bims-placeb Biomed News
on Placental cell biology
Issue of 2026–01–11
seven papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences
  1. Image-Based Profiling of Induced Trophoblast Stem Cells Identifies Signatures Associated with Sex, Schizophrenia Genomic Risk and Placental Stress.
  2. Placental serotonergic system dysregulation is associated with early impairments in infant neurodevelopment.
  3. Disruption of the Placenta-Brain Axis in Transgenic Mice Lacking Serotonin Transporter (SERT) in Trophoblast Cells.
  4. The Effect of Cigarette Exposure on Placental Epigenetics: A Systematic Review.
  5. What is placenta accreta?
  6. Endogenous retrovirus IAP forms virus-like particles and traffics across the maternal-fetal barrier.
  7. Maternal placental mitochondrial dysfunction, oxidative stress, and autophagy by regulating ferroptosis in pregnant ewe model.
  1. bioRxiv. 2025 Dec 25. pii: 2025.12.23.695254. [Epub ahead of print]
    Image-Based Profiling of Induced Trophoblast Stem Cells Identifies Signatures Associated with Sex, Schizophrenia Genomic Risk and Placental Stress.
    Frank J Piscotta, Jiyoung Kim, Jisu Ha, Bonna Sheehan, Julia Johnston, John Peters, Thomas M Hyde, Brady J Maher, Juan Caicedo, Daniel R Weinberger, Evgeny Shlevkov, Gianluca Ursini.
      Schizophrenia (SCZ) is a neurodevelopmental disorder where both genetic and environmental risks converge during pregnancy. Recent studies have highlighted the importance of placental biology in influencing risk of developing SCZ. However, the pathways by which genetic risk factors for SCZ interact with environmental influences to alter placental development are poorly understood. Through image-based profiling using Cell Painting, we leveraged trophoblast cultures derived from human induced pluripotent stem cells (hiPSCs) from male and female SCZ and neurotypical donors with varying placental genomic risk scores (PlacGRS) to explore the developmental dynamics of placental cells under normal growth and hypoxic stress. We employed both classical (e.g., CellProfiler) and deep learning feature extraction combined with downstream supervised machine learning to analyze high-dimensional data obtained from this hiPSC-derived model system, highlighting that these approaches overcome the inherent line-to-line variability in phenotypic analysis. Our findings reveal a salient nucleus-localized SCZ risk signature across cell lines, along with clear sexual dimorphism. This research underscores the capability of hiPSC-derived placenta models to elucidate complex interactions between genetic risk and environmental factors implicated in the neurodevelopment of SCZ, paving the way for future studies aimed at developing targeted therapeutic and prevention strategies.
    DOI:  https://doi.org/10.64898/2025.12.23.695254
  2. Front Endocrinol (Lausanne). 2025 ;16 1694018
    Placental serotonergic system dysregulation is associated with early impairments in infant neurodevelopment.
    Arturo A Canul-Euan, Arturo Flores-Pliego, Juan M Solis-Paredes, Aurora Espejel-Nuñez, Sandra B Parra-Hernández, Tahiri Mendoza-Hernández, María Del Carmen Hernandez-Chavez, Gabriela Gil-Martínez, Carmen J Zamora-Sánchez, Otilia Perichart-Perera, Guadalupe Estrada-Gutierrez, Ignacio Camacho-Arroyo.
       Introduction: Serotonin (5-hydroxytryptamine [5-HT]) plays a fundamental role in fetal neurodevelopment. While 5-HT is synthesized in the fetal brain, the placenta contributes significantly to fetal 5-HT levels during early gestation. However, little is known about the influence of placental serotonergic components on early neurodevelopmental outcomes. In this study, we have evaluated the association between the expression of key components of the placental serotonergic system and neurodevelopmental status in infants of mother-child dyads enrolled in the Origen Bioquímico y Epigenético del Sobrepeso y la Obesidad (OBESO) perinatal cohort at the first month of life.
    Methods: We analyzed 5-HT concentrations in maternal serum, umbilical cord serum, and placental tissue, and investigated the expression of key proteins of the serotonergic system in the placenta. All samples were obtained from full-term healthy pregnancies. 5-HT levels were measured by ELISA, and protein expression in placental tissue was evaluated by Western blot. Neurodevelopment was assessed at 1 month of age using the Bayley Infant Development Scale III (BSID-III). Infants with two or more BSID-III domain scores ≤ 7 were grouped as having altereded neurodevelopment.
    Results: Placentas from infants with altered neurodevelopment exhibited higher expression of tryptophan hydroxylase types 1 and 2 (TPH1 and TPH2)-the rate-limiting enzymes in 5-HT synthesis-as well as the serotonin transporter (SERT), compared to those from infants with normal neurodevelopment. In contrast, expression of monoamine oxidase-A (MAO-A), the primary degrading enzyme, was significantly lower in the altered group. Interestingly, 5-HT levels and the expression of 5-HT1E and 5-HTR5A receptors were similar between groups.
