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Problem: Various etiological factors, such as infection and inflammation, may induce the adverse outcomes of pregnancy of miscarriage, stillbirth, or preterm birth. The pathogenic mechanisms associated with these adverse pregnancies are yet unclear. We hypothesized that a common pathogenic mechanism may underlie variant adverse outcomes of pregnancy, which are induced by genetic‐environmental factors. The specific objective of the current study is to uncover the common molecular mechanism(s) by identifying the specific transcripts that are present in variant subtypes of pregnancy loss and preterm birth. Method of Study: Transcriptomic profiling was performed with RNA expression microarray or RNA sequencing of placentas derived from pregnancy loss (which includes spontaneous miscarriage, recurrent miscarriage, and stillbirth) and spontaneous preterm birth, followed by bioinformatic analysis of multi‐omic integration to identify pathogenic molecules and pathways involved in pathological pregnancies. Results: The enrichment of common differentially expressed genes between full‐term birth and preterm birth and pregnancy loss of miscarriage and stillbirth revealed different pathophysiological pathway(s), including cytokine signaling dysregulated in spontaneous preterm birth, defense response, graft‐versus‐host disease, antigen processing and presentation, and T help cell differentiation in spontaneous miscarriage. Thirty‐three genes shared between spontaneous preterm birth and spontaneous miscarriage were engaged in pathways of interferon gamma–mediated signaling and of antigen processing and presentation. For spontaneous miscarriage, immune response was enriched in the fetal tissue of chorionic villi and in the maternal facet of the placental sac. The transcript of nerve growth factor receptor was identified as the common molecule that is differentially expressed in all adverse pregnancies: spontaneous preterm birth, stillbirth, spontaneous miscarriage, and recurrent miscarriage. Superoxide dismutase 2 was up‐regulated in all adverse outcomes of pregnancy except for recurrent miscarriage. Cytokine‐cytokine receptor interaction was the common pathway in spontaneous preterm birth and spontaneous miscarriage. Defense response was enriched in the fetal tissue of miscarriage and in the maternal tissue in spontaneous miscarriage. Conclusions: Our results indicated that the chemokine‐cytokine pathway may play important roles in and function as a common pathogenic mechanism associated with, the different adverse outcomes of pregnancy, which demonstrated that differentially expressed transcripts could result from a common pathogenic mechanism associated with pregnancy loss and spontaneous preterm birth, although individual pregnancy outcomes may differ from each other phenotypically. [ABSTRACT FROM AUTHOR]

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Problem We have previously determined that long non-coding RNAs (lnc RNAs) are differentially expressed in preterm premature rupture of membranes ( PPROM) and hypothesized that the collagenolysis ubiquitin-proteasome system may be activated by infection and inflammation. However, direct evidence of the involvement of lnc RNAs in transcriptional and posttranscriptional regulation of the infection-triggered alteration of collagen is lacking. Method of study A previously developed mouse model with MHV68 viral infection was assessed to determine whether viral infection may induce differential expression of lnc RNAs in mouse placentas and amniotic sacs. Results Differential expression of lnc RNAs that are associated with collagen was found in HMV68 viral-infected, compared to non-infected, mouse placentas and amniotic sacs. Differential expression of messenger RNAs ( mRNAs) of collagen was also documented. Conclusions Our data demonstrate, for the first time, that viral infection may induce the differential expression of lnc RNAs that are associated with collagen. Based on this finding, we propose that lnc RNA may have involved in regulating of infection-induced collagen transcription. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lnc RNAs) are long single-stranded RNAs without translation potential. Lnc RNAs function in regulating epigenetic and cellular processes through various mechanisms. Nowadays, rapidly growing evidence has shown that abnormally expressed lnc RNAs were involved in various inflammation-related states or diseases. Abnormal inflammation responses contribute to reproductive pathology and play vital roles in developing most disorders of the female reproductive system. In this review, we discussed the history of nc RNAs including lnc RNAs, methodologies for lnc RNA identification, mechanisms of lnc RNA expression and regulation and mainly discussed the expression and function of lnc RNAs in the female reproductive system with special focus on the inflammation and infection pathway. By analyzing the present available studies of lnc RNA transcripts within the reproductive system and the current understanding of the biology of lnc RNAs, we have suggested the important diagnostic and therapeutic roles of lnc RNAs in the etiology of reproductive disorders. [ABSTRACT FROM AUTHOR]

