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Cells
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Cellular Mechanisms in Pregnancy and Foetal Development
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Cellular Mechanisms in Pregnancy and Foetal Development

A Special Issue of Cells (ISSN 2073-4409).

Deadline for manuscript submissions: 15 October 2026 | Viewed by 7036

Editors

Dr. Anya L. Arthurs

E-Mail Website
Guest Editor
Flinders Health and Medical Research Institute, Flinders University, Adelaide, SA 5042, Australia
Interests: metabolism; cell culture; metabolic flux; glycolysis; placenta; ace2; organoid; RNA
Dr. Giovanni Levi

E-Mail Website
Guest Editor
Département Adaptations du Vivant, Centre National de la Recherche Scientifique UMR 7221, Muséum National d'Histoire Naturelle, Paris, France
Interests: deficit hyperactivity disorder; neural crest; developmental biology; dlx genes; evolution; craniofacial develipment; neuronal differentiation; behavior; homeobox genes; reproduction
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Pregnancy is a finely orchestrated process involving complex cellular and molecular interactions among the mother, the placenta, and the developing foetus. Disruption to these processes can lead to pregnancy complications with lifelong consequences for maternal and child health. A deeper understanding of the cellular mechanisms that underlie fertilisation, implantation, placental development, foetal growth, and maternal adaptation is therefore essential in improving pregnancy outcomes worldwide.

Despite remarkable advances in clinical care and technology, our knowledge of the fundamental biology of pregnancy remains incomplete. For example, even the basic mechanisms of placental ageing are only just beginning to be unravelled, yet these processes are increasingly recognised as critical drivers of complications such as foetal growth restriction and stillbirth. This gap between mechanistic understanding and clinical application limits our ability to achieve real-world advances in healthcare, underscoring the urgency of further discovery research.

This Special Issue will explore fundamental and translational advances in this field. Topics of interest include cellular pathways regulating trophoblast and placental development; foetal and maternal cell signalling; immune interactions at the maternal–foetal interface; mechanisms of placental ageing and dysfunction; the epigenetic and transcriptional regulation of foetal growth; the metabolic and endocrine control of pregnancy; mechanisms involved in fertility and implantation; and innovative in vitro and in vivo models to investigate cellular dynamics. We particularly encourage contributions addressing how these mechanisms intersect with pregnancy complications.

Dr. Anya L. Arthurs
Dr. Giovanni Levi
Guest Editors

Manuscript Submission Information

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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-anonymized peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cells is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). 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
  • fetus
  • reproduction
  • placenta
  • maternal
  • fertility
  • preeclampsia
  • fetal growth restriction
  • gestational diabetes
  • stillbirth

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Published Papers (5 papers)