    Conclusion: These findings suggest that dysregulation of the placental serotonergic system, independent of total 5-HT levels, could be associated with early neurodevelopmental impairments, highlighting the importance of placental serotonin signaling in fetal brain development.
    Keywords:  humans; infant; neurodevelopment; placenta; serotonin
    DOI:  https://doi.org/10.3389/fendo.2025.1694018
  3. Int J Mol Sci. 2025 Dec 31. pii: 436. [Epub ahead of print]27(1):
    Disruption of the Placenta-Brain Axis in Transgenic Mice Lacking Serotonin Transporter (SERT) in Trophoblast Cells.
    David T Ellenberger, Zhen Lyu, Rosalind T B Herrington, Jessica A Kinkade, Gustavo W Leone, Ji Ying Sze, Nathan J Bivens, R Frank Baker, R Michael Roberts, Trupti Joshi, Cheryl S Rosenfeld.
      Serotonin reuptake inhibitors (SSRIs) are commonly prescribed to pregnant women experiencing depression. Such drugs, however, might adversely affect placenta and fetal brain development. Parietal trophoblast giant cells (pTGCs) in the mouse placenta are postulated to internalize maternal serotonin (5-HT) via transport through SERT, encoded by Slc6a4, and to provide the initial source of 5-HT to the emerging brain via the placental-brain axis. Genetic deletion of Slc6a4 in pTGCs has been hypothesized to impact placental and fetal brain development. A transgenic mouse line with high-affinity SERT, encoded by Slc6a4, was selectively deleted by pairing mice with Cre recombinase linked to Prl2c2, with LoxP sites flanking the Slc6a4 gene. PRL2C2 is solely expressed by pTGCs and other giant cells of the placenta. To compare placental and fetal brain development in selective Slc6a4 KO and WT mice, 5-HT content in the placenta and fetal brains of conceptuses was measured. No significant differences in 5-HT content were evident between knockout (KO) and wild-type (WT) placentas or fetal brains. However, there were significantly fewer pTGCs in KO placentas compared to WT (p ≤ 0.05). Sexually dimorphic differences in gene expression were evident in the placenta and fetal brain between KO and WT counterparts, with female conceptuses showing the most dramatic responses, including decrease in Prl7a2, Prl5a1, Prl3a1, Slc28a3, and Ceacam 15 in female placental samples. These findings suggest that ablation of Slc6a4 in pTGC disrupts the placenta-brain axis in a sex-dependent manner. The results might have important clinical ramifications for pregnant women being treated with SSRIs.
    Keywords:  fetus; neural development; placenta; selective serotonin reuptake inhibitors; trophoblast giant cells
    DOI:  https://doi.org/10.3390/ijms27010436
  4. Reprod Toxicol. 2026 Jan 05. pii: S0890-6238(26)00002-X. [Epub ahead of print] 109159
    The Effect of Cigarette Exposure on Placental Epigenetics: A Systematic Review.
    Raina D Pang, Sarah A Herman, Hannah Ruck, Katrina Huynh, Alexandra McGough, Brian T Nguyen, Kimberly D Siegmund, Melissa L Wilson.
      Tobacco use during pregnancy is a modifiable risk factor contributing to adverse birth outcomes. The placenta is the master regulator of fetal growth and development and contributes to the overall health of the pregnant person and fetus throughout pregnancy. The primary aim of our systematic review was to investigate the impact of tobacco product use during pregnancy on placental epigenetics. A secondary aim of the review was to investigate how tobacco-related alterations in the placental epigenome are associated with maternal and fetal health outcomes. Twenty papers were included in the review. All studies included investigated combustible cigarette smoking only and the majority (85%) studied full term placentas. Using data from studies that included data on methylation changes in 30 or more CpG loci and/or genes, the three most common molecular pathways identified across all the genes were binding, catalytic activity, and transcription regulator activity. However, a large proportion of the genes were not assigned to a specific category. Additional research is needed to understand whether non-cigarette tobacco products also disrupt placenta epigenetics.
    Keywords:  DNA methylation; placenta; placental epigenetics; pregnancy; smoking; tobacco
    DOI:  https://doi.org/10.1016/j.reprotox.2026.109159
  5. Am J Obstet Gynecol. 2026 Jan;pii: S0002-9378(25)00224-8. [Epub ahead of print]233(6S): S630-S640
    What is placenta accreta?
    Eric Jauniaux, Brett D Einerson, Ahmed M Hussein, Robert M Silver, Graham J Burton.
