Reflections on Rodent Implantation

Jeeyeon, M.; Dey, Sudhansu K.

doi:10.1007/978-3-319-15856-3_5

Cited by 15 publications

(7 citation statements)

References 88 publications

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“…Additionally, cultured NELF-B UtcKO mouse stromal cells had altered extracellular matrix components, weakening their attachment to the culture dish. In the mouse, embryos implant on 4.5 dpc; initially stromal cell proliferation occurs, followed by stromal cell transformation into polyploid decidual cells surrounding the implanted embryo at implantation sites, apparent by 6-8 dpc (26,27). When we experimentally induce decidualization, the intraluminal oil injection is designed to mimic embryo apposition and attachment to the uterine lumen before implantation (4 dpc).…”

Section: Discussionmentioning

confidence: 99%

Negative elongation factor is essential for endometrial function

Hewitt

Adams

et al. 2018

FASEB j.

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Pausing of RNA polymerase II (Pol II) during early transcription, mediated by the negative elongation factor (NELF) complex, allows cells to coordinate and appropriately respond to signals by modulating the rate of transcriptional pause release. Promoter proximal enrichment of Pol II occurs at uterine genes relevant to reproductive biology; thus, we hypothesized that pausing might impact endometrial response by coordinating hormonal signals involved in establishing and maintaining pregnancy. We deleted the NELF‐B subunit in the mouse uterus using PgrCre (NELF‐B UtcKO). Resulting females were infertile. Uterine response to the initial decidual stimulus of NELF‐B UtcKO was similar to that of control mice; however, subsequent full decidual response was not observed. Cultured NELF‐B UtcKO stromal cells exhibited perturbances in extracellular matrix components and also expressed elevated levels of the decidual prolactin Prl8a2, as well as altered levels of transcripts encoding enzymes involved in prostaglandin synthesis and metabolism. Because endometrial stromal cell decidualization is also critical to human reproductive health and fertility, we used small interfering to suppress NELF‐B or NELF‐E subunits in cultured human endometrial stromal cells, which inhibited decidualization, as reflected by the impaired induction of decidual markers PRL and IGFBP1. Overall, our study indicates NELF‐mediated pausing is essential to coordinate endometrial responses and that disruption impairs uterine decidual development during pregnancy.—Hewitt, S. C., Li, R., Adams, N., Winuthayanon, W., Hamilton, K. J., Donoghue, L. J., Lierz, S. L., Garcia, M., Lydon, J. P., DeMayo, F. J., Adelman, K., Korach, K. S. Negative elongation factor is essential for endometrial function. FASEB J. 33, 3010–3023 (2019). http://www.fasebj.org

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Section: Discussionmentioning

confidence: 99%

Negative elongation factor is essential for endometrial function

Hewitt

Adams

et al. 2018

FASEB j.

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“…Implantation in ruminants differs from that of rodents and primates where the conceptus enters a receptive uterus, hatches and almost immediately attaches to the uterine luminal epithelium (haemochorial placentation) (Cha & Dey 2015, Su & Fazleabas 2015. In contrast, the ruminant conceptus remains unattached for almost 3 weeks prior to implantation, during which time it rapidly elongates prior to implantation (synepitheliochorial placentation) (Lonergan & Forde 2014.…”

Section: Introductionmentioning

confidence: 99%

Global transcriptomic response of bovine endometrium to blastocyst-stage embryos

et al. 2019

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The aims of this study were (i) to investigate changes in the global transcriptome of bovine endometrial explants induced by exposure to blastocysts, (ii) to investigate if male and female blastocysts elicit a differential response in the endometrial transcriptome in vitro and (iii) to determine whether bovine endometrium responds to the presence of murine embryos. In Experiment 1, endometrial explants from the same uterus were cultured for 6 h with or without 20 in vitro-produced bovine blastocysts. In Experiment 2, endometrial explants were cultured with male or female bovine blastocysts produced in vitro by IVF either using sex-sorted semen or conventional unsorted semen followed by embryo sexing based on a biopsy. In Experiment 3, endometrial explants were cultured alone or in the presence of bovine blastocysts (n = 25) or murine blastocysts (n = 25). Following culture, explants were snap frozen and stored at −80°C until RNA extraction, qPCR or RNA-Seq. Culture with bovine blastocysts increased endometrial expression of 40 transcripts, all of which were interferon-tau induced. Culture with male or female bovine blastocysts increased transcript abundance of five classic interferon-stimulated genes (MX1, MX2, ISG15, OASY1, RSAD2) in explants; however, there was no difference in abundance of transcripts previously reported to be related to embryonic sex (IFNAR1, IFNAR2, CTGF, ARTN, SLC2A1, SLC2A5). Exposure to murine blastocysts did not elicit any detectable change in transcript abundance. These findings, coupled with our previous data, indicate that very local, interferon-tau-induced changes in endometrial gene expression occur in response to blastocysts; whether such changes play any role in subsequent pregnancy recognition remains to be established.

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“…Human pregnancy is a multi-faceted and highly regulated process that requires the intricate and timely control of numerous signaling pathways. Failure to properly control the pathways involved in pregnancy leads to complications that ultimately result in a change of fertility outcome (Fazleabas et al 2004, Wang & Dey 2006, Cha & Dey 2014, 2015. Recently, Wnt signaling was shown to be essential for various processes, including embryo-uterine crosstalk, implantation, decidualization and placentation (Mohamed et al 2005, Sonderegger et al 2010, Dunlap et al 2011, Franco et al 2011.…”

Section: Introductionmentioning

confidence: 99%

Regulation of porcupine-dependent Wnt signaling is essential for uterine development and function

et al. 2018

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Six members of the Wnt family are expressed in the female reproductive tract. Their collective function ensures proper development of the uterus, preparing it for pregnancy during adulthood. Here, we take advantage of the fact that a prerequisite for all Wnt secretion, is located on the X chromosome, to generate females that were mosaic for throughout the reproductive tract. females were mated with progesterone receptor ()-Cre males ( ) to generate females that were heterozygous for Porcupine in all tissues of the female reproductive tract, resulting in mosaicism due to random X-inactivation. We demonstrated that mosaic females are extremely subfertile and exhibit a large spectrum of phenotypes ranging from morphologically normal uteri to uteri with extremely enlarged cystic glands. Decreased fertility in Porcupine mosaic females was not associated with phenotype severity and was observed regardless of whether or not cystic glands were enlarged. By crossing-in a GFP reporter on the wild-type X chromosome, we were able to correlate endometrial gland hyperplasia with a mostly mutant stroma, demonstrating the role of stromal Wnts in the regulation of endometrial gland proliferation. Finally, we demonstrated that fertility issues within mosaic females were due to a reduced response to estrogen and to abnormal Tcf/Lef signaling across the mesometrial-anti-mesometrial axis during the window of implantation.

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Reflections on Rodent Implantation

Cited by 15 publications

References 88 publications

Negative elongation factor is essential for endometrial function

Negative elongation factor is essential for endometrial function

Global transcriptomic response of bovine endometrium to blastocyst-stage embryos

Regulation of porcupine-dependent Wnt signaling is essential for uterine development and function

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