Investigating the global research landscape, barriers, and facilitators of scientific productivity in fetal membrane research | Placenta and Reproductive Medicine

Investigating the global research landscape, barriers, and facilitators of scientific productivity in fetal membrane research

Global fetal membrane research

Authors

  • Mariana de C. Silva Department of Pathology, Botucatu Medical School, Universidade Estadual Paulista, UNESP, Botucatu, São Paulo, Brazil
  • Giovana F. C. Bento Department of Pathology, Botucatu Medical School, Universidade Estadual Paulista, UNESP, Botucatu, São Paulo, Brazil
  • Vitória C. Troitino Department of Pathology, Botucatu Medical School, Universidade Estadual Paulista, UNESP, Botucatu, São Paulo, Brazil
  • Ramkumar Menon Division of Basic Science & Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX, USA
  • Ourlad Alzeus Tantengco University of the Philippines Manila

DOI:

https://doi.org/10.54844/prm.2023.0391

Keywords:

amnion, bibliometrics, chorion, obstetrics, pregnancy, preterm birth

Abstract

Fetal membrane (FM; amniochorion) studies are an essential field of research for understanding their role during pregnancy maintenance and mechanisms associated with parturition. This paper determined the landscape and characteristics of published FM research, identified socioeconomic indicators related to FM research productivity and impact and proposed major studies using this tissue. A review of the literature about FM from 2000 to 2021 was performed using the Scopus database. Bibliometric information was obtained from Scopus, statistical analysis was conducted using GraphPad Prism, and network visualization was conducted using VOSviewer software. A total of 1131 articles were analyzed in this study. The number of publications in the past decade increased linearly. Most of the research outputs were produced by researchers from the United States of America (USA), followed by China and Australia. The most productive institutions were primarily from the USA and Australia. The current research trends based on keywords analysis were related to FM weakening, such as aging, bacterial infections and inflammations, biomechanical weakening, exosomes, immunomodulation, and sterile inflammation. Gross domestic product and the number of collaborations with other countries were the most significantly correlated indicators with increased scientific productivity and impact in FM research. We emphasize the need to increase investment and support to researchers doing FM studies, especially in developing countries. These will contribute to advancing this field and may help provide more evidence to control and manage pregnancy complications, such as preterm premature rupture of membranes and preterm birth.

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Published

2023-09-27

How to Cite

1.
Silva M de C, Bento GFC, Troitino VC, Menon R, Tantengco OA. Investigating the global research landscape, barriers, and facilitators of scientific productivity in fetal membrane research: Global fetal membrane research. PRM. 2023;2. doi:10.54844/prm.2023.0391

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Vol. 2 (2023)

Section

Review Article

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REVIEW ARTICLE

Investigating the global research landscape, barriers, and facilitators of scientific productivity in fetal membrane research


Mariana de C. Silva1, Giovana F. C. Bento1,2, Vitória C. Troitino1, Ramkumar Menon2, Ourlad Alzeus G. Tantengco3,4

1Department of Pathology, Botucatu Medical School, Universidade Estadual Paulista, UNESP, Botucatu 18600-000, São Paulo, Brazil;

2Division of Basic Science & Translational Research, Department of Obstetrics & Gynecology, The University of Texas Medical Branch at Galveston, Galveston, TX 77555, USA;

3Department of Physiology, College of Medicine, University of the Philippines Manila, Manila 1000, Philippines;

4Department of Biology, College of Arts and Sciences, University of the Philippines Manila, Manila 1000, Philippines.


Corresponding Author:

Ph.D. Ourlad Alzeus G. Tantengco, Email: ogtantengco@up.edu.ph; http://orcid.org/0000-0002-4535-8837


Received: 2 May 2023 Accepted: 30 August 2023 Published: 27 September 2023


ABSTRACT

Fetal membrane (FM; amniochorion) studies are an essential field of research for understanding their role during pregnancy maintenance and mechanisms associated with parturition. This paper determined the landscape and characteristics of published FM research, identified socioeconomic indicators related to FM research productivity and impact and proposed major studies using this tissue. A review of the literature about FM from 2000 to 2021 was performed using the Scopus database. Bibliometric information was obtained from Scopus, statistical analysis was conducted using GraphPad Prism, and network visualization was conducted using VOSviewer software. A total of 1131 articles were analyzed in this study. The number of publications in the past decade increased linearly. Most of the research outputs were produced by researchers from the United States of America (USA), followed by China and Australia. The most productive institutions were primarily from the USA and Australia. The current research trends based on keywords analysis were related to FM weakening, such as aging, bacterial infections and inflammations, biomechanical weakening, exosomes, immunomodulation, and sterile inflammation. Gross domestic product and the number of collaborations with other countries were the most significantly correlated indicators with increased scientific productivity and impact in FM research. We emphasize the need to increase investment and support to researchers doing FM studies, especially in developing countries. These will contribute to advancing this field and may help provide more evidence to control and manage pregnancy complications, such as preterm premature rupture of membranes and preterm birth.

