Inactivation of porcine interleukin-1β results in failure of rapid conceptus elongation

Whyte, Jeffrey J.; Meyer, Ashley E; Spate, Lee D.; Benne, Joshua A.; Cecil, Raissa F.; Samuel, Melissa; Murphy, Clifton N.; Prather, Randall S.; Geisert, Rodney D.

doi:10.1073/pnas.1718004115

Cited by 46 publications

(31 citation statements)

References 62 publications

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“…To gain molecular insights into the pig elongation process, we examined DEGs between Pre-TEs and Post-TEs in both monkey and pig. Our results showed that genes such as IL1B , BMP2/4/7 , SPP1 , SMAD5 , FGF4 , and FGFR2 14 , 15 , 53 , 54 , which have been implicated in regulating embryo elongation, were upregulated in pig Post-TEs, but not in monkey Post-TEs (Fig. 6f ).…”

Section: Resultsmentioning

confidence: 69%

Cross-species single-cell transcriptomic analysis reveals pre-gastrulation developmental differences among pigs, monkeys, and humans

Liu

et al. 2021

Cell Discov

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Interspecies blastocyst complementation enables organ-specific enrichment of xenogeneic pluripotent stem cell (PSC) derivatives, which raises an intriguing possibility to generate functional human tissues/organs in an animal host. However, differences in embryo development between human and host species may constitute the barrier for efficient chimera formation. Here, to understand these differences we constructed a complete single-cell landscape of early embryonic development of pig, which is considered one of the best host species for human organ generation, and systematically compared its epiblast development with that of human and monkey. Our results identified a developmental coordinate of pluripotency spectrum among pigs, humans and monkeys, and revealed species-specific differences in: (1) pluripotency progression; (2) metabolic transition; (3) epigenetic and transcriptional regulations of pluripotency; (4) cell surface proteins; and (5) trophectoderm development. These differences may prevent proper recognition and communication between donor human cells and host pig embryos, resulting in low integration and survival of human cells. These results offer new insights into evolutionary conserved and divergent processes during mammalian development and may be helpful for developing effective strategies to overcome low human–pig chimerism, thereby enabling the generation of functional human organs in pigs in the future.

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Section: Resultsmentioning

confidence: 69%

Cross-species single-cell transcriptomic analysis reveals pre-gastrulation developmental differences among pigs, monkeys, and humans

Liu

et al. 2021

Cell Discov

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“…Interleukin 1 beta 2 (IL1B2), released specifically by pig conceptus at its elongation time (at gestational day 12, pre-attachment stage), is an alternative transcript of pro-inflammatory IL1B [ 48 , 49 ]. IL1B2 can mediate conceptus elongation and active nuclear factor kappa-B (NF-κB) by upregulating NF-κB responsive genes ( PTGS2 and IKBA ) in the endometrial luminal epithelium [ 49 , 50 ]. Consistently, IL1B2 was only expressed in the conceptuses micro-dissected from gestational day 12 and expressions of a number of genes in the nuclear factor kappa-B (NF-κB) pathway were higher in the LE-M on gestational day 12.…”

Section: Discussionmentioning

confidence: 99%

Integrating LCM-Based Spatio-Temporal Transcriptomics Uncovers Conceptus and Endometrial Luminal Epithelium Communication that Coordinates the Conceptus Attachment in Pigs

Wang

Zhao

Deng

et al. 2021

IJMS

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Attachment of conceptus to the endometrial luminal epithelium (LE) is a critical event for early placentation in Eutheria. Since the attachment occurs at a particular site within the uterus, a coordinated communication between three spatially distinct compartments (conceptus and endometrial LE from two anatomical regions of the uterus to which conceptus attaches and does not attach) is essential but remains to be fully characterized. Using the laser capture microdissection (LCM) technique, we firstly developed an approach that can allow us to pair the pig conceptus sample with its nearby endometrial epithelium sample without losing the native spatial information. Then, a comprehensive spatio-temporal transcriptomic profile without losing the original conceptus-endometrium coordinates was constructed. The analysis shows that an apparent difference in transcriptional responses to the conceptus exists between the endometrial LE from the two anatomically distinct regions in the uterus. In addition, we identified the communication pathways that link the conceptus and endometrial LE and found that these pathways have important roles in conceptus attachment. Furthermore, a number of genes whose expression is spatially restricted in the two different anatomical regions within the uterus were characterized for the first time and two of them (SULT2A1 and MEP1B) may cooperatively contribute to establish conceptus attachment in pigs. The results from our study have implications in understanding of conceptus/embryo attachment in pigs and other large polytocous species.

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“…Approximately at day 12, pig embryo secretes IFNs (γ and δ), and IL (1B and 6) (Bazer, ). Specifically, the expression of interleukin 1β, IL1B2, increases in the pig embryo on approximately day 14, indicating cytokine requirement for conceptus elongation and attachment to the uterine wall (Whyte et al, ). Other interleukins, such as IL‐2 or IL‐4, are produced by the foetal and maternal placentas from day 30, suggesting their role in maternal–foetal recognition (Vélez et al, ).…”

Section: Cytokinesmentioning

confidence: 99%

Embryo gene expression in pig pregnancy

Llobat

2020

Reprod Domestic Animals

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Pregnancy is a complex process in which significant changes occur continually in both the corpora lutea and in the endometrium of the females and varies depending on the embryonic, pre‐implantation or foetal stages. In the embryonic stages, the majority of genes expressed in the pig embryo correspond to the loss of cellular pluripotency. In contrast, the implantation consists of three phases: elongation of the conceptus, adhesion and union of the embryo to the endometrial epithelium. During these phases, many factors are expressed, including growth factors, molecules that facilitate adhesion and cytokines. All these changes are ultimately regulated by different lipid and hormonal substances, specifically by progesterone, oestradiol and prostaglandins, which regulate the expression of many proteins necessary for the development of the embryo, endometrial remodelling and embryo–maternal communication. This paper is a review of primary gene regulatory mechanisms in pigs during different stages of implantation.

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Inactivation of porcine interleukin-1β results in failure of rapid conceptus elongation

Cited by 46 publications

References 62 publications

Cross-species single-cell transcriptomic analysis reveals pre-gastrulation developmental differences among pigs, monkeys, and humans

Cross-species single-cell transcriptomic analysis reveals pre-gastrulation developmental differences among pigs, monkeys, and humans

Integrating LCM-Based Spatio-Temporal Transcriptomics Uncovers Conceptus and Endometrial Luminal Epithelium Communication that Coordinates the Conceptus Attachment in Pigs

Embryo gene expression in pig pregnancy

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