bims-placeb 2025-10-05 papers

bims-placeb

Biomed News

on Placental cell biology

Issue of 2025–10–05
fifteen papers selected by
Carlos M Guardia, National Institute of Environmental Health Sciences

Trophoblast Organoids: Capturing the Complexity of Early Placental Development In Vitro.
Hydrogen sulfide in placental development and pregnancy disorders: mechanisms, therapeutic potential, and translational challenges.
Characterization of placental pathology in Beckwith-Wiedemann Syndrome due to alterations in the KCNQ1OT1:TSS-DMR region.
Maternal body composition and the placental-fetal unit under maternal high-fat feeding partially improve by metformin treatment or lifestyle interventions during pregnancy in a mouse model.
NNMT expression in preeclampsia: Analyses on placental tissues and cell lines.
Building the start: Unlocking advanced stem cell-based embryo models.
Impact of dietary salicylates on angiogenic factors and biochemical parameters in a rat model of preeclampsia.
Hofbauer cell alterations and potential role in the pathophysiology of HELLP syndrome.
Metabolomic landscape of fetal organ development during late gestation in mice.
Bisphenol A impairs developmental potential of mouse blastoids through oxidative stress.
Does high serum oestradiol during stimulation influence obstetrical outcomes and placental pathology in subsequent frozen embryo transfers?
LAG-3 palmitoylation-inducing dysfunction of decidual CD4+T cells is associated with recurrent pregnancy loss.
Centrosomes regulate pronuclear apposition ensuring parental genome unification in cattle.
Liquid biopsy of embryo culture medium for assessing human embryo viability using Raman spectroscopy.
Effects of Perfluorobutane Sulfonate (PFBS) on Female Reproduction, Pregnancy, and Birth Outcomes.

Organoids. 2024 Sep;3(3): 174-193

Trophoblast Organoids: Capturing the Complexity of Early Placental Development In Vitro.

Brady M Wessel, Jenna N Castro, Victoria H J Roberts.

  First trimester placental development comprises some of the most critical yet understudied events that impact fetal development. Improper placentation leads to a host of health issues that not only impact the fetal period but also influence offspring throughout their lives. Thus, a paradigm to study early placental development is necessary, and this has spurred on the pursuit of new in vitro model systems that recapitulate specific aspects of placentation. One of the most complex and translationally valid models to arise are organoids, three-dimensional structures comprising multiple differentiated cell types that originate from a common progenitor population. Trophoblasts are the progenitor cells of the placenta, serving as the proliferative base for placental development. Recent advances have enabled the derivation of organoids from primary tissue, yet access to first trimester human samples is ethically constrained; derivation from established trophoblast stem cell lines is an alternative source. Organoids have already proven useful in generating insights into molecular events that underlie trophoblast differentiation, with the identification of new cell subtypes that are primed to differentiate down different paths. In this review, (1) we recap early pregnancy development events, (2) provide an overview of the cellular complexity of the placenta, (3) discuss the generation of organoids from tissue versus cellular sources, (4) highlight the value of translational animal models, and (5) focus on the complexities of the molecular regulation of trophoblast organoid development, differentiation, and function.

Keywords:  differentiation; first trimester placenta; in vitro model; nonhuman primate; trophoblast; trophoblast organoids

DOI:  https://doi.org/10.3390/organoids3030012
Reprod Biol Endocrinol. 2025 Sep 30. 23(1): 129

Hydrogen sulfide in placental development and pregnancy disorders: mechanisms, therapeutic potential, and translational challenges.

Lijia Du, Rui Zheng, Weina Ren, Yingru Liu, Xiaoxiong Zhu, Shiyang Chang, Zhifen Yang.

  The placenta plays a crucial role in maintaining pregnancy stability, regulating fetal growth, and facilitating maternal-fetal exchange. Its proper development relies on placental vasculogenesis and angiogenesis, along with adaptive remodeling of the maternal uterine vasculature. However, the mechanisms underlying placental development and the successful establishment of the maternal-fetal interface remain incompletely understood. As the third gaseous signaling molecule identified after nitric oxide (NO) and carbon monoxide (CO), hydrogen sulfide (H₂S) has been demonstrated to regulate vascular adaptation during pregnancy by promoting angiogenesis and neovascularization. Dysregulated H₂S biosynthesis has been implicated in pregnancy complications, including preeclampsia (PE), fetal growth restriction (FGR), and preterm birth (PTB), underscoring its potential as a therapeutic target. Recent studies have revealed that H₂S regulates placental function via multiple signaling pathways, including activating adenosine triphosphate (ATP)-sensitive K+ (KATP) channels, large-conductance calcium-activated potassium channels (BKCa channels), endothelial nitric oxide synthase (eNOS) signaling, and mitochondrial dynamics. Notably, H₂S-mediated persulfidation of mitochondrial Rho GTPase 2 (Miro2) has been shown to maintain trophoblast invasiveness and promote placental vascular homeostasis. Additionally, exogenous H₂S donors (e.g., GYY4137 and NaHS) have demonstrated therapeutic potential in experimental models, effectively reversing PE-like pathologies, improving placental perfusion, and restoring trophoblast function. Research further indicates that BKCa channels play a key role in H₂S-mediated vasodilation by modulating intracellular Ca²⁺ flux, which influences placental vascular tone and perfusion, reinforcing the importance of H₂S in maternal-fetal circulation regulation. This review provides a comprehensive summary of H₂S biosynthesis and metabolism and its regulatory role in early placental development. Notably, elevated estrogen levels during pregnancy have been identified as key regulators of H₂S production, and we discuss the molecular mechanisms by which estrogen modulates H₂S synthesis. Furthermore, we discuss the vascular-protective and anti-inflammatory properties of H₂S donors and dual-donor strategies. As research continues to reveal H₂S-mediated mechanisms in placental function and pregnancy disorders, optimizing the pharmacological application and clinical translation of H₂S donors and combination therapies will be a key research focus. Advancing H₂S metabolic regulation, signaling pathways, and targeted delivery systems may drive the development of novel diagnostic tools and therapeutic strategies for pregnancy complications.

Keywords:  Estradiol-β; Fetal growth restriction (FGR); Hydrogen sulfide (H2S); H₂S donors; Placental development; Preeclampsia (PE); Spiral artery remodeling (SAR); Uterine blood flow (UtBF)

DOI:  https://doi.org/10.1186/s12958-025-01465-1
Placenta. 2025 Sep 27. pii: S0143-4004(25)00705-2. [Epub ahead of print]171 102-110

Characterization of placental pathology in Beckwith-Wiedemann Syndrome due to alterations in the KCNQ1OT1:TSS-DMR region.

Sanam L Kavari, Andrew M George, Rebecca L Linn, Jennifer M Kalish.

   INTRODUCTION: Beckwith-Wiedemann Syndrome (BWS) is an imprinting disorder characterized by fetal and placental overgrowth. BWS is most often caused by genetic and epigenetic alterations involving the KCNQ1OT1-TSS:DMR (IC2) imprinting control region which alters expression of CDKN1C (p57KIP2). Here we report a cohort of patients with BWS primarily due to defects at IC2 compared to a well matched, non-BWS cohort to establish the placental features associated with these BWS subtypes.
METHODS: This is a retrospective case-control study. Our cohort of 28 patients with BWS were matched to a non-BWS cohort of 28 unaffected patients. The rate of clinical and pathological features in the BWS and non-BWS cohorts were compared. Additionally, the associations between loss of p57KIP2 staining in the BWS cohort, placental pathology, and clinical outcomes were analyzed.
RESULTS: We identified key pathological features in the placenta associated with BWS including placentomegaly, umbilical cord edema, abnormal chorionic vascular pattern, macroscopic cysts, stem villous stromal expansion, and abnormal extravillous trophoblast (EVT) morphology. We found that placental overgrowth in BWS is disproportionate to fetal overgrowth. We also identified associations between abnormal EVT morphology, loss of p57KIP2 staining, and rates of prematurity in patients with BWS.
DISCUSSION: Novel features associated with BWS identified in this work can be used to inform the diagnosis of BWS when examining the placenta. Additionally, by establishing associations between adverse pregnancy outcomes and abnormal EVT morphology, we identified a potential mechanism for the increased risk of prematurity in pregnancies complicated by BWS.

Keywords:  Beckwith-Wiedemann Syndrome; Extravillous trophoblast; Gestational hypertensive disorders; Placental mesenchymal dysplasia; Placentomegaly; Prematurity

DOI:  https://doi.org/10.1016/j.placenta.2025.09.020
Placenta. 2025 Sep 24. pii: S0143-4004(25)00701-5. [Epub ahead of print]171 91-101

Maternal body composition and the placental-fetal unit under maternal high-fat feeding partially improve by metformin treatment or lifestyle interventions during pregnancy in a mouse model.

Tobias Kretschmer, Eva-Maria Turnwald, Antje Thiele, Ciara Kallage, Lena Neweling, Merlin Kammerer, Ruth Janoschek, Peter Zentis, Marion Handwerk, Maria Wohlfarth, Simone Kalis, Eva Nüsken, Kai-Dietrich Nüsken, Inga Bae-Gartz, Angela Köninger, Alexandra Gellhaus, Dirk Gründemann, Eva Hucklenbruch-Rother, Jörg Dötsch, Miguel A Alejandre Alcazar, Sarah Appel.

   INTRODUCTION: Studies showed that metabolic imbalances during pregnancy in obesity impair the maternal-fetal axis, resulting in fetal growth disturbances with higher risk later in life. Since research has linked many of maternal and fetal sequelae to placental dysfunction, we tested if treatment with an anti-diabetic drug (metformin) or lifestyle interventions improve maternal body weight, placental status or fetal growth.
METHODS: Mice were either fed a control or high-fat diet. After mating, high-fat diet mice were split into 4 subgroups, 1 received no intervention while the other 3 received either metformin treatment, a nutritional intervention (NI) or an exercise intervention (RUN). At gestational day 15.5, mice were sacrificed.
RESULTS: All interventions improved body weight of high-fat diet dams, but only NI and RUN maintained fetal growth compared to HFD. Investigation of the placenta showed that (i) NI reduced lipid accumulation in the labyrinth zone (LZ) but neither NI nor RUN attenuated calcification and oxidative stress. Endothelial gammaH2AX staining was decreased in the LZ by both NI and RUN. (ii) Metformin did not attenuate lipid accumulation in the LZ, placental calcification and oxidative stress, however, protein levels of the endothelial cell marker CD31 were restored in whole placenta lysates. No changes were detected for fetal vessel capillary surface or length of the LZ under any intervention group.
DISCUSSION: Although all tested interventions had beneficial effects on the mother and the placental-fetal unit, NI seems to be most promising. Our findings highlight that preventive strategies for women with obesity should aim for pre-counseling advisory service. In particular, NI and RUN protected from endothelial stress response and metformin was vasculo-protective, offering strategies to preserve the physiological placental-fetal unit and materno-fetal nutrient supply.

Keywords:  Calcification; Endothelial DNA damage; Maternal obesity; Oxidative stress; Placenta; Placental fetal vasculature

DOI:  https://doi.org/10.1016/j.placenta.2025.09.016
Placenta. 2025 Sep 26. pii: S0143-4004(25)00702-7. [Epub ahead of print]171 111-120

NNMT expression in preeclampsia: Analyses on placental tissues and cell lines.

Giovanni Tossetta, Roberto Campagna, Sonia Fantone, Nicoletta Di Simone, Veronica Pompei, Stefano Raffaele Giannubilo, Andrea Ciavattini, Davide Sartini, Monica Emanuelli, Daniela Marzioni.

   OBJECTIVE: Preeclampsia (PE) is a multisystem disorder characterized by new onset hypertension and proteinuria during pregnancy. Nicotinamide N-methyltransferase (NNMT) is an enzyme that catalyzes the N-methylation of nicotinamide (NAM) to form 1-methylnicotinamide (MNA) and S-adenosyl-L-homocysteine (SAH). The aim of this study was to investigate NNMT expression in normal and PE placentas, and evaluate whether hypoxia, oxidative stress and inflammation could modulate NNMT expression.
MATERIALS AND METHODS: Immunohistochemistry and Western blot were performed on first trimester, normal term and PE placentas. NNMT expression was also evaluated in HTR-8/SVneo and BeWo cell lines under hypoxic, oxidative stress (by H2O2) and inflammatory (by TNF-α) conditions.
RESULTS: NNMT was expressed in cytotrophoblast and syncytiotrophoblast of first, third and PE placentas. Endothelial vessels were positive for NNMT expression in first and third trimester but mainly negative in PE placentas. NNMT expression did not change from first to third trimester but significantly decreased in PE placentas compared to control placentas. NNMT was expressed in the cytoplasm of both HTR-8/SVneo and BeWo cell lines, and its expression was not altered by syncytialization. Hypoxia decreased NNMT expression in BeWo but not HTR-8/SVneo cells while oxidative stress did not alter NNMT expression in both cell lines. TNF-α treatment significantly decreased NNMT expression in both cell lines.
CONCLUSIONS: Low NNMT expression found in PE placentas may represent a response to the hypoxia and inflammation featuring this disorder. Therefore, the enzyme could contribute to the normal human placental development, by defending trophoblast cells form PE-induced damages.

Keywords:  BeWo; HTR-8/SVneo; Hypoxia; Nicotinamide N-Methyltransferase; Placenta; Preeclampsia

DOI:  https://doi.org/10.1016/j.placenta.2025.09.017
Cell Stem Cell. 2025 Oct 02. pii: S1934-5909(25)00331-5. [Epub ahead of print]32(10): 1477-1478

Building the start: Unlocking advanced stem cell-based embryo models.

Zekun Wu, Hongan Ren, Leqian Yu.

Two recent studies from the Silva and Hanna groups optimized chemical induction and culture conditions to derive extraembryonic lineages directly from embryonic stem cells (ESCs) without transgenes, enabling mouse stem cell-based embryo models (SCBEMs) to reproducibly advance to the E8.5-E8.75 stage.

DOI: https://doi.org/10.1016/j.stem.2025.08.016
PLoS One. 2025 ;20(9): e0333543

Impact of dietary salicylates on angiogenic factors and biochemical parameters in a rat model of preeclampsia.

Joanna Suliburska, Rafsan Syabani Cholik, Marta Karaźniewicz-Łada, Dorota Wronka, Anna Karlik, Agnieszka Waśkiewicz, Katarzyna Skrypnik, Paweł Kołodziejski, Adam Cieślak, Łukasz Przybył.

BACKGROUND: The pathophysiology of preeclampsia involves impaired cytotrophoblastic invasion, placental ischemia, inflammation, and angiogenic imbalance. Prophylactic low-dose aspirin can reduce the risk of preeclampsia and fetal growth restriction in high-risk women. This study evaluated the effect of dietary salicylates on the development of preeclampsia in rats treated with L-NAME (NG-nitro-L-arginine-methyl ester).
METHODOLOGY: Pregnant Sprague-Dawley rats were randomly assigned to six groups and treated with dietary salicylates at two dose levels (1 and 10 mg/kg diet) or aspirin (doses adjusted to dietary salicylates). Preeclampsia was induced by administering L-NAME in drinking water from gestational days 6-19.
RESULTS: Neither dietary salicylates nor aspirin, at either dose, affected blood pressure in L-NAME-treated rats. The lower dose of dietary salicylates significantly reduced urinary albumin levels. Both interventions prevented an increase in the sFlt/PLGF ratio and mitigated histopathological placental changes in preeclamptic rats. The higher dose of aspirin reduced placental VEGFR2 protein levels.
CONCLUSION: Dietary salicylate supplementation does not provide clear preventive effects against preeclampsia.

DOI: https://doi.org/10.1371/journal.pone.0333543
Hum Cell. 2025 Sep 29. 38(6): 167

Hofbauer cell alterations and potential role in the pathophysiology of HELLP syndrome.

Ayano Ezaki, Akihito Sagara, Yoshihiro Komohara, Cheng Pan, Hiromu Yano, Shukang Zhao, Mayuko Yamamoto, Anri Imamura, Hinano Akita, Jie Su, Ren Shirotani, Tomoka Takahashi, Daiki Yoshii, Yukio Fujiwara, Masahiro Yamamoto, Munekage Yamaguchi, Eiji Kondoh.

  HELLP syndrome, a severe pregnancy complication characterized by hemolysis, elevated liver enzymes, and low platelet count, is a subtype of preeclampsia (PE). However, its rapid onset and unique clinical features suggest distinct underlying mechanisms. Although Hofbauer cells are essential for maintaining immune homeostasis, their involvement in HELLP syndrome remains unclear. We conducted transcriptomic analysis of public data sets to assess macrophage-associated gene expression in placentas from control, PE, and HELLP cases. Immunohistochemistry and image analysis were performed on formalin-fixed paraffin-embedded placental tissues to quantify macrophage density and size, and electron microscopy was conducted to evaluate ultrastructural features. Gene expression analysis revealed a significant reduction in AIF1 (Iba1) and CD163 expression in PE placentas, while CD163 expression was relatively preserved in HELLP. Immunohistochemistry confirmed decreased Hofbauer cell density in PE placentas, whereas enlarged Hofbauer cells with increased rough endoplasmic reticulum, suggesting enhanced activation status, were seen in HELLP. Hofbauer cells exhibit distinct morphological and molecular changes in HELLP syndrome compared with PE, which implicates their potential involvement in the pathophysiology of HELLP. These findings provide new insights into the fetal immune environment in pregnancy-related hypertensive disorders.