Key words: amnion, bibliometrics, chorion, obstetrics, pregnancy, preterm birth

INTRODUCTION

The human fetal membrane (FM) represents the tissue that overlays the amniotic cavity.[1] It comprises two layers of cells, the amnion cells and the chorion trophoblast cells[2,3] (Figure 1). Both layers are connected by an extracellular matrix (ECM), rich in various collagens and mesenchymal cells, creating a barrier capable of maintaining and protecting the fetus during the gestational period.[1,4] The two cell layers are attached to the ECM through a Type Ⅳ collagen-rich basement membrane. The end of pregnancy is characterized by a physiological mechanism of labor resulting from complex events involving the endocrine and immune systems.[5] During parturition, the FM undergoes a process of weakening and rupture, accompanied by a pro-inflammatory response.[1,4]

Figure 1

Figure 1. Schematic structure of the fetal membrane. The amnion represents the innermost layer, composed of epithelial cells (purple), which are connected to the basement membrane (red strips) and compact layer (red) and amnion mesenchymal cells (green). The outer layer, called the chorion layer, is composed of the reticular layer (green) and chorion trophoblast cells.

Despite the worldwide research efforts in understanding preterm birth (PTB) and preterm premature rupture of membranes (pPROM), the causes, risk factors, pathways, and effective management remain unclear. A possible explanation is the complexity and heterogeneity of the pathophysiology involving PTB and pPROM.[6–8] PTB can be caused by multiple etiologies, including cervicovaginal infection that can lead to intraamniotic infection, sterile inflammation, autoimmune diseases, cervical insufficiency, placental abruption, multifetal pregnancy, and preeclampsia.[8,9] Furthermore, most studies related to spontaneous PTB (SPTB) tend to investigate the maternal tissues, while the role of the FM in SPTB has been emerging in the past decades.

The limited number of studies focused on FM research can be attributed to several challenges. Obtaining FM tissues during pregnancy presents practical difficulties, primarily feasible only in cases of preterm delivery. However, preterm deliveries are frequently accompanied by complications like infection, sterile inflammation, and preeclampsia. These complications can introduce confounding variables that affect the outcomes of FM studies. Additionally, acquiring intact FM tissues for research purposes proves challenging, often requiring samples from term pregnancies that are not in labor, which are typically accessible during elective Cesarean deliveries.[10] Furthermore, existing animal models used for FM research lack the accurate histological resemblance and rupture physiology to human FM tissues.[11]

There is still no systematic analysis of worldwide research trends in FMs. Bibliometric analysis is a review methodology that can identify authors, researchers, and collaborations related to a specific topic in a quantitative manner.[12] It can be a valuable tool to help the scientific community identify possible gaps and trends in the FM field. This method has been applied in research in obstetrics and gynecology,[13,14] cervical remodeling during pregnancy,[15] and preeclampsia.[16] Since FMs are functionally highly relevant tissues and their role in pregnancy, parturition at term and preterm are rapidly emerging. This paper determined the landscape and characteristics of published FM research. This study also proposed future research areas to understand the contribution of FM in pregnancy and parturition. We also identified socioeconomic indicators associated with FM research productivity and impact.

METHODS

A systematic review of the literature was performed using the Scopus database. Scopus is one of the largest databases of research articles. The search strategy can be found in the supplementary materials. All electronic searches were performed from February to March 2022. All FM-related articles from 2000 to 2021 were included in the study. The following information was obtained for each article: authors, year of publication, title, journal, institution, country, title, keywords, citation frequency, source of funding, and subject area of the FM studies. These were used to investigate FM research's knowledge domain and development trends worldwide.

Four publication indicators were used to evaluate the publication performance of countries and institutions: total number of articles (TP), total number of citations (TC) until the time of database search in Scopus, citations per paper (TP/TC, CPP) and number of papers with citation number ≥ H (h-index).

Spearman's rank-order correlation determined correlations between country-specific characteristics with the different bibliometric indices. The socioeconomic indicators were obtained from the World Bank. The Spearman's correlation coefficient (ρ) was considered significant if the P-value was less than 0.05. This statistical analysis was done using GraphPad Prism software (version 8.0.1, GraphPad Software, San Diego, CA). The visualization of collaboration networks of countries and keywords used for FM research was conducted using VOSviewer (version 1.6.16, Leiden University, Leiden, Netherlands).[17]

RESULTS

Trends over time of FM publications

We obtained 1131 articles related to the FM in the Scopus database from 2000 to 2021. We observed an increase in the research outputs on FM starting in 2010, which peaked in 2020 (Figure 2).

Figure 2

Figure 2. Annual number of research outputs in fetal membrane research from 2000 to 2021.

FM publications by country

The most productive countries in FM research were the USA with 368 papers, which received 10,154 citations, followed by China with 116 publications and 1176 citations, and Australia with 108 publications and 3046 citations. Canada had the highest citations per publication at 36.94, while the USA had the highest h-index at 56 (Table 1).

Table 1: Most productive and influential countries in fetal membrane research
Country TP TC CPP h-index
United States 368 10154 27.59 56
China 116 1176 10.14 19
Australia 108 3046 28.20 29
United Kingdom 90 4105 45.61 32
Japan 71 1519 21.39 20
Canada 49 1810 36.94 24
Brazil 40 507 12.68 13
Germany 38 928 24.42 18
France 35 649 18.54 15
Italy 35 716 20.46 16
Switzerland 35 968 27.66 19
Turkey 35 217 6.20 7
TP: total number of articles; TC: total number of citations; CPP: citations per paper

Figure 3 shows the inter-country collaboration for FM research. We observed a strong linkage between the most productive countries, including the USA, China, and Canada. These countries also had the highest number of FM articles with international co-authorship.

