Uterine Selection of Human Embryos at Implantation

Brosens, Jan J.; Salker, Madhuri S.; Teklenburg, Gijs; Nautiyal, Jaya; Salter, Scarlett; Lucas, Emma S.; Steel, Jennifer H.; Christian, Mark; Chan, Yi Wah; Boomsma, Carolien M.; Moore, Jonathan D.; Hartshorne, Geraldine M.; Šućurović, Sandra; Mulac‐Jeričević, Biserka; Heijnen, Cobi J.; Quenby, Siobhán; Koerkamp, Marian J. A. Groot; Holstege, Frank C.P.; Shmygol, Anatoly; Macklon, Nick S.

doi:10.1038/srep03894

Cited by 258 publications

(211 citation statements)

References 46 publications

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“…However, it is interesting that Hsc70 is strongly induced, since it is generally believed that Hsp70 is the major inducible isoform. However, cases where Hsc70 can be induced, such as from heat shock, ethanol treatment, virus infection, or pesticide toxicity, have been described, but such cases are not prominent in the literature (21,23,(75)(76)(77). Hsc70 isoforms have been induced during baculovirus infection but only very modestly (78).…”

Section: Resultsmentioning

confidence: 99%

Cucumber Necrosis Virus Recruits Cellular Heat Shock Protein 70 Homologs at Several Stages of Infection

Alam

Rochon

2016

J Virol

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RNA viruses often depend on host factors for multiplication inside cells due to the constraints of their small genome size and limited coding capacity. One such factor that has been exploited by several plant and animal viruses is heat shock protein 70 (HSP70) family homologs which have been shown to play roles for different viruses in viral RNA replication, viral assembly, disassembly, and cell-to-cell movement. Using next generation sequence analysis, we reveal that several isoforms of Hsp70 and Hsc70 transcripts are induced to very high levels during cucumber necrosis virus (CNV) infection of Nicotiana benthamiana and that HSP70 proteins are also induced by at least 10-fold. We show that HSP70 family protein homologs are co-opted by CNV at several stages of infection. We have found that overexpression of Hsp70 or Hsc70 leads to enhanced CNV genomic RNA, coat protein (CP), and virion accumulation, whereas downregulation leads to a corresponding decrease. Hsc70-2 was found to increase solubility of CNV CP in vitro and to increase accumulation of CNV CP independently of viral RNA replication during coagroinfiltration in N. benthamiana. In addition, virus particle assembly into virus-like particles in CP agroinfiltrated plants was increased in the presence of Hsc70-2. HSP70 was found to increase the targeting of CNV CP to chloroplasts during infection, reinforcing the role of HSP70 in chloroplast targeting of host proteins. Hence, our findings have led to the discovery of a highly induced host factor that has been co-opted to play multiple roles during several stages of the CNV infection cycle. IMPORTANCEBecause of the small size of its RNA genome, CNV is dependent on interaction with host cellular components to successfully complete its multiplication cycle. We have found that CNV induces HSP70 family homologs to a high level during infection, possibly as a result of the host response to the high levels of CNV proteins that accumulate during infection. Moreover, we have found that CNV co-opts HSP70 family homologs to facilitate several aspects of the infection process such as viral RNA, coat protein and virus accumulation. Chloroplast targeting of the CNV CP is also facilitated, which may aid in CNV suppression of host defense responses. Several viruses have been shown to induce HSP70 during infection and others to utilize HSP70 for specific aspects of infection such as replication, assembly, and disassembly. We speculate that HSP70 may play multiple roles in the infection processes of many viruses. C ucumber necrosis virus (CNV) is a positive-strand RNA virus in the genus Tombusvirus, family Tombusviridae (1). The CNV genome is monopartite and consists of ϳ4.7 kb of positive polarity single-stranded RNA. The genome contains five open reading frames (ORFs) which encode five different proteins: the auxiliary replicase factor (p33), the RNA-dependent RNA polymerase (RdRp) (p92), the coat protein (CP; p41), the movement protein (p21), and the silencing suppressor (p20) (Fig. 1A). The UAG stop codon of the p...

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Section: Resultsmentioning

confidence: 99%

Cucumber Necrosis Virus Recruits Cellular Heat Shock Protein 70 Homologs at Several Stages of Infection

Alam

Rochon

2016

J Virol

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“…Decidualized endometrial stromal cells respond to a poor-quality embryo with profound downregulation of the HSPA8 gene to induce a proteotoxic stress response (24). Embryonic metabolism may influence signaling, as poor-quality embryos are more active Stratified by treatment assignment LDA This analysis included data from 1,039 participants who had hsCRP measured at randomization and completed follow-up.…”

Section: Discussionmentioning

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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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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“…DC participate in the trophic relationships between mother and fetus and hormonal regulation of pregnancy, their specific functions include the prevention of the development of inflammation in the endometrium and the regulation of immunological conflict between mother and fetus [4]. In accord with modern results a human embryos influence embryo implantation and functional state of DC depending on the state of embryos [5].…”

Section: Introductionmentioning

confidence: 91%

Further Characteristics of Pregnant Вone Marrow Cells Action on Rat Development during Early Pregnancy

Vm¹,

Av²,

Ns³

et al. 2017

J Genet Syndr Gene Ther

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There were early results that effect of single intravenous transplantation of pregnant rats Percoll derived mononuclear bone marrow cells (BMC) suspention of 4-5, 7-9 or 11-12 pregnant days to rats with the same date of pregnancy depends on gestation period of transplantation. The weight of 18th day fetuses after intravenous transplantation during 7-9 days was increased with significant difference in comparison with weight of normal fetuses. In case of intravenous BMC transplantation during placentation at 11-12 days of pregnancy the weight of fetuses was decreased, the weight of placentas was increased and survival of fetuses was disturbed. There are several explanations of increase of weight of fetuses after intravenous BMC transplantation within gastrulation including paracrine effect of allogenic transplanted cells on the DC development, the apoptosis and proliferation of embryonal cells and possible epigenetic action. The retardation of fetuses growth after intravenous BMC transplantation during placenta formation at pregnant 11-12 days may be explained by cytotoxic action of uNK cells for embryo. At the same time the sub-dermal BMC transplantation at 11 and 13 pregnant days stopped the embryotoxic action of uNK cells and increased the weight of fetuses and preserved the survival of embryos.

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Uterine Selection of Human Embryos at Implantation

Cited by 258 publications

References 46 publications

Cucumber Necrosis Virus Recruits Cellular Heat Shock Protein 70 Homologs at Several Stages of Infection

Cucumber Necrosis Virus Recruits Cellular Heat Shock Protein 70 Homologs at Several Stages of Infection

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

Further Characteristics of Pregnant Вone Marrow Cells Action on Rat Development during Early Pregnancy

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