Uterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success

Kelleher, Andrew M.; Milano-Foster, Jessica; Behura, Susanta K.; Spencer, Thomas E.

doi:10.1038/s41467-018-04848-8

Cited by 142 publications

(145 citation statements)

References 72 publications

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“…Estrogen upregulates Leukemia inhibitory factor (Lif) expression in the uterus, and supplementation with Lif restores implantation and decidualization in ovariectomized mice and mice lacking uterine estrogen receptor expression . Lif is secreted by the uterine glands promotes embryo‐uterine communication and contributes to embryo attachment and decidualization …”

Section: Discussionmentioning

confidence: 99%

Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

Al-Kaabi

Hamdan

Al-Matubsi

2020

J of Obstet and Gynaecol

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Aims To evaluate plasma kisspeptin‐10 (KP‐10) as a marker for preeclampsia and assess its relation to altered reproductive hormones in preeclamptic pregnant women. Methods First time pregnant women (n = 100) at 20 weeks of gestation participated in this study and divided into preeclamptics (n = 60) and normotensives (n = 40). KP‐10, luteinizing hormone (LH), follicle stimulating hormone (FSH), beta‐human chorionic gonadotropin (β‐hCG), estradiol (E2) and progesterone were evaluated during 2nd and 3rd trimesters of pregnancy for all women. Results Kisspeptin‐10 levels were reduced in preeclampsia (PE) women compared with normotensive pregnancies. In the 2nd trimester, area under receiver–operator characteristic (ROC) curve was 0.662, positive and negative predictive values were 32.8 and 94.6, and test sensitivity and specificity were 55% and 87.5%, respectively. In the 3rd trimester, area under ROC curve was 0.747 positive and negative predictive values were 22.2 and 97.3, and test sensitivity and specificity were 83.3% and 67.5%, respectively. In PE patients, plasma KP‐10 demonstrated an inverse correlation with E2 (during the 2nd trimester), LH and FSH (during the 3rd trimester), and positively correlated with β‐hCG (during the 3rd trimester). Conclusion This study showed significantly reduced plasma KP‐10 levels in PE women. This suggests that KP‐10 may play an important role in the pathophysiology of PE. Therefore, combined with previous studies, to diagnose the PE, testing for maternal KP‐10 plasma levels may be useful as an effective screening, but because of low positive predictive value and inadequate test sensitivity, screening cannot be recommended. Furthermore, KP‐10 in PE patients demonstrated significant positive correlation with β‐hCG.

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Section: Discussionmentioning

confidence: 99%

Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

Al-Kaabi

Hamdan

Al-Matubsi

2020

J of Obstet and Gynaecol

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“…Adult female Foxa2 conditional knockout (cKO) mice were generated by breeding C57BL/6J lactotransferrin Cre (Ltf-iCre) knock-in mice with C57BL/6J floxed Foxa2 mice as described by our laboratory (26). Adult Foxa2 cKO (Ltf iCre/+ Foxa2 f/f ) mice are infertile because of defects in embryo implantation caused by an absence of leukemia inhibitory factor (LIF) expression by the glands of the uterus (27). To rescue implantation and pregnancy establishment, adult female Foxa2 cKO mice (n = 4) received intraperitoneal injections of 10 mg recombinant mouse LIF (BioLegend, San Diego, CA, USA) in sterile PBS at 10:00 AM and 6:00 PM on GD4 as previously described (27).…”

Section: Animal Breeding and Sample Collectionmentioning

confidence: 99%

“…Adult Foxa2 cKO (Ltf iCre/+ Foxa2 f/f ) mice are infertile because of defects in embryo implantation caused by an absence of leukemia inhibitory factor (LIF) expression by the glands of the uterus (27). To rescue implantation and pregnancy establishment, adult female Foxa2 cKO mice (n = 4) received intraperitoneal injections of 10 mg recombinant mouse LIF (BioLegend, San Diego, CA, USA) in sterile PBS at 10:00 AM and 6:00 PM on GD4 as previously described (27). The mice were necropsied on GD15, and the placenta and FB from each implantation site were isolated, washed, and frozen as previously described.…”

Section: Animal Breeding and Sample Collectionmentioning

confidence: 99%

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Evidence for functional interactions between the placenta and brain in pregnant mice

2018

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The placenta plays a pivotal role in the development of the fetal brain and also influences maternal brain function, but our understanding of communication between the placenta and brain remains limited. Using a gene expression and network analysis approach, we provide evidence that the placenta transcriptome is tightly interconnected with the maternal brain and fetal brain in d 15 pregnant C57BL/6J mice. Activation of serotonergic synapse signaling and inhibition of neurotrophin signaling were identified as potential mediators of crosstalk between the placenta and maternal brain and fetal brain, respectively. Genes encoding specific receptors and ligands were predicted to affect functional interactions between the placenta and brain. Paralogous genes, such as sex comb on midleg homolog 1/scm‐like with 4 mbt domains 2 and polycomb group ring finger (Pcgf) 2/Pcgf5, displayed antagonistic regulation between the placenta and brain. Additionally, conditional ablation of forkhead box a2 (Foxa2) in the glands of the uterus altered the transcriptome of the d 15 placenta, which provides novel evidence of crosstalk between the uterine glands and placenta. Furthermore, expression of cathepsin 6 and monocyte to macrophage differentiation associated 2 was significantly different in the fetal brain of Foxa2 conditional knockout mice compared with control mice. These findings provide a better understanding of the intricacies of uterus‐placenta‐brain interactions during pregnancy and provide a foundation and model system for their exploration.—Behura, S. K., Kelleher, A. M., Spencer, T. E. Evidence for functional interactions between the placenta and brain in pregnant mice. FASEB J. 33, 4261–4272 (2019). http://www.fasebj.org

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“…Considered the first major physical embryo‐maternal interaction, successful implantation requires synchronized communication between an embryo that has developed to the blastocyst stage and a receptive uterus . Such coordination is thought to be regulated primarily by soluble factors secreted by maternal tissues.…”

Section: Introductionmentioning

confidence: 99%

Extracellular vesicles and their roles in stem cell biology

2020

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Stem cells use a variety of mechanisms to help maintain their pluripotency and promote self‐renewal, as well as, at the appropriate time, to differentiate into specialized cells. One such mechanism that is attracting significant attention from the stem cell, development, and regenerative medicine research communities involves a form of intercellular communication, specifically, the ability of cells to form and release nontraditional membrane‐enclosed structures, referred to as extracellular vesicles (EVs). There are two major classes of EVs, microvesicles (MVs), which are generated through the outward budding and fission of the plasma membrane, and exosomes, which are formed as multivesicular bodies (MVBs) in the endo‐lysosomal pathway that fuse with the cell surface to release their contents. Although they differ in how they are formed, both MVs and exosomes have been shown to contain a diverse array of bioactive cargo, such as proteins, RNA transcripts, microRNAs, and even DNA, which can be transferred to other cells and promote phenotypic changes. Here, we will describe what is currently known regarding EVs and the roles they play in stem cell biology and different aspects of early development. We will also highlight how the EVs produced by stem cells are being aggressively pursued for clinical applications, including their potential use as therapeutic delivery systems and for their regenerative capabilities.

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Uterine glands coordinate on-time embryo implantation and impact endometrial decidualization for pregnancy success

Cited by 142 publications

References 72 publications

Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

Maternal plasma kisspeptin‐10 level in preeclamptic pregnant women and its relation in changing their reproductive hormones

Evidence for functional interactions between the placenta and brain in pregnant mice

Extracellular vesicles and their roles in stem cell biology

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