Figure 3

Figure 3. Network visualization of international collaboration for fetal membrane research. The size of the circle is proportional to the number of collaborations in the cooperation network. The thickness of the lines indicates the link strength between countries.

FM publications by institutions

The most productive institutions were the University of Texas Medical Branch at Galveston, USA, with 57 papers and 1353 citations, followed by the University of Melbourne, Australia, with 52 papers and 1419 citations, and Mercy Hospital for Women, Australia, with 43 papers and 1197 citations (Table 2). These institutions were also from the most productive countries in FM research.

Table 2: Most productive and influential institutions in fetal membrane research
Institution Location TP TC CPP h-index
University of Texas Medical Branch at Galveston USA 57 1353 23.74 23
University of Melbourne Australia 52 1419 27.29 19
Mercy Hospital for Women Australia 43 1197 27.84 17
Monash University Australia 29 1065 36.72 17
Case Western Reserve University USA 27 1084 40.15 17
Instituto Nacional de Perinatologia Mexico 24 785 32.71 15
Hudson Institute of Medical Research Australia 23 972 42.26 16
Yale School of Medicine USA 22 701 31.86 15
University of Toronto Canada 21 915 43.57 15
Perinatal Research Center USA 20 878 43.90 15
Imperial College London UK 20 957 47.85 16
Oregon Health & Science University USA 20 352 17.60 10
UniversitatsSpital Zurich Switzerland 20 454 22.70 14
Shanghai Jiao Tong University China 20 213 10.65 9
TP: total number of articles; TC: total number of citations; CPP: citations per paper

FM publications by categories and journals

Most of the published articles on FM research were classified in Scopus in the field of Medicine (72.59%), Biochemistry, Genetics, and Molecular Biology (42.53%), and Agricultural and Biological Sciences (7.96%). Interestingly, there were also studies classified as Engineering (4.86%), Pharmacology, Toxicology, Pharmaceutics (2.65%), and Materials Science (2.03%) (Supplementary Figure 1).

The most productive journal in FM research was Placenta, with 85 publications and 2543 citations (Table 3). On the other hand, the most-cited journal was the American Journal of Obstetrics and Gynecology, with 2835 total citations and an h-index of 35. The Journal of Clinical Endocrinology and Metabolism had the highest citations per paper (TC/TP) at 51.53.

Table 3: Most productive and influential journals that published fetal membrane research
Journal TP TC CPP h-index
Placenta 85 2543 29.92 32
American Journal of Obstetrics and Gynecology 57 2853 50.05 35
Biology of Reproduction 40 1984 49.60 24
Reproductive Sciences 36 579 16.08 14
Molecular Human Reproduction 31 1571 50.68 18
American Journal of Reproductive Immunology 28 482 17.21 13
Plos One 23 651 28.30 14
Journal of Clinical Endocrinology and Metabolism 19 979 51.53 16
Journal of Maternal Fetal and Neonatal Medicine 19 160 8.42 6
Journal of the Society for Gynecologic Investigation 16 479 29.94 12
TP: total number of articles; TC: total number of citations; CPP: citations per paper

Research funding for FM research

During the 21st century, 159 funding agencies supported FM research (Supplementary Figure 2). The Eunice Kennedy Shriver National Institute of Child Health and Human Development in the USA provided funding for 128 FM research outputs. This accounts for 11.31% of the total FM research outputs in the 21st century. The National Institutes of Health supported 113 research outputs, the US Department of Health and Human Services funded 39 research outputs (3.45%), the UK National Health and Medical Research Council funded 36 research outputs (3.18%), and the National Natural Science Foundation of China supported 33 research outputs (2.92%).

FM research trends

Network visualization using VOSViewer was performed to determine the evolution of keywords used in FM research from 2000 to 2021 (Figure 4). During the early years of the 21st century, the keywords used include tissues and cells involved in pregnancy and parturition, such as cervix, uterus, trophoblast, and leukocytes. It also had keywords about the mechanism of labor, such as cytokines, interleukin (IL)-1β, lipopolysaccharide, MMP-9, and prostaglandin. From 2010 to 2015, the most common keywords include biomechanics, inflammation, oxidative stress, thrombin, and tumor necrosis factor-α. The most recent keywords in FM research include other compounds and cytokines involved in FM weakening, such as α-lipoic acid and granulocyte-macrophage colony-stimulating factor. Some current keywords were related to new concepts associated with FM weakening, such as aging, bacteria, biomechanical weakening, exosomes, immunomodulation, and sterile inflammation.

Figure 4

Figure 4. Network visualization of author keywords linked to fetal membrane research.

Country-specific socioeconomic indicators associated with scientific productivity in FM research

Correlation analysis was performed to determine the socioeconomic indicators associated with increased scientific productivity in FM research (Table 4). We observed that the gross domestic product (GDP) (TP: r = 0.7987; TC: r = 0.7559; CPP: r = 0.5112; h-index: r = 0.7695) and the number of collaborations with other countries (TP: r = 0.8016; TC: r = 0.7879; CPP: r = 0.4996; h-index: r = 0.7848) were the most significantly correlated with increased scientific productivity and research impact. Other socioeconomic indicators such as the country's GDP per capita, research and development (R&D) expenditure, physicians per million people, and researchers in R&D per million people also positively correlated with increased research outputs in FM research.

