MiR-142-3p Regulates ILC1s by Targeting HMGB1 via the NF-κB Pathway in a Mouse Model of Early Pregnancy Loss.

OBJECTIVE: Innate lymphoid cells (ILCs) are a class of newly discovered immunocytes. Group 1 ILCs (ILC1s) are identified in the decidua of humans and mice. High mobility group box 1 (HMGB1) is predicted to be one of the target genes of miR-142-3p, which is closely related to pregnancy-related diseases. Furthermore, miR-142-3p and HMGB1 are involved in regulating the NF-κB signaling pathway. This study aimed to examine the regulatory effect of miR-142-3p on ILC1s and the underlying mechanism involving HMGB1 and the NF-κB signaling pathway. METHODS: Mouse models of normal pregnancy and abortion were constructed, and the alterations of ILC1s, miR-142-3p, ILC1 transcription factor (T-bet), and pro-inflammatory cytokines of ILC1s (TNF-α, IFN-γ and IL-2) were detected in mice from different groups. The targeting regulation of HMGB1 by miR-142-3p in ILC1s, and the expression of HMGB1 in normal pregnant mice and abortive mice were investigated. In addition, the regulatory effects of miR-142-3p and HMGB1 on ILC1s were detected in vitro by CCK-8, Annexin-V/PI, ELISA, and RT-PCR, respectively. Furthermore, changes of the NF-κB signaling pathway in ILC1s were examined in the different groups. For the in vivo studies, miR-142-3p-Agomir was injected in the uterus of abortive mice to evaluate the abortion rate and alterations of ILC1s at the maternal-fetal interface, and further detect the expression of HMGB1, pro-inflammatory cytokines, and the NF-κB signaling pathway. RESULTS: The number of ILC1s was significantly increased, the level of HMGB1 was significantly upregulated, and that of miR-142-3p was considerably downregulated in the abortive mice as compared with the normal pregnant mice (all P<0.05). In addition, miR-142-3p was found to drastically inhibit the activation of the NF-κB signaling pathway (P<0.05). The number of ILC1s and the levels of pro-inflammatory cytokines were significantly downregulated and the activation of the NF-κB signaling pathway was inhibited in the miR-142-3p Agomir group (all P<0.05). CONCLUSION: miR-142-3p can regulate ILC1s by targeting HMGB1 via the NF-κB signaling pathway, and attenuate the inflammation at the maternal-fetal interface in abortive mice.

Retrospective Analysis of Clinical Characteristics and Neonatal Outcomes of Pregnant Women with SARS-COV-2 Infection.

This retrospective study aimed to investigate the clinical characteristics and neonatal outcomes of pregnant women with SARS-COV-2 in Wuhan Children's Hospital and further suggested a possible management strategy for infected pregnant women under epidemic situation. In this study, 8 pregnant women with SARS-COV-2 who were admitted into Wuhan Children's Hospital, China from February 1, 2020 to March 30, 2020 and the clinical features, laboratory data, maternal and neonatal outcomes were analyzed. The mean age of the women at the time of admission was 30.6 years. The mean gestational age of the women was 37 weeks+4 days, and one woman presented with dichorionic diamniotic (DCDA) twin pregnancy. Except for one woman who was febrile, others had no typical clinical symptoms. For all pregnant women, the count of white blood cells and lymphocytes appeared normal, but 6 had a lower percentage of lymphocytes. C-reactive protein (CRP) levels were normal for all the women. One neonate was tested positive for the coronavirus IgG and IgM antibodies. The clinical symptoms of the pregnant women with SARS-COV-2 were mild, and the laboratory data showed similar characteristics to those of non-infected pregnant women. Since one neonate was tested positive for coronavirus, there is a possibility of vertical transmission of SARS-CoV-2. Prompt and efficient screening, triage, and isolation of pregnant women are effective management strategies to reduce nosocomial infection during the SARS-COV-2 epidemic.

Molecular detection of uterine innate lymphoid cells in the immunological mouse model of pregnancy loss.

