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New Frontiers in Placental Development and Fetal Growth: Focus on Molecular Regulatory Mechanisms and Pharmacology

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

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 14640

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Special Issue Editors

Dr. Padma Murthi

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Guest Editor

1. Department of Pharmacology, Monash Biomedicine Discovery Institute, Monash University, Melbourne, VIC 3168, Australia
2. Department of Obstetrics and Gynecology, The University of Melbourne, Parkville, VIC 3010, Australia
Interests: placenta; preeclampsia; fetal medicine; fetal growth restriction; fetal development; placental insufficiency
Special Issues, Collections and Topics in MDPI journals

Dr. Nadia Alfaidy

E-Mail Website
Guest Editor

Biology and Biotechnology for Health, Biosanté, INSERM U1292, Grenoble, France
Interests: pregnancy pathologies; biological barriers; inflammasomes; angiogenesis; inflammation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The placenta is the primary regulator of nutrient supply to the growing embryo during gestation. As such, adequate placental development and function are instrumental for fetal development throughout gestation. Malfunctioning of the placenta leads to pregnancy complications including fetal growth restriction (FGR), preeclampsia (PE) and stillbirth. Placental malfunction is also strongly linked with abnormal cardiovascular and brain development in the offspring. Over the last few decades, several methods have been developed aiming to improve placental function and fetal outcome in different clinical and experimental settings. Although accumulating evidence shows the potential positive effects of various protective strategies, multiple challenges remain to be solved.

This Special Issue will cover a selection of original articles and state-of-the-art comprehensive review articles on recent research topics in the field of basic and translational placental research and fetal growth and development. This includes current knowledge in understanding the types of placental defects in pregnancy pathologies, placental physiology and molecular regulators of placental development and function, various in vitro, ex vivo and in vivo model systems available to investigate a broad spectrum of pharmacological treatments using synthetic or biological agents to investigate improved placental function. Clinical trials and studies will also be considered if they deliver mechanistic insights using molecular biological methods. Nevertheless, contributions are not strictly limited to the fields that are mentioned in the keywords.

Dr. Padma Murthi
Dr. Nadia Alfaidy
Guest Editors

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

pregnancy pathologies
placental physiology
placental development
placenta
fetal growth restriction
preeclampsia

Published Papers (6 papers)

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Research

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22 pages, 6314 KiB

Open AccessArticle

Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight

by Oliver C. Watkins, Hannah E. J. Yong, Tania Ken Lin Mah, Victoria K. B. Cracknell-Hazra, Reshma Appukuttan Pillai, Preben Selvam, Neha Sharma, Amaury Cazenave-Gassiot, Anne K. Bendt, Keith M. Godfrey, Rohan M. Lewis, Markus R. Wenk and Shiao-Yng Chan

Int. J. Mol. Sci. 2022, 23(15), 8685; https://doi.org/10.3390/ijms23158685 - 4 Aug 2022

Cited by 4 | Viewed by 2175

Abstract

Pregnancy complications such as maternal hyperglycemia increase perinatal mortality and morbidity, but risks are higher in males than in females. We hypothesized that fetal sex-dependent differences in placental palmitic-acid (PA) and oleic-acid (OA) metabolism influence such risks. Placental explants (n = 22) were incubated with isotope-labeled fatty acids (¹³C-PA or ¹³C-OA) for 24 or 48 h and the production of forty-seven ¹³C-PA lipids and thirty-seven ¹³C-OA lipids quantified by LCMS. Linear regression was used to investigate associations between maternal glycemia, BMI and fetal sex with ¹³C lipids, and between ¹³C lipids and birthweight centile. Placental explants from females showed greater incorporation of ¹³C-OA and ¹³C-PA into almost all lipids compared to males. Fetal sex also influenced relationships with maternal glycemia, with many ¹³C-OA and ¹³C-PA acylcarnitines, ¹³C-PA-diacylglycerols and ¹³C-PA phospholipids positively associated with glycemia in females but not in males. In contrast, several ¹³C-OA triacylglycerols and ¹³C-OA phospholipids were negatively associated with glycemia in males but not in females. Birthweight centile in females was positively associated with six ¹³C-PA and three ¹³C-OA lipids (mainly acylcarnitines) and was negatively associated with eight ¹³C-OA lipids, while males showed few associations. Fetal sex thus influences placental lipid metabolism and could be a key modulator of the impact of maternal metabolic health on perinatal outcomes, potentially contributing toward sex-specific adaptions in which females prioritize survival. Full article

