Pub Date : 2026-01-01DOI: 10.1016/j.placenta.2025.02.002
María S. Martinez , Yair A. Chocobar , Yamila Fariz , Daniela A. Paira , Virginia E. Rivero , Rubén D. Motrich
This review explores the critical role of semen inflammation in sperm quality, embryo implantation, placentation, and its broader implications on reproductive health. Chronic inflammation of the male genital tract has been increasingly recognized as a significant factor contributing to infertility. This inflammation not only impairs semen quality but also disrupts the intricate immune cross-talk between the male and female genital tracts, which is essential for successful implantation, placentation and pregnancy. The review synthesizes existing research on the mechanisms by which inflammatory mediators in semen influence the female immune environment, leading to altered uterine receptivity, placental formation, and embryo implantation. Furthermore, the impact of these disruptions on the health and development of the offspring is discussed, highlighting the transgenerational effects of male genital tract inflammation. Through an examination of both animal models and human studies, this review underscores the need for a deeper understanding of the immune interactions in reproductive biology and the potential for novel therapeutic interventions aimed at mitigating the adverse outcomes associated with semen inflammation.
{"title":"Effects of semen inflammation on embryo implantation, placentation, pregnancy outcomes and offspring health","authors":"María S. Martinez , Yair A. Chocobar , Yamila Fariz , Daniela A. Paira , Virginia E. Rivero , Rubén D. Motrich","doi":"10.1016/j.placenta.2025.02.002","DOIUrl":"10.1016/j.placenta.2025.02.002","url":null,"abstract":"<div><div>This review explores the critical role of semen inflammation in sperm quality, embryo implantation<span>, placentation<span>, and its broader implications on reproductive health<span><span><span>. Chronic inflammation of the male genital tract has been increasingly recognized as a significant factor contributing to infertility. This inflammation not only impairs semen quality but also disrupts the intricate immune cross-talk between the male and female genital tracts, which is essential for successful implantation, </span>placentation<span><span> and pregnancy. The review synthesizes existing research on the mechanisms by which inflammatory mediators in semen influence the female immune environment, leading to altered uterine receptivity, placental formation, and </span>embryo implantation. Furthermore, the impact of these disruptions on the health and development of the offspring is discussed, highlighting the transgenerational effects of male genital tract inflammation. Through an examination of both animal models and human studies, this review underscores the need for a deeper understanding of the immune interactions in </span></span>reproductive biology<span> and the potential for novel therapeutic interventions aimed at mitigating the adverse outcomes associated with semen inflammation.</span></span></span></span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 140-152"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143409918","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.placenta.2025.05.003
Pietro Presicce , Marco Morselli , Anhyo Jeong , Marie Altendahl , Guadalupe Martinez , Giorgia Del Vecchio , Sherin U. Devaskar , Matteo Pellegrini , Yalda Afshar , Suhas G. Kallapur
Background
COVID-19 infection in pregnancy is associated with preterm birth and an increased risk of severe disease, needing intensive care admission for management of maternal multi-organ failure. The placenta, a fetal organ, functions as a barrier at the maternal interface and expresses the SARS-CoV-2 viral receptors. However, placental infection and transplacental transfer of virus are rare, suggesting placental resistance to viral infection. Here, we seek to determine the impact of severe COVID-19 infection on maternal, newborn, and placental outcomes.
Methods
A prospectively recruited cohort of pregnant COVID-19 patients (n = 204) at a quaternary perinatal academic center were retrospectively analyzed. During pregnancy umbilical artery (UA) Doppler assessment was performed to assess placental function. At delivery, maternal and fetal outcomes were assessed, with paired maternal peripheral blood and placenta samples collected (n = 26) for bulk RNA sequencing (RNA-seq). Post-sequencing analysis with single cell deconvolution and pathway analysis was performed.
Results
Maternally-indicated preterm births were more frequent in severe, but not asymptomatic or mild/moderate COVID-19 infection. In severe COVID-19 infection, UA Doppler assessment was normal. Rates of fetal growth restriction and placenta:birth weight ratios were similar between groups. RNA-seq showed a distinct adaptive immune activation signature in peripheral blood while placental transcripts showed no significant changes in immune cell types.
Conclusion
Despite multi-organ failure, severe COVID-19 did not significantly impact placental function and transcriptomics with iatrogenic preterm birth indicated for maternal-indications.
{"title":"Placental Privilege: Evidence of organ resilience in severe COVID-19 in pregnancy","authors":"Pietro Presicce , Marco Morselli , Anhyo Jeong , Marie Altendahl , Guadalupe Martinez , Giorgia Del Vecchio , Sherin U. Devaskar , Matteo Pellegrini , Yalda Afshar , Suhas G. Kallapur","doi":"10.1016/j.placenta.2025.05.003","DOIUrl":"10.1016/j.placenta.2025.05.003","url":null,"abstract":"<div><h3>Background</h3><div><span>COVID-19 infection in pregnancy is associated with preterm birth<span> and an increased risk of severe disease, needing intensive care admission for management of maternal multi-organ failure. The placenta, a </span></span>fetal organ<span><span>, functions as a barrier at the maternal interface and expresses the SARS-CoV-2 viral receptors. However, placental infection and </span>transplacental transfer<span> of virus are rare, suggesting placental resistance to viral infection. Here, we seek to determine the impact of severe COVID-19 infection on maternal, newborn, and placental outcomes.</span></span></div></div><div><h3>Methods</h3><div><span>A prospectively recruited cohort of pregnant COVID-19 patients (n = 204) at a quaternary perinatal academic center were retrospectively analyzed. During pregnancy umbilical artery (UA) Doppler assessment was performed to assess </span>placental function<span>. At delivery, maternal and fetal outcomes were assessed, with paired maternal peripheral blood and placenta samples collected (n = 26) for bulk RNA sequencing (RNA-seq). Post-sequencing analysis with single cell deconvolution and pathway analysis was performed.</span></div></div><div><h3>Results</h3><div>Maternally-indicated preterm births were more frequent in severe, but not asymptomatic or mild/moderate COVID-19 infection. In severe COVID-19 infection, UA Doppler assessment was normal. Rates of fetal growth<span> restriction and placenta:birth weight ratios were similar between groups. RNA-seq showed a distinct adaptive immune activation signature in peripheral blood while placental transcripts showed no significant changes in immune cell types.</span></div></div><div><h3>Conclusion</h3><div>Despite multi-organ failure, severe COVID-19 did not significantly impact placental function and transcriptomics<span> with iatrogenic preterm birth indicated for maternal-indications.</span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 78-86"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144094559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.placenta.2025.04.002
Rafaela José da Silva , Marcos Paulo Oliveira Almeida , Angelica Oliveira Gomes , Priscila Silva Franco , Guilherme de Souza , Alessandra Monteiro Rosini , Iliana Claudia Balga Milian , João Paulo Silva Servato , José Roberto Mineo , Tiago Wilson Patriarca Mineo , Neide Maria Silva , Eloisa Amália Vieira Ferro , Bellisa Freitas Barbosa
The placenta acts as a critical barrier against pathogens during pregnancy, although Toxoplasma gondii can breach this defense, leading to congenital infections. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule involved in immune responses, including leukocyte recruitment and pathogen clearance. Here, we investigate the role of ICAM-1 in gestational success and T. gondii infection using wild-type (WT) and ICAM-1 knockout (ICAM-1−/−) mice across early, mid- and late pregnancy stages. In early pregnancy, ICAM-1−/− mice infected with T. gondii exhibited a significantly higher embryonic loss rate (63 %) compared to WT mice (5 %). This was accompanied by an increased parasite burden in uterine tissues and elevated systemic and local IFN-γ levels, despite a reduced local inflammatory response. In contrast, mid-pregnancy showed no significant differences in fetal loss or implantation success among groups, suggesting ICAM-1 plays a limited role at this stage. During late pregnancy, ICAM-1−/− mice experienced higher embryonic loss rates (40 %) compared to WT mice (26.2 %), along with reduced implantation success and elevated IFN-γ levels, though parasite burden remained unchanged. Histological analysis revealed a less severe inflammatory profile in infected ICAM-1−/− uterine tissues, marked by reduced necrosis and hyperemia compared to WT mice. FOXP3 expression, a marker of regulatory T cells, was unaffected by ICAM-1, although a trend towards reestablishment was observed in infected ICAM-1−/− mice. Our findings underscore the critical role of ICAM-1 in ensuring gestational success during T. gondii infection, particularly in early pregnancy, by modulating immune responses at the maternal-fetal interface.