Keywords:  AIF1; CD163; HELLP; Hofbauer cell; Iba-1; PE

DOI:  https://doi.org/10.1007/s13577-025-01297-6
Commun Biol. 2025 Oct 03. 8(1): 1423

Metabolomic landscape of fetal organ development during late gestation in mice.

Chanyi Li, Wuping Liu, Xiaodong Li, Bo Lv, Jiaying Qin, Ning Yi, Bianling Xu, Jing Xu, Zhigang Xue, Hongli Yan, Jinfeng Xue.

Metabolism is the critical basis for mammalian physiological functions. The systematic metabolic characteristics of major organ development during late gestation to adapt to postnatal environmental changes are still absent. Here, we detected metabolic patterns of the ICR mouse fetal organs, including the heart, stomach, liver, brain, and placenta, from embryonic days (E)15.5 to 19.5 using liquid chromatography-mass spectrometry combined with RNA sequencing and proteomics data. Our metabolic and multi-omics data showed that organs exhibited their unique metabolic characteristics during late gestation, and significant metabolic pattern transitions, especially the enhancement of digesting the fatty acids and proteins, occurred at the E16.5 to E18.5 stage. Additionally, we found the abundance of carnosine and histidine in the placenta may serve as a way to test their levels in the newborn brain in vitro. Our dataset provides a comprehensive metabolic landscape of mammalian organ development in late gestation.

DOI: https://doi.org/10.1038/s42003-025-08820-3
Environ Int. 2025 Sep 28. pii: S0160-4120(25)00571-9. [Epub ahead of print]204 109820

Bisphenol A impairs developmental potential of mouse blastoids through oxidative stress.

Yookyung Kang, Yeji Lee, Seung Yeon Oh, Kwonho Hong, Jeong Tae Do.

  Bisphenol A (BPA) is a widely encountered environmental endocrine disruptor with detrimental effects on embryonic development and implantation. Conventional reproductive toxicity tests often rely on animal-derived gametes or embryos. However, these approaches are invasive and limited in their ability to assess early germline development. To address these limitations, we used a synthetic embryo model derived from pluripotent stem cells (PSCs) to evaluate BPA-induced embryotoxicity without using actual oocytes or embryos. Mouse PSCs were converted into chemically induced totipotent-like stem cells (ciTotiSCs) using a defined small-molecule combination. These ciTotiSCs generated blastoids (ciToti-blastoids) through three-dimensional aggregation in inverted pyramid-shaped microwell plates (AggreWell system) and cultured for 5 d. To investigate the impact of environmental toxicants on early embryogenesis, blastoids were exposed to 5  μM BPA during formation. Blastoid formation efficiency was reduced to approximately 14 % following treatment with 5 μM BPA, compared with approximately 73 % in the control. To assess implantation potential, established blastoids were further cultured on the Matrigel-coated dish. BPA-treated blastoids exhibited a reduction in inner cell mass (ICM) area and in trophectoderm (TE) area, approximately 96 % and 72 %, respectively, indicating impaired implantation potential. These detrimental effects of BPA were accompanied by elevated reactive oxygen species (ROS) levels during ciToti-blastoid formation. Co-treatment with the antioxidant glutathione (GSH; 0.5 mM), a ROS scavenger, restored blastoid formation efficiency (approximately 54 %) and resulted in a similar normalized ICM and TE areas comparable to control. Transcriptomic analysis revealed that BPA induced endoplasmic reticulum stress, DNA damage, and apoptosis, all of which were mitigated by GSH treatment. These results highlight the role of oxidative stress in BPA-induced embryotoxicity and support the utility of stem cell-derived blastoid models as egg-free platforms for assessing the reproductive toxicity of environmental chemicals.

