Previous studies on the pneumonia outbreak caused by the 2019 novel coronavirus disease (COVID-19) were based on information from the general population. Limited data are available for pregnant women ...with COVID-19 pneumonia. This study aimed to evaluate the clinical characteristics of COVID-19 in pregnancy and the intrauterine vertical transmission potential of COVID-19 infection.
Clinical records, laboratory results, and chest CT scans were retrospectively reviewed for nine pregnant women with laboratory-confirmed COVID-19 pneumonia (ie, with maternal throat swab samples that were positive for severe acute respiratory syndrome coronavirus 2 SARS-CoV-2) who were admitted to Zhongnan Hospital of Wuhan University, Wuhan, China, from Jan 20 to Jan 31, 2020. Evidence of intrauterine vertical transmission was assessed by testing for the presence of SARS-CoV-2 in amniotic fluid, cord blood, and neonatal throat swab samples. Breastmilk samples were also collected and tested from patients after the first lactation.
All nine patients had a caesarean section in their third trimester. Seven patients presented with a fever. Other symptoms, including cough (in four of nine patients), myalgia (in three), sore throat (in two), and malaise (in two), were also observed. Fetal distress was monitored in two cases. Five of nine patients had lymphopenia (<1·0 × 10⁹ cells per L). Three patients had increased aminotransferase concentrations. None of the patients developed severe COVID-19 pneumonia or died, as of Feb 4, 2020. Nine livebirths were recorded. No neonatal asphyxia was observed in newborn babies. All nine livebirths had a 1-min Apgar score of 8–9 and a 5-min Apgar score of 9–10. Amniotic fluid, cord blood, neonatal throat swab, and breastmilk samples from six patients were tested for SARS-CoV-2, and all samples tested negative for the virus.
The clinical characteristics of COVID-19 pneumonia in pregnant women were similar to those reported for non-pregnant adult patients who developed COVID-19 pneumonia. Findings from this small group of cases suggest that there is currently no evidence for intrauterine infection caused by vertical transmission in women who develop COVID-19 pneumonia in late pregnancy.
Hubei Science and Technology Plan, Wuhan University Medical Development Plan.
In the past several months, the outbreak of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2)‐associated infection (coronavirus disease 2019 COVID‐19) developed rapidly and has turned into ...a global pandemic. Although SARS‐CoV‐2 mainly attacks respiratory systems, manifestations of multiple organs have been observed. A great concern was raised about whether COVID‐19 may affect male reproductive functions. In this study, we collected semen specimens from 12 male COVID‐19 patients for virus detection and semen characteristics analysis. No SARS‐CoV‐2 was found in semen specimens. Eight out of 12 patients had normal semen quality. We also compared the sex‐related hormone levels between 119 reproductive‐aged men with SARS‐CoV‐2 infection and 273 age‐matched control men. A higher serum luteinizing hormone (LH) and a lower ratio of testosterone (T) to LH were observed in the COVID‐19 group. Multiple regression analysis indicated that serum T: LH ratio was negatively associated with white blood cell counts and C‐reactive protein levels in COVID‐19 patients. It's the first report about semen assessment and sex‐hormone evaluation in reproductive‐aged male COVID‐19 patients. Although further study is needed to clarify the reasons and underlying mechanisms, our study presents an abnormal sex hormone secretion among COVID‐19 patients, suggesting that attention should be paid to reproductive function evaluation in the follow‐up.
Highlights
Sex‐hormone levels were evaluated in reproductive‐aged male COVID‐19 patients. Semen assessment was performed in recovering male COVID‐19 patients. No SARS‐CoV‐2 virus was found in semen from recovering COVID‐19 patients.
Purpose
We performed a systematic review and meta-analysis of available literature to investigate the efficacy of the intracytoplasmic sperm injection (ICSI) in couples with non-male factor with ...respect to the clinical outcomes.
Methods
The literature search was based on EMBASE, PubMed, and the Cochrane Library. All studies published after 1992 until February 2020 and written in English addressing patients in the presence of normal semen parameters subjected to ICSI and in vitro fertilization (IVF) were eligible. Reference lists of retrieved articles were hand-searched for additional studies. The primary outcomes were fertilization rate, clinical pregnancy rate, and implantation rate; the secondary outcomes were good-quality embryo rate, miscarriage rate, and live birth rate.