{"title":"Intercellular adhesion molecule (ICAM)-1 is required to control Toxoplasma gondii infection in uterine tissues and establish a successful gestation in a murine model of congenital toxoplasmosis","authors":"Rafaela José da Silva , Marcos Paulo Oliveira Almeida , Angelica Oliveira Gomes , Priscila Silva Franco , Guilherme de Souza , Alessandra Monteiro Rosini , Iliana Claudia Balga Milian , João Paulo Silva Servato , José Roberto Mineo , Tiago Wilson Patriarca Mineo , Neide Maria Silva , Eloisa Amália Vieira Ferro , Bellisa Freitas Barbosa","doi":"10.1016/j.placenta.2025.04.002","DOIUrl":"10.1016/j.placenta.2025.04.002","url":null,"abstract":"<div><div>The placenta acts as a critical barrier against pathogens during pregnancy, although <span><span>Toxoplasma gondii</span></span><span><span> can breach this defense, leading to congenital infections<span>. Intercellular adhesion molecule-1 (ICAM-1) is an adhesion molecule<span> involved in immune responses, including leukocyte recruitment and </span></span></span>pathogen clearance. Here, we investigate the role of ICAM-1 in gestational success and </span><em>T. gondii</em> infection using wild-type (WT) and ICAM-1 knockout (ICAM-1<sup>−/−</sup><span>) mice across early, mid- and late pregnancy<span> stages. In early pregnancy, ICAM-1</span></span><sup>−/−</sup> mice infected with <em>T. gondii</em><span><span> exhibited a significantly higher embryonic loss rate (63 %) compared to WT mice (5 %). This was accompanied by an increased parasite burden in uterine tissues and elevated systemic and local IFN-γ levels, despite a reduced local </span>inflammatory response<span>. In contrast, mid-pregnancy showed no significant differences in fetal loss or implantation success among groups, suggesting ICAM-1 plays a limited role at this stage. During late pregnancy, ICAM-1</span></span><sup>−/−</sup> mice experienced higher embryonic loss rates (40 %) compared to WT mice (26.2 %), along with reduced implantation success and elevated IFN-γ levels, though parasite burden remained unchanged. Histological analysis revealed a less severe inflammatory profile in infected ICAM-1<sup>−/−</sup><span><span><span> uterine tissues, marked by reduced necrosis and hyperemia compared to WT mice. </span>FOXP3 expression, a marker of </span>regulatory T cells, was unaffected by ICAM-1, although a trend towards reestablishment was observed in infected ICAM-1</span><sup>−/−</sup> mice. Our findings underscore the critical role of ICAM-1 in ensuring gestational success during <em>T. gondii</em> infection, particularly in early pregnancy, by modulating immune responses at the maternal-fetal interface.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 50-62"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144035393","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.placenta.2025.04.027
Evangelina Capobianco , Irune Pirrone
The Paternal Origins of Health and Disease (POHaD) paradigm emerges from the well-known Developmental Origins of Health and Disease (DOHaD) concept. Research into the programming of metabolic diseases originating from the paternal germline began over 20 years ago, focusing on the father's pre-conceptional exposure, such as metabolic disorders and lifestyle habits (kind of diet, exercise, smoking, drugs consumption, etc.). This exposure can lead to epigenetic marks not only in his germ cells but also in other components of the semen that impact the health of future generations.
The significant role of the paternal genome in the fetal component of the placenta and the recognition of the placenta's involvement in postnatal disease programming underscore the importance of studying the placenta in paternal programming research. The aim of this work is to review what we know so far about paternal programming highlighting the variations in the phenotype of the placenta and the influence of it in the programming of metabolic pathologies in the offspring of fathers exposed to metabolic disorders such as obesity and diabetes.
{"title":"The POHaD paradigm: role of the placenta in paternal programming","authors":"Evangelina Capobianco , Irune Pirrone","doi":"10.1016/j.placenta.2025.04.027","DOIUrl":"10.1016/j.placenta.2025.04.027","url":null,"abstract":"<div><div><span>The Paternal Origins of Health and Disease (POHaD) paradigm emerges from the well-known Developmental Origins of Health and Disease (DOHaD) concept. Research into the programming of metabolic diseases originating from the paternal </span>germline<span> began over 20 years ago, focusing on the father's pre-conceptional exposure, such as metabolic disorders and lifestyle habits (kind of diet, exercise, smoking, drugs consumption, etc.). This exposure can lead to epigenetic marks not only in his germ cells but also in other components of the semen that impact the health of future generations.</span></div><div>The significant role of the paternal genome in the fetal component of the placenta and the recognition of the placenta's involvement in postnatal disease programming underscore the importance of studying the placenta in paternal programming research. The aim of this work is to review what we know so far about paternal programming highlighting the variations in the phenotype of the placenta and the influence of it in the programming of metabolic pathologies in the offspring of fathers exposed to metabolic disorders such as obesity and diabetes.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 160-165"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144064544","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Maternal diabetes increases the risk of adverse maternal, perinatal and offspring outcomes. This study aimed to address whether alterations in uterine decidualization are programmed in the prepubertal offspring from diabetic rats fed diets enriched or not in extra virgin olive oil (EVOO).
Methods
Control and mild pregestational diabetic female rats (F0) were mated with control males and fed diets enriched or not with 6 % EVOO during pregnancy. Offspring (F1) were evaluated on postnatal day 30, after induction of uterine decidualization (PMSG 50 IU- hCG 50 IU). Signaling pathways involved in decidualization, including prolactin, PPAR and mTOR pathways as well as microRNAs (miRs) regulating these pathways were evaluated by Western blot or qPCR in the decidualized uteri.
Results
The offspring from diabetic rats evidenced reduced prolactin and prolactin receptor levels in the decidualized uteri. Additionally, these tissues showed increased PPARγ levels and reduced levels of its negative regulators miR-19b and miR-155. MiR-21, a microRNA that targets both PPARα and mTOR pathway regulators was reduced, whereas PPARα, PTEN and FOXO1 mRNA levels were increased in the decidualized uteri of the offspring from diabetic rats. The mTOR pathway activity was reduced in the decidualized uteri of the offspring from diabetic rats. Most of the observed alterations were prevented by the EVOO-enriched maternal diet.
Discussion
Impaired pathways relevant to decidualization are programmed in the uteri of prepubertal offspring from diabetic dams, alterations capable of being prevented by maternal diets enriched in EVOO.
{"title":"Maternal dietary olive oil protects diabetic rat offspring from impaired uterine decidualization","authors":"Cintia Romina Gatti , Florencia Schibert , Virginia Soledad Taylor , Evangelina Capobianco , Verónica Montero , Romina Higa , Alicia Jawerbaum","doi":"10.1016/j.placenta.2024.11.010","DOIUrl":"10.1016/j.placenta.2024.11.010","url":null,"abstract":"<div><h3>Introduction</h3><div><span>Maternal diabetes increases the risk of adverse maternal, perinatal and offspring outcomes. This study aimed to address whether alterations in uterine </span>decidualization<span> are programmed in the prepubertal offspring from diabetic rats fed diets enriched or not in extra virgin olive oil (EVOO).</span></div></div><div><h3>Methods</h3><div><span><span>Control and mild pregestational diabetic female rats (F0) were mated with control males and fed diets enriched or not with 6 % EVOO during pregnancy. Offspring (F1) were evaluated on postnatal day 30, after induction of uterine decidualization (PMSG 50 IU- </span>hCG<span> 50 IU). Signaling pathways<span><span><span> involved in decidualization, including prolactin, </span>PPAR and </span>mTOR<span> pathways as well as microRNAs (miRs) regulating these pathways were evaluated by </span></span></span></span>Western blot<span> or qPCR in the decidualized uteri.</span></div></div><div><h3>Results</h3><div><span>The offspring from diabetic rats evidenced reduced prolactin and prolactin receptor<span> levels in the decidualized uteri. Additionally, these tissues showed increased PPARγ levels and reduced levels of its negative regulators miR-19b and miR-155. MiR-21, a microRNA that targets both PPARα and mTOR pathway regulators was reduced, whereas PPARα, </span></span>PTEN<span> and FOXO1<span> mRNA levels were increased in the decidualized uteri of the offspring from diabetic rats. The mTOR pathway activity was reduced in the decidualized uteri of the offspring from diabetic rats. Most of the observed alterations were prevented by the EVOO-enriched maternal diet.</span></span></div></div><div><h3>Discussion</h3><div>Impaired pathways relevant to decidualization are programmed in the uteri of prepubertal offspring from diabetic dams, alterations capable of being prevented by maternal diets enriched in EVOO.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 2-11"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142751045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.placenta.2025.07.086