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Research

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15 pages, 2777 KB  
Article
Repeated Short-Term Intratracheal Exposure to Urban Particulate Matter Has No Apparent Adverse Effects on Female Reproductive Outcomes in Mice
by Seo Hyeon Mun, Hyunsun Park, Doh Hee Kim, Jae Hyeok Heo, Myeong Jin Yeon, Sun-Hee Lee and Haengseok Song
Cells 2026, 15(17), 1522; https://doi.org/10.3390/cells15171522 - 24 Aug 2026
Viewed by 437
Abstract
Urban particulate matter (UPM) is a major environmental pollutant known to induce systemic inflammation. While its respiratory toxicity is well-documented, the potential vulnerability of the female reproductive system to inhaled UPM remains a critical concern. In this study, we evaluated female reproductive outcomes [...] Read more.
Urban particulate matter (UPM) is a major environmental pollutant known to induce systemic inflammation. While its respiratory toxicity is well-documented, the potential vulnerability of the female reproductive system to inhaled UPM remains a critical concern. In this study, we evaluated female reproductive outcomes in a murine model following repeated short-term intratracheal instillation of UPM (40–200 mg/kg) for a month. Our results demonstrate that while UPM exposure induced robust, dose-dependent pulmonary inflammation, characterized by immune cell infiltration (CD45+, F4/80+, and Ly6G+) and upregulation of pro-inflammatory (Il-6, Il-1β, and Tnfα) and fibrotic (Col1a1 and Tgfβ1) markers, no apparent adverse effects were observed in the reproductive endpoints examined. No significant alterations were observed in maternal pregnancy outcomes, including oocyte recovery rates, fertilization competence, gestation duration, litter size, and postnatal development of pups. Furthermore, the mRNA expression of inflammatory markers in the ovaries and uteri was not detectable. Direct in vitro exposure of two-cell embryos to UPM did not interfere with preimplantation embryo development. Although benzanthracene slightly reduced the blastocyst formation rate, UPM and polycyclic aromatic hydrocarbons, major toxic components of UPM, did not severely compromise preimplantation embryo development in vitro. In conclusion, these findings suggest that marked UPM-induced pulmonary inflammation is not accompanied by substantial alterations in the female reproductive outcomes examined under short-term exposure conditions. Full article
(This article belongs to the Special Issue Cellular Mechanisms in Pregnancy and Foetal Development)
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16 pages, 1256 KB  
Article
Liraglutide-Driven Weight Loss Modulates Placental Remodeling in Obese Pregnancies in Mice
by Natassia Rodrigo, Dunja Aksentijevic, Nikayla Patel, Carol A. Pollock, Lana McClements and Sarah J. Glastras
Cells 2025, 14(24), 2009; https://doi.org/10.3390/cells14242009 - 17 Dec 2025
Cited by 1 | Viewed by 1215
Abstract
Background: The placenta stands at the maternal–fetal interface and is a key organ regulating the intrauterine environment. In pregnancies exposed to obesity, placental function, signaling, and nutrient handling are adversely altered. Pre-conception weight loss is a potential intervention to alter an obesogenic milieu [...] Read more.
Background: The placenta stands at the maternal–fetal interface and is a key organ regulating the intrauterine environment. In pregnancies exposed to obesity, placental function, signaling, and nutrient handling are adversely altered. Pre-conception weight loss is a potential intervention to alter an obesogenic milieu of pregnancy, which we investigated in a mouse model of maternal obesity using diet or administration of the glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide. Methods: Pre-pregnancy weight loss in C57BL/6 high-fat diet (HFD)-fed dams was induced in the pre-pregnancy period by switching diet from HFD to chow diet or administering liraglutide (0.3 mg/kg/day subcutaneously for 4 weeks) whilst continuing HFD. In addition, a group of HFD-fed dams were switched to chow diet post-conception. The metabolomic profile and gene expression within the placenta was compared at day 18–20 of gestation. Results: 1H NMR spectroscopy metabolomic analysis of placenta of HFD mice showed an altered amino acid metabolomic profile, with lower aspartate, glutamate, and glutamine levels compared to the placenta of chow-fed mice (p < 0.05). Meanwhile, gene expression analysis identified both oxidative stress and inflammation in the placentas of HFD-fed dams. Whilst dietary modification alone was sufficient to reduce markers of oxidative stress and inflammation, liraglutide treatment modulated pathological changes, including placental metabolic stress but not inflammation. Conclusions: These findings highlight the importance of dietary or pharmacological interventions in the pre- or immediate post-conception period, with pre-conception offering a critical window to reduce aberrant placental changes induced by obesity. Full article
(This article belongs to the Special Issue Cellular Mechanisms in Pregnancy and Foetal Development)
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Review

