scholarly journals Dysfunction of Shh signaling activates autophagy to inhibit trophoblast motility in recurrent miscarriage

2021 ◽  
Author(s):  
Yibin Pan ◽  
Lili Yan ◽  
Qiaoqiao Chen ◽  
Cheng Wei ◽  
Yongdong Dai ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Gestational Age ◽  
Human Placenta ◽  
Recurrent Miscarriage ◽  
Shh Signaling ◽  
Protein Levels ◽  
Shh Pathway ◽  
Normal Controls ◽  
Jar Cells ◽  
Motility Inhibition

AbstractIn early pregnancy, the placenta anchors the conceptus and supports embryonic development and survival. This study aimed to investigate the underlying functions of Shh signaling in recurrent miscarriage (RM), a serious disorder of pregnancy. In the present study, Shh and Gli2 were mainly observed in cytotrophoblasts (CTBs), Ptch was mainly observed in syncytiotrophoblasts (STBs), and Smo and Gli3 were expressed in both CTBs and STBs. Shh signaling was significantly impaired in human placenta tissue from recurrent miscarriage patients compared to that of gestational age-matched normal controls. VEGF-A and CD31 protein levels were also significantly decreased in recurrent miscarriage patients. Furthermore, inhibition of Shh signaling impaired the motility of JAR cells by regulating the expression of Gli2 and Gli3. Intriguingly, inhibition of Shh signaling also triggered autophagy and autolysosome accumulation. Additionally, knockdown of BECN1 reversed Gant61-induced motility inhibition. In conclusion, our results showed that dysfunction of Shh signaling activated autophagy to inhibit trophoblast motility, which suggests the Shh pathway and autophagy as potential targets for RM therapy.

scholarly journals Dysfunction of Shh signaling impaired trophoblast motility and autophagy is involved in poor placentation of recurrent miscarriage

2020 ◽  
Author(s):  
Yibin Pan ◽  
Lili Yan ◽  
Qiaoqiao Chen ◽  
Cheng Wei ◽  
Yongdong Dai ◽  
...  
Keyword(s):  
Target Genes ◽  
Recurrent Miscarriage ◽  
Shh Signaling ◽  
Invasion And Migration ◽  
Protein Levels ◽  
Villous Trophoblast ◽  
Normal Human ◽  
And Migration ◽  
Jar Cells ◽  
Motility Inhibition

Abstract Background: In early pregnancy, the placenta anchors the conceptus and supports embryonic development and survival. This study aimed to investigate the underlying functions of Shh signaling on recurrent miscarriage, an serious disorder of pregnancy. Methods: Immunofluorescence and immunohistochemistry were used to detect protein expression and its location in placental tissues. Quantitative real-time RT-PCR and Western blot analysis were performed to examine mRNA and protein levels, respectively. Lentiviruses expressing short hairpin RNA were used to knock down the target genes. Cell invasion and migration were performed by with or without Matrigel-coated transwell, respectively. Primary trophoblast migration was performed by villous explant assay. RNA-sequence was used to investigate the genes transcription profile. CCK-8 assay was used to evaluate cell viability. Flow cytometry was used to evaluate cell apoptosis. Results: Our results showed that Shh and Gli2 were mainly located in cytotrophoblasts (CTBs), Ptch was mainly located in syncytiotrophoblasts (STBs), while Smo and Gli3 were expressed in both CTBs and STBs. Compared to the gestational age-matched normal human placenta, the expression of Shh was significantly decreased in recurrent miscarriage. Furthermore, inhibition of Shh signaling impaired motility of JAR cells via regulating the expression of Gli2 and Gli3 to decrease AKT Ser473 phosphorylation, elevate E-cadherin and VEGFA. Intriguingly, inhibition of Shh signaling also enhanced autophagy and autolysosome. Additionally, knockdown BECN1 reversed the effect of Gant61 on motility inhibition. Conclusion: Our results indicated that dysfunction of Shh signaling impaired trophoblast motility, angiogenesis and activated autophagy in villous trophoblast, which would contribute to the pathophysiology of recurrent miscarriage.