J.S. Beltrame , F. Scheffer , V.A. Cañumil , F.L. De la Cruz Borthiry , M. Cella , M.E. Bogetti , A.M. Franchi , M.L. Ribeiro
Subclinical infections cause an imbalance of immune homeostasis that could have severe consequences for pregnancy and progeny development. We investigated if lipopolysaccharide (LPS)-induced subclinical infection affects vascular adaptations during gestation and offspring health.
Wistar female rats received intraperitoneal vehicle (saline, control) or low doses of LPS from Escherichia coli (20 μg/kg on day 6 + 50 μg/kg on days 7–9 of gestation). Several parameters were evaluated on day 10 or 15 of pregnancy and the litter.
No signs of infection or premature birth were registered after LPS treatment. Maternal survival was not affected by LPS administration. There were no differences in the number of implantation sites or fetuses between groups. However, the blood contained in the uterine and arcuate arteries, and the placentas from LPS-treated mothers exhibited a dark reddish-brown color. Moreover, LPS increased uterine and arcuate arteries' transversal length and decreased the number of vessels in the mesometrial decidua. These vessels showed a larger perimeter. Interestingly, LPS treatment decreased intrauterine fetus growth. No differences were observed in placental efficiency and placental zone areas. An imbalance in the levels of pro-inflammatory cytokines and vascular mediators was detected in the implantation sites and placenta. Furthermore, the offspring showed sex-specific impaired weight gain and neurodevelopment, although maturation milestones were not altered.
Our findings show that LPS-induced subclinical infection affects pregnancy and offspring. These alterations are associated with deficiencies in key vascular processes and an imbalance in pro-inflammatory and vascular mediators at the maternal-fetal interface.
{"title":"Lipopolysaccharide-induced subclinical infection affects pregnancy and impairs offspring development in an early gestation rat model","authors":"J.S. Beltrame , F. Scheffer , V.A. Cañumil , F.L. De la Cruz Borthiry , M. Cella , M.E. Bogetti , A.M. Franchi , M.L. Ribeiro","doi":"10.1016/j.placenta.2025.07.086","DOIUrl":"10.1016/j.placenta.2025.07.086","url":null,"abstract":"<div><div>Subclinical infections cause an imbalance of immune homeostasis that could have severe consequences for pregnancy and progeny development. We investigated if lipopolysaccharide (LPS)-induced subclinical infection affects vascular adaptations during gestation and offspring health.</div><div>Wistar female rats received intraperitoneal vehicle (saline, control) or low doses of LPS from <em>Escherichia coli</em> (20 μg/kg on day 6 + 50 μg/kg on days 7–9 of gestation). Several parameters were evaluated on day 10 or 15 of pregnancy and the litter.</div><div>No signs of infection or premature birth were registered after LPS treatment. Maternal survival was not affected by LPS administration. There were no differences in the number of implantation sites or fetuses between groups. However, the blood contained in the uterine and arcuate arteries, and the placentas from LPS-treated mothers exhibited a dark reddish-brown color. Moreover, LPS increased uterine and arcuate arteries' transversal length and decreased the number of vessels in the mesometrial decidua. These vessels showed a larger perimeter. Interestingly, LPS treatment decreased intrauterine fetus growth. No differences were observed in placental efficiency and placental zone areas. An imbalance in the levels of pro-inflammatory cytokines and vascular mediators was detected in the implantation sites and placenta. Furthermore, the offspring showed sex-specific impaired weight gain and neurodevelopment, although maturation milestones were not altered.</div><div>Our findings show that LPS-induced subclinical infection affects pregnancy and offspring. These alterations are associated with deficiencies in key vascular processes and an imbalance in pro-inflammatory and vascular mediators at the maternal-fetal interface.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 111-123"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144800008","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Neural tube defects (NTD) are congenital malformations influenced by genetic and environmental factors. Mouse embryos deficient in Scavenger Receptor Class B Type 1 (SR-B1) exhibit female-skewed cranial NTD (exencephaly). This defect is preventable by maternal vitamin E supplementation in a C57BL/6J:129S1/SvImJ (B6:129) 1:1 background. In humans, genetic variability—such as differences across races or ethnic groups—modulates NTD penetrance and severity.
Aim and methods
This study compared reproductive outcomes and NTD incidence in two colonies of SR-B1-deficient mice (SR-B1 and SR-B1/J) with shared origin but differing backcrossing histories. The genetic background of each strain was determined using single-nucleotide-polymorphism (SNP)-based sequencing analysis.
Results
SR-B1/J mice showed significantly smaller litter sizes, slower development, and higher NTD incidence in SR-B1 KO embryos at gestational day 9.5 (E9.5) compared to SR-B1 mice. SNP analysis revealed a 50 % contribution of the 129 strain in SR-B1 mice versus 80 % in SR-B1/J mice. We also evaluated the preventive effect of maternal vitamin E supplementation in the SR-B1/J colony. Feeding dams a vitamin E-enriched diet reduced NTD incidence in the SR-B1/J colony, consistent with previous findings in the SR-B1 colony.
Discussion
This study highlights the critical influence of genetic background on NTD susceptibility in SR-B1 KO mice and demonstrates that vitamin E can reduce NTD risk across different genetic backgrounds. These findings underscore the importance of considering genetic variability in translational research and pave the way for further exploration of genetic modifiers that could enhance our understanding and prevention of NTD.
{"title":"Genetic background influences susceptibility to exencephaly in Scavenger receptor Class B type 1-deficient mouse embryos","authors":"Camila Romero-Muñoz , Patricia Romo-Toledo , Gabriela Belledonne , Dolores Busso","doi":"10.1016/j.placenta.2025.05.016","DOIUrl":"10.1016/j.placenta.2025.05.016","url":null,"abstract":"<div><h3>Introduction</h3><div><span><span><span>Neural tube defects (NTD) are </span>congenital malformations influenced by </span>genetic and </span>environmental factors<span>. Mouse embryos<span> deficient in Scavenger Receptor Class B Type 1<span> (SR-B1) exhibit female-skewed cranial NTD (exencephaly). This defect is preventable by maternal vitamin E<span> supplementation in a C57BL/6J:129S1/SvImJ (B6:129) 1:1 background. In humans, genetic variability—such as differences across races or ethnic groups—modulates NTD penetrance and severity.</span></span></span></span></div></div><div><h3>Aim and methods</h3><div>This study compared reproductive outcomes and NTD incidence in two colonies of SR-B1-deficient mice (SR-B1 and SR-B1/J) with shared origin but differing backcrossing histories. The genetic background of each strain was determined using single-nucleotide-polymorphism (SNP)-based sequencing analysis.</div></div><div><h3>Results</h3><div><span><span>SR-B1/J mice showed significantly smaller litter sizes, slower development, and higher NTD incidence in SR-B1 KO embryos at gestational day 9.5 (E9.5) compared to SR-B1 mice. SNP analysis revealed a 50 % contribution of the 129 strain in SR-B1 mice versus 80 % in SR-B1/J mice. We also evaluated the preventive effect of maternal </span>vitamin E supplementation in the SR-B1/J colony. Feeding dams </span>a vitamin E-enriched diet reduced NTD incidence in the SR-B1/J colony, consistent with previous findings in the SR-B1 colony.</div></div><div><h3>Discussion</h3><div><span><span>This study highlights the critical influence of genetic background on NTD susceptibility in SR-B1 KO mice and demonstrates that </span>vitamin E can reduce NTD risk across different genetic backgrounds. These findings underscore the importance of considering </span>genetic variability<span> in translational research and pave the way for further exploration of genetic modifiers that could enhance our understanding and prevention of NTD.</span></div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 87-94"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144182459","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.placenta.2025.02.001
Yollyseth Medina , Nazarena Fernandez , Matías N Sierra , Mauricio Castro Parodi , Alicia E Damiano
Preeclampsia is associated with increased oxidative and nitrative stress, resulting in elevated protein nitration and potential functional impairment. Previously, we found an increased expression of AQP9 protein with a loss of function in preeclamptic placentas. However, the link between nitrative stress and AQP9 has not yet been explored.