Keywords:  Bisphenol A; Blastoid; Embryotoxicity; Oxidative stress

DOI:  https://doi.org/10.1016/j.envint.2025.109820
Zygote. 2025 Sep 29. 1-6

Does high serum oestradiol during stimulation influence obstetrical outcomes and placental pathology in subsequent frozen embryo transfers?

Inbal Navon, Hadas Ganer, Alexander Volodarsky-Perel, Tuyet Nhung Ton Nu, Alexandre Machado-Gedeon, Yiming Cui, Jonathan Shaul, Michael H Dahan.

   AIM: High oestradiol levels during in vitro fertilization (IVF) fresh cycles have been linked to adverse obstetric outcomes, yet whether this is due to endometrial or oocyte effects remains unclear. Investigating subsequent frozen embryo transfer (FET) cycles can help clarify the origins of these effects. This study aimed to evaluate obstetric outcomes and placental histology in FET cycles for patients with elevated serum oestradiol levels during the ovarian stimulation cycle in which the embryos were created.
METHODS: A single centre retrospective cohort study of live singleton deliveries after IVF with programmed FET from 2009 to 2017. High oestradiol during ovarian stimulation was defined as ≥10,000 pmol/L. We compared obstetric outcomes and placental findings between pregnancies with high oestradiol levels in the preceding ovarian stimulation cycle and a control group.
RESULTS: We analyzed 114 deliveries in the high oestradiol group and 194 in the control group. Baseline demographics were comparable between groups. No significant differences were observed in obstetric outcomes, including low birth weight, preeclampsia and preterm delivery. The placental macroscopic and histopathological findings did not significantly differ between the groups as well.
CONCLUSION: High oestradiol during the ovarian stimulation cycle used to create embryos is not associated with adverse obstetric outcomes or placental pathologies in pregnancies following FET. This is consistent with an endometrial effect of high oestradiol and thus support the practice of a freeze all approach in high oestradiol cycles.

Keywords:  frozen embryo transfer; in vitro fertilization; oestradiol; placenta

DOI:  https://doi.org/10.1017/S0967199425100154
Mol Med. 2025 Sep 29. 31(1): 298

LAG-3 palmitoylation-inducing dysfunction of decidual CD4+T cells is associated with recurrent pregnancy loss.

Liyuan Cui, Fengrun Sun, Xinhang Meng, Yujie Luo, Jinfeng Qian, Songcun Wang.

  Recurrent pregnancy loss (RPL) profoundly impacts not only the physical health but also the psychological well-being of women. Despite its profound effects, the underlying pathophysiological mechanisms of RPL remain largely elusive, with few discernible warning signs. Lymphocyte activation gene-3 (LAG-3) is a crucial immune checkpoint that modulates immune responses during infection and tumor. In the present study, we examined the expression of LAG-3 on CD4+T cells during pregnancy via cytometry by time-of-flight and flow cytometry. Our findings revealed a higher frequency of LAG-3+ decidual CD4+T (dCD4+T) cells in response to trophoblasts during normal pregnancy. This specific LAG-3+ subset of dCD4+T cells was found to produce a greater number of anti-inflammatory cytokines. Notably, blocking LAG-3 was highly effective in inhibiting the production of anti-inflammatory cytokines, which is detrimental to the maintenance of pregnancy. A decrease in the number of LAG-3+dCD4+T cells was correlated with miscarriage. Interestingly, the RNA level of LAG-3 (data analyzed from the two published single-cell databases) remained stable in RPL. Palmitoylation might play a role in regulating LAG-3 expression during RPL, as the palmitoylation of LAG-3+dCD4+T cells was increased in RPL. Additionally, the general palmitoylation inhibitor 2-bromopalmitate was found to upregulate LAG-3 expression on dCD4+T cells both in vitro and in vivo. Collectively, these findings highlighted the significant roles of LAG-3 in regulating the function of dCD4+T cell and maintaining normal pregnancy. Furthermore, they suggested that lower LAG-3 expression on dCD4+T cells could serve as a potential biomarker for diagnosis of RPL.

Keywords:  Decidual CD4+T cells; LAG-3; Palmitoylation; Pregnancy; Recurrent pregnancy loss

DOI:  https://doi.org/10.1186/s10020-025-01361-9
Reproduction. 2025 Nov 01. pii: e250067. [Epub ahead of print]170(5):

Centrosomes regulate pronuclear apposition ensuring parental genome unification in cattle.

Yuki Takada, Shu Hashimoto, Yoshiharu Morimoto.

   In brief: Mammalian zygotes often fail to unify their genomes. This study showed that the position of the centrosome is crucial for regulation of pronuclear apposition and genome unification.
Abstract: After the sperm enters the ovum, male and female pronuclei carrying the genetic information of both parents are formed. These pronuclei migrate to the center of the ovum, followed by genome unification upon mitosis onset. However, the genomes of some gametes fail to unify. The mechanism by which parental genetic information fails to unify is not yet fully understood. Here, we used immunofluorescence staining and live imaging techniques to study pronuclear migration in fertilized bovine ova. Microtubules play a more important role in pronuclear migration than actin. Centrosomal microtubules regulate the localization of motor dynein bound to the pronuclear membrane. The presence of at least one centrosome between the male and female pronuclei is necessary for apposition of the two pronuclei and genome unification. Our data highlight the importance of centrosome positioning in the apposition of pronuclei and parental genome unification.

Keywords:  microtubule; pronuclear migration; zygote

DOI:  https://doi.org/10.1530/REP-25-0067
Sci Rep. 2025 Sep 30. 15(1): 33986

Liquid biopsy of embryo culture medium for assessing human embryo viability using Raman spectroscopy.

Mika Ishigaki, Runa Tamano, Nao Inagaki, Hiromitsu Shirasawa, Yukiyo Kumazawa, Kazumasa Takahashi, Yukihiro Terada.

This study investigated the potential of assessing human embryo viability through the analysis of the embryo culture medium used in assisted reproductive technology (ART) via Raman spectroscopy. Two types of culture media-one for early development (medium A) and one for recovery after vitrifying/warming (medium B)-were analyzed. Our results showed that protein concentrations were higher in medium A in which embryos reached the blastocyst stage compared to those in which embryos arrested before this stage. Moreover, the pH of medium A associated with higher-grade blastocysts tended to be more acidic than that associated with lower-grade blastocysts. Conversely, in medium B, pregnancy did not occur even with high-grade blastocysts when the medium was contaminated by residual vitrifying/warming agents or had slightly elevated component concentrations due to water evaporation. Furthermore, medium B tended to be slightly alkaline with higher-grade blastocysts, in contrast to medium A. The noncontact, noninvasive, and label-free Raman spectroscopic method for assessing human embryo viability based on culture media analysis may serve as a liquid biopsy in the near future. As ART has become an important treatment for infertility, this method, which may enhance its safety and efficacy, is expected to contribute to human welfare.

DOI: https://doi.org/10.1038/s41598-025-11195-4
Obstet Gynecol Surv. 2025 Oct;80(10): 657-672

Effects of Perfluorobutane Sulfonate (PFBS) on Female Reproduction, Pregnancy, and Birth Outcomes.

Namya Mellouk, Melissa J Marchese, Fumei Gao, Shuang Liang, Liping Feng.

Importance: Perfluorobutane sulfonate (PFBS) is a short-chain per- and polyfluoroalkyl substance (PFAS) that has emerged as a significant public health concern due to its widespread environmental contamination and persistent nature. While PFBS is considered to have a shorter half-life in the environment and human body compared to other PFAS compounds, there are still growing concerns about its potential impacts on human health, particularly on female reproduction and birth outcomes.
Objective: This literature review critically examines the impact of PFBS exposure on female reproductive health, pregnancy outcomes, and fetal development, synthesizing the most recent data from both human and animal studies.
Evidence Acquisition: A comprehensive literature search was conducted using data from peer-reviewed articles, clinical trials, animal models, and regulatory reports.
Results: These studies suggest that PFBS may have adverse effects on fertility, pregnancy health, and fetal development. It also explores the current regulatory landscape for PFBS, focusing on policies in Europe, the United States, and Asia while emphasizing the growing global efforts to establish more stringent guidelines and develop effective treatment technologies to mitigate PFBS exposure. Given the bioaccumulative properties of PFBS and its increasing detection through environmental surveillance, ongoing research, especially targeted studies in human populations, is urgently needed to fully elucidate its reproductive toxicity, including its potential transgenerational effects.
Conclusion and Relevance: This review underscores the importance of understanding PFBS mechanisms of action at the molecular and epigenetic levels, as this knowledge will be essential for informing public health strategies, shaping regulatory policies, and developing interventions to reduce human and environmental exposure.

DOI: https://doi.org/10.1097/OGX.0000000000001440