bims-placeb 2026-06-28 papers

bims-placeb

Biomed News

on Placental cell biology

Issue of 2026–06–28
25 papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences

A single-cell transcriptomic atlas of the pigtail macaque placenta in late gestation.
aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with Hippo signaling kinase LATS1.
Attenuated estrogen signaling disrupts placentation and drives trophoblast defects in Down syndrome.
Phosphorylated HAND1 contributes to trophoblast cell migration during placentation by activating the Vav2-Rac1-PAK signaling.
Susceptibility of the Placenta and Fetal Brain to Maternal Probiotic Supplementation.
Base editing reveals an essential role for NANOG in human embryogenesis.
Gestational inhalation of nanoparticles disrupts placental zone structure and induces vascular placentation in rats.
Trophoblast stem cells and syncytiotrophoblasts lack inflammatory responses to LPS but retain robust interferon-mediated antiviral immunity.
Engineered bipaternal mice reveal the consequences of life without a maternal genomic contribution.
Imbalanced mitochondrial fusion/fission in human placenta: a potential link to preeclampsia.
Maternal-fetal interface organoids: a new era in pregnancy research.
Efficient Derivation and Transcriptional Characterization of Mouse Extra-Embryonic Endoderm Stem Cell Lines Generated by Somatic Cell Nuclear Transfer.
Vertical transmission of Nipah virus in an experimentally infected nonhuman primate; a brief report and description of histopathological lesions.
Effects of HFPO-DA (GenX) exposure on placental glycolysis and metabolic microenvironment in pregnant rats.
CRH expression and function in mouse uterus during early pregnancy.
Maternal vaccination protects dams and prevents in utero transmission of Rift Valley fever virus in rats.
Perfluorooctanoic acid induces mitochondrial dysfunction-driven apoptosis and PINK1/Parkin-mediated mitophagy in testicular cells.
Kisspeptin as a Precision Biomarker in Personalized Pharmacy: Implications for Individualized Monitoring of Early Pregnancy Viability.
Fetal pulmonary vascular volume is impaired in mothers with early onset preeclampsia - a proof of concept study.
Sorbent Intervention to Reduce Per- and Polyfluoroalkyl Substances (PFAS) in Maternal Reproductive Tissues and Transgenerational Translocation in Sprague-Dawley Rats.
Transplacental transfer of osimertinib and alectinib using an ex vivo human placental perfusion model.
Association of Retained Placenta After Spontaneous Separation With Conversion to Hysterectomy in Cases of Cesarean Sections With Suspected Placenta Accreta Spectrum.
Perinatal Semaglutide Treatment Improves Maternal Health and Mitigates Offspring Metabolic Dysfunction in a Mouse Model of Maternal Obesity.
Luteolin decreases sFlt-1 and mean arterial pressure in the RUPP animal model of placental ischemia.
A predictive model for high-quality blastocyst formation using Day 3 morphological scores in women of advanced maternal age.

BMC Genomics. 2026 Jun 26.

A single-cell transcriptomic atlas of the pigtail macaque placenta in late gestation.

Amanda Li, Richard Li, Hazel Huang, Hong Zhao, Briana Del Rosario, Miranda Li, Edmunda Li, Andrew Vo, Gygeria Manuel, Orlando Cervantes, Raj P Kapur, Jeff Munson, Austyn Orvis, Michelle Coleman, Melissa Berg, Britni Curtis, Brenna Menz, Jin Dai, Inah Golez, Solomon Wangari, Chris English, Audrey Baldessari, Lakshmi Rajagopal, John Cornelius, Kristina M Adams Waldorf.

   BACKGROUND: The placenta is a complex organ with multiple immune and non-immune cell types that promote fetal tolerance and facilitate the transfer of nutrients and oxygen. The nonhuman primate (NHP) is a key experimental model for studying human pregnancy complications, in part due to similarities in placental structure, which makes it essential to understand how single-cell populations compare across the human and NHP maternal-fetal interface. We constructed a single-cell RNA-Seq (scRNA-Seq) atlas of the placenta from the pigtail macaque (Macaca nemestrina) in the third trimester, comprising three different tissues at the maternal-fetal interface: the chorionic villi (placental disc), chorioamniotic membranes, and the maternal decidua. Each tissue was separately dissociated into single cells and processed through the 10X Genomics and Seurat pipeline, followed by aggregation, unsupervised clustering, and cluster annotation. Next, we determined the maternal-fetal origins of cell populations and analyzed single-cell RNA trajectory, Gene Ontology enrichment, and cell-cell communication.
RESULTS: Single-cell populations in the pigtail macaque were strikingly similar in their identity and frequency to those found in the human placenta, including cells from trophoblast, stromal cell, immune, and macrophage lineages. An advantage of our approach was the deep sequencing of three tissues at the maternal-fetal interface, which yielded a rich diversity of common and rare single-cell populations.
CONCLUSIONS: Single-cell populations from the third-trimester pigtail macaque placenta are highly concordant with those from the human placenta. This scRNA-Seq atlas provides a powerful resource for understanding experimental perturbations on the NHP placenta.

Keywords:  Chorioamniotic membrane; Chorionic villous; Decidua; Fetus; Nonhuman primate; Pigtail macaque; Placenta

DOI:  https://doi.org/10.1186/s12864-026-13095-x
Stem Cell Reports. 2026 Jun 25. pii: S2213-6711(26)00186-4. [Epub ahead of print] 102975

aPKC-ζ III promotes trophoblast fusion by altering Par-3 interactions with Hippo signaling kinase LATS1.

Sumaiyah Z Shaha, Wendy K Duan, Juan Garcia Rivas, Ivan K Domingo, Meghan Riddell.

  The first trimester of pregnancy is a critical developmental period for the placenta. In humans, the maternal-facing exchange surface is formed by a single giant multinucleate syncytium: the syncytiotrophoblast (ST). The ST arises from villous lineage commitment of trophoblast stem cells (TSC) and the differentiation and fusion of progenitor cytotrophoblasts (pCT) to form the multinucleate syncytium. The Hippo signaling co-transcription factor YAP1 promotes pCT maintenance and TSC stemness; however, how Hippo signaling is regulated remains unknown. We have identified a novel PRKCZ-encoded aPKC isoform, aPKC-ζ III, that is highly expressed in pCT and ST. Here, we establish that aPKC-ζ III promotes pCT fusion by activation of Hippo signaling. Specifically, aPKC-ζ III outcompetes the Hippo kinase LATS1 for scaffolding protein Par-3 binding, resulting in YAP1 inactivation and pCT fusion. Our findings identify a key modulator of Hippo signaling in human trophoblasts that is critical for first-trimester ST differentiation.

