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Integrated Insight into the Molecular Mechanisms of Spontaneous Abortion during Early Pregnancy in Pigs.

ABSTRACT: Due to the high rate of spontaneous abortion (SAB) in porcine pregnancy, there is a major interest and concern on commercial pig farming worldwide. Whereas the perturbed immune response at the maternal-fetal interface is an important mechanism associated with the spontaneous embryo loss in the early stages of implantation in porcine, data on the specific regulatory mechanism of the SAB at the end stage of the implantation remains scant. Therefore, we used high-throughput sequencing and bioinformatics tools to analyze the healthy and arresting endometrium on day 28 of pregnancy. We identified 639 differentially expressed lncRNAs (DELs) and 2357 differentially expressed genes (DEGs) at the end stage of implantation, and qRT-PCR was used to verify the sequencing data. Gene set variation analysis (GSVA), gene set enrichment analysis (GSEA), and immunohistochemistry analysis demonstrated weaker immune response activities in the arresting endometrium compared to the healthy one. Using the lasso regression analysis, we screened the DELs and constructed an immunological competitive endogenous RNA (ceRNA) network related to SAB, including 4 lncRNAs, 11 miRNAs, and 13 genes. In addition, Blast analysis showed the applicability of the constructed ceRNA network in different species, and subsequently determined HOXA-AS2 in pigs. Our study, for the first time, demonstrated that the SAB events at the end stages of implantation is associated with the regulation of immunobiological processes, and a specific molecular regulatory network was obtained. These novel findings may provide new insight into the possibility of increasing the litter size of sows, making pig breeding better and thus improving the efficiency of animal husbandry production.

SUBMITTER: Zang X

PROVIDER: S-EPMC8235555 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThe risk of relapse of depression or the diagnosis of some other psychiatric disorders during pregnancy necessitates the use of antidepressants despite possible adverse effects. Whether such use increases the risk of spontaneous abortion is still being debated. We evaluated the risk of spontaneous abortion in relation to the use of antidepressants during pregnancy.MethodsUsing a nested case-control study design, we obtained data from the Quebec Pregnancy Registry for 5124 women who had a clinically detected spontaneous abortion. For each case, we randomly selected 10 controls from the remaining women in the registry who were matched by the case's index date (date of spontaneous abortion) and gestational age at the time of spontaneous abortion. Use of antidepressants was defined by filled prescriptions and was compared with nonuse. We also studied the classes, types and doses of antidepressants.ResultsA total of 284 (5.5%) of the women who had a spontaneous abortion had at least one prescription for an antidepressant filled during the pregnancy, as compared with 1401 (2.7%) of the matched controls (odds ratio [OR] 2.09, 95% confidence interval [CI] 1.83-2.38). After adjustment for potential confounders, we found that the use of antidepressants during pregnancy was associated with an increased risk of spontaneous abortion (OR 1.68, 95%CI 1.38-2.06). Stratified analyses showed that use of selective serotonin reuptake inhibitors alone (OR 1.61, 95% CI 1.28-2.04), serotonin-norepinephrine reuptake inhibitors alone (OR 2.11, 95% CI 1.34-3.30) and combined use of antidepressants from different classes (OR 3.51, 95% CI 2.20-5.61) were associated with an increased risk of spontaneous abortion. When we looked at antidepressant use by type versus no use, paroxetine use alone (OR 1.75, 95% CI 1.31-2.34) and venlafaxine use alone (OR 2.11, 95% CI 1.34-3.30) were associated with an increased risk of spontaneous abortion.InterpretationThe use of antidepressants, especially paroxetine, venlafaxine or the combined use of different classes of antidepressants, during pregnancy was associated with an increased risk of spontaneous abortion.

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Integrated Insight into the Molecular Mechanisms of Spontaneous Abortion during Early Pregnancy in Pigs.

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