scholarly journals The regulation of oxytocin and oxytocin receptor in human placenta according to gestational age

2017 ◽  
Vol 59 (3) ◽  
pp. 235-243 ◽  
Author(s):  
Seung-Chul Kim ◽  
Jae-Eon Lee ◽  
Seong Soo Kang ◽  
Hoe-Saeng Yang ◽  
Sun Suk Kim ◽  
...  
Keyword(s):  
Gestational Age ◽  
Human Placenta ◽  
Late Stage ◽  
Critical Role ◽  
Peptide Hormone ◽  
Dot Blot ◽  
Western Blot Assay ◽  
Protein Levels ◽  
Bewo Cells ◽  
Normal Placenta

Oxytocin (OXT) is a peptide hormone that plays a central role in the regulation of parturition and lactation. OXT signaling is mediated by OXT receptor (OXTR), which shows species- and tissue-specific expressions and gene regulation. In the present study, we examined the synthesis of OXT and OXTR in human placenta tissue according to gestational age. A total of 48 placentas were divided into early preterm, late preterm and term groups depending on gestational age, and expression of OXT and OXTR was evaluated. First, OXT and OXTR mRNA and protein were detected in normal placenta tissue via Q-PCR, Dot-blot and Western blot assay. Both OXT and OXTR levels in normal placenta increased gradually in the late stage of pregnancy, suggesting that local OXT may play a critical role in the function of the placenta. To determine the regulatory mechanism of OXT, placental BeWo cells were administrated estrogen (E2) or progesterone (P4), and expression of OXT and OXTR was tested. The mRNA and protein levels of OXT and OXTR were upregulated by E2 but blocked by co-treatment with P4. In order to confirm the estrogen receptor (ESR)-mediated signaling, we administrated ESR antagonists together with E2 to BeWo cells. As a result, both OXT and OXTR were significantly altered by ESR1 antagonist (MPP) while moderately regulated by ESR2 antagonist (PHTPP). These results suggest that OXT and OXTR are controlled mainly by E2 in the placenta via ESR1 and thus may play physiological functions in the human placenta during the late stage of pregnancy.

Establishment of Early Pregnancy Related Thyroid Hormone Models and Reference Intervals for Pregnant Women in China Based on Real World Data

2021 ◽  
Vol 53 (04) ◽  
pp. 272-279
Author(s):  
Chaochao Ma ◽  
Xiaoqi Li ◽  
Lixin Liu ◽  
Xinqi Cheng ◽  
Fang Xue ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Pregnant Women ◽  
Early Pregnancy ◽  
Gestational Age ◽  
Dynamic Change ◽  
Reference Intervals ◽  
Thyroid Stimulating Hormone ◽  
Free Thyroxine ◽  
Stimulating Hormone

AbstractThyroid hormone reference intervals are crucial for diagnosing and monitoring thyroid dysfunction during early pregnancy, and the dynamic change trend of thyroid hormones during pregnancy can assist clinicians to assess the thyroid function of pregnant women. This study aims to establish early pregnancy related thyroid hormones models and reference intervals for pregnant women. We established two derived databases: derived database* and derived database#. Reference individuals in database* were used to establish gestational age-specific reference intervals for thyroid hormones and early pregnancy related thyroid hormones models for pregnant women. Individuals in database# were apparently healthy non-pregnant women. The thyroid hormones levels of individuals in database# were compared with that of individuals in database* using nonparametric methods and the comparative confidence interval method. The differences in thyroid stimulating hormone and free thyroxine between early pregnant and non-pregnant women were statistically significant (p<0.0001). The reference intervals of thyroid stimulating hormone, free thyroxine and free triiodothyronine for early pregnant women were 0.052–3.393 μIU/ml, 1.01–1.54 ng/dl, and 2.51–3.66 pg/ml, respectively. Results concerning thyroid stimulating hormone and free thyroxine reference intervals of early pregnancy are comparable with those from other studies using the same detection platform. Early pregnancy related thyroid hormones models showed various change patterns with gestational age for thyroid hormones. Early pregnancy related thyroid hormones models and reference intervals for pregnant women were established, so as to provide accurate and reliable reference basis for the diagnosing and monitoring of maternal thyroid disfunction in early pregnancy.