Keywords:  Hippo; Trophoblast; aPKC; placenta; single-nuclei RNA sequencing; trophoblast stem cells

DOI:  https://doi.org/10.1016/j.stemcr.2026.102975
bioRxiv. 2026 Jun 08. pii: 2026.06.03.729739. [Epub ahead of print]

Attenuated estrogen signaling disrupts placentation and drives trophoblast defects in Down syndrome.

Deirdre M Logsdon, Isabela T Pereira, Kindyll L Wetta, Lauren Ohler, Mika Nevo, Bo D Thorstenson, Brian F Niemeyer, Bilge Birsoy, Lynae Smith, Cameron Hebert, John Rinn, Matthew D Galbraith, Mary Allen, Robin Dowell, Joaquin M Espinosa, Danny J Schust, Justin Brumbaugh.

Proper establishment of the primitive placenta and subsequent tissue homeostasis in the mature placenta are critical for successful pregnancy in humans. Placental insufficiency is associated with adverse pregnancy outcomes, including fetal growth restriction, preeclampsia, and pregnancy loss. Moreover, emerging evidence suggests that placental defects are associated with long-term health challenges that manifest well into adulthood; yet the etiologies of such diseases are largely unknown. Defining the mechanistic basis for placental deficiencies, therefore, has important implications for improving both reproductive health and the lifelong well-being of affected children. Down syndrome is characterized by placental defects of unknown mechanistic origin, and notably, individuals with Down syndrome are at increased risk of developing diseases commonly associated with placental insufficiency later in life. Using induced pluripotent stem cells from Down syndrome patients, we found that stem cell-based embryo models (i.e., blastoids) and directed differentiation systems recapitulate trophoblast cell fate defects observed in placentas affected by Down syndrome. Furthermore, we demonstrate that attenuated estrogen signaling contributes to placental syncytialization defects and identify NRIP1, a transcriptional corepressor of estrogen receptor that is located on chromosome 21, as a key driver of trophoblast cell fate defects. Increased gene dosage of NRIP1 in an otherwise diploid cell line phenocopies cell fate defects observed in trophoblasts affected by Down syndrome. Our study suggests that estrogen signaling is a crucial regulator of trophoblast development and may serve as a potential target for therapeutic intervention.
Highlights and eTOC blurb: Estrogen signaling mediates syncytiotrophoblast fusionHuman iPS cells provide a tractable model for trophoblast defects in Down syndromeTrophoblast differentiation and estrogen signaling are disrupted in Down syndromeIncreased NRIP1 expression is sufficient to induce trophoblast defectsLogsdon and colleagues apply patient-derived induced pluripotent stem cells to recapitulate placentation defects observed in Down syndrome. The authors demonstrate that attenuated estrogen signaling disrupts trophoblast differentiation and identify NRIP1, a gene found on chromosome 21 that dampens estrogen signaling, as a regulator of trophoblast maturation. NRIP1 and estrogen signaling may represent important therapeutic targets for infertility and Down syndrome.

DOI: https://doi.org/10.64898/2026.06.03.729739
Eur J Pharmacol. 2026 Jun 26. pii: S0014-2999(26)00578-9. [Epub ahead of print] 179096

Phosphorylated HAND1 contributes to trophoblast cell migration during placentation by activating the Vav2-Rac1-PAK signaling.

Weifeng Ye, Chongying Zhu, Yiyao Bao, Lin Li, Zihao An, Yan Song, Qiang Xu, Meiyuan Jin, Chao Tang.

  Trophoblastic cell migration is essential for the attachment of the placenta to uterine wall, which is a critical step for fetal development. Aberrant migration of trophoblastic cells can lead to pregnant pathologies such as preeclampsia (PE), while the molecular mechanisms remain largely unknown. The current study investigated the effects and molecular mechanisms of the HAND1-Rac1-PAK axis in trophoblast migration using the HTR-8/SVneo cell line, isolated human primary cytotrophoblasts, and human placental tissues. We report herein that HAND1 is highly expressed in human early placenta and promotes trophoblastic cell migration. Mechanistically, HAND1 potentiates human trophoblastic cell migration via activating Vav2/Rac1/PAKs signaling, and the elevated capacity of HAND1 in inducing migration is dependent on its Serine/Threonine phosphorylation status, which is reciprocally regulated by PAK2 and is directly associated with the subsequent degradation of HAND1 protein, thereby generating a positive feed-back for HAND1-mediated trophoblasts migration during human pregnancy. The data suggest that HAND1 is essential for regulating human trophoblast function, potentially enhancing our understanding of pregnancy maintenance and contributing to new therapies for gestational disorders.

Keywords:  HAND1; Migration; Placenta; Pregnancy; Trophoblast

DOI:  https://doi.org/10.1016/j.ejphar.2026.179096
Microorganisms. 2026 May 22. pii: 1175. [Epub ahead of print]14(6):

Susceptibility of the Placenta and Fetal Brain to Maternal Probiotic Supplementation.

Rosalind T B Herrington, Zhen Lyu, David T Ellenberger, Nathan J Bivens, Zhentian Lei, Tanhaul Islam, Lloyd W Sumner, R Michael Roberts, Trupti Joshi, Cheryl S Rosenfeld.

  Probiotic supplements are increasingly being touted to have health benefits for pregnant women consuming such supplements and their unborn offspring. The placenta is in direct communication with maternal blood, and bioactive agents can thus easily be transferred to this organ where they may influence gene expression by the different trophoblast (TB) cell lineages. The underlying hypothesis assessed herein is that maternal probiotic supplementation can influence the placenta and fetal brain. The composition of bacterial short-chain fatty acids (SCFAs) was examined in fecal boli of mouse dams on a maternal probiotic supplement relative to control dams. Further, SCFA and transcriptomic profiles were examined in placenta and fetal brain from conceptuses derived from dams on the probiotic supplement and conceptuses from control dams. While this treatment did not affect bacterial SCFAs, placenta and fetal brain changes were evident in male and female conceptuses carried by dams receiving probiotics relative to controls. For the placenta, females were more sensitive to maternal probiotic supplementation, whereas the opposite was the case for the fetal brain. Slc6a4 showed increased expression in female placenta from probiotic-treated dams, which could enhance uptake of maternal 5-HT. Male placenta from probiotic-treated dams had dramatic reduction in Hsd11b2 that may render them more vulnerable to maternal stress. In the fetal brain, maternal probiotic supplementation was associated with genes linked to forebrain development, suggesting this treatment might impact life-long neurobehavioral responses. Current studies suggest that maternal probiotic supplementation might lead to adverse changes in the placenta and fetal brain of their unborn children.