Here, we aimed to evaluate the effect of nitrative stress on placental AQP9 and its role in the pathogenesis of preeclampsia.
In silico analysis was conducted on the amino acid sequences of AQP9 to identify potential nitration sites. Levels of 3NyT-AQP9 were assessed by immunoprecipitation in normal and preeclamptic placentas. AQP9 expression and function were evaluated by culturing normal placental explants with 0, 25, 50, 100, and 200 μM ONOO- to induce nitrative stress. Viability and integrity of the explants and stress markers were determined. Water uptake and utilization of lactate mediated by AQP9 were studied along with the molecular expression of AQP9 and 3-NyT-AQP9.
The in silico analysis showed that AQP9 is more susceptible to nitration than other AQPs. The abundance of nitrated AQP9 significantly increased in preeclamptic placentas compared to normal ones (n = 4; p < 0.05). Peroxynitrite treatment also increased AQP9 protein expression without altering its gene expression and impaired the transport of water and lactate mediated by this protein.
Our findings provide evidence that nitrative stress induces the nitration of AQP9 protein, leading to the accumulation of a non-functional protein in the syncytiotrophoblasts. Therefore, this altered protein may play a pivotal role in the pathogenesis of preeclampsia by disrupting cellular homeostasis.
{"title":"Nitrative stress-induced dysregulation of placental AQUAPORIN-9: A potential key player in preeclampsia pathogenesis","authors":"Yollyseth Medina , Nazarena Fernandez , Matías N Sierra , Mauricio Castro Parodi , Alicia E Damiano","doi":"10.1016/j.placenta.2025.02.001","DOIUrl":"10.1016/j.placenta.2025.02.001","url":null,"abstract":"<div><div><span>Preeclampsia<span> is associated with increased oxidative and nitrative stress, resulting in elevated protein nitration and potential functional impairment. Previously, we found an increased expression of </span></span>AQP9<span> protein with a loss of function in preeclamptic placentas. However, the link between nitrative stress<span> and AQP9 has not yet been explored.</span></span></div><div>Here, we aimed to evaluate the effect of nitrative stress on placental AQP9 and its role in the pathogenesis of preeclampsia.</div><div><em>In silico</em><span><span><span> analysis was conducted on the amino acid sequences of AQP9 to identify potential nitration sites. Levels of 3NyT-AQP9 were assessed by </span>immunoprecipitation<span> in normal and preeclamptic placentas. AQP9 expression and function were evaluated by culturing normal placental explants<span> with 0, 25, 50, 100, and 200 μM ONOO- to induce nitrative stress. Viability and integrity of the explants and stress markers were determined. </span></span></span>Water uptake and utilization of lactate mediated by AQP9 were studied along with the molecular expression of AQP9 and 3-NyT-AQP9.</span></div><div>The <em>in silico analysis</em><span> showed that AQP9 is more susceptible to nitration than other AQPs<span><span>. The abundance of nitrated AQP9 significantly increased in preeclamptic placentas compared to normal ones (n = 4; p < 0.05). Peroxynitrite treatment also increased AQP9 </span>protein expression without altering its gene expression and impaired the transport of water and lactate mediated by this protein.</span></span></div><div><span>Our findings provide evidence that nitrative stress induces the nitration of AQP9 protein, leading to the accumulation of a non-functional protein in the syncytiotrophoblasts. Therefore, this altered protein may play a pivotal role in the pathogenesis of preeclampsia by disrupting cellular </span>homeostasis.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 21-32"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143425904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-01DOI: 10.1016/j.placenta.2025.08.332
Rosanna Ramhorst , Lourdes Materazzi , Ana Schafir , Lara Castagnola , Laura Fernández , Elizabeth Soczewski , Esteban Grasso , Gustavo Martinez , Diego Gnocchi , Antonio Cattaneo , Lautaro Tessari , Marcela Irigoyen , Claudia Perez Leirós , Soledad Gori