Table 4: Correlation analysis between socioeconomic indicators and scientific productivity and impact of fetal membrane research
Country-specific characteristics Bibliometric indices r P-value
Gross domestic product (GDP) TP 0.7987 <0.001
TC 0.7559 <0.001
CPP 0.5112 <0.001
h-index 0.7695 <0.001
GDP per capita TP 0.3885 0.002
TC 0.527 <0.001
CPP 0.6415 <0.001
h-index 0.4618 <0.001
R&D expenditure (% GDP) TP 0.5116 <0.001
TC 0.569 <0.001
CPP 0.4384 <0.001
h-index 0.5326 <0.001
Physicians (per million people) TP 0.2932 0.035
TC 0.4077 <0.001
CPP 0.5276 <0.001
h-index 0.3341 <0.001
Researcher in R&D (per million people) TP 0.4513 0.001
TC 0.5459 <0.001
CPP 0.5639 <0.001
h-index 0.4973 <0.001
International collaborations TP 0.8016 <0.001
TC 0.7879 <0.001
CPP 0.4996 <0.001
h-index 0.7848 <0.001
R&D: research and development; TP: total number of articles; TC: total number of citations; CPP: citations per paper

DISCUSSION

This study observed a linear increase in published research on FMs. From 2000 to the end of 2021, there were 1131 articles. This trend paralleled the general increase in the research publications in obstetrics and gynecology.[13] This study showed that the most productive institutions in FM research were from developed countries. The USA still has higher proportions of publications and elite researchers in the past years.[18] There was limited evidence and information from developing countries, especially countries with higher adverse pregnancy outcomes. This regional imbalance in knowledge generation will hinder our understanding of the pathologic conditions involving FMs (i.e., chorioamnionitis, intraamniotic infection, and pPROM) associated with adverse pregnancy outcomes. Our study showed that the country's GDP per capita, R&D expenditure, and the number of researchers were correlated with scientific productivity in FM research. This result agrees with previous bibliometric analyses that reported that financial support and human resources are necessary factors linked to research productivity.[19–21] Therefore, we emphasize the need for financial support to improve FM research in developing countries. This financial support should focus on research facilities and researchers' training and capacity building.

Academic and scientific societies such as the American Society for Reproductive Immunology, Fetal Membrane Society, International Federation of Placenta Associations, Preterm Birth International Collaborative Inc., and Society for Reproductive Investigation also play a considerable role in advancing our knowledge on the role of FM in pregnancy. These societies support investigative research in FM and are usually more common in developed countries than in developing countries. Hence, strengthening the presence of these academic societies in developing countries may increase FM research and promote advancements in the field.

This study also showed that the most productive countries in FM research have more international collaborations. This result emphasizes the role of partnerships in increasing the research outputs and scientific impact of FM research in a country.[22] Previous bibliometric analyses also showed that the research groups and institutions open to collaboration have higher research outputs and scientific impact.[19,21] Furthermore, collaborations promote better research quality, broader connections for future works, and increased knowledge.[23,24] Therefore, researchers from developing countries should consider forming partnerships and collaborations with researchers in productive countries in FM research.

The most influential journals that published articles related to FM research were written in English. Most of the top journals that published FM research were specialty journals related to obstetrics, gynecology, and reproductive sciences. These journals also have reasonable impact factors and are indexed in reputable databases. This result shows that FM researchers prefer publishing in specialty journals targeting reproductive science researchers. Previous studies showed that the relevance of the research field, impact factors, and indexation are the primary determinants of the submission choice of seasoned authors for publishing their research results.[25,26] The FM can be a helpful research model for understanding its structure, function, and biomechanics, enabling a relevant comprehension of term and preterm parturition. Furthermore, it can provide a set of immune and endocrine functions and a stem cell source, making the FM a vital model to study. Based on the most common keywords used in the recently published articles in the FM, the current trends and potential direction of FM research were on aging, bacteria, biomechanical weakening, exosomes, immunomodulation, and sterile inflammation. These keywords inform us of the current trends and potential areas of investigation in FM research. The role of aging and senescence in FM weakening and rupture have been extensively studied. Senescent cells, due to changes in their phenotypes, can produce a set of biomarkers,[27] such as cytokines, chemokines, and growth factors, forming the senescence-associated secretory phenotype, increasing the pro-inflammatory profile and leading to labor.[28] The aging of the FM, related to the senescence process, has been associated with labor induction signaling.[29]

The role of biomechanical weakening of the FMs has been previously studied.[30,31] Different research groups a combined biochemical, histologic, and bioengineering approaches to understanding the physiologic mechanisms involved in FM weakening and rupture. These ex vivo studies using human FM tissues studies demonstrated that cytokines, such as granulocyte-macrophage colony-stimulating factor, thrombin, and tumor necrosis factor-alpha, promote inflammation and collagen degradation in the FMs.[31–35]

Extracellular vesicles (EVs), including exosomes and microvesicles, have been shown to function in paracrine signaling to promote fetal and maternal inflammation in pregnancy and parturition. [36–39]In vivo studies in animal models, in vitro studies using monoculture and organ-on-a-chip devices (OOC), and clinical studies on the functional role of different EVs from gestational tissues and cells, trafficking in the feto-maternal interface, and mechanisms of biogenesis will advance the knowledge in the field, including the application of EVs as a diagnostic or prognostic biomarker in pregnancy.[40–43]

Lastly, in vitro, in vivo, and clinical studies on the role of sterile inflammation and infection in FMs also increased in the past few years.[44–46] Damage-associated molecular patterns, such as uric acid, high-mobility group box 1 (HMGB1), IL-1, and cell-free fetal DNA, were implicated in inflammation in FM.[47] Moreover, oxidative stress can promote sterile inflammation and increase inflammatory markers, such as Nrf2 and HMGB1, and an alarmin.[44–46] The response of FM cells against some species, such as genital mycoplasmas,[48,49]Streptococcus agalactiae,[50] and Escherichia coli[51] was also studied since intra-amniotic infection and inflammation are closely related to PTB and a critical matter to the obstetrics field.

Aside from these current research trends, we propose new models and systems to study the role of FM in pregnancy and parturition. Microfluidic organs-on-a-chip that mimic the FM have recently gained much interest and attention.[52–54] These devices mimic the physiologic microenvironment of tissues and organs. The amnion membrane OOC and feto-maternal interface OOC (FMi-OOC), which mimic the different layers of the FMs (i.e., amnion epithelial, amnion mesenchymal, chorion trophoblast, and decidual cells), have helped study infection, inflammation, and EV-mediated signaling in the different FM cellular layers. FMi-OOC has also been helpful in pharmacokinetic studies (e.g., rosuvastatin and pravastatin). Statins permeated the maternal–fetal cell layers of the FMi-OOC and demonstrated cell and time-specific statin metabolites from various cell types without causing any cytotoxicity in the FM cells.[55,56] OOC devices were also used in studying FM cellular response to environmental toxins, such as cadmium. Recently, studies using 3D culture of FM cells are also increasing to optimize therapeutic techniques for PTB.[57,58] These newer models will improve our understanding of FM biology and its role in pregnancy and parturition.

The utility of FMs was well recognized outside the field of reproduction and perinatal medicine.[59,60] Stem cell properties of this tissue are useful to investigators and industries in regenerative medicine. Multipotent fetal stem cells have gained significant attention in the realm of reproductive biology research and clinical applications, particularly in the context of tissue repair and regeneration. Utilizing FMs as a source of these stem cells carries distinct advantages, primarily due to the absence of ethical concerns and stringent legal limitations often associated with other sources. FMs hold the potential for banking these multipotent stem cells for later autologous utilization. This approach offers the prospect of harnessing these cells for therapeutic purposes in an individual's future, contributing to personalized medicine and long-term health management.[60,61] The articles published in this area are not considered for this review.

CONCLUSION

FMs are traditionally ignored tissue by perinatal and reproductive biologists for research purposes to understand pregnancy and parturition. FM studies were ignored with the notion that FMs are a mere extension of the placenta, and exclusive studies using FM are necessary. This has led to misclassification of this tissue, lack of funding for its research, and produced a plethora of data using placental cells that were wrongfully denoted as FM data. A handful of investigators have helped steer this field of research in the past couple of decades, and their attempts have been fruitful, as seen in this bibliometric analysis. This bibliometric analysis showed a linear increase in FM research worldwide. Most significant research outputs were conducted by institutions from developed countries, with the USA as the most productive country in FM research. Countries from South America and Africa lacked substantial scientific outputs in the FM field. This study showed that economic status, research funding, and international collaborations are significantly associated with scientific productivity in FM research. We emphasize the need to increase investment and support to researchers doing FM studies, especially in developing countries. These will contribute to advancing this field and may help provide more evidence to control and manage pregnancy complications, such as pPROM and PTB.

DECLARATIONS

Supplementary materials

Supplementary materials mentioned in this article are online available at the journal’s official site only.

Author contributions

de C. Silva M, Bento GFC, Troitino VC, and Tantengco OAG performed the systematic review, analyzed the data, and wrote the manuscript. Menon R helped in analyzing and interpreting the data and writing the manuscript. All authors read and approved the final manuscript.

Source of funding

This research received no external funding.

Consent to participate

Not applicable

Ethics approval

Not applicable.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Availability of data and material