Keywords:  SCFA; bacterial metabolites; gut microbiome; metabolomics; pregnancy; short-chain fatty acids; transcriptomics; trophoblast

DOI:  https://doi.org/10.3390/microorganisms14061175
Nature. 2026 Jun 25.

Base editing reveals an essential role for NANOG in human embryogenesis.

Oliver J Bower, Ana E R Orsi, Riley McMahon, Desislava Staneva, Josephine Blagrove, Kashish Singh, Claire S Simon, Afshan McCarthy, Patricia Garcia, Valerie Shaikly, Mohamed Taranissi, Martin Wilding, Paul Serhal, Rabi A Odia, Mina Vasilic, Meenakshi Choudhary, Athanasios Papathanasiou, Kay Elder, Phil Snell, Leila Christie, Mandana Arbab, David R Liu, Mary Herbert, Katarina Harasimov, Kathy K Niakan.

Understanding how the first cell lineages in human development are specified and maintained has fundamental importance and clinical implications for regenerative medicine, infertility and pregnancy loss. While mouse models have provided valuable insights into transcription factors regulating early development, translating these findings to human embryos has been limited by ethical, technical and biological constraints. Functional studies of transcription factors in human embryos have been hindered by nuclease-based genome-editing approaches that induce genotoxicity1-3. To overcome this, we applied adenine base editing (ABE8e)4,5 to precisely target an exon splice donor site, resulting in a splicing defect and functional knockout of NANOG, representing the first application of base editing to study a developmental regulator in human embryos. This approach did not trigger genotoxicity and showed limited off-target editing. Loss of NANOG disrupts pluripotent epiblast specification and instead cells differentiate toward a primitive endoderm (yolk sac) or trophectoderm (placental) transcriptional programme. Retention of primitive endoderm differentiation in NANOG-edited human embryos reveals a functional compensation distinct from mouse, underscoring the importance of directly investigating human development. Our findings demonstrate an essential role for NANOG in human pluripotency and epiblast specification, and highlight the utility of base editing for functional interrogation of human development.

DOI: https://doi.org/10.1038/s41586-026-10792-1
bioRxiv. 2026 Jun 11. pii: 2026.06.08.730946. [Epub ahead of print]

Gestational inhalation of nanoparticles disrupts placental zone structure and induces vascular placentation in rats.

Talia Seymore, Destiny McWilliams, Kevin Ozkuyumcu, Pedro Louro, Chelsea Cary, Michael Goedken, Laurie Joseph, Phoebe Stapleton.

Airborne contaminants represent a significant environmental health concern for vulnerable populations, including pregnant individuals. In particular, maternal inhalation of particulate matter (PM) during pregnancy has been linked to adverse outcomes such as fetal growth restriction (FGR). Increasing evidence identifies placental dysfunction as a mechanism for this condition. Placental efficiency, defined as the ratio of fetal mass to placental mass, is frequently altered in FGR. Many aspects contribute to placental efficiency including surface area available for nutrient and waste exchange and placental vascularization. In this study, we hypothesized that maternal inhalation of ultrafine PM during pregnancy would reduce the size and/or number of placental structures that are necessary for nutrient transport. Engineered titanium dioxide nanoparticles (nano-TiO2) were used as a proxy for ultrafine PM and pregnant Sprague Dawley rats were exposed via whole-body inhalation to nano-TiO2 aerosols (9.23 +/- 0.39 mg/m3) from gestational day (GD) 5 to 19. On GD 20, placentas were collected and processed for histological evaluation. While gestational inhalation of nano-TiO2 did not affect placental weight or efficiency, it reduced decidua and labyrinth zone size. Exposed placentas exhibited compensatory adaptations characterized by increased blood space number and maternal blood space expansion. Together, these findings indicate that inhalation of nanoparticles disrupts placental structure while simultaneously eliciting adaptive vascular responses that may preserve nutrient exchange capacity. By characterizing the effects of PM exposure on placental morphology and structure, this study highlights the placenta as a vulnerable target of inhaled pollutants and provides mechanistic insight into pathways contributing to PM-induced FGR.

DOI: https://doi.org/10.64898/2026.06.08.730946
Reprod Fertil. 2026 Jun 23. pii: RAF-25-0176. [Epub ahead of print]

Trophoblast stem cells and syncytiotrophoblasts lack inflammatory responses to LPS but retain robust interferon-mediated antiviral immunity.

Cristine R Camp, Joshua Baskaran, Matthew Brown, Carly Parker, Paige Drotos, Rachel C West.

  Early pregnancy requires a tightly regulated pro-inflammatory environment shared between the primitive placenta and decidua. While immune balance supports successful implantation and placental invasion, disruptions in immune signaling during this period can impair implantation and lead to embryo loss. In this study, we investigated the molecular mechanisms underlying immune imbalance during implantation using a trophoblast stem cell (TSC) model. TSCs were cultured in either stem cell or syncytiotrophoblast (STB) differentiation medium and treated with either lipopolysaccharides (LPS) or interferon beta (IFNB). RT-qPCR and Western blotting revealed that LPS failed to induce a pro-inflammatory cytokine response in TSCs or STBs. In contrast, IFNB triggered a strong antiviral response in both TSCs and STBs. RNA-sequencing of IFNB-treated TSC and STB 3D spheroids revealed subtle differences between the TSCs and STB responses to interferons. Both TSC and STB IFNB-treated spheroids mount an interferon-mediated antiviral response; however, STB spheroid genes associated with the type I interferon response, viral RNA/DNA sensing, and antigen processing were upregulated. We also compared the interferon response between the CT27 (female) and CT29 (male) TSCs and STBs. While STBs showed minimal differences, the CT29 TSCs exhibited a markedly stronger interferon response than the CT27 TSCs. Collectively, these findings suggest that the primitive placenta is selectively responsive to interferon signaling rather than direct pathogen-associated stimuli. This implies that maternal immune activation, rather than microbial invasion, likely drives that placental immune response and embryo success at this stage. Understanding these dynamics underscores the importance of the maternal immune balance in early pregnancy success.

Keywords:  LPS; innate immune response; interferon beta; sex differences; syncytiotrophoblast; trophoblast stem cell

DOI:  https://doi.org/10.1530/RAF-25-0176
PLoS Biol. 2026 Jun;24(6): e3003871

Engineered bipaternal mice reveal the consequences of life without a maternal genomic contribution.

Si-Nan Ma, Fan Li, Yu-Long Zhao, Xue-Han Sun, Xue-Song Chen, Tian-Shi Pan, Qing-Tong Shan, Chao Liu, Gui-Hai Feng, Zhi-Kun Li, Qi Zhou, Wei Li.

