The association between COVID-19 and infertility: Mendelian randomization analysis.

Since December 2019, COVID-19 has triggered a global pandemic. The association of COVID-19 with the long-term reproductive situation of women and males is not clear. Thus, our aim was to assess the causal association between COVID-19 and infertility using Mendelian randomization (MR) analysis based on the OpenGWAS database. Two-sample MR analysis was conducted using one genome-wide association study (GWAS) on COVID-19 and infertility in individuals of European ancestry. The summary data of genetic variation come from the GWAS in European populations. We applied several MR methods, including MR Egger, weighted median, inverse variance weighