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Placental Transcription Profiling in 6-23 Weeks' Gestation Reveals Differential Transcript Usage in Early Development.

ABSTRACT: The human placenta is a rapidly developing transient organ that is key to pregnancy success. Early development of the conceptus occurs in a low oxygen environment before oxygenated maternal blood begins to flow into the placenta at ~10-12 weeks' gestation. This process is likely to substantially affect overall placental gene expression. Transcript variability underlying gene expression has yet to be profiled. In this study, accurate transcript expression profiles were identified for 84 human placental chorionic villus tissue samples collected across 6-23 weeks' gestation. Differential gene expression (DGE), differential transcript expression (DTE) and differential transcript usage (DTU) between 6-10 weeks' and 11-23 weeks' gestation groups were assessed. In total, 229 genes had significant DTE yet no significant DGE. Integration of DGE and DTE analyses found that differential expression patterns of individual transcripts were commonly masked upon aggregation to the gene-level. Of the 611 genes that exhibited DTU, 534 had no significant DGE or DTE. The four most significant DTU genes ADAM10, VMP1, GPR126, and ASAH1, were associated with hypoxia-responsive pathways. Transcript usage is a likely regulatory mechanism in early placentation. Identification of functional roles will facilitate new insight in understanding the origins of pregnancy complications.

SUBMITTER: Bogias KJ

PROVIDER: S-EPMC9105363 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Placental Transcription Profiling in 6-23 Weeks' Gestation Reveals Differential Transcript Usage in Early Development.

Bogias Konstantinos J KJ Pederson Stephen M SM Leemaqz Shalem S Smith Melanie D MD McAninch Dale D Jankovic-Karasoulos Tanja T McCullough Dylan D Wan Qianhui Q Bianco-Miotto Tina T Breen James J Roberts Claire T CT

International journal of molecular sciences 20220419 9

The human placenta is a rapidly developing transient organ that is key to pregnancy success. Early development of the conceptus occurs in a low oxygen environment before oxygenated maternal blood begins to flow into the placenta at ~10-12 weeks' gestation. This process is likely to substantially affect overall placental gene expression. Transcript variability underlying gene expression has yet to be profiled. In this study, accurate transcript expression profiles were identified for 84 human pla ...[more]

PMID: 35562897

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Project description:OBJECTIVE:To estimate whether stillbirth at 23 weeks of gestation or more is associated with increased risk of severe maternal morbidity compared with live birth, when stratified by maternal comorbidities. METHODS:This retrospective cohort study used International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) diagnosis and procedure codes within the Healthcare Cost and Utilization Project's Florida State Inpatient Database. The first delivery of female Florida residents aged 13-54 years old from 2005 to 2014 was included. The exposure was an ICD-9-CM code of stillbirth at 23 weeks of gestation or more; the control was an ICD-9-CM code of singleton live birth. Deliveries were stratified by the presence of 1 or more conditions within a well-validated maternal morbidity composite using ICD-9-CM codes during delivery hospitalization. The primary outcome was an ICD-9-CM diagnosis or procedure code during delivery hospitalization of any indices within the Centers for Disease Control and Prevention's severe maternal morbidity composite. Multivariable analyses adjusted for maternal sociodemographic factors and delivery mode to compare outcomes after stillbirth with live-birth delivery. RESULTS:Nine thousand five hundred twenty-three women who delivered stillborn fetuses and 1,353,044 with liveborn neonates were included. Among 6,590 stillbirths and 935,913 live births without maternal comorbidities, severe maternal morbidity was significantly more common during stillbirth delivery (n=345 [5.2%]), corresponding to a seven-fold increased risk compared with live birth (n=8,318 [0.9]; adjusted odds ratio [aOR] 7.05 [95% CI 6.27-7.93]). Among 2,933 stillbirths and 417,131 live births with maternal comorbidities, severe maternal morbidity was significantly more common during stillbirth delivery (n=390 [13.3%]): the risk was more than six-fold higher comparatively (n=11,122 [2.7%]; aOR 6.21 [95% CI 5.54-6.96]). Most maternal comorbidities were individually associated with higher risk of severe maternal morbidity during stillbirth compared with live-birth delivery. CONCLUSION:Though severe maternal morbidity is overall uncommon, delivering a stillborn fetus 23 weeks of gestation or greater is associated with increased likelihood of severe maternal morbidity, particularly among women with comorbidities, suggesting health care providers must be vigilant about severe maternal morbidity during stillbirth delivery.

Project description:ObjectiveTo utilise combined diffusion-relaxation MRI techniques to interrogate antenatal changes in the placenta prior to extreme preterm birth among both women with PPROM and membranes intact, and compare this to a control group who subsequently delivered at term.DesignObservational study.SettingTertiary Obstetric Unit, London, UK.PopulationCases: pregnant women who subsequently spontaneously delivered a singleton pregnancy prior to 32 weeks' gestation without any other obstetric complications.Controlspregnant women who delivered an uncomplicated pregnancy at term.MethodsAll women consented to an MRI examination. A combined diffusion-relaxation MRI of the placenta was undertaken and analysed using fractional anisotropy, a combined T2*-apparent diffusion coefficient model and a combined T2*-intravoxel incoherent motion model, in order to provide a detailed placental phenotype associated with preterm birth. Subgroup analyses based on whether women in the case group had PPROM or intact membranes at time of scan, and on latency to delivery were performed.Main outcome measuresFractional anisotropy, apparent diffusion coefficients and T2* placental values, from two models including a combined T2*-IVIM model separating fast- and slow-flowing (perfusing and diffusing) compartments.ResultsThis study included 23 women who delivered preterm and 52 women who delivered at term. Placental T2* was lower in the T2*-apparent diffusion coefficient model (p < 0.001) and in the fast- and slow-flowing compartments (p = 0.001 and p < 0.001) of the T2*-IVIM model. This reached a higher level of significance in the preterm prelabour rupture of the membranes group than in the membranes intact group. There was a reduced perfusion fraction among the cases with impending delivery.ConclusionsPlacental diffusion-relaxation reveals significant changes in the placenta prior to preterm birth with greater effect noted in cases of preterm prelabour rupture of the membranes. Application of this technique may allow clinically valuable interrogation of histopathological changes before preterm birth. In turn, this could facilitate more accurate antenatal prediction of preterm chorioamnionitis and so aid decisions around the safest time of delivery. Furthermore, this technique provides a research tool to improve understanding of the pathological mechanisms associated with preterm birth in vivo.

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Placental Transcription Profiling in 6-23 Weeks' Gestation Reveals Differential Transcript Usage in Early Development.

Publications

Placental Transcription Profiling in 6-23 Weeks' Gestation Reveals Differential Transcript Usage in Early Development.

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