Successful mammalian development normally requires contributions from both maternal and paternal genomes, yet how these parental components jointly shape organismal development remains incompletely understood. Using engineered bipaternal mice generated from androgenetic embryonic stem cells carrying extensive imprinting-region modifications and produced through tetraploid complementation, we examined developmental and physiological consequences of development supported exclusively by paternal genomes. Placental analyses revealed partial normalization of placental growth but persistent differences among conceptuses. Transcriptomic profiling across embryos and postnatal tissues similarly showed broad alterations in gene expression states involving both imprinted and non-imprinted genes. Despite these differences during development, adult physiology showed a more coherent endpoint: integrated transcriptomic and metabolomic analyses revealed that adult livers converge toward an altered metabolic configuration characterized by coordinated perturbations of the tricarboxylic acid cycle and associated lipid metabolism, accompanied by hepatic lipid accumulation and increased systemic fat mass. These findings indicate that paternal-only mammalian development can proceed across multiple stages but follows altered developmental trajectories that culminate in distinct physiological states, providing insight into how maternal and paternal genomic contributions interact to shape mammalian development and physiology.

DOI: https://doi.org/10.1371/journal.pbio.3003871
Sci Rep. 2026 Jun 26.

Imbalanced mitochondrial fusion/fission in human placenta: a potential link to preeclampsia.

Jianying Liu, Yujing Xu, Hong Sun, Shasha Yu, Rong Hou, Ruofan Wang, Qian Li, Xiaoyi Yin, Yuchun Zhu, Guanglei Wang.

  We aimed to examine how placental dysfunction and impaired mitochondrial fusion/fission balance correlate with preeclampsia (PE) in human placentas, shedding light on the underlying etiology of PE. Twenty-eight pregnant women who received antenatal care at the Obstetrics Medical Center of Weifang People's Hospital between November 2024 and May 2025. They were divided into a PE group (n = 14) and a normal control group (n = 14). Placental tissues from pregnant women with PE or with healthy control were analyzed. Compared to controls, the PE group exhibited impaired placental function (evidenced by decreased PlGF and increased sFlt-1) and disrupted mitochondrial dynamics (characterized by reduced MFN1/2 and elevated p-DRP1). These alterations were accompanied by increased oxidative stress and apoptosis, alongside decreased ATP production. Imbalanced mitochondrial fusion/fission may contribute to placental dysfunction through mechanisms involving oxidative stress, disturbed energy metabolism, and cell apoptosis, leading to the occurrance of PE.

Keywords:  Fission; Fusion; Mitochondrial; Oxidative stress; Placenta; Preeclampsia

DOI:  https://doi.org/10.1038/s41598-026-57067-3
Front Bioeng Biotechnol. 2026 ;14 1842889

Maternal-fetal interface organoids: a new era in pregnancy research.

Jingran Gao, Hangyu Sun, Shuqi Yang, Xiaoying Yao.

  The maternal-fetal interface is the core site of pregnancy occurrence and maintenance. Its complex physiological and pathological processes have long been concentrated in two-dimensional cell models and animal models. Organoids represent a novel in vitro three-dimensional model that offers a powerful platform for elucidating the complexities of human pregnancy, investigating pregnancy-related diseases, and developing novel treatment strategies. Organoids primarily employ pluripotent stem cells or tissue-derived progenitor cells to generate miniature "organs" that emulate the configuration of placental villi and/or endometrium under the influence of specific factors. The development of organoids has undergone substantial advancement. In the domain of reproductive medicine, maternal-fetal interface organoids have emerged as a versatile tool for simulating embryo implantation, elucidating maternal-fetal communication mechanisms, and facilitating etiological investigation and disease modeling of significant pregnancy complications, including recurrent miscarriage and preeclampsia. Furthermore, they can play an instrumental role in the realm of drug screening and research on vertical transmission of pathogens. The advancement of this field is contingent upon the synergistic integration of organoid culture technology and research methodologies, including imaging and multi-omics analysis. However, the field of maternal-fetal interface organoids is still in its nascent stages and faces many challenges. These include limitations in cell type completeness, tissue complexity, and functional maturity of existing models. In addition, there are standardization, reproducibility, and related ethical issues of culture. In the future, the development of this field will be driven by several key directions. These include the construction of additional physiological models, the integration of the immune and vascular systems, the promotion of standardization and clinical translation, and the establishment of clear ethical guidelines. These developments are expected to ultimately lead to breakthroughs in unlocking the early secrets of life's origins and preventing reproductive disorders.

Keywords:  maternal-fetal interface; organoids; placenta; pregnancy-related diseases; reproductive medicine

DOI:  https://doi.org/10.3389/fbioe.2026.1842889
Stem Cells Int. 2026 ;2026 1968738

Efficient Derivation and Transcriptional Characterization of Mouse Extra-Embryonic Endoderm Stem Cell Lines Generated by Somatic Cell Nuclear Transfer.

Shuaipeng Li, Shu Wei, Guomeng Li, Mei Hu, Jiangwei Lin, Wandong Bao.

  Somatic cell nuclear transfer (SCNT) holds great promise for regenerative medicine and agriculture, but its application is severely hampered by low efficiency, primarily attributable to aberrant epigenetic reprogramming. Although embryonic stem cells (ESCs) and trophoblast stem cells (TSCs) have been successfully derived from cloned embryos, an in vitro counterpart of the primitive endoderm (PrE) lineage has remained unavailable. To address this gap, this study reports the first successful establishment of extra-embryonic endoderm stem cell lines (XENs) from mouse SCNT-derived blastocysts (NT-XENs). Under conventional culture conditions, NT-XENs were generated from hybrid B6D2F1 blastocysts at a high efficiency of 55%, statistically comparable to that of fertilization-derived XEN lines (FD-XENs, 50%), whereas derivation from inbred C57BL/6J SCNT-derived blastocysts was markedly lower (12.5%). Immunofluorescence and NanoString multiplex gene expression profiling confirmed that NT-XENs robustly expressed specific marker genes for PrE/XENs (e.g., Gata4, Gata6, and Sox17), while exhibiting negligible or absent expression of pluripotency and trophoblast markers. Based on NanoString assay data, NT-XENs and FD-XENs shared highly similar gene expression patterns, yet also exhibited some nonnegligible differences, exemplified by the differentially expressed genes (DEGs) Pecam1, Gtl2, Thbd, and Xlr3b. These differences raise a preliminary hypothesis that the NT-XENs might exhibit a slight transcriptional propensity toward a more differentiated state, and potentially reflect lingering traces of SCNT-associated epigenetic errors, such as localized dysregulation of imprinted genes and X-linked transcripts. In summary, this study successfully establishes NT-XEN cell lines, providing a valuable in vitro model for investigating the reprogramming scenarios of PrE lineage in SCNT and the mechanisms underlying developmental failure of cloned embryos.