scholarly journals Maternal biological age assessed in early pregnancy is associated with gestational age at birth

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Eva E. Lancaster ◽  
Dana M. Lapato ◽  
Colleen Jackson-Cook ◽  
Jerome F. Strauss ◽  
Roxann Roberson-Nay ◽  
...  
Keyword(s):  
Risk Factors ◽  
Preterm Birth ◽  
Early Pregnancy ◽  
Gestational Age ◽  
Cellular Aging ◽  
Biological Age ◽  
Potential Candidate ◽  
A Genome ◽  
Gestational Age At Birth ◽  
Age At Birth

AbstractMaternal age is an established predictor of preterm birth independent of other recognized risk factors. The use of chronological age makes the assumption that individuals age at a similar rate. Therefore, it does not capture interindividual differences that may exist due to genetic background and environmental exposures. As a result, there is a need to identify biomarkers that more closely index the rate of cellular aging. One potential candidate is biological age (BA) estimated by the DNA methylome. This study investigated whether maternal BA, estimated in either early and/or late pregnancy, predicts gestational age at birth. BA was estimated from a genome-wide DNA methylation platform using the Horvath algorithm. Linear regression methods assessed the relationship between BA and pregnancy outcomes, including gestational age at birth and prenatal perceived stress, in a primary and replication cohort. Prenatal BA estimates from early pregnancy explained variance in gestational age at birth above and beyond the influence of other recognized preterm birth risk factors. Sensitivity analyses indicated that this signal was driven primarily by self-identified African American participants. This predictive relationship was sensitive to small variations in the BA estimation algorithm. Benefits and limitations of using BA in translational research and clinical applications for preterm birth are considered.

scholarly journals Does Lack of Multinutrient Supplementation During Early Pregnancy Increase Vulnerability to Alcohol-Related Preterm or Small-for-Gestational-Age Births?

2010 ◽  
Vol 15 (8) ◽  
pp. 1324-1332 ◽  
Author(s):  
Lyndsay Ammon Avalos ◽  
Lee Kaskutas ◽  
Gladys Block ◽  
Barbara Abrams ◽  
De-Kun Li
Keyword(s):  
Early Pregnancy ◽  
Gestational Age ◽  
Small For Gestational Age

scholarly journals Disruption of SHH signaling cascade by SBE attenuates lung cancer progression and sensitizes DDP treatment

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Jing Du ◽  
Weiwei Chen ◽  
Lijuan Yang ◽  
Juanjuan Dai ◽  
Jiwei Guo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Cell Cycle Progression ◽  
Lung Cancer Cells ◽  
Human Lung Cancer ◽  
Cycle Progression ◽  
Shh Signaling ◽  
Shh Pathway

Abstract Deregulated Sonic Hedgehog (SHH) pathway facilitates the initiation, progression, and metastasis of Non-small cell lung cancer (NSCLC), confers drug resistance and renders a therapeutic interference option to lung cancer patients with poor prognosis. In this study, we screened and evaluated the specificity of a Chinese herb Scutellariabarbata D. Don extraction (SBE) in repressing SHH signaling pathway to block NSCLC progression. Our study confirmed that aberrant activation of the SHH signal pathway conferred more proliferative and invasive phenotypes to human lung cancer cells. This study revealed that SBE specifically repressed SHH signaling pathway to interfere the SHH-mediated NSCLC progression and metastasis via arresting cell cycle progression. We also found that SBE significantly sensitized lung cancer cells to chemotherapeutic agent DDP via repressing SHH components in vitro and in vivo. Mechanistic investigations indicated that SBE transcriptionally and specifically downregulated SMO and consequently attenuated the activities of GLI1 and its downstream targets in SHH signaling pathway, which interacted with cell cycle checkpoint enzymes to arrest cell cycle progression and lead to cellular growth inhibition and migration blockade. Collectively, our results suggest SBE as a novel drug candidate for NSCLC which specifically and sensitively targets SHH signaling pathway.