Problem Spontaneous abortion ( SA) occurs before 20 gestational weeks. Approximately, half of recurrent SA has no identifiable cause. No report has yet been investigated the possible involvement of lnc RNA in pregnancy loss. Method of Study Sixteen pairs of pregnancies with spontaneous abortions ( SA) and induced abortions ( IA) were studied. Embryonic sacs and decidua were collected for each pregnancy. A Human Lnc RNA Array was employed to profile genomewide lnc RNAs, which were then validated by RT- PCR. Results Differentially expressed lnc RNAs were identified. Biological pathways were categorized into six major groups: infection and inflammation, metabolism, signaling and transcriptional regulation, smooth muscle contraction, cell process, and coagulation. Conclusions Infection and inflammation pathways regulated by lnc RNAs were determined as the predominant pathogenetic factors underlying the SA. Finding that antisense lnc RNAs have been either up- or down-regulated suggests that they may have both cis- and trans-regulations. [ABSTRACT FROM AUTHOR]

Problem: We have previously determined that long non-coding RNAs (lncRNAs) are differentially expressed in preterm premature rupture of membranes (PPROM) and hypothesized that the collagenolysis ubiquitin-proteasome system may be activated by infection and inflammation. However, direct evidence of the involvement of lncRNAs in transcriptional and posttranscriptional regulation of the infection-triggered alteration of collagen is lacking., Method of Study: A previously developed mouse model with MHV68 viral infection was assessed to determine whether viral infection may induce differential expression of lncRNAs in mouse placentas and amniotic sacs., Results: Differential expression of lncRNAs that are associated with collagen was found in HMV68 viral-infected, compared to non-infected, mouse placentas and amniotic sacs. Differential expression of messenger RNAs (mRNAs) of collagen was also documented., Conclusions: Our data demonstrate, for the first time, that viral infection may induce the differential expression of lncRNAs that are associated with collagen. Based on this finding, we propose that lncRNA may have involved in regulating of infection-induced collagen transcription., (© 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Problem: Spontaneous abortion (SA) occurs before 20 gestational weeks. Approximately, half of recurrent SA has no identifiable cause. No report has yet been investigated the possible involvement of lncRNA in pregnancy loss., Method of Study: Sixteen pairs of pregnancies with spontaneous abortions (SA) and induced abortions (IA) were studied. Embryonic sacs and decidua were collected for each pregnancy. A Human LncRNA Array was employed to profile genomewide lncRNAs, which were then validated by RT-PCR., Results: Differentially expressed lncRNAs were identified. Biological pathways were categorized into six major groups: infection and inflammation, metabolism, signaling and transcriptional regulation, smooth muscle contraction, cell process, and coagulation., Conclusions: Infection and inflammation pathways regulated by lncRNAs were determined as the predominant pathogenetic factors underlying the SA. Finding that antisense lncRNAs have been either up- or down-regulated suggests that they may have both cis- and trans-regulations., (© 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Fragile X syndrome, one of the most common forms of inherited mental retardation, results from the absence of the fragile X mental retardation protein (FMRP), which is encoded by the fragile X mental retardation gene 1 (FMR1). FMRP is an RNA-binding protein involved in translational regulation of targeted mRNAs. Identification of targeted mRNAs associated with FMRP is important to understand the function of FMRP and the pathogenic basis of the fragile X syndrome. Employing a yeast three-hybrid system and a human fetal hippocampus cDNA library, we identified 22 candidate target mRNAs, and 18 of them were confirmed to be associated with FMRP in vitro by gel retardation. Some of these mRNAs code for structural proteins, enzymes or proteins involved in cellular processes, especially in the development and function of neural system. To further investigate the role of FMRP in regulating targeted gene expression, we analyzed the expression profile of TXNRD1, one of the candidate mRNAs, after knocking down the expression of endogenous FMRP by siRNA. The results showed that endogenous TXNRD1 translation increased along with depletion of FMRP, which suggested FMRP negatively regulates TXNRD1 translation., (2007 Wiley-Liss, Inc.)