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Embryo Implantation and Placental Development 2.0

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (30 November 2023) | Viewed by 6677

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Special Issue Editor

Dr. Luisa Campagnolo

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Guest Editor

Department of Biomedicine and Prevention, Università degli Studi di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy
Interests: mechanisms of embryo implantation; placenta; developmental toxicity of nanomaterials; placental barrier
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Human reproduction has been defined by many as a highly inefficient biological process. This is a consequence of the numerous coordinated and finely regulated molecular pathways which drive the different stages of embryonic development, from fertilization to implantation and placentation. Synchronization between the acquisition of blastocyst competence and uterine receptivity appears a limiting step in implantation, and the timely release of growth factors and cytokines is central for the establishment of a successful pregnancy. Over the last few years, many of the players involved in the regulation of such an intricated process have been identified, and their altered expression in pathological conditions has been recognized in some cases. The role of novel factors is emerging, possibly opening new paths for the interpretation of what is still defined as idiopathic infertility.

As volume 1 of the special issue “Embryo Implantation and Placental Development ” in the International Journal of Molecular Sciences (https://www.mdpi.com/journal/ijms, ISSN 1422-0067, IF 6.208, JCR Category Q1)has been successful, we decided to reopen for msnuscript submissions. This second Issue aims at providing up to date insights into the mechanisms regulating embryo implantation and placental development. In parallel, the special issue also plans to give an overview of our current knowledge on the different signaling pathways governing the early steps of implantation and placentation and on the pathological alterations which may impair the establishment of a physiological pregnancy. Submissions focused on each of these steps, which would contribute to present a comprehensive picture of what has been discovered and what should be further investigated, are welcome. Clinical and basic science contributions, consisting of original papers or reviews, will be equally considered.

Dr. Luisa Campagnolo
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

endometrium
endometrial epithelium
implantation
immunology of implantation
placental development
placental barrier
trophoblast
Epidermal growth factor-like domain 7 (EGFL7)
endothelium
preeclampsia
placentopathies

Published Papers (5 papers)

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Research

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16 pages, 662 KiB

Open AccessArticle

The Impact of Essential Trace Elements on Ovarian Response and Reproductive Outcomes following Single Euploid Embryo Transfer

by Roberto Gonzalez-Martin, Andrea Palomar, Alicia Quiñonero, Nuria Pellicer, Rocio Fernandez-Saavedra, Estefania Conde-Vilda, Alberto J. Quejido, Christine Whitehead, Richard T. Scott, Jr. and Francisco Dominguez

Int. J. Mol. Sci. 2023, 24(13), 10968; https://doi.org/10.3390/ijms241310968 - 30 Jun 2023

Cited by 4 | Viewed by 1402

Abstract

Essential trace elements are required in extremely small amounts and obtained through diet. This research focuses on detecting major trace elements in different biofluids of sixty women undergoing ICSI with PGT-A and SET/FET at IVI-RMA, New Jersey, and assessing their impact on their IVF outcomes. Urine, plasma, and follicular fluid samples were collected on the vaginal oocyte retrieval day to measure the concentrations of eight essential trace elements (copper, zinc, molybdenum, lithium, selenium, manganese, chromium, and iron) using ICP-MS. After analysis, ovarian response and preimplantation outcomes had significant positive associations with both copper alone and the copper/zinc ratio in the follicular fluid and plasma, in addition to plasma manganese. Alternatively, elevated follicular fluid lithium concentrations were significantly associated with poor preimplantation outcomes while the urinary molybdenum concentration was significantly associated with a lower probability of implantation, clinical pregnancy, and live birth. Urinary lithium and chromium concentrations were significantly associated with a lower probability of achieving a live birth. Our results suggest that the essential trace elements present in follicular fluid, plasma, and urine of women are directly associated with their reproductive outcomes, with copper and manganese exerting positive effects and lithium and molybdenum exerting negative effects. Full article

(This article belongs to the Special Issue Embryo Implantation and Placental Development 2.0)

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12 pages, 681 KiB

Open AccessArticle

Phytoestrogens Present in Follicular Fluid and Urine Are Positively Associated with IVF Outcomes following Single Euploid Embryo Transfer

by Roberto Gonzalez-Martin, Andrea Palomar, Alicia Quiñonero, Nuria Pellicer, Caroline Zuckerman, Christine Whitehead, Richard T. Scott, Jr. and Francisco Dominguez

Int. J. Mol. Sci. 2023, 24(13), 10852; https://doi.org/10.3390/ijms241310852 - 29 Jun 2023

Viewed by 1056

Abstract

The impact and safety of phytoestrogens, plant-derived isoflavones with estrogenic activity predominantly present in soy, on female reproductive health and IVF outcomes continues to be hotly debated. In this prospective cohort study, 60 women attending IVI-RMA New Jersey undergoing IVF with single frozen embryo transfer (SET/FET) of good-quality euploid blastocyst after PGT-A analysis were recruited. Concentrations of two phytoestrogens (daidzein and genistein) in follicular fluid (FF) and urine (U) were measured by UPLC–MSMS, both collected on vaginal oocyte retrieval day. These measurements correlated with IVF clinical outcomes. In models adjusted for age, BMI, race/ethnicity, and smoking status, higher FF phytoestrogen concentrations were significantly associated with higher serum estradiol, enhanced probability of implantation, clinical pregnancy, and live birth. Moreover, higher urine phytoestrogen concentrations were significantly associated with improved oocyte maturation and fertilization potential and increased probability of clinical pregnancy and live birth. Finally, higher FF and urine phytoestrogen concentrations were associated with a higher probability of live birth from a given IVF cycle. Our results suggest that dietary phytoestrogens improved reproductive outcomes of women undergoing IVF treatment. However, additional prospective studies are needed to optimize the use of phytoestrogens to further enhance reproductive outcomes and/or protect against reproductive insults. Full article

(This article belongs to the Special Issue Embryo Implantation and Placental Development 2.0)

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23 pages, 2619 KiB

Open AccessArticle

Dynamics of the Equine Placental DNA Methylome and Transcriptome from Mid- to Late Gestation

by Daniela Orellana-Guerrero, José M. Uribe-Salazar, Hossam El-Sheikh Ali, Kirsten E. Scoggin, Barry Ball, Peter Daels, Carrie J. Finno and Pouya Dini

Int. J. Mol. Sci. 2023, 24(8), 7084; https://doi.org/10.3390/ijms24087084 - 11 Apr 2023

Viewed by 1373

Abstract

The placenta is a temporary organ that is essential for the survival of the fetus, with a lifelong effect on the health of both the offspring and the dam. The functions of the placenta are controlled by its dynamic gene expression during gestation. In this study, we aimed to investigate the equine placental DNA methylome as one of the fundamental mechanisms that controls the gene expression dynamic. Chorioallantois samples from four (4M), six (6M), and ten (10M) months of gestation were used to map the methylation pattern of the placenta. Globally, methylation levels increased toward the end of gestation. We identified 921 differentially methylated regions (DMRs) between 4M and 6M, 1225 DMRs between 4M and 10M, and 1026 DMRs between 6M and 10M. A total of 817 genes carried DMRs comparing 4M and 6M, 978 comparing 4M and 10M, and 804 comparing 6M and 10M. We compared the transcriptomes between the samples and found 1381 differentially expressed genes (DEGs) when comparing 4M and 6M, 1428 DEGs between 4M and 10M, and 741 DEGs between 6M and 10M. Finally, we overlapped the DEGs and genes carrying DMRs (DMRs-DEGs). Genes exhibiting (a) higher expression, low methylation and (b) low expression, high methylation at different time points were identified. The majority of these DMRs-DEGs were located in introns (48.4%), promoters (25.8%), and exons (17.7%) and were involved in changes in the extracellular matrix; regulation of epithelial cell migration; vascularization; and regulation of minerals, glucose, and metabolites, among other factors. Overall, this is the first report highlighting the dynamics in the equine placenta methylome during normal pregnancy. The findings presented serve as a foundation for future studies on the impact of abnormal methylation on the outcomes of equine pregnancies. Full article

(This article belongs to the Special Issue Embryo Implantation and Placental Development 2.0)

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14 pages, 2488 KiB

Open AccessArticle

Insulin Elevates ID2 Expression in Trophoblasts and Aggravates Preeclampsia in Obese ASB4-Null Mice

by Yukako Kayashima, W. H. Davin Townley-Tilson, Neeta L. Vora, Kim Boggess, Jonathon W. Homeister, Nobuyo Maeda-Smithies and Feng Li

Int. J. Mol. Sci. 2023, 24(3), 2149; https://doi.org/10.3390/ijms24032149 - 21 Jan 2023

Viewed by 1459

Abstract

Obesity is a risk factor for preeclampsia. We investigated how obesity influences preeclampsia in mice lacking ankyrin-repeat-and-SOCS-box-containing-protein 4 (ASB4), which promotes trophoblast differentiation via degrading the inhibitor of DNA-binding protein 2 (ID2). Asb4^−/− mice on normal chow (NC) develop mild preeclampsia-like phenotypes during pregnancy, including hypertension, proteinuria, and reduced litter size. Wild-type (WT) and Asb4^−/− females were placed on a high-fat diet (HFD) starting at weaning. At the age of 8–9 weeks, they were mated with WT or Asb4^−/− males, and preeclamptic phenotypes were assessed. HFD-WT dams had no obvious adverse outcomes of pregnancy. In contrast, HFD-Asb4^−/− dams had significantly more severe preeclampsia-like phenotypes compared to NC-Asb4^−/− dams. The HFD increased white fat weights and plasma leptin and insulin levels in Asb4^−/− females. In the HFD-Asb4^−/− placenta, ID2 amounts doubled without changing the transcript levels, indicating that insulin likely increases ID2 at a level of post-transcription. In human first-trimester trophoblast HTR8/SVneo cells, exposure to insulin, but not to leptin, led to a significant increase in ID2. HFD-induced obesity markedly worsens the preeclampsia-like phenotypes in the absence of ASB4. Our data indicate that hyperinsulinemia perturbs the timely removal of ID2 and interferes with proper trophoblast differentiation, contributing to enhanced preeclampsia. Full article

(This article belongs to the Special Issue Embryo Implantation and Placental Development 2.0)

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Review

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28 pages, 1181 KiB

Open AccessReview

When the Embryo Meets the Endometrium: Identifying the Features Required for Successful Embryo Implantation

by Valentina Lacconi, Micol Massimiani, Ilenia Carriero, Claudia Bianco, Carlo Ticconi, Valentina Pavone, Alessandra Alteri, Ludovico Muzii, Rocco Rago, Valerio Pisaturo and Luisa Campagnolo

Int. J. Mol. Sci. 2024, 25(5), 2834; https://doi.org/10.3390/ijms25052834 - 29 Feb 2024

Viewed by 804

Abstract

Evaluation of the optimal number of embryos, their quality, and the precise timing for transfer are critical determinants in reproductive success, although still remaining one of the main challenges in assisted reproduction technologies (ART). Indeed, the success of in vitro fertilization (IVF) treatments relies on a multitude of events and factors involving both the endometrium and the embryo. Despite concerted efforts on both fronts, the overall success rates of IVF techniques continue to range between 25% and 30%. The role of the endometrium in implantation has been recently recognized, leading to the hypothesis that both the “soil” and the “seed” play a central role in a successful pregnancy. In this respect, identification of the molecular signature of endometrial receptivity together with the selection of the best embryo for transfer become crucial in ART. Currently, efforts have been made to develop accurate, predictive, and personalized tests to identify the window of implantation and the best quality embryo. However, the value of these tests is still debated, as conflicting results are reported in the literature. The purpose of this review is to summarize and critically report the available criteria to optimize the success of embryo transfer and to better understand current limitations and potential areas for improvement. Full article

(This article belongs to the Special Issue Embryo Implantation and Placental Development 2.0)

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