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

REFERENCES

  1. Menon R, Richardson LS, Lappas M. Fetal membrane architecture, aging and inflammation in pregnancy and parturition. Placenta. 2019;79:40–45.    DOI: 10.1016/j.placenta.2018.11.003    PMID: 30454905
  2. Leal-Marin S, Kern T, Hofmann N, et al. Human Amniotic Membrane: a review on tissue engineering, application, and storage. J Biomed Mater Res B Appl Biomater. 2021;109(8):1198–1215.    DOI: 10.1002/jbm.b.34782    PMID: 33319484
  3. Richardson LS, Radnaa E, Urrabaz-Garza R, Lavu N, Menon R. Stretch, scratch, and stress: Suppressors and supporters of senescence in human fetal membranes. Placenta. 2020;99:27–34.    DOI: 10.1016/j.placenta.2020.07.013    PMID: 32750642
  4. Menon R, Moore JJ. Fetal membranes, not a mere appendage of the placenta, but a critical part of the fetal-maternal interface controlling parturition. Obstet Gynecol Clin North Am. 2020;47(1):147–162.    DOI: 10.1016/j.ogc.2019.10.004    PMID: 32008665
  5. Liao JB, Buhimschi CS, Norwitz ER. Normal labor: mechanism and duration. Obstet Gynecol Clin North Am. 2005;32(2):145–164,vii.    DOI: 10.1016/j.ogc.2005.01.001    PMID: 15899352
  6. Goldenberg RL, Hauth JC, Andrews WW. Intrauterine infection and preterm delivery. N Engl J Med. 2000;342(20):1500–1507.    DOI: 10.1056/NEJM200005183422007    PMID: 10816189
  7. Goldenberg RL, Gravett MG, Iams J, et al. The preterm birth syndrome: issues to consider in creating a classification system. Am J Obstet Gynecol. 2012;206(2):113–118.    DOI: 10.1016/j.ajog.2011.10.865    PMID: 22177186
  8. Goldenberg RL, Culhane JF, Iams JD, Romero R. Epidemiology and causes of preterm birth. Lancet. 2008;371(9606):75–84.    DOI: 10.1016/S0140-6736(08)60074-4    PMID: 18177778
  9. Tantengco OAG, Menon R. Breaking Down the Barrier: The Role of Cervical Infection and Inflammation in Preterm Birth. Front Glob Women's Heal. 2022;18:777643.    DOI: 10.3389/fgwh.2021.777643
  10. Menon R, Lappas M, Zakar T. Editorial: The Role of the Fetal Membranes in Pregnancy and Birth. Front Physiol. 2021;12:653084.    DOI: 10.3389/fphys.2021.653084    PMID: 33679457
  11. Amberg BJ, Hodges RJ, Rodgers KA, Crossley KJ, Hooper SB, DeKoninck PLJ. Why do the fetal membranes rupture early after fetoscopy? A review. Fetal Diagn Ther. 2021;48(7):493–503.    DOI: 10.1159/000517151    PMID: 34404043
  12. Agarwal A, Durairajanayagam D, Tatagari S, et al. Bibliometrics: tracking research impact by selecting the appropriate metrics. Asian J Androl. 2016;18(2):296–309.    DOI: 10.4103/1008-682X.171582    PMID: 26806079
  13. Palacios-Marqués AM, Carratala-Munuera C, Martínez-Escoriza JC, et al. Worldwide scientific production in obstetrics: a bibliometric analysis. Ir J Med Sci. 2019;188(3):913–919.    DOI: 10.1007/s11845-018-1954-3    PMID: 30627959
  14. Mitra AN, Aurora N, Grover S, Ananth CV, Brandt JS. A bibliometric analysis of obstetrics and gynecology articles with highest relative citation ratios, 1980 to 2019. Am J Obstet Gynecol MFM. 2021;3(1):100293.    DOI: 10.1016/j.ajogmf.2020.100293    PMID: 33451619
  15. Tantengco OAG, Vink JY, Menon R. Trends, gaps, and future directions of research in cervical remodeling during pregnancy: a bibliometric analysis. J Matern Fetal Neonatal Med. 2022;35(25):8355–8363.    DOI: 10.1080/14767058.2021.1974387    PMID: 34549687
  16. Wang HTY, Ong AGJ, Kemper JM, Mol BW, Rolnik DL. Quality of evidence on pre-eclampsia in the last three decades: an analysis of published literature. Pregnancy Hypertens. 2019;18:67–74.    DOI: 10.1016/j.preghy.2019.09.005    PMID: 31546155
  17. van Eck NJ, Waltman L. Software survey: VOSviewer, a computer program for bibliometric mapping. Scientometrics. 2010;84(2):523–538.    DOI: 10.1007/s11192-009-0146-3
  18. Nielsen MW, Andersen JP. Global citation inequality is on the rise. Proc Natl Acad Sci U S A. 2021;118(7):e2012208118.    DOI: 10.1073/pnas.2012208118    PMID: 33558230
  19. Tantengco OAG, Rojo RD. Bibliometric analysis of schistosomiasis research in Southeast Asia (1908-2020). Acta Trop. 2022;228:106322.    DOI: 10.1016/j.actatropica.2022.106322    PMID: 35065014
  20. Ornos EDB, Tantengco OAG. Research trends, gaps, and prospects for viral hepatitis in southeast Asia: a bibliometric analysis. Sci Technol Libr. 2023;42(1):136–148.
  21. Ilagan-Vega MKC, Tantengco OAG, Paz-Pacheco E. A bibliometric analysis of polycystic ovary syndrome research in Southeast Asia: insights and implications. Diabetes Metab Syndr. 2022;16(2):102419.    DOI: 10.1016/j.dsx.2022.102419    PMID: 35152063