Embryo implantation requires a tight immune homeostatic control that activates regulatory circuits. One interlocutor is the embryo, which produces soluble ligands and expresses receptors for different autocrine and paracrine factors. The other interlocutor is the receptive endometrium, which produces mediators to regulate proliferation, differentiation, adhesion and invasiveness of the embryo, among other processes. Here, we are going to discuss experimental evidence regarding human embryo-endometrial dialogue and give a new insight of the relevance of the immune cells to coordinate embryo implantation. In this sense, decidualization of endometrial stromal cells is a multistep process that gives rise to mature decidual cells and senescent decidual cells. The first subpopulation secretes pro-implantation factors and begins migration by encapsulating the embryo. In turn, the second does not complete differentiation but rather suffers a process of premature senescence that is characterized by the production of pro-inflammatory factors (SASP, senescence-associated secretory phenotype), which contribute to embryo implantation. However, alterations in these processes or in their regulation through microRNAs lead to the perpetuation of an inflammatory response and alterations in endometrial receptivity. Considering that decidual cells acquire the ability to differentially respond to embryo quality, here we also explored how the soluble factors produced by embryos (classified according to their quality) impact on the inflammatory response and shape dendritic and other immune cell recruitment during the peri implantation period. To address these aspects, we present experimental evidence that links endoplasmic reticulum stress, senescence and inflammation and we discuss whether embryos reprogram the immune response.
{"title":"Insights into embryo-endometrium immune interactions","authors":"Rosanna Ramhorst , Lourdes Materazzi , Ana Schafir , Lara Castagnola , Laura Fernández , Elizabeth Soczewski , Esteban Grasso , Gustavo Martinez , Diego Gnocchi , Antonio Cattaneo , Lautaro Tessari , Marcela Irigoyen , Claudia Perez Leirós , Soledad Gori","doi":"10.1016/j.placenta.2025.08.332","DOIUrl":"10.1016/j.placenta.2025.08.332","url":null,"abstract":"<div><div>Embryo implantation requires a tight immune homeostatic control that activates regulatory circuits. One interlocutor is the embryo, which produces soluble ligands and expresses receptors for different autocrine and paracrine factors. The other interlocutor is the receptive endometrium, which produces mediators to regulate proliferation, differentiation, adhesion and invasiveness of the embryo, among other processes. Here, we are going to discuss experimental evidence regarding human embryo-endometrial dialogue and give a new insight of the relevance of the immune cells to coordinate embryo implantation. In this sense, decidualization of endometrial stromal cells is a multistep process that gives rise to mature decidual cells and senescent decidual cells. The first subpopulation secretes pro-implantation factors and begins migration by encapsulating the embryo. In turn, the second does not complete differentiation but rather suffers a process of premature senescence that is characterized by the production of pro-inflammatory factors (SASP, senescence-associated secretory phenotype), which contribute to embryo implantation. However, alterations in these processes or in their regulation through microRNAs lead to the perpetuation of an inflammatory response and alterations in endometrial receptivity. Considering that decidual cells acquire the ability to differentially respond to embryo quality, here we also explored how the soluble factors produced by embryos (classified according to their quality) impact on the inflammatory response and shape dendritic and other immune cell recruitment during the peri implantation period. To address these aspects, we present experimental evidence that links endoplasmic reticulum stress, senescence and inflammation and we discuss whether embryos reprogram the immune response.</div></div>","PeriodicalId":20203,"journal":{"name":"Placenta","volume":"173 ","pages":"Pages 166-174"},"PeriodicalIF":2.5,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145064983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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