      Accreta placentation is a clinicopathologic diagnosis at delivery when 1 or more placental lobules are abnormally attached into a myometrial scar or congenital defect requiring surgical removal. Over 90% of cases of placenta accreta spectrum are found in patients with a prior history of cesarean delivery presenting with a low-lying placenta or a placenta previa developing inside a lower uterine segment scar. Placenta previa accreta is a complex obstetric condition, and management strategies and clinical outcomes are directly linked to the quality of epidemiology data. We have recently questioned the concept of overinvasive placentation and placenta percreta, providing evidence that surgical manipulation of a dehiscent lower uterine segment covering a placenta previa is responsible for the extrusion of part of the placental tissue. Similarly, there is no evidence that villous tissue and extravillous trophoblastic cells can cross the entire uterine wall in accreta areas. Placenta accreta spectrum is the consequence of placental development at sites where the normal decidual and myometrial mechanisms limiting the migration of the extravillous trophoblastic cells are missing, rather than being due to inherently abnormally invasive villous tissue. Placenta accreta has also been increasingly reported in patients with no prior uterine surgery or pathology using clinical criteria similar to those used for uterine atonia and simple placental retention. Cases where a cleavage plane can be identified and the placenta fully detached manually at the time of birth or during gross examination of hysterectomy or partial myometrial resection specimens should not be reported as accreta. Traditional reliance on the absence of the decidua basalis with villous tissue simply apposed to the superficial myometrium to confirm the diagnosis of accreta placentation at histopathologic examination is inadequate and possibly misleading. Instead, pathologists should focus on other diagnostic features, such as deep villous attachment within the scar tissue and distortion of the uteroplacental interface with thick fibrinoid deposition on microscopic examination. There is a need to develop a new clinicopathologic classification based on a detailed topographic intraoperative description of the location and size of the accreta area and the changes associated with uterine remodeling postscarification.
    Keywords:  abnormal villous attachment; invasive placentation; placenta accreta spectrum disorders; placenta increta; placenta percreta; uterine atony
    DOI:  https://doi.org/10.1016/j.ajog.2025.04.017
  6. bioRxiv. 2025 Dec 22. pii: 2025.12.19.695612. [Epub ahead of print]
    Endogenous retrovirus IAP forms virus-like particles and traffics across the maternal-fetal barrier.
    Abby J Bergman, Guillaume Cornelis, Julie C Baker.
      For 50 years, virus-like particles (VLPs) have been observed in the placentas of many species, but their source and function remain unexplored. Here, we identify intracisternal a-type particle (IAP) elements, specifically the IAPEz-int family, as the likely source of VLPs in the mouse placenta. IAPEz-int instances are expressed throughout placentation and contain intact gag and env sequences critical for the formation of immature and mature particles, respectively. To elucidate a role for IAPEz-int derived VLPs in the mouse placenta, we generated a knock-in mouse containing a full-length element tagged with HA/FLAG. Using this line, we demonstrate that fetal IAPEz-int traffics into and across the maternal decidua. In total, we suggest that placental VLPs derive from IAPEz-int, and demonstrate their potential to traffic into maternal tissues, suggesting a role for these structures in maternal-fetal communication at the placental interface.
    DOI:  https://doi.org/10.64898/2025.12.19.695612
  7. Anim Reprod Sci. 2026 Jan 01. pii: S0378-4320(25)00335-5. [Epub ahead of print]286 108096
    Maternal placental mitochondrial dysfunction, oxidative stress, and autophagy by regulating ferroptosis in pregnant ewe model.
    Feiyang He, Huisi Wu, Gao Liu, Jianing Wang, Bei Zhang, Xingyu Du, Mabrouk Elsabagh, Mengzhi Wang, Hao Zhang.
      Elevated prenatal testosterone (T) induces placental insufficiency and fetal growth restriction (FGR) in sheep, a process hypothesized to involve oxidative stress (OS), mitochondrial dysfunction, autophagy, and ferroptosis. While ferroptosis is recognized as a significant contributor to placental pathophysiology, its specific role in T-mediated ovine placental dysfunction required further investigation. To address this, an in vivo study was conducted wherein pregnant Hu sheep received intramuscular injections of 100 mg T propionate or a control vehicle twice weekly from gestational day (GD) 60-130. Complementarily, in vitro experiments utilized dihydrotestosterone (DHT)-exposed ovine trophoblast cells (OTCs), which were further treated with the ferroptosis activator Erastin or inhibitor Ferrostatin-1 (Fer-1) to directly probe the functional impact of ferroptosis. Our results demonstrated that T administration in vivo recapitulated the pathological phenotype, triggering placental OS, mitochondrial dysfunction, ferroptosis, autophagy, and culminating in FGR. Consistent with these findings, DHT exposure in OTCs induced a similar suite of cellular stresses, including OS, mitochondrial impairment, ferroptosis, and autophagy. Crucially, the inhibition of ferroptosis with Fer-1 in DHT-treated OTCs was found to attenuate these detrimental effects, notably alleviating OS, iron overload, mitochondrial dysfunction, and autophagic activity. Conversely, the co-administration of the ferroptosis inducer Erastin effectively abolished the protective changes conferred by Fer-1, thereby substantiating a central role for ferroptosis in the cascade of T-induced placental dysfunction.
    Keywords:  Autophagy; Ferroptosis; Mitochondrial function; Oxidative stress; Placenta; Sheep
    DOI:  https://doi.org/10.1016/j.anireprosci.2025.108096
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