Keywords:  NanoString multiplex gene expression profiling; aberrant epigenetic reprogramming; extra-embryonic endoderm stem cell line; imprinting errors; primitive endoderm; somatic cell nuclear transfer

DOI:  https://doi.org/10.1155/sci/1968738
J Infect Dis. 2026 Jun 20. pii: jiag321. [Epub ahead of print]

Vertical transmission of Nipah virus in an experimentally infected nonhuman primate; a brief report and description of histopathological lesions.

Declan D Pigeaud, Natalie S Dobias, Antoinette Lona, Christopher C Broder, Robert W Cross, Thomas W Geisbert, Karla A Fenton.

  Nipah virus (NiV) is a highly pathogenic henipavirus which causes severe, often fatal disease in humans and animals. African green monkeys (AGM) have been used extensively to investigate NiV disease and are the only nonhuman primate (NHP) model that accurately recapitulates human NiV pathogenesis. Here, we describe histopathological lesions in the reproductive tissues of an incidentally pregnant female AGM that succumbed to NiV disease. We employed multiplex immunohistochemistry techniques to profile specific cell populations which identified NiV antigen in both maternal and fetal cells of the placenta, which has not been previously described in NHP models of NiV disease.

Keywords:  Animal models; Medical countermeasures; Nipah virus; Nonhuman primate; Pathogenesis; Pregnancy; Vertical transmission

DOI:  https://doi.org/10.1093/infdis/jiag321
Toxicology. 2026 Jun 23. pii: S0300-483X(26)00139-3. [Epub ahead of print]526 154532

Effects of HFPO-DA (GenX) exposure on placental glycolysis and metabolic microenvironment in pregnant rats.

Yiming Pang, Zhenzhong Wang, Yijun Liu, Chuanteng Feng, Yuchun Song, Shannan Cao, Dong Wang, Lianshuang Zhang, Peng Lu, Li Yu.

  Hexafluoropropylene oxide dimer acid (HFPO-DA; GenX) is an environmentally persistent per- and polyfluoroalkyl substance (PFAS) alternative whose placental toxicity remains poorly understood. Pregnant Sprague-Dawley rats (n = 20, 5 dams/group) received oral HFPO-DA at 0, 1, 10, or 100 mg/kg·day from gestational day (GD) 0-19. Placental tissues collected on GD20 were analysed by targeted metabolomics, lipidomics, histopathology, immunohistochemistry (IHC), and immunofluorescence (IF). After false discovery rate (FDR) correction, three energy metabolites were significantly altered (q < 0.05): oxaloacetate and glutamate were downregulated, while pyruvate was dose-dependently upregulated, consistent with restricted TCA cycle entry. Lipidomics identified 148 nominally significant lipid species, with elevated ceramides and long-chain fatty acids alongside reduced triglycerides, a pattern suggestive of impaired mitochondrial β-oxidation capacity. Histopathology revealed dose-dependent villous hyperplasia, trophoblast disorganization, and vascular lesions at the high dose. Protein analysis showed decreased SDHB, increased HIF-1α and PDK1, and a non-significant rise in PDHA1, collectively consistent with a shift toward Warburg-like metabolic reprogramming. These findings suggest that gestational HFPO-DA exposure may disrupt placental energy and lipid homeostasis at supra-environmental doses, identifying placental metabolism as a potentially sensitive target of next-generation PFAS.

Keywords:  HFPO-DA; Metabolism; PFAS alternatives; Placental; Rats

DOI:  https://doi.org/10.1016/j.tox.2026.154532
Reprod Fertil Dev. 2026 Jul 10. pii: RD26104. [Epub ahead of print]38(10):

CRH expression and function in mouse uterus during early pregnancy.

Qi-Man Shen, Ling Liu, Zai-Mei Wang, Qi-Tian Fu, Zeng-Ming Yang.

   CONTEXT: Embryo implantation and decidualization are essential to the establishment and maintenance of pregnancy. However, the underlying mechanism on embryo implantation and decidualization remains unclear. Although the regulation and role of hypothalamic corticotropin-releasing hormone (CRH) during early pregnancy have been extensively studied, uterine CRH is still poorly defined.
AIMS: This study examined CRH expression in mouse uterus during early pregnancy and evaluated the regulation and role of CRH during embryo implantation and decidualization.
METHODS: Immunofluorescence was used to show CRH protein concentrations in mouse uterus. The inhibitor for CRH receptor CRHR1 and recombinant CRH protein were applied to analyze the function of CRH on mouse in vitro decidualization.
KEY RESULTS: CRH is expressed in luminal epithelium of mouse uterus from Day 1 to Day 4 of pregnancy. At implantation site on Day 5 of pregnancy, CRH is strongly localized in primary decidua. Verucerfont, a CRHR1 inhibitor, significantly suppresses mouse in vitro decidualization.
CONCLUSIONS: Our results indicated that CRH is strong expressed in primary decidua and should play a role during mouse decidualization.
IMPLICATIONS: This result should shed lights on understanding the underlying mechanism during embryo implantation and decidualization.

Keywords:  CRH; corticosteroid; decidualization; embryo implantation; epithelial organoids; pregnancy; uterine receptivity; verucerfont

DOI:  https://doi.org/10.1071/RD26104
mBio. 2026 Jun 22. e0025326

Maternal vaccination protects dams and prevents in utero transmission of Rift Valley fever virus in rats.

Austin T Hertel, Cynthia M McMillen, Ryan M Hoehl, Zachary D Frey, Anita K McElroy, Amy L Hartman.

  In utero transmission and spontaneous fetal death are hallmarks of Rift Valley fever virus (RVFV) infection in pregnant animals. Compounding evidence indicates pregnant individuals are particularly vulnerable to RVFV, as in utero transmission and increased rates of miscarriage have been reported in people infected during pregnancy. Further, human placenta explants are permissive to RVFV infection. Viable vaccine candidates intended for veterinary or human use must protect vulnerable populations, including pregnant individuals and fetuses. Using a pregnant rat model, we show that maternal vaccination with a live-attenuated RVFV lacking the non-structural proteins NSs and NSm (RVFV-delNSs/NSm) is immunogenic, safe, and protective. Dams vaccinated either prior to or during pregnancy were protected from virulent challenge during pregnancy, and we found no evidence of infectious virus in the placentas and fetuses of challenged animals. These studies offer important pre-clinical data in a tractable pregnancy model and serve as a blueprint for evaluating future vaccine approaches designed to protect pregnant individuals and their fetuses.
IMPORTANCE: Rift Valley fever virus (RVFV) poses a formidable threat to pregnant animals and potentially to pregnant individuals and their developing fetuses. Despite this risk, pregnant individuals are rarely included in vaccine trials, leaving this potentially vulnerable population unprotected. Using a live-attenuated RVFV vaccine, we demonstrate that maternal vaccination is safe and protects both pregnant rats and their fetuses from congenital Rift Valley fever. Because live-attenuated vaccines are often contraindicated during pregnancy due to theoretical safety concerns, we further show that vaccination prior to pregnancy provides equivalent protection throughout future pregnancy. Taken together, these findings provide a blueprint for the preclinical evaluation of RVFV vaccines during pregnancy.