Results
Four RCTs and twenty-two cohort studies fulfilling the inclusion criteria were included. Collectively, a meta-analysis of the outcomes in RCTs showed that compared to IVF, ICSI has no obvious advantage in fertilization rate (RR = 1.16, 95% CI: 0.83–1.62), clinical pregnancy rate (RR = 1.04, 95% CI: 0.66–1.64), implantation rate (RR = 1.12, 95% CI: 0.67–1.86), and live birth rate (RR = 1.17, 95% CI: 0.43–3.15). Pooled results of cohort studies demonstrated a statistically significant higher fertilization rate (RR = 1.16, 95% CI: 1.03–1.31) and miscarriage rate (RR = 1.04, 95% CI: 1.01–1.06) in the ICSI group; furthermore, higher clinical pregnancy rate (RR = 0.85, 95% CI: 0.77–0.94), implantation rate (RR = 0.78, 95% CI: 0.65–0.95), and live birth rate (RR = 0.86, 95% CI: 0.79–0.94) was founded in the IVF group; no statistically significant difference was observed in good-quality embryo rate (RR = 0.98, 95% CI: 0.93–1.04).
Conclusion
ICSI has no obvious advantage in patients with normal semen parameters. Enough information is still not available to prove the efficacy of ICSI in couples with non-male factor infertility comparing to IVF.
Decidualization of human endometrial stromal cells (HESCs) is a vital step for successful pregnancy. However, the process by which micro-RNAs (miRNAs) regulate decidualization remains elusive. Our ...current study was designed to identify the mechanism of miRNA miR-542-3p and its potential targets in regulating decidualization. The results showed that miR-542-3p was down-regulated in HESCs. Luciferase assay confirmed that integrin-linked kinase (ILK) is a direct target of miR-542-3p. Overexpression of miR-542-3p resulted in decreased ILK and downstream transforming growth factor β1 (TGF-β1) and SMAD family member 2 (SMAD2) expression. Additional expression of ILK attenuates the miR542-3p-induced down-regulation of TGF-β1 and SMAD2, changes properties such as suppression of proliferation and invasion, and induction of apoptosis, thereby affecting the differentiation of HESCs. Moreover, miR-542-3p overexpression caused down-regulation of the angiogenic factors vascular endothelial growth factor (VEGF), cyclooxygenase-2 (COX-2) and matrix metalloproteinase-9 (MMP-9), and the supernatant of HESCs overexpressing miR-542-3p inhibited the formation of tubular structures in human umbilical vein endothelial cells (HUVECs), suggesting that miR-542-3p inhibits angiogenesis of HUVECs. Furthermore, in our mouse model, following injection of miR-542-3p mimic into the endometrium of mice at pregnancy day 8 (D8), we found decreased miR-542-3p expression and loss of embryo implantation sites. In conclusion, miR-542-3p can affect the process of endometrial decidualization by down-regulating ILK. The present study adds further understanding of the process and regulation of decidualization.
At present, there are still ambiguous reports about the perinatal infection of infants born to mothers infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The dynamic ...characteristics of infantile serum antibodies born to mother with SARS-CoV-2 has not been well described. In this study, we analyzed the seroconversion of 27 newborns born to 26 pregnant women infected with SARS-CoV-2. The SARS-CoV-2 IgG positive rate of parturient was 80.8%, and half of their infants obtained maternal IgG. IgG transfer rates were 18.8% and 81.8% in those infants whose mother infected less and more than 2 weeks before delivery. In the first two months of life, the IgG level of infants dropped sharply to one tenth of that at birth. These results suggest that maternal SARS-CoV-2 IgG provides limited protection for infants.
