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There are around 300 million adolescent pregnancies worldwide, accounting for 11% of all births worldwide. Accumulating evidence demonstrates that many adverse perinatal outcomes are associated with adolescent pregnancies. However, how and why these abnormalities occur remain to be defined. In this study, pregnancy at different stages was compared between 25- and 30- day-old and mature female mice. We found that the litter size of adolescent pregnancy is significantly decreased from F1 to F3 generations compared to mature pregnancy. On days 8 and 12 of pregnancy, multiple abnormalities in decidual and placental development appear in F3 adolescent pregnancy. On days 5 and 8, uterine endoplasmic reticulum stress is dysregulated in F3 adolescent pregnancy. Embryo implantation and decidualization are also compromised in adolescent pregnancy. Many genes are abnormally expressed in adolescent estrous uteri. The abnormal endocrine environment and abnormal implantation from uterine immaturity may result in multiple pregnancy failures in adolescent pregnancy. The aim of this study is to shed light on human adolescent pregnancy.

Decidualization is essential to the establishment of pregnancy in rodents and primates. Laminin A5 (encoding by Laminin α5) is a member of the laminin family, which is mainly expressed in the basement membranes. Although laminins regulate cellular phenotype maintenance, adhesion, migration, growth, and differentiation, the expression, function, and regulation of laminin A5 during early pregnancy are still unknown. Therefore, we investigated the expression and role of laminin A5 during mouse and human decidualization. Laminin A5 is highly expressed in mouse decidua and artificially induced deciduoma. Laminin A5 is significantly increased under in vitro decidualization. Laminin A5 knockdown significantly inhibits the expression of Prl8a2, a marker for mouse decidualization. Progesterone stimulates the expression of laminin A5 in ovariectomized mouse uterus and cultured mouse stromal cells. We also show that progesterone regulates laminin A5 through the PKA-CREB-C/EBPβ pathway. Laminin A5 is also highly expressed in human pregnant decidua and cultured human endometrial stromal cells during in vitro decidualization. Laminin A5 knockdown by siRNA inhibits human in vitro decidualization. Collectively, our study reveals that laminin A5 may play a pivotal role during mouse and human decidualization via the PKA-CREB-C/EBPβ pathway.

The solubilities of 2-oxindole in 12 pure organic solvents including acetonitrile (MeCN), dichloromethane, 1,4-dioxane, ethyl acetate (EtOAc), acetone, toluene, methanol, ethanol, 2-propanol, tetra...

Background: There are around 300 million adolescent pregnancies worldwide, accounting for 11% of all births worldwide. Accumulating evidence demonstrates that many adverse perinatal outcomes are associated with adolescent pregnancies. However, how and why these abnormalities occur remain to be defined. Methods: To compare uterine maturity, implantation, decidualization and placental development between 25-30 days old and 3 months old mature female CD-1 strain mice. Both in vivo mouse pregnancy and in vitro cell culture were used. Western blot, real time RT-PCR, immunostaining and immunofluorescence were used to study the progress of pregnancy during two groups.Results: We found the litter size of adolescent pregnancy is significantly decreased from F1 to F3 generations compared to mature pregnancy. On days 8 and 12 of pregnancy, multiple abnormalities in placental and decidual developments appear in F3 adolescent pregnancy. On days 5 and 8, uterine endoplasmic reticulum stress is dysregulated compared to mature pregnancy. Embryo implantation and decidualization are also compromised in adolescent pregnancy. Many genes are abnormally expressed in adolescent estrous uteri. Conclusion: The uterine immaturities and abnormal implantation may cause multiple pregnancy failures in adolescent pregnancy.

Background: Embryo implantation and decidualization are essential to the establishment and maintenance of successful pregnancy in both rodents and primates. Receptive endometrium synergism with well-developed blastocyst is prerequisite for successful embryo implantation. Melatonin, which is mainly synthesized by the pineal gland in vertebrates, promotes human blastocyst development and increases pregnancy rate. However, the role and underlying mechanism of melatonin on human endometrial receptivity and decidualization still remains poorly defined. Methods: Trophoblast JEG-3 spheroids were cocultured with endometrial epithelial cells. Real-time PCR, Western blot, siRNA transfection, epithelial-stromal cell coculture system, and assay of Ishikawa cell-conditioned medium were used to explore the effects of melatonin on human endometrial decidualization and the underlying molecular pathways. Findings: In this study, we showed that melatonin induces the expression of the endometrial receptive markers, integrin β3 and HOXA10 in the less-receptive endometrial epithelial cell line AN3 CA and increased the attachment rate of trophoblast JEG-3 spheroids on endometrial epithelial AN3 CA cells. In an epithelial-stromal coculture system, we further proved that melatonin-stimulated IFN-γ secretion from Ishikawa cells promotes in vitro decidualization of stromal cells through regulating progesterone receptor B (PRB). Under in vitro decidualization, IFN-γ significantly increases the levels IGFBP1 and PRL, which is abrogated by suppressing PRB. Under in vitro decidualization of endometrial stromal cells, the expression of the decidualization markers, IGFBP1 and PRL, is significantly stimulated by melatonin treatment. Melatonin obviously increases phosphorylated STAT3 level and decreases p-Akt level. Interpretation: Melatonin may play crucial roles in human endometrial receptivity and decidualization. The dialogue between endometrial epithelial and stromal cell mediated by melatonin should be beneficial for decidual process. Funding: National Key R&D Program of China (2018YFC1004403) and National Natural Science Foundation of China (31671563, 31871511). Declaration of Interests: The authors declare that there is no conflict of interest. Ethics Approval Statement: All human procedures were approved by the Institutional Committee on the Use of Human Subjects in Medical Research of Southern Medical University with written consent.

Maintenance of a suitable uterine milieu is important for embryo development and subsequent implantation during early pregnancy. High estrogen level in proestrous and estrous stages is essential for uterine anti-bacterial activity during preimplantation period. Lipocalin-2 is an essential molecule which prevents bacterial infection by sequestering iron. In this study, the highest expression of lipocalin-2 is observed in the endometrial epithelium on day 1 of normal pregnancy and pseudopregnancy, which exhibit a similar hormone scenario. By injecting the agonists for estrogen receptor α and estrogen receptor β in ovariectomized mice, we found estrogen receptor α is the dominant member for estrogen regulation on lipocalin-2 expression. Estrogen treatment in estrogen receptor α-knockout mice further confirmed the role of estrogen receptor α. Using published data from whole-genome estrogen receptor α binding site assay, significant estrogen receptor α recruitment peaks are found at the downstream of lipocalin-2 gene after estrogen treatment. Furthermore, to study the anti-bacterial activity of lipocalin-2 in uterus, Escherichia coli is injected to mimic bacterial infection. Our results showed an obvious induction of lipocalin-2 in Escherichia coli-treated group. Taken together, this study indicates estrogen regulation of lipocalin-2 in uterine epithelium is mediated by estrogen receptor α, and lipocalin-2 may have anti-bacterial activity during early pregnancy.

In order to achieve the fault diagnostic and degradation assessment of the electro-hydraulic servo valve, a system of prognostic and health management based on the data-driven approach for the electro-hydraulic servo valve is presented. FMMEA performed in this study considered the degree of sub-components in electro-hydraulic servo valve. In order to use only five parameters to assess the cause of degradation, a physical model of the EH servo valve was built up to simulate the failure modes. The simulation results are very useful because the methods can be applied to assess the cause of degradation such as leakage, jamming, clogging and so on.