Keywords:  RNA virus; Rift Valley fever; bunyavirus; pregnancy; vaccine; vertical transmission

DOI:  https://doi.org/10.1128/mbio.00253-26
Toxicology. 2026 Jun 23. pii: S0300-483X(26)00137-X. [Epub ahead of print]526 154530

Perfluorooctanoic acid induces mitochondrial dysfunction-driven apoptosis and PINK1/Parkin-mediated mitophagy in testicular cells.

Banu Orta Yilmaz, Yasemin Aydin.

  Per- and polyfluoroalkyl substances (PFAS) have become an important focus of research in recent years due to their widespread use and environmental persistence. Perfluorooctanoic acid (PFOA) has attracted considerable attention due to its effects on the reproductive system, yet its molecular mechanisms in testicular cells remain unclear. This study aimed to investigate the effects of PFOA on oxidative stress, mitochondrial function, and interconnected programmed cell death pathways. Mouse Sertoli (TM4) and spermatogonial (GC-1) cells were exposed to PFOA at concentrations of 200-800 µM for 24 h, and its effects on cell viability and cytotoxicity were evaluated. Oxidative stress levels were determined by measuring reactive oxygen species production, malondialdehyde levels, antioxidant enzyme activities, and mitochondrial membrane potential. In addition, the potential cell death pathways, including apoptosis, autophagy, mitophagy, and ferroptosis, were assessed by analyzing gene and protein expression using RT-qPCR and Western blot. PFOA exposure resulted in a concentration-dependent and significant increase in intracellular ROS levels, accompanied by a significant decrease in mitochondrial membrane potential in both cell lines. The antioxidant defense system and NRF2 signaling were markedly suppressed. PFOA exposure also significantly activated intrinsic apoptotic pathways, as supported by increased apoptotic gene expression and elevated caspase-3 protein levels. A clear increase in autophagy- and mitophagy-related markers was observed, suggesting that cells develop an adaptive response to mitochondrial damage. These findings provide important mechanistic insights into mitochondrial dysfunction and associated cell death processes in PFOA-exposed testicular cells.

Keywords:  Apoptosis; Ferroptosis; Mitochondrial dysfunction; Mitophagy; Oxidative stress; Perfluorooctanoic acid; Testicular cells

DOI:  https://doi.org/10.1016/j.tox.2026.154530
Pharmacy (Basel). 2026 Jun 09. pii: 84. [Epub ahead of print]14(3):

Kisspeptin as a Precision Biomarker in Personalized Pharmacy: Implications for Individualized Monitoring of Early Pregnancy Viability.

Ani Paunova, Angelina Mollova-Kyosebekirova, Maria Koleva, Ekaterina Uchikova, Nikoleta Parahuleva.

   BACKGROUND: Precision medicine aims to improve early, individualized risk stratification using biologically relevant biomarkers. In early pregnancy, markers reflecting placental function remain limited. Kisspeptin, a placentally derived peptide that rises during normal gestation, has emerged as a potential indicator of pregnancy viability.
OBJECTIVES: We aimed to evaluate evidence on maternal serum kisspeptin levels and placental KISS1/KISS1R expression in early pregnancy loss, and to assess its potential relevance as a precision biomarker within personalized pharmacy and individualized monitoring frameworks.
METHODS: A systematic search of PubMed, Scopus, Web of Science, and Google Scholar (up to 2025) was conducted according to the PRISMA 2020 guidelines. Studies assessing circulating kisspeptin and/or placental expression in early pregnancy loss versus viable pregnancies were included. A formal meta-analysis was not performed due to substantial heterogeneity in study design, biological material, assay methods, gestational age, and outcome reporting formats. Under these conditions, quantitative pooling was considered methodologically inappropriate; therefore, qualitative synthesis was performed.
RESULTS: Six studies met the inclusion criteria. Most reported significantly lower maternal serum kisspeptin levels in early pregnancy loss, with good discriminatory accuracy. Immunohistochemical analyses showed reduced placental and choriodecidual KISS1/KISS1R expression in miscarriage and recurrent pregnancy loss, indicating disrupted local signaling. Concordant systemic and tissue findings suggest that circulating kisspeptin reflects placental dysfunction.
CONCLUSIONS: Kisspeptin appears to be a promising precision biomarker for monitoring early pregnancy viability and supporting individualized pharmaceutical care. Standardized assays and large prospective studies are needed before routine clinical implementation.

Keywords:  early pregnancy loss; immunohistochemistry; individualized monitoring; kisspeptin; miscarriage; pharmaceutical care; placental biomarkers; precision medicine

DOI:  https://doi.org/10.3390/pharmacy14030084
Pregnancy Hypertens. 2026 Jun 26. pii: S2210-7789(26)00082-6. [Epub ahead of print]45 101494

Fetal pulmonary vascular volume is impaired in mothers with early onset preeclampsia - a proof of concept study.

Katinka Weller, Alex J Eggink, Robbert J Rottier, Irwin K M Reiss, Eric A P Steegers, Nina C J Peters.

   OBJECTIVES: Children of mothers with early-onset preeclampsia (EOPE) are at increased risk of respiratory morbidity due to factors including fetal growth restriction, prematurity, and impaired pulmonary vascular development. While animal studies suggest compromised fetal pulmonary vasculature in preeclampsia, human data remain limited. This study aimed to compare fetal pulmonary vascular volume in EOPE pregnancies with healthy controls as a proof of concept.
STUDY DESIGN AND MAIN OUTCOME MEASURES: Pregnant women with EOPE and healthy controls were prospectively recruited. Ultrasound assessments were performed at three gestational intervals: 19 + 0-24 + 0 weeks (US1), 24 + 1-29 + 6 weeks (US2), and 30 + 0-32 + 0 weeks (US3). Using 3D Power Doppler ultrasound, fetal right pulmonary vascular volume (R-PVV), right lung volume (R-LV), and the R-PVV/LV ratio were measured. Perinatal parameters were also evaluated.
RESULTS: Seventy-two controls and 36 EOPE fetuses were included. EOPE fetuses showed significantly reduced R-PVV at US2 and US3 compared to controls. The R-PVV/LV ratio remained significantly lower at both time points, suggesting impaired vascular development independent of lung size. Maternal BMI, gestational age at birth, and neonatal outcomes differed significantly between groups.
CONCLUSIONS: This is the first human study to demonstrate impaired fetal pulmonary vascular development in EOPE. These findings offer insight into the pathophysiological effects of EOPE on fetal lung health.

Keywords:  Early onset preeclampsia; Fetal development; Pulmonary vasculature

DOI:  https://doi.org/10.1016/j.preghy.2026.101494
J Hazard Mater Adv. 2026 May;pii: 101232. [Epub ahead of print]22

Sorbent Intervention to Reduce Per- and Polyfluoroalkyl Substances (PFAS) in Maternal Reproductive Tissues and Transgenerational Translocation in Sprague-Dawley Rats.

Johnson O Oladele, Kelly J Rivenbark, Damilare A Adekomi, Timothy D Phillips, Meichen Wang.

  Per- and polyfluoroalkyl substances (PFAS) are persistent environmental contaminants, posing significant health risks, particularly during critical exposure windows such as gestation and lactation. In this study, following prenatal and postnatal exposure to 0.95 mg PFAS/kg-bw/day in F0 Sprague-Dawley rats, their toxicity to maternal reproductive tissues and translocation to offspring were measured. On postnatal day (PND) 21, PFAS (especially PFOS) were detected in F0 ovaries and testes with histopathological ovarian damage. PFAS time-dependently accumulated in maternal milk and transferred approximately 1% to F1 serum and 3.7-6.0% to F1 livers, except for PFBS. PFAS exposure reduced offspring birth weight and growth by 20.8% (p≤0.01), and induced systemic inflammation and hepatotoxicity, as shown by the imbalanced liver function parameters, antioxidants, and pro-inflammatory cytokines. These findings suggest that long-term health implications may result from early-life PFAS exposure. To mitigate PFAS toxicity, generally recognized as safe (GRAS) sorbents were orally administered during PFAS exposure. Activated carbon (AC) and acid-processed montmorillonite (APM) treatments most significantly reduced total PFAS in maternal ovaries by 47-49%, testes by 40-43%, and milk by 40-74% (p≤0.01), and restored ovarian histoarchitecture. Although sorbents only slightly reduced PFAS concentrations in the offspring liver and serum by 5%, they prevented PFAS-induced oxidative stress, inflammation, and liver damage. These findings emphasize the urgent need for targeted short-term interventions to reduce PFAS exposure and toxicity, especially during vulnerable periods. Enterosorbent treatments offer a promising preventive approach by reducing the systemic bioavailability of PFAS and interrupting toxic effects in two generations.

Keywords:  Adsorption; Carbon; Clay; Exposure; Offspring; Pregnancy; Reproductive toxicity

DOI:  https://doi.org/10.1016/j.hazadv.2026.101232
Placenta. 2026 May 26. pii: S0143-4004(26)00186-4. [Epub ahead of print]182 116-122

Transplacental transfer of osimertinib and alectinib using an ex vivo human placental perfusion model.

Laure Benoit, David Combarel, Marie-Noëlle Dieudonne, Yoann Rodriguez, Estelle Heggarty, Olivier Mir, Stanislas Grassin Delyle, Elodie Lamy, Angelo Paci, François Vialard, Paul Berveiller.

   BACKGROUND: The incidence of non-small cell lung cancer (NSCLC) is increasing in women, including those of childbearing age. While recent drugs such as osimertinib and alectinib have improved the prognosis of specific molecular subtypes (e.g., EGFR-mutant and ALK-rearranged NSCLC), their potential use during pregnancy remains inadequately supported by pharmacological data.
OBJECTIVE: To assess the transplacental transfer and placental cotyledon accumulation of osimertinib and alectinib, using a human ex vivo placental perfusion model.
STUDY DESIGN: Term placentas from normal pregnancies were collected after delivery and perfused with osimertinib or alectinib (in combination with alectinib major active metabolite M4) doses simulating steady state plasma concentrations observed in maternal plasma. Fetal transfer rate, clearance index, and cotyledon accumulation were evaluated, with antipyrine used as a control marker. Samples were collected during a 90-min procedure.
RESULTS: Significant transplacental transfer of osimertinib was observed, with a fetal transfer rate of 9.5% and a CI of 0.41, and cotyledon accumulation of 28.9%. In contrast, neither alectinib nor M4 were detected in fetal samples, although both were found to accumulate substantially in placental tissues (370.7% and 178.3%, respectively).
CONCLUSION: These findings suggest that osimertinib crosses the placenta with a moderate tissue uptake, while alectinib and its metabolite M4 do not appear to be transferred to the fetus but accumulate significantly within the placental tissue. Further studies are needed to guide treatment selection for NSCLC in pregnant women.

Keywords:  Alectinib; Lung cancer; Osimertinib; Placenta; Placental transfer; Pregnancy

DOI:  https://doi.org/10.1016/j.placenta.2026.05.024
J Obstet Gynaecol Res. 2026 Jul;52(7): e70386

Association of Retained Placenta After Spontaneous Separation With Conversion to Hysterectomy in Cases of Cesarean Sections With Suspected Placenta Accreta Spectrum.

Fumitaka Mukouyama, Akiko Omoto, Makiko Anbe, Yoshiko Shinohara, Mika Sato, Akiko Nagasawa, Emiri Nakada, Hiroshi Ishikawa, Kaori Koga.

   AIM: To identify clinical parameters for conversion to cesarean hysterectomy (CH) due to uncontrollable hemorrhage in cesarean sections performed for placenta previa with suspected placenta accreta spectrum (PAS).
METHODS: We retrospectively analyzed 44 cases of cesarean sections for placenta previa with suspected PAS performed between 2008 and 2025. Outcomes were assessed based on the intraoperative status of placental separation, with particular emphasis on cases exhibiting placental separation. Univariable analyses were conducted to identify factors associated with increased blood loss.
RESULTS: CH was performed in 21 cases without placental separation according to institutional management protocols. Among the 23 cases with placental separation, 12 required CH due to uncontrollable hemorrhage, whereas uterine preservation was successfully accomplished in 11. Within this subgroup, blood loss was significantly greater in cases requiring CH (p = 0.045), and the presence of partial placental remnants was more frequent (odds ratio, 19.25; 95% confidence interval, 1.76-209.5; p = 0.0094). Additionally, the presence of partial placental remnants was associated with increased blood loss (p = 0.015).
CONCLUSIONS: Intraoperative placental remnants after spontaneous placental separation were associated with uncontrollable hemorrhage requiring CH. When partial placental remnants are identified after placental separation, careful attention to hemorrhage management and intraoperative decision-making is required.

