Cellular and Molecular Mechanisms of Placental Development and Function

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Reproductive Cells and Development".

Deadline for manuscript submissions: 15 September 2026 | Viewed by 216

Editors


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Guest Editor
Department of Obstetrics and Gynecology, C.S. Mott Center for Human Growth and Development, School of Medicine, Wayne State University, 275 E Hancock St, Rm 195, Detroit, MI 48201, USA
Interests: reproductive immunology; fetal immune development; viral infection; environmental exposure; placenta signaling; sexual dimorphism
Department of Obstetrics, Gynecology and Reproductive Sciences, Yale School of Medicine, 330 Cedar St, New Haven, CT 06510, USA
Interests: extracellular vesicles; trophoblast function; decidualization; innate immune signaling; neutrophil biology; viral infection; environmental exposure; sex-specific effects

Special Issue Information

Dear Colleagues,

The placenta is a transient but essential organ that supports fetal growth by mediating maternal–fetal exchange and establishing immune tolerance during pregnancy. Its proper development and function rely on highly coordinated interactions among trophoblasts, immune cells, decidual cells, and vascular components, as well as tightly regulated signaling pathways that respond to physiological and environmental exposures. Consistent with the Developmental Origins of Health and Disease (DOHaD) framework, perturbations in placental regulatory pathways during critical windows of development can have lasting consequences for fetal programming and long-term offspring health. Over the past decade, significant progress has been made in defining the cellular composition of the placenta and elucidating molecular mechanisms governing placental development, immune regulation, and endocrine function. However, many fundamental questions remain unresolved. For example, how do placental immune and inflammatory pathways maintain homeostasis while protecting against infection? How do environmental stressors, metabolic disturbances, or maternal inflammation perturb placental cellular networks and contribute to adverse pregnancy outcomes? To what extent does placental dysfunction program fetal development and long-term offspring health in a sex-specific manner?

Addressing these questions requires continued investigation of placental biology at the cellular, molecular, and systems levels, integrating advances in single-cell technologies, spatial analyses, and functional models. A deeper understanding of regulatory mechanisms at play in the placenta will not only clarify the pathogenesis of pregnancy-related disorders, including preeclampsia, fetal growth restriction, and preterm birth, but will also provide insight into developmental programming of immune and metabolic disease.

The purpose of this Special Issue is to highlight recent advances in placental research, with a particular emphasis on cellular interactions, immune regulation, and signaling pathways at the maternal–fetal interface in health and disease. We welcome original research articles and reviews that can advance our understanding of mechanisms that underlie maternal-fetal communication during pregnancy that have long-lasting impacts from the start of gestation to decades after birth.

Dr. Jiahui Ding
Dr. Mancy Tong
Guest Editors

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Keywords

  • placenta
  • trophoblast
  • maternal-fetal interface
  • pregnancy complications
  • obstetric
  • inflammation
  • immune
  • fetal programming
  • developmental origins of health and disease (DOHaD)
  • environmental exposure

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Published Papers (1 paper)

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Review

35 pages, 1503 KB  
Review
Placental Pathophysiology in Psychoactive Substances Use: A Multidimensional Review of Biological, Clinical and Forensic Implications
by Oscar Fraile-Martinez, Natalia Rubio-Bedoya, Cielo García-Montero, Diego Liviu Boaru, Patricia de Castro-Martinez, Julia Bujan, Laura López-González, Raul Díaz-Pedrero, Natalio García-Honduvilla, Melchor Álvarez-Mon, Miguel A. Saez, Juan A. De León-Luis, Coral Bravo and Miguel A. Ortega
Cells 2026, 15(12), 1128; https://doi.org/10.3390/cells15121128 (registering DOI) - 22 Jun 2026
Abstract
Maternal psychoactive substance use during pregnancy represents a major threat to placental integrity and fetal development. As the central interface for maternal–fetal exchange, the placenta is highly susceptible to psychoactive substances, including alcohol, tobacco, cannabis, cocaine, opioids, and synthetic drugs, which can cross [...] Read more.
Maternal psychoactive substance use during pregnancy represents a major threat to placental integrity and fetal development. As the central interface for maternal–fetal exchange, the placenta is highly susceptible to psychoactive substances, including alcohol, tobacco, cannabis, cocaine, opioids, and synthetic drugs, which can cross the placental barrier and induce structural and functional alterations. This review synthesizes current evidence on the biological mechanisms, diagnostic approaches, and forensic relevance of psychoactive substances-induced placental pathology. We summarize how different substances disrupt placental vascularization, oxidative balance, epigenetic regulation, and cellular viability, leading to impaired nutrient and oxygen transfer and increasing the risk of adverse outcomes such as intrauterine growth restriction, preterm birth, congenital anomalies, and long-term neurodevelopmental impairment. We further discuss the role of placental tissue in identifying prenatal drug exposure and reconstructing exposure timelines. Beyond its clinical relevance, placental examination provides objective evidence with potential forensic value in cases of suspected maternal substance use, while also informing non-punitive, evidence-based interventions. Overall, integrating placental pathology into reproductive health research and prenatal care offers a multidisciplinary framework to improve maternal–fetal outcomes and guide public health strategies addressing substance use during pregnancy. Full article
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