who had high levels of baseline inflammation, we suspect that inflammation may be hazardous to the conception or survival of male embryos. This is in agreement with in vivo animal studies (11,12).…”

Section: 2supporting

confidence: 92%

“…More dramatic decreases in this ratio have been associated with parental exposure to environmental hazards, such as smoking (6), dioxin (7), methylmercury (8), and earthquakes (9,10), suggesting that parental exposure to toxic chemicals and stress is particularly hazardous to male conception or survival. One potential pathway to altered sex ratios is maternal inflammation, which exhibits sex-dependent embryonic effects in bovines (11) and mice (12). In humans, a decidual proteotoxic stress response prevents implantation of nonviable embryos (13), and increased endometrial inflammation is associated with recurrent pregnancy loss (13,14).…”

Section: Introductionmentioning

confidence: 99%

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Sex ratio following preconception low-dose aspirin in women with prior pregnancy loss

Radin

Silver

Lesher

et al. 2015

Journal of Clinical Investigation

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alter the sex ratio of pregnancies among women with a history of pregnancy loss, given the sex-dependent embryonic effects of maternal inflammation.BACKGROUND. Several lines of evidence suggest that male embryos may have greater vulnerability than female embryos to disordered inflammation; therefore, antiinflammatory drugs, such as low-dose aspirin (LDA), may alter the sex ratio. Here, we assessed the effect of LDA on male live birth and male offspring, incorporating pregnancy losses (n = 56) via genetic assessment, as part of a parallel-design, block-randomized, placebo-controlled trial of preconception LDA. METHODS.Participants (615 treated with LDA, 613 treated with placebo) ranged in age from 18 to 40 years of age, with 1 to 2 prior pregnancy losses. We estimated the intention-to-treat (ITT) risk ratio (RR) and 95% CI and assessed interaction with baseline high-sensitivity C-reactive protein (hsCRP) serum concentration -a marker of systemic inflammation. RESULTS.Among the 1,078 women who completed follow-up (535 treated with LDA, 543 treated with placebo), the male live birth ITT RR equaled 1.31 (95% CI: 1.07-1.59). With increasing tertile of hsCRP, the proportion of males at birth decreased in the placebo group, and the effect of LDA on male live birth increased (first tertile: 48% male in LDA vs. 52% in placebo, ITT RR = 0.97, 95% CI: 0.70-1.35; second tertile: 57% male in LDA vs. 43% in placebo, ITT RR = 1.36, 95% CI: 0.98-1.90; third tertile: 53% male in LDA vs. 35% in placebo, ITT RR = 1.70, 95% CI: 1.13-2.57; P interaction = 0.03). Analysis of pregnancy with male offspring yielded similar results. CONCLUSION.Initiation of LDA prior to conception restored numbers of male live births and pregnancy with male offspring among women with 1 to 2 prior pregnancy losses. Moreover, our data suggest that LDA modulates inflammation that would otherwise reduce the conception or survival of male embryos. TRIAL REGISTRATION. ClinicalTrials.gov NCT00467363.

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Section: 2supporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Sex ratio following preconception low-dose aspirin in women with prior pregnancy loss

Radin

Silver

Lesher

et al. 2015

Journal of Clinical Investigation

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“…Thus, even in utero, initiation of TE specification can take place without TEAD4, but these embryos subsequently succumb to developmental failure due to oxidative stress (Betts and Madan, 2008 −/− blastocysts probably reflects differences in the ability of individual embryos to manage oxidative stress. Such differential sensitivity of individual wild-type embryos to oxidative stress has been attributed, at least in part, to the gene dosage of X-linked glucose 6-phosphate dehydrogenase, an enzyme crucial for relieving oxidative stress (Pérez-Crespo et al, 2005). Furthermore, a commonly used substrain of C57BL mice (6J substrain) contains a mutation in nicotinamide nucleotide transhydrogenase, a genetic modifier that mediates oxidative stress (Huang et al, 2006).…”