The selection of suitable reference genes (RGs), especially the identification of the proper combination of RGs is the key to obtain reliable results of gene expression for quantitative real-time ...polymerase chain reaction (qRT-PCR). To date, there is no relevant study dealing with the stability of RGs in rat placenta. In this study, the geNorm, NormFinder, and BestKeeper software were used to analyze the expression stability of the candidate RGs in placenta under physiological and prenatal caffeine exposure (PCE) conditions. The expression of
Tbp
,
Gapdh
and
Ywhaz
in female and
Polr2a
,
Gapdh
and
Ywhaz
in male placenta were highly stable under physiological conditions, and there was no obvious gender difference. We further found that two RGs were sufficient for reliable normalization in female and male placenta and the combination of
Ywhaz
and
Gapdh
was the most suitable compound RGs under physiological conditions. Under PCE conditions,
Ywhaz
,
Gapdh
and
Polr2a
were the most stable genes in both female and male placenta. Among them,
Ywhaz
and
Gapdh
were chosen as the best paring. Finally, selected RGs were employed for normalization of the expression of a clear target gene and the results of standardization supported our choice. In conclusion, our study confirmed that
Ywhaz/Gapdh
combination was the most suitable RGs in rat placenta under physiological and PCE pathological conditions and provided a theoretical and experimental basis for physiological and pathological research of the rat placenta.
We aimed to develop inhibitory short peptides that can prevent protein interactions of SOS1/EPS8/ABI1 tri-complex, a key component essential for ovarian cancer metastasis.
Plasmids containing various ...regions of HA-tagged ABI1 were co-transfected into ovarian cancer cells with Flag-tagged SOS1 or Myc-tagged EPS8. Co-immunoprecipitation and GST-pulldown assay were used to identify the regions of ABI1 responsible for SOS1 and EPS8 binding. Inhibitory short peptides of these binding regions were synthesized and modified with HIV-TAT sequence. The blocking effects of the peptides on ABI1-SOS1 or ABI1-EPS8 interactions in vitro and in vivo were determined by GST-pulldown assay. The capability of these short peptides in inhibiting invasion and metastasis of ovarian cancer cell was tested by Matrigel invasion assay and peritoneal metastatic colonization assay.
The formation of endogenous SOS1/EPS8/ABI1 tri-complex was detected in the event of LPA-induced ovarian cancer cell invasion. In the tri-complex, ABI1 acted as a scaffold protein holding together SOS1 and EPS8. The SH3 and poly-proline+PxxDY regions of ABI1 were responsible for SOS1 and EPS8 binding, respectively. Inhibitory short peptides p + p-8 (ppppppppvdyedee) and SH3-3 (ekvvaiydytkdkddelsfmegaii) could block ABI1-SOS1 and ABI1-EPS8 interaction in vitro. TAT-p + p-8 peptide could disrupt ABI1-EPS8 interaction and suppress the invasion and metastasis of ovarian cancer cells in vivo.
TAT-p + p-8 peptide could efficiently disrupt the ABI1-EPS8 interaction, tri-complex formation, and block the invasion and metastasis of ovarian cancer cells.
Azithromycin, a commonly used macrolide antibiotic for treating chlamydial infections during pregnancy, has sparked investigations into its potential effects on offspring development. Despite these ...inquiries, there remains uncertainty about the specific impact of prenatal azithromycin exposure (PAzE) on offspring ovarian development and the precise "effect window". Pregnant mice, following clinical guidelines for azithromycin dosing, were orally administered azithromycin at different gestational stages (gestational day, GD) 10–12 or GD 15–17, doses (50, 100, or 200 mg/kg·d), and courses (single or multiple). On GD 18, we collected offspring blood and ovaries to examine changes in fetal serum estradiol (E2) levels, fetal ovarian morphology, pre-granulosa cell function, and oocyte development. Multiple courses of PAzE resulted in abnormal fetal ovarian morphological development, disorganized germ cell nests, enhanced ovarian cell proliferation, and reduced apoptosis. Simultaneously, multiple courses of PAzE significantly increased fetal serum E2 levels, elevated ovarian steroidogenic function (indicated by Star, 3β-hsd, and Cyp19 expression), disrupted oocyte development (indicated by Figlα and Nobox expression), and led to alterations in the MAPK signal pathway in fetal ovaries, particularly in the high-dose treatment group. In contrast, a single course of PAzE reduced fetal ovarian cell proliferation, decreased steroidogenic function, and inhibited oocyte development, particularly through the downregulation of Mek2 expression in the MAPK signal pathway. These findings suggest that PAzE can influence various aspects of fetal mouse ovarian cell development. Multiple courses enhance pre-granulosa cell estrogen synthesis function and advance germ cell development, while a single terminal gestation dose inhibits germ cell development. These differential effects may be associated with changes in the MAPK signal pathway.