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31 pages, 1644 KB  
Review
Molecular Determinants of Unexplained Stillbirth: Genetic, Immune-Mediated, and Pharmacogenomic Contributors
by Petra Priscakova, Lajos Gergely, Ivana Shawkatova, Lubica Milosovicova, Vanda Repiska and Helena Gbelcova
Cells 2026, 15(15), 1354; https://doi.org/10.3390/cells15151354 - 28 Jul 2026
Viewed by 585
Abstract
Intrauterine fetal death, also termed stillbirth, remains a major clinical challenge, with a substantial proportion of cases unresolved despite standard postmortem evaluation, limiting effective risk stratification and prevention. This structured narrative review synthesizes evidence from genetic, immune-mediated, and pharmacogenetic studies to summarize possible [...] Read more.
Intrauterine fetal death, also termed stillbirth, remains a major clinical challenge, with a substantial proportion of cases unresolved despite standard postmortem evaluation, limiting effective risk stratification and prevention. This structured narrative review synthesizes evidence from genetic, immune-mediated, and pharmacogenetic studies to summarize possible contributors to stillbirth with potential application in precision-oriented diagnostics and prevention of unexplained stillbirth. Integration of cytogenetic and sequencing approaches enhances detection of clinically relevant abnormalities in previously unexplained cases, while exome sequencing reveals additional molecular diagnoses beyond conventional chromosomal analyses. Genetic contributors include chromosomal abnormalities and a wide spectrum of heterogeneous monogenic disorders affecting cardiac electrophysiology, neuromuscular function, metabolic homeostasis, and early developmental processes. Immune-mediated placental dysfunction, particularly obstetric antiphospholipid syndrome, emerges as a clinically actionable mechanism characterized by vascular and inflammatory injury and associated angiogenic imbalance. Emerging pharmacogenetic evidence indicates that genetic variability in drug metabolism and receptor signaling may influence therapeutic response in placenta-mediated complications. Collectively, these findings support an integrated, mechanism-based framework combining genomic, immune, and pharmacogenetic data with phenotypic characterization to advance etiologic resolution, improve recurrence risk assessment, and enable precision-based diagnostic and preventive strategies in stillbirth. Full article
(This article belongs to the Special Issue Cellular Mechanisms in Pregnancy and Foetal Development)
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27 pages, 1126 KB  
Review
Cervical Glycosaminoglycans and Extracellular Matrix Remodeling: New Insights and the Therapeutic Promise of Tafoxiparin
by Wojciech Flis, Mateusz Wartęga, Julia Sowińska and Maciej W. Socha
Cells 2025, 14(24), 1934; https://doi.org/10.3390/cells14241934 - 5 Dec 2025
Cited by 1 | Viewed by 1327
Abstract
Cervical ripening is a multifaceted process involving endocrine, inflammatory, and biomechanical signals that act on the cervical extracellular matrix. While previous reviews have focused on hormonal and immune mechanisms, the specific role of cervical glycosaminoglycans (GAGs)—particularly hyaluronan and heparan sulfate—has received limited dedicated [...] Read more.
Cervical ripening is a multifaceted process involving endocrine, inflammatory, and biomechanical signals that act on the cervical extracellular matrix. While previous reviews have focused on hormonal and immune mechanisms, the specific role of cervical glycosaminoglycans (GAGs)—particularly hyaluronan and heparan sulfate—has received limited dedicated attention. This review addresses that gap by exploring how these GAGs function as integrators of hormonal cues, immune activation, and extracellular matrix remodeling during pregnancy and labour. We conducted a narrative synthesis of experimental, translational, and clinical studies on GAG composition, metabolism, and signaling, with particular attention to tafoxiparin, a heparan-sulfate-based compound with minimal anticoagulant activity. Available evidence suggests that alterations in hyaluronan and heparan sulfate content influence collagen disorganization, tissue hydration, immune cell infiltration, and prostaglandin production—collectively contributing to cervical softening and dilatation. Although tafoxiparin may replicate some actions of endogenous GAGs, current clinical data remain sparse and inconclusive. Thus, targeting cervical GAG biology represents a mechanistic yet still investigational strategy, requiring further studies to determine its therapeutic value. Full article
(This article belongs to the Special Issue Cellular Mechanisms in Pregnancy and Foetal Development)
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19 pages, 1706 KB  
Review
Maternal Thymus Adaptations and Hormone Regulation During Pregnancy
by Ling Yang, Xinxin Wang and Leying Zhang
Cells 2025, 14(19), 1534; https://doi.org/10.3390/cells14191534 - 30 Sep 2025
Cited by 5 | Viewed by 2637
Abstract
The thymus is necessary for the development of T lymphocytes and central tolerance, and adaptations in the maternal thymus are required during pregnancy. In the present paper, maternal thymic cellular anatomy, T-cell development in the thymus, and related progress are reviewed. In addition, [...] Read more.
The thymus is necessary for the development of T lymphocytes and central tolerance, and adaptations in the maternal thymus are required during pregnancy. In the present paper, maternal thymic cellular anatomy, T-cell development in the thymus, and related progress are reviewed. In addition, the recent progress in maternal thymic adaptations during pregnancy is discussed, including adaptations in thymic cellular anatomy, T-cell development, and immune-related cytokines. Finally, the latest information about hormones that regulate thymic immunology during pregnancy is summarized. In summary, there are many factors, including a lot of hormones, which are involved in maternal thymic immunological adaptations during pregnancy, and may be used to prevent pregnancy-related thymic diseases and preterm birth. Full article
(This article belongs to the Special Issue Cellular Mechanisms in Pregnancy and Foetal Development)
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