(This article belongs to the Special Issue New Frontiers in Placental Development and Fetal Growth: Focus on Molecular Regulatory Mechanisms and Pharmacology)

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9 pages, 1931 KiB

Open AccessArticle

Androgens Upregulate Pathogen-Induced Placental Innate Immune Response

by Seline Vancolen, Taghreed Ayash, Mariela Segura, Marie-Julie Allard, Bernard Robaire and Guillaume Sébire

Int. J. Mol. Sci. 2022, 23(9), 4978; https://doi.org/10.3390/ijms23094978 - 29 Apr 2022

Cited by 3 | Viewed by 1679

Abstract

Group B Streptococcus (GBS) is a leading cause of placental infection, termed chorioamnionitis. Chorioamnionitis is associated with an increased risk of neurobehavioral impairments, such as autism spectrum disorders, which are more prominent in males than in female offspring. In a pre-clinical model of chorioamnionitis, a greater inflammatory response was observed in placenta associated with male rather than female fetuses, correlating with the severity of subsequent neurobehavioral impairments. The reason for this sex difference is not understood. Our hypothesis is that androgens upregulate the placental innate immune response in male fetuses. Lewis dams were injected daily from gestational day (G) 18 to 21 with corn oil (vehicle) or an androgen receptor antagonist (flutamide). On G 19, dams were injected with saline (control) or GBS. Maternal, fetal sera and placentas were collected for protein assays and in situ analyses. Our results showed that while flutamide alone had no effect, a decrease in placental concentration of pro-inflammatory cytokines and infiltration of polymorphonuclear cells was observed in flutamide/infected compared to vehicle/infected groups. These results show that androgens upregulate the placental innate immune response and thus may contribute to the skewed sex ratio towards males observed in several developmental impairments resulting from perinatal infection/inflammation. Full article

(This article belongs to the Special Issue New Frontiers in Placental Development and Fetal Growth: Focus on Molecular Regulatory Mechanisms and Pharmacology)

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17 pages, 2300 KiB

Open AccessArticle

Placental Transcription Profiling in 6–23 Weeks’ Gestation Reveals Differential Transcript Usage in Early Development

by Konstantinos J. Bogias, Stephen M. Pederson, Shalem Leemaqz, Melanie D. Smith, Dale McAninch, Tanja Jankovic-Karasoulos, Dylan McCullough, Qianhui Wan, Tina Bianco-Miotto, James Breen and Claire T. Roberts

Int. J. Mol. Sci. 2022, 23(9), 4506; https://doi.org/10.3390/ijms23094506 - 19 Apr 2022

Cited by 3 | Viewed by 2704

Abstract

The human placenta is a rapidly developing transient organ that is key to pregnancy success. Early development of the conceptus occurs in a low oxygen environment before oxygenated maternal blood begins to flow into the placenta at ~10–12 weeks’ gestation. This process is likely to substantially affect overall placental gene expression. Transcript variability underlying gene expression has yet to be profiled. In this study, accurate transcript expression profiles were identified for 84 human placental chorionic villus tissue samples collected across 6–23 weeks’ gestation. Differential gene expression (DGE), differential transcript expression (DTE) and differential transcript usage (DTU) between 6–10 weeks’ and 11–23 weeks’ gestation groups were assessed. In total, 229 genes had significant DTE yet no significant DGE. Integration of DGE and DTE analyses found that differential expression patterns of individual transcripts were commonly masked upon aggregation to the gene-level. Of the 611 genes that exhibited DTU, 534 had no significant DGE or DTE. The four most significant DTU genes ADAM10, VMP1, GPR126, and ASAH1, were associated with hypoxia-responsive pathways. Transcript usage is a likely regulatory mechanism in early placentation. Identification of functional roles will facilitate new insight in understanding the origins of pregnancy complications. Full article

(This article belongs to the Special Issue New Frontiers in Placental Development and Fetal Growth: Focus on Molecular Regulatory Mechanisms and Pharmacology)

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Review

Jump to: Research

16 pages, 2153 KiB

Open AccessReview

Association of Vascular Endothelial Growth Factors (VEGFs) with Recurrent Miscarriage: A Systematic Review of the Literature

by Nadine Abu-Ghazaleh, Shaun Brennecke, Padma Murthi and Vijaya Karanam

Int. J. Mol. Sci. 2023, 24(11), 9449; https://doi.org/10.3390/ijms24119449 - 29 May 2023