Section: Trophectoderm Specificationmentioning

confidence: 99%

TEAD4 establishes the energy homeostasis essential for blastocoel formation

Kaneko

DePamphilis

2013

Development

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SUMMARYIt has been suggested that during mouse preimplantation development, the zygotically expressed transcription factor TEAD4 is essential for specification of the trophectoderm lineage required for producing a blastocyst. Here we show that blastocysts can form without TEAD4 but that TEAD4 is required to prevent oxidative stress when blastocoel formation is accompanied by increased oxidative phosphorylation that leads to the production of reactive oxygen species (ROS). Both two-cell and eight-cell Tead4 -/− embryos developed into blastocysts when cultured under conditions that alleviate oxidative stress, and Tead4 −/− blastocysts that formed under these conditions expressed trophectoderm-associated genes. Therefore, TEAD4 is not required for specification of the trophectoderm lineage. Once the trophectoderm was specified, Tead4 was not essential for either proliferation or differentiation of trophoblast cells in culture. However, ablation of Tead4 in trophoblast cells resulted in reduced mitochondrial membrane potential. Moreover, Tead4 suppressed ROS in embryos and embryonic fibroblasts. Finally, ectopically expressed TEAD4 protein could localize to the mitochondria as well as to the nucleus, a property not shared by other members of the TEAD family. These results reveal that TEAD4 plays a crucial role in maintaining energy homeostasis during preimplantation development. KEY WORDS:Tead4, Blastocyst, Trophectoderm, Blastocoel, Oxidative stress, Anti-oxidant, Mouse TEAD4 establishes the energy homeostasis essential for blastocoel formation Kotaro J. Kaneko* and Melvin L. DePamphilis DEVELOPMENT 3681 RESEARCH ARTICLE Tead4 and energy homeostasis that are derived from TE (Tanaka et al., 1998;Yagi et al., 2007). The requirement for TEAD4 during preimplantation development is specific for TE, because Tead4 −/− embryos continue to express genes characteristic of the ICM and can produce embryonic stem cells that are derived from the ICM. Thus, Tead4 is the earliest zygotically expressed transcription factor reported to be essential for blastocoel formation and expression of TE-associated genes. Tead4 might also be required for post-implantation development, because it is expressed selectively in extra-embryonic ectoderm as well as in developing placenta (Jacquemin et al., 1996; Jacquemin et al., 1998).In an effort to understand how TEAD4 specifies TE, we made the surprising discovery that Tead4 −/− embryos could form a blastocoel, express TE-associated genes and produce trophoblast giant cells. Therefore, TEAD4 is not essential for specifying the TE lineage. It is, however, essential for blastocoel formation and expansion, but only under conditions that promote oxidative phosphorylation and therefore oxidative stress. By managing oxidative stress in vitro, the requirement for TEAD4 can be bypassed. In fact, analysis of ectopic Tead4 gene expression as well as ablation of Tead4 gene expression suggested that Tead4 is unique among TEAD members in that TEAD4 can localize to mitochondria and affect mitochondrial activi...

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“…The increased expression of X-linked genes may also explain the observation that male embryos are more sensitive to heat stress-induced oxidative damage than female embryos (Perez-Crespo et al 2005). A further X-linked gene of potential interest is O-linked N-acetyl glucosamine transferase (OGT), which is involved in the metabolism of UDP-N-acetyl glucosamine, and is more highly expressed in female bovine blastocysts (Bermejo-Alvarez et al 2010a).…”

Section: ; Figs 1 and 2)mentioning

confidence: 99%

Transcriptional sexual dimorphism during preimplantation embryo development and its consequences for developmental competence and adult health and disease

Bermejo-Álvarez¹,

Rizos²,

Lonergan³

et al. 2011

Reproduction

110

103

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In adult tissues, sexual dimorphism is largely attributed to sex hormone effects, although there is increasing evidence for a major role of sex chromosome dosage. During preimplantation development, male and female embryos can display phenotypic differences that can only be attributed to the transcriptional differences resulting from their different sex chromosome complements. Thus, all expressed Y-linked genes and those X-linked genes that totally or partially escape X-chromosome inactivation at each specific developmental stage display transcriptional sexual dimorphism. Furthermore, these differentially expressed sex chromosome transcripts can regulate the transcription of autosomal genes, leading to a large transcriptional sexual dimorphism. The sex-dependent transcriptional differences may affect several molecular pathways such as glucose metabolism, DNA methylation and epigenetic regulation, and protein metabolism. These molecular differences may have developmental consequences, including sex-selective embryo loss and sex-specific epigenetic responses to environmental hazards, leading to long-term effects. This review discusses transcriptional sexual dimorphism in preimplantation embryos, its consequences on sex ratio biases and on the developmental origin of health and disease, and its significance for transcriptional studies and adult sexual dimorphism.

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Differential sensitivity of male and female mouse embryos to oxidative induced heat-stress is mediated by glucose-6-phosphate dehydrogenase gene expression

Cited by 87 publications

References 42 publications

Sex ratio following preconception low-dose aspirin in women with prior pregnancy loss

Sex ratio following preconception low-dose aspirin in women with prior pregnancy loss

TEAD4 establishes the energy homeostasis essential for blastocoel formation

Transcriptional sexual dimorphism during preimplantation embryo development and its consequences for developmental competence and adult health and disease

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