Sexual Dimorphism in Developmental Programming of the Bovine Preimplantation Embryo Caused by Colony-Stimulating Factor 21

Dobbs, Kyle B.; Gagné, Dominique; Fournier, Éric; Dufort, Isabelle; Robert, Claude; Block, J.; Sirard, Marc‐André; Bonilla, L.; Ealy, Alan D.; Loureiro, B.; Hansen, Peter J.

doi:10.1095/biolreprod.114.121087

Cited by 44 publications

(58 citation statements)

References 75 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%

“…However, the observed effect would implantation embryos exhibit sexually dimorphic physiology (22,23). In bovines, maternally derived colony-stimulating factor 2 cytokine decreased length and interferon-tau secretion of female embryos but increased length and interferon-tau secretion of male embryos (11). Colony-stimulating factor 2 also caused sex-dependent changes in the embryonic transcriptome and methylome (11), indicating that maternal inflammation may exert broader, sexually dimorphic effects.…”

Section: Discussionmentioning

confidence: 98%

“…In bovines, maternally derived colony-stimulating factor 2 cytokine decreased length and interferon-tau secretion of female embryos but increased length and interferon-tau secretion of male embryos (11). Colony-stimulating factor 2 also caused sex-dependent changes in the embryonic transcriptome and methylome (11), indicating that maternal inflammation may exert broader, sexually dimorphic effects. In mice, heat stress resulted in lower survival and higher hydrogen peroxide production among male preimplantation embryos relative to those of female preimplantation embryos (12).…”

Section: Discussionmentioning

confidence: 99%

“…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: Discussionmentioning

confidence: 98%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

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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“…Recent experiments in cattle suggest this is true for CSF2 (Siqueira and Hansen 2015). Furthermore, the consequence is that embryonic function later in development is altered by CSF2 in a sex-dependent manner (Dobbs et al 2014). …”

Section: Introductionmentioning

confidence: 99%

Sex and the preimplantation embryo: implications of sexual dimorphism in the preimplantation period for maternal programming of embryonic development

et al. 2015

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The developmental program of the embryo displays a plasticity that can result in long-acting effects that extend into post-natal life. In mammals, adult phenotype can be altered by changes in the maternal environment during the preimplantation period. One characteristic of developmental programming during this time is that the change in adult phenotype is often different for female offspring than for male offspring. In this paper, we propose the hypothesis that sexual dimorphism in preimplantation programming is mediated, at least in part, by sex-specific responses of embryos to maternal regulatory molecules whose secretion is dependent on maternal environment. The strongest evidence for this idea comes from the study of colony-stimulating factor 2 (CSF2). Expression of CSF2 from the oviduct and endometrium is modified by environmental factors of the mother, in particular seminal plasma and obesity. Additionally, CSF2 alters several properties of the preimplantation embryo and has been shown to alleviate negative consequences of culture of mouse embryos on postnatal phenotype in a sex-dependent manner. In cattle, exposure of preimplantation bovine embryos to CSF2 causes sex-specific changes in gene expression, interferon-τ secretion, and DNA methylation later in pregnancy (day 15 of gestation). It is likely that several embryokines can alter postnatal phenotype through actions directed towards the preimplantation embryo. Identification of these molecules and elucidation of the mechanisms by which sexually-disparate programming is established will lead to new insights into the control and manipulation of embryonic development.

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Exposure to colony stimulating factor 2 during preimplantation development increases postnatal growth in cattle

Kannampuzha-Francis

Denicol

Loureiro

et al. 2015

Molecular Reproduction Devel

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The microenvironment of a preimplantation embryo can influence changes in development that affect postnatal phenotypes. One of the potential mediators of this effect in many species is colony-stimulating factor (CSF2), which can increase an embryo's ability to establish pregnancy after its transfer into recipients. Exposure of embryos to CSF2 during early development can also affect the pattern of development later in pregnancy in a sex-dependent manner. We therefore hypothesized that treatment of in vitro-produced embryos with CSF2 in culture would alter birth weight and postnatal growth of the resultant calf. Body weight and withers height were measured for Holstein heifer calves produced in vitro with or without 10 ng/ml CSF2 and for calves produced by artificial insemination. There were no differences in birth weight between groups; thereafter, however, calves from the CSF2-treated group experienced greater increases in body weight through 13 months of age, with only small differences in withers height. These results support the model that an embryo's postnatal characteristics can be programmed during the preimplantation period, and that CSF2 is one of the embryokines through which programming is directed. Mol. Reprod. Dev. 82: 892-897, 2015. © 2015 Wiley Periodicals, Inc.

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Sexual Dimorphism in Developmental Programming of the Bovine Preimplantation Embryo Caused by Colony-Stimulating Factor 21

Cited by 44 publications

References 75 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

Sex and the preimplantation embryo: implications of sexual dimorphism in the preimplantation period for maternal programming of embryonic development

Exposure to colony stimulating factor 2 during preimplantation development increases postnatal growth in cattle

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