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•Prenatal azithromycin exposure affects the fetal ovarian development.•Azithromycin disrupts offspring’s steroid hormone synthesis and the development of primordial follicle.•MAPK signaling pathway may mediate the effect of azithromycin on ovarian development in offspring.
Dysregulation of microRNAs in endometrial cells plays a pivotal role in the pathogenesis of endometriosis (EM). This study aims to investigate the implication of aberrant miR-202-3p expression in EM ...and the underlying mechanisms. We demonstrated that miR-202-3p was significantly downregulated in eutopic endometrium of EM in comparison to normal endometrial samples (P < 0.05). Primary endometrial stromal cells (ESCs) isolated from eutopic or ectopic endometrium also showed a significant decrease in miR-202-3p level compared to ESCs from normal endometrium (P < 0.01). Functional studies using MTT, wound healing assay and transwell assay indicated that overexpression of miR-202-3p greatly impaired cell viability, migration, and invasion, whereas suppression of miR-202-3p exhibited the opposite effects (P < 0.05 or P < 0.01). miR-202-3p mimics or inhibitors transfection significantly decreased or increased expression of Rho-associated, coiled-coil containing protein kinase 1 (ROCK1), respectively, in ESCs (P < 0.01). Using dual luciferase reporter assay, we validated ROCK1 as a direct target of miR-202-3p. Moreover, negative correlations between miR-202-3p and ROCK1 mRNA/protein levels were determined in both eutopic and normal control endometrium (P < 0.01). In conclusion, these findings suggest that suppression of miR-202-3p in ESCs results in enhanced cell viability, invasion, and migration at least partially via upregulation of its target ROCK1, which eventually contributes to the development of endometriosis.
Prenatal adverse environments can cause fetal intrauterine growth retardation (IUGR) and higher susceptibility to multiple diseases after birth, related to multi-organ development programming changes ...mediated by intrauterine overexposure to maternal glucocorticoids. As a glucocorticoid barrier, P-glycoprotein (P-gp) is highly expressed in placental syncytiotrophoblasts; however, the effect of P-gp on the occurrence of IUGR remains unclear.
Human placenta and fetal cord blood samples of IUGR fetuses were collected, and the related indexes were detected. Pregnant Wistar rats were administered with 30 mg/kg·d (low dose) and 120 mg/kg·d (high dose) caffeine from gestational day (GD) 9 to 20 to construct the rat IUGR model. Pregnant mice were administered with caffeine (120 mg/kg·d) separately or combined with sodium ferulate (50 mg/kg·d) from gestational day GD 9 to 18 to confirm the intervention target on fetal weight loss caused by prenatal caffeine exposure (PCE). The fetal serum/placental corticosterone level, placental P-gp expression, and related indicator changes were analyzed. In vitro, primary human trophoblasts and BeWo cells were used to confirm the effect of caffeine on P-gp and its mechanism.
The placental P-gp expression was significantly reduced, but the umbilical cord blood cortisol level was increased in clinical samples of the IUGR neonates, which were positively and negatively correlated with the neonatal birth weight, respectively. Meanwhile, in the PCE-induced IUGR rat model, the placental P-gp expression of IUGR rats was decreased while the corticosterone levels of the placentas/fetal blood were increased, which were positively and negatively correlated with the decreased placental/fetal weights, respectively. Combined with the PCE-induced IUGR rat model, in vitro caffeine-treated placental trophoblasts, we confirmed that caffeine decreased the histone acetylation and expression of P-gp via RYR/JNK/YB-1/P300 pathway, which inhibited placental and fetal development. We further demonstrated that P-gp inducer sodium ferulate could reverse the inhibitory effect of caffeine on the fetal body/placental weight. Finally, clinical specimens and other animal models of IUGR also confirmed that the JNK/YB-1 pathway is a co-regulatory mechanism of P-gp expression inhibition, among which the expression of YB-1 is the most stable. Therefore, we proposed that YB-1 could be used as the potential early warning target for the opening of the placental glucocorticoid barrier, the occurrence of IUGR, and the susceptibility of a variety of diseases.
This study, for the first time, clarified the critical role and epigenetic regulation mechanism of P-gp in mediating the opening mechanism of the placental glucocorticoid barrier, providing a novel idea for exploring the early warning, prevention, and treatment strategies of IUGR.
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