Keywords:  cesarean section; hysterectomy; placenta accreta; placenta previa

DOI:  https://doi.org/10.1111/jog.70386
bioRxiv. 2026 Jun 11. pii: 2026.06.07.730723. [Epub ahead of print]

Perinatal Semaglutide Treatment Improves Maternal Health and Mitigates Offspring Metabolic Dysfunction in a Mouse Model of Maternal Obesity.

Ananthi Rajamoorthi, Taylor Hollingsworth, Yuxia Guan, Sara E Pinney, Rebecca A Simmons.

Early-life exposures during critical periods of development significantly impact lifelong metabolic risk and likely contribute to the rising rates of obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease (MASLD) in children. Here, we evaluated the safety and metabolic effects of semaglutide, a GLP-1 receptor agonist (GLP-1 RA), administered from preconception through lactation in dams fed a high-fat diet (HFD) or standard diet, and assessed metabolic outcomes in dams and their offspring. Offspring were weaned to a standard diet. We found that semaglutide improved body composition and glucose metabolism in HFD-fed dams during pregnancy. These maternal changes persisted 10 weeks after weaning despite discontinuation of semaglutide treatment. HFD exposure impaired glucose homeostasis and promoted hepatic steatosis in offspring at 18 weeks. These effects were ameliorated by maternal semaglutide treatment. Importantly, metabolic improvements in dams and offspring occurred without adverse effects on conception rate or fetal viability. These findings suggest that GLP-1 RA during the perinatal period can improve maternal and offspring metabolic health in a mouse model of obesity and support further investigation of GLP-1-based therapies to mitigate maternal metabolic dysfunction and improve metabolic risk in children.
ARTICLE HIGHLIGHTS: Rates of obesity, type 2 diabetes, and fatty liver disease are rising in children, in part due to maternal obesity and insulin resistance that program offspring metabolic risk during the perinatal period.We asked whether the GLP-1 receptor agonist (GLP-1 RA), semaglutide, administered during critical developmental windows could prevent adverse outcomes in offspring using a diet-induced mouse model of maternal obesity.Semaglutide, given to dams from preconception through lactation, improved maternal metabolism and ameliorated metabolic dysfunction in offspring caused by maternal high-fat diet.These findings highlight a potential role for perinatal GLP-1 receptor agonism to improve maternal metabolic health and reduce metabolic risk in offspring.

DOI: https://doi.org/10.64898/2026.06.07.730723
Placenta. 2026 Jun 20. pii: S0143-4004(26)00299-7. [Epub ahead of print]182 150-157

Luteolin decreases sFlt-1 and mean arterial pressure in the RUPP animal model of placental ischemia.

Adrian C Eddy, Bhavisha A Bakrania, Weiwei Yang, Augustine Rajakumar, Eric M George, Joey P Granger, Sarosh Rana.

   OBJECTIVES: Preeclampsia (PE) is a complication of pregnancy and a leading cause of maternal and fetal morbidity and mortality. Despite being prevalent and highly morbid, there are no approved treatments to relieve PE signs and symptoms. Many studies have established that elevated levels of circulating anti-angiogenic soluble fms-like tyrosine kinase 1 (sFlt-1) protein drives the maternal syndrome observed in PE, and reductions in sFlt-1 improved symptoms. We have previously reported that the bioflavonoid luteolin reduces sFlt-1 expression and the vasoconstrictor endothelin-1 (ET-1) in vitro and dilates uterine arteries ex vivo. Here, we set out to determine whether luteolin reduces mean arterial pressure (MAP), sFlt-1, and ET-1, and improves uterine artery resistance index (UARI) in the reduced uterine perfusion pressure (RUPP) rat model of PE.
STUDY DESIGN: On gestation day (GD) 14, animals were randomly separated into 4 groups: sham or RUPP treated with vehicle or luteolin (20 mg/kg/day). On GD19, MAP and UARI were measured, followed by blood and tissue collection.
MAIN OUTCOME MEASURES: Placental protein expression of sFlt-1 and HIF-1α (Western blot) and circulating levels of sFlt-1, placental growth factor (PlGF) and ET-1 were measured (ELISA).
RESULTS: RUPP animals treated with luteolin demonstrated significant decreases in MAP, UARI, sFlt-1, and ET-1 compared to RUPP animals given a vehicle. There were no differences in sham animals treated with luteolin, and no adverse maternal or fetal outcomes were observed.
CONCLUSIONS: Luteolin effectively reduced blood pressure, improved uterine artery flow impedance, and reduced antiangiogenic markers in the RUPP model of PE without any observable adverse effects.

Keywords:  ET-1; Hypertension; Luteolin; Preeclampsia; RUPP; sFlt-1

DOI:  https://doi.org/10.1016/j.placenta.2026.06.010
BMC Pregnancy Childbirth. 2026 Jun 22.

A predictive model for high-quality blastocyst formation using Day 3 morphological scores in women of advanced maternal age.

Tingting Zheng, Ningjing Chen, Xiaofei Wang, Jianqiang Guo, Hong Ye.

   OBJECTIVE: To develop and validate a simple predictive model based on Day 3 embryo morphology to guide blastocyst culture strategy and optimize transfer outcomes for women of advanced maternal age (AMA).
METHODS: This retrospective study analyzed a total of 6840 cleavage-stage embryos from 1102 fresh oocyte retrieval cycles with subsequent blastocyst culture in AMA patients. Key parameters including the number of oocytes retrieved, Day 2 and Day 3 cell numbers, embryo fragmentation, embryo grade, and the number of high-quality Day 3 embryos were assessed. Their associations with the blastocyst formation rate (BR), high-quality blastocyst formation rate (HBR) and clinical outcomes were evaluated.
RESULTS: Logistic regression identified the number of high-quality Day 3 embryos as a pivotal independent predictor. A threshold of ≥ 4 high-quality embryos was established. For cycles meeting this criterion, the risk of having no Day 5 transferable blastocyst was 19.30%. Within this group, Day 5 blastocyst transfer was associated with significantly higher clinical pregnancy and live birth rates, a lower multiple pregnancy rate, and improved neonatal outcomes (higher gestational age and birth weight) compared to Day 3 cleavage-stage transfer. The threshold showed good predictive performance in a temporally separated validation cohort (AUC 0.91).
CONCLUSION: In AMA patients, a threshold of ≥ 4 high-quality Day 3 embryos may serve as a practical, low-cost criterion to guide blastocyst culture and elective single blastocyst transfer. The approach is associated with favorable clinical and neonatal outcomes but requires prospective validation in unselected populations.

Keywords:  Advanced maternal age; Blastocyst culture; Blastocyst formation rate; Day 3 high-quality embryo; High-quality blastocyst formation rate; Single blastocyst transfer

DOI:  https://doi.org/10.1186/s12884-026-09542-y