scholarly journals Objective assessment of alcohol consumption in early pregnancy using phosphatidylethanol: a cross‐sectional study

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Leonieke J. Breunis ◽  
Sophie Wassenaar ◽  
Barbara J. Sibbles ◽  
Ab A. Aaldriks ◽  
Hilmar H. Bijma ◽  
...  
Keyword(s):  
Alcohol Consumption ◽  
Early Pregnancy ◽  
Gestational Age ◽  
Care Provider ◽  
Objective Assessment ◽  
Obstetric Care ◽  
Tertiary Hospital ◽  
Maternal Blood ◽  
Added Value ◽  
Cross Sectional

Abstract Background Alcohol consumption during pregnancy is associated with major birth defects and developmental disabilities. Questionnaires concerning alcohol consumption during pregnancy underestimate alcohol use while the use of a reliable and objective biomarker for alcohol consumption enables more accurate screening. Phosphatidylethanol can detect low levels of alcohol consumption in the previous two weeks. In this study we aimed to biochemically assess the prevalence of alcohol consumption during early pregnancy using phosphatidylethanol in blood and compare this with self-reported alcohol consumption. Methods To evaluate biochemically assessed prevalence of alcohol consumption during early pregnancy using phosphatidylethanol levels, we conducted a prospective, cross-sectional, single center study in the largest tertiary hospital of the Netherlands. All adult pregnant women who were under the care of the obstetric department of the Erasmus MC and who underwent routine blood testing at a gestational age of less than 15 weeks were eligible. No specified informed consent was needed. Results The study was conducted between September 2016 and October 2017. In total, we received 1,002 residual samples of 992 women. After applying in- and exclusion criteria we analyzed 684 samples. Mean gestational age of all included women was 10.3 weeks (SD 1.9). Of these women, 36 (5.3 %) tested positive for phosphatidylethanol, indicating alcohol consumption in the previous two weeks. Of women with a positive phosphatidylethanol test, 89 % (n = 32) did not express alcohol consumption to their obstetric care provider. Conclusions One in nineteen women consumed alcohol during early pregnancy with a high percentage not reporting this use to their obstetric care provider. Questioning alcohol consumption by an obstetric care provider did not successfully identify (hazardous) alcohol consumption. Routine screening with phosphatidylethanol in maternal blood can be of added value to identify women who consume alcohol during pregnancy.

scholarly journals Menstrual flow as a non-invasive source of endometrial organoids

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Tereza Cindrova-Davies ◽  
Xiaohui Zhao ◽  
Kay Elder ◽  
Carolyn J. P. Jones ◽  
Ashley Moffett ◽  
...  
Keyword(s):  
Early Pregnancy ◽  
Recurrent Miscarriage ◽  
Milk Proteins ◽  
Receptor Expression ◽  
In Vitro Fertilisation ◽  
Non Invasive ◽  
Menstrual Flow ◽  
Pregnancy Hormones

AbstractAssessment of the endometrium often necessitates a biopsy, which currently involves an invasive, transcervical procedure. Here, we present an alternative technique based on deriving organoids from menstrual flow. We demonstrate that organoids can be derived from gland fragments recovered from menstrual flow. To confirm they faithfully reflect the in vivo state we compared organoids derived from paired scratch biopsies and ensuing menstrual flow from patients undergoing in vitro fertilisation (IVF). We demonstrate that the two sets of organoids share the same transcriptome signature, derivation efficiency and proliferation rate. Furthermore, they respond similarly to sex steroids and early-pregnancy hormones, with changes in morphology, receptor expression, and production of ‘uterine milk’ proteins that mimic those during the late-secretory phase and early pregnancy. This technique has wide-ranging impact for non-invasive investigation and personalised approaches to treatment of common gynaecological conditions, such as endometriosis, and reproductive disorders, including failed implantation after IVF and recurrent miscarriage.

Sign in / Sign up

Export Citation Format

Share Document