  22. Muriithi P, Horner D, Pemberton L. Understanding factors influencing the effect of scientific collaboration on productivity in a developing country: Kenya. Proc Am Soc Info Sci Tech. 2013;50(1):1–10.    DOI: 10.1002/meet.14505001065
  23. Vaudano E. Research collaborations and quality in research: foes or friends? In: Bespalov A, Michel MC, Steckler T, eds. Good Research Practice in Non-Clinical Pharmacology and Biomedicine. Springer International Publishing; 2019: 383–398.
  24. Nyström ME, Karltun J, Keller C, Gäre BA. Collaborative and partnership research for improvement of health and social services: researcher’s experiences from 20 projects. Health Res Policy Syst. 2018;16(1):46.    DOI: 10.1186/s12961-018-0322-0    PMID: 29843735
  25. Gasparyan AY. Choosing the target journal: do authors need a comprehensive approach? J Korean Med Sci. 2013;28(8):1117–1119.    DOI: 10.3346/jkms.2013.28.8.1117    PMID: 23960434
  26. Rowley J, Sbaffi L, Sugden M, Gilbert A. Factors influencing researchers’ journal selection decisions. J Inf Sci. 2022;48(3):321–335.    DOI: 10.1177/0165551520958591
  27. Lopes-Paciencia S, Saint-Germain E, Rowell MC, Ruiz AF, Kalegari P, Ferbeyre G. The senescence-associated secretory phenotype and its regulation. Cytokine. 2019;117:15–22.    DOI: 10.1016/j.cyto.2019.01.013    PMID: 30776684
  28. Young ARJ, Narita M. SASP reflects senescence. EMBO Rep. 2009;10(3):228–230.    DOI: 10.1038/embor.2009.22    PMID: 19218920
  29. Menon R. Human fetal membranes at term: dead tissue or signalers of parturition? Placenta. 2016;44:1–5.    DOI: 10.1016/j.placenta.2016.05.013    PMID: 27452431
  30. Sinkey RG, Guzeloglu-Kayisli O, Arlier S, et al. Thrombin-induced decidual colony-stimulating factor-2 promotes abruption-related preterm birth by weakening fetal membranes. Am J Pathol. 2020;190(2):388–399.    DOI: 10.1016/j.ajpath.2019.10.020    PMID: 31955792
  31. Sharma A, Kumar D, Moore RM, et al. Granulocyte macrophage colony stimulating factor (GM-CSF), the critical intermediate of inflammation-induced fetal membrane weakening, primarily exerts its weakening effect on the choriodecidua rather than the amnion. Placenta. 2020;89:1–7.    DOI: 10.1016/j.placenta.2019.10.003    PMID: 31665659
  32. Kumar D, Moore RM, Sharma A, Mercer BM, Mansour JM, Moore JJ. In an in-vitro model using human fetal membranes, α-lipoic acid inhibits inflammation induced fetal membrane weakening. Placenta. 2018;68:9–14.    DOI: 10.1016/j.placenta.2018.06.305    PMID: 30055672
  33. Kumar D, Schatz F, Moore RM, et al. The effects of thrombin and cytokines upon the biomechanics and remodeling of isolated amnion membrane, in vitro. Placenta. 2011;32(3):206–213.    DOI: 10.1016/j.placenta.2011.01.006    PMID: 21300402
  34. Kumar D, Moore RM, Nash A, et al. Decidual GM-CSF is a critical common intermediate necessary for thrombin and TNF induced in-vitro fetal membrane weakening. Placenta. 2014;35(12):1049–1056.    DOI: 10.1016/j.placenta.2014.10.001    PMID: 25454284
  35. Kumar D, Moore RM, Mercer BM, et al. In an in-vitro model using human fetal membranes, 17-α hydroxyprogesterone caproate is not an optimal progestogen for inhibition of fetal membrane weakening. Am J Obstet Gynecol. 2017;217(6):695.e1–695.e14.    DOI: 10.1016/j.ajog.2017.10.004    PMID: 29031893
  36. Sheller S, Papaconstantinou J, Urrabaz-Garza R, et al. Amnion-epithelial-cell-derived exosomes demonstrate physiologic state of cell under oxidative stress. PLoS One. 2016;11(6):e0157614.    DOI: 10.1371/journal.pone.0157614    PMID: 27333275
  37. Sheller-Miller S, Lei J, Saade G, Salomon C, Burd I, Menon R. Feto-maternal trafficking of exosomes in murine pregnancy models. Front Pharmacol. 2016;7:432.    DOI: 10.3389/fphar.2016.00432    PMID: 27895585
  38. Shahin HI, Radnaa E, Tantengco OAG, et al. Microvesicles and exosomes released by amnion epithelial cells under oxidative stress cause inflammatory changes in uterine cells. Biol Reprod. 2021;105(2):464–480.
  39. Radnaa E, Richardson LS, Sheller-Miller S, et al. Extracellular vesicle mediated feto-maternal HMGB1 signaling induces preterm birth. Lab Chip. 2021;21(10):1956–1973.    DOI: 10.1039/d0lc01323d    PMID: 34008619
  40. Janockova J, Matejova J, Moravek M, et al. Small extracellular vesicles derived from human chorionic MSCs as modern perspective towards cell-free therapy. Int J Mol Sci. 2021;22(24):13581.    DOI: 10.3390/ijms222413581    PMID: 34948379
  41. Fokina V, Patrikeeva S, Wang X, et al. Physicochemical and biological properties of membrane vesicles derived from human term placentas. J Biomed Nanotechnol. 2022;18(2):589–599.    DOI: 10.1166/jbn.2022.3255    PMID: 35484740
  42. Monsivais LA, Sheller-Miller S, Russell W, et al. Fetal membrane extracellular vesicle profiling reveals distinct pathways induced by infection and inflammation in vitro. Am J Reprod Immunol. 2020;84(3):e13282.    DOI: 10.1111/aji.13282    PMID: 32506769