Cited by 2 | Viewed by 1471

Abstract

Recurrent miscarriage (RM) can be defined as two or more consecutive miscarriages before 20 weeks’ gestation. Vascular endothelial growth factors (VEGFs) play an important role in endometrial angiogenesis and decidualization, prerequisites for successful pregnancy outcomes. We conducted a systematic review of the published literature investigating the role of VEGFs in RM. In particular, we explored the methodological inconsistencies between the published reports on this topic. To our knowledge, this is the first systematic literature review to examine the role of VEGFs in RM. Our systematic search followed PRISMA guidelines. Three databases, Medline (Ovid), PubMed, and Embase, were searched. Assessment-bias analyses were conducted using the Joanna Bigger Institute critical appraisal method for case-control studies. Thirteen papers were included in the final analyses. These studies included 677 cases with RM and 724 controls. Endometrial levels of VEGFs were consistently lower in RM cases compared to controls. There were no consistent significant findings with respect to VEGFs levels in decidua, fetoplacental tissues, and serum when RM cases were compared to controls. The interpretation of studies that explored the relationship between VEGFs and RM is hampered by inconsistencies in defining clinical, sampling, and analytical variables. To clarify the association between VEGF and RM in future studies, researchers ideally should use similarly defined clinical groups, similar samples collected in the same way, and laboratory analyses undertaken using the same methods. Full article

(This article belongs to the Special Issue New Frontiers in Placental Development and Fetal Growth: Focus on Molecular Regulatory Mechanisms and Pharmacology)

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15 pages, 1031 KiB

Open AccessReview

Chromogranin A: An Endocrine Factor of Pregnancy

by Michalina Bralewska, Tadeusz Pietrucha and Agata Sakowicz

Int. J. Mol. Sci. 2023, 24(5), 4986; https://doi.org/10.3390/ijms24054986 - 5 Mar 2023

Cited by 1 | Viewed by 1728

Abstract

Pregnancy is a state of physiological and hormonal changes. One of the endocrine factors involved in these processes is chromogranin A, an acidic protein produced, among others, by the placenta. Although it has been previously linked to pregnancy, no existing articles have ever managed to clarify the role of this protein regarding this subject. Therefore, the aim of the present study is to gather knowledge of chromogranin A’s function with reference to gestation and parturition, clarify elusive information, and, most importantly, to formulate hypotheses for the future studies to verify. Full article

(This article belongs to the Special Issue New Frontiers in Placental Development and Fetal Growth: Focus on Molecular Regulatory Mechanisms and Pharmacology)

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18 pages, 1326 KiB

Open AccessReview

Human Chorionic Villous Differentiation and Placental Development

by Junya Kojima, Masanori Ono, Naoaki Kuji and Hirotaka Nishi

Int. J. Mol. Sci. 2022, 23(14), 8003; https://doi.org/10.3390/ijms23148003 - 20 Jul 2022

Cited by 17 | Viewed by 3936

Abstract

In humans, the placenta provides the only fetomaternal connection and is essential for establishing a pregnancy as well as fetal well-being. Additionally, it allows maternal physiological adaptation and embryonic immunological acceptance, support, and nutrition. The placenta is derived from extra-embryonic tissues that develop rapidly and dynamically in the first weeks of pregnancy. It is primarily composed of trophoblasts that differentiate into villi, stromal cells, macrophages, and fetal endothelial cells (FEC). Placental differentiation may be closely related to perinatal diseases, including fetal growth retardation (FGR) and hypertensive disorders of pregnancy (HDP), and miscarriage. There are limited findings regarding human chorionic villous differentiation and placental development because conducting in vivo studies is extremely difficult. Placental tissue varies widely among species. Thus, experimental animal findings are difficult to apply to humans. Early villous differentiation is difficult to study due to the small tissue size; however, a detailed analysis can potentially elucidate perinatal disease causes or help develop novel therapies. Artificial induction of early villous differentiation using human embryonic stem (ES) cells/induced pluripotent stem (iPS) cells was attempted, producing normally differentiated villi that can be used for interventional/invasive research. Here, we summarized and correlated early villous differentiation findings and discussed clinical diseases. Full article

(This article belongs to the Special Issue New Frontiers in Placental Development and Fetal Growth: Focus on Molecular Regulatory Mechanisms and Pharmacology)

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