Innate lymphoid cells (ILCs) are newly identified members of the innate lymphocyte family, which can function as adaptive T cells and act as critical modulators of inflammatory processes within different tissues and immune diseases. The role of uterine ILCs (uILCs) has recently been elucidated alongside changes associated with normal pregnancy. However, the proportions of uterine ILCs and their role in unsuccessful pregnancy remain unclear. We analyzed the characterization of uILC subsets and the expression of signature cytokines associated with ILCs in a mouse model of unsuccessful pregnancy induced by LPS, and we describe the dynamic changes they undergo during this process. We found that mice exposed to LPS display significantly higher levels of uNK cells, and uILC3s. However, a lower proportion of uILC2s and uILC1s were detected in abortion mice. In addition, we found that abortion mice display markedly higher expression of IFN-γ and IL-A17, and lower levels of IL-5. No significant differences in the expression of IL-13 and IL-22 were observed. The findings suggest that uILCs play distinct non-redundant roles during pregnancy, and uILCs may affect maternal-fetal tolerance via IL-17A, IL-5, and IFN-γ production.

45,XO/47,XXX/46,XX Male Sex Reversal Syndrome. A Case Report.

BACKGROUND: Sex reversal syndrome is a genetic anomaly caused by the disorder of sex development (DSD) with the characteristics of inconsistent phenotype normal penile size but small testes and infertility re- stulting from azoospermia. CASE: A male patient was diagnosed with the karyo- type of 45,XO/47,XXX/46,XX male sex reversal syn- drome with normal pubic hair and normal penile size, high levels of follicle-stimulating hormone and luteiniz- ing hormone, but small testes and infertility resulting from azoospermia. CONCLUSION: Sex reversal syndrome is a genetic con- dition caused by DSD. Many factors can lead to DSD, but the accurate mechanism has not been completely discovered. between gonadal sexuality and chromosome sexuality, including 46,XX male and 46,XY female for the most part, but the rare type 45,XO male also can be found. Approximately 80% of males with 46,XX present' with normal pubic hair and.

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet.

PURPOSE: The study aims to elucidate the changes in testicular spermatogenic function in high-fat diet (HFD)-induced obese rats and to evaluate the protective effects of metformin intervention. METHODS: Male Sprague-Dawley rats (n = 18) were randomly divided into a control group (standard diet), an HFD group, and a metformin group (HFD + metformin at 100 mg/kg, once daily by oral gavage). After 8 weeks, rats were euthanized, and the weights of body and testes were measured. Testis and epididymis were dissected and hematoxylin-eosin-stained for histopathological examination and semen parameter analysis. Blood samples were collected for assessment of sex hormones and metabolic parameters (serum glucose, insulin, and leptin). Spermatogenic cell apoptosis was accessed by TUNEL. RESULTS: Compared with the control group, the final body weight and weight gain were significantly higher in HFD rats, while the testicle weight and coefficients were lower. In HFD rats, metformin treatment induced weight loss and increased testicle weight (P < 0.05). In HFD rats, obvious pathological changes in the testicular tissue were characterized by small, atrophic, and distorted seminiferous tubules and destroyed basement membrane. Metformin treatment protected against the HFD-induced decrease in the number of spermatogonia, Sertoli cells, and Leydig cells (P < 0.05); ameliorated the HFD-induced increases in serum glucose, insulin, leptin, and estrogen; and decreased serum testosterone (P < 0.05) and reduced the rate of testicular cell apoptosis in obese male rats. Finally, metformin significantly improved semen parameters (including concentration, viability, motility, and normal morphology) in HFD rats (P < 0.05). CONCLUSIONS: HFD-induced obesity in rats results in detrimental effects on spermatogenesis, semen quality, endogenous hormones, and testicular cell apoptosis. Metformin intervention improved the semen parameters, possibly due to its effects on weight loss, increased testicular weight, reduced testicular cell apoptosis, and resulted in restoration of hormonal homeostasis and correction of metabolic disorder.