  43. Dixon CL, Sheller-Miller S, Saade GR, et al. Amniotic fluid exosome proteomic profile exhibits unique pathways of term and preterm labor. Endocrinology. 2018;159(5):2229–2240.    DOI: 10.1210/en.2018-00073    PMID: 29635386
  44. Romero R, Miranda J, Chaemsaithong P, et al. Sterile and microbial-associated intra-amniotic inflammation in preterm prelabor rupture of membranes. J Matern Fetal Neonatal Med. 2015;28(12):1394–1409.    DOI: 10.3109/14767058.2014.958463
  45. Menon R, Papaconstantinou J. p38 Mitogen activated protein kinase (MAPK):a new therapeutic target for reducing the risk of adverse pregnancy outcomes. Expert Opin Ther Targets. 2016;20(12):1397–1412.    DOI: 10.1080/14728222.2016.1216980    PMID: 27459026
  46. Polettini J, Richardson LS, Menon R. Oxidative stress induces senescence and sterile inflammation in murine amniotic cavity. Placenta. 2018;63:26–31.    DOI: 10.1016/j.placenta.2018.01.009    PMID: 29486853
  47. Nadeau-Vallée M, Obari D, Palacios J, et al. Sterile inflammation and pregnancy complications: a review. Reproduction. 2016;152(6):R277–R292.    DOI: 10.1530/REP-16-0453    PMID: 27679863
  48. Noda-Nicolau NM, Polettini J, da Silva MG, Peltier MR, Menon R. Polybacterial stimulation suggests discrete IL-6/IL-6R signaling in human fetal membranes: potential implications on IL-6 bioactivity. J Reprod Immunol. 2018;126:60–68.    DOI: 10.1016/j.jri.2018.02.007    PMID: 29524791
  49. Noda-Nicolau NM, Polettini J, Peltier MR, da Silva MG, Menon R. Combinations and loads of bacteria affect the cytokine production by fetal membranes: an in vitro study. Am J Reprod Immunol. 2016;76(6):504–511.    DOI: 10.1111/aji.12596    PMID: 27870156
  50. Mohamed NA, Hinge M, Larsen OH, Sørensen UBS, Uldbjerg N, Nejsum LN. Streptococcus agalactiae do not penetrate human chorioamniotic membranes in vitro but alter their biomechanical properties. Acta Obstet Gynecol Scand. 2021;100(10):1814–1821.    DOI: 10.1111/aogs.14232    PMID: 34255864
  51. Olmos-Ortiz A, Hernández-Pérez M, Flores-Espinosa P, et al. Compartmentalized Innate Immune Response of Human Fetal Membranes against Escherichia coli Choriodecidual Infection. Int J Mol Sci. 2022;23(6):2994.    DOI: 10.3390/ijms23062994    PMID: 35328414
  52. Richardson L, Jeong S, Kim S, Han A, Menon R. Amnion membrane organ-on-chip: an innovative approach to study cellular interactions. FASEB J. 2019;33(8):8945–8960.    DOI: 10.1096/fj.201900020RR    PMID: 31039044
  53. Richardson LS, Kim S, Han A, Menon R. Modeling ascending infection with a feto-maternal interface organ-on-chip. Lab Chip. 2020;20(23):4486–4501. [PMID: 33112317 DOI: 10.1039/d0lc00875c.
  54. Richardson L, Kim S, Menon R, Han A. Organ-on-chip technology: the future of feto-maternal interface research? Front Physiol. 2020;11:715.    DOI: 10.3389/fphys.2020.00715    PMID: 32695021
  55. Richardson LS, Kammala AK, Costantine MM, et al. Testing of drugs using human feto-maternal interface organ-on-chips provide insights into pharmacokinetics and efficacy. Lab Chip. 2022;22(23):4574–4592.    DOI: 10.1039/d2lc00691j    PMID: 36322152
  56. Kammala AK, Richardson LS, Radnaa E, Han A, Menon R. Microfluidic technology and simulation models in studying pharmacokinetics during pregnancy. Front Pharmacol. 2023;14:1241815.    DOI: 10.3389/fphar.2023.1241815
  57. Gallo A, Cuscino N, Contino F, et al. Changes in the transcriptome profiles of human amnion-derived mesenchymal stromal/stem cells induced by three-dimensional culture: a potential priming strategy to improve their properties. Int J Mol Sci. 2022;23(2):863.    DOI: 10.3390/ijms23020863    PMID: 35055049
  58. Yin F, Zhu Y, Wang H, Wang Y, Li D, Qin J. Microengineered hiPSC-derived 3D amnion tissue model to probe amniotic inflammatory responses under bacterial exposure. ACS Biomater Sci Eng. 2020;6(8):4644–4652.    DOI: 10.1021/acsbiomaterials.0c00592    PMID: 33455183
  59. Lim R. Concise review: fetal membranes in regenerative medicine: new tricks from an old dog? Stem Cells Transl Med. 2017;6(9):1767–1776.    DOI: 10.1002/sctm.16-0447    PMID: 28834402
  60. Ilancheran S, Moodley Y, Manuelpillai U. Human fetal membranes: a source of stem cells for tissue regeneration and repair? Placenta. 2009;30(1):2–10.    DOI: 10.1016/j.placenta.2008.09.009    PMID: 18995896
  61. Rosner M, Horer S, Feichtinger M, Hengstschläger M. Multipotent fetal stem cells in reproductive biology research. Stem Cell Res Ther. 2023;14(1):157.    DOI: 10.1186/s13287-023-03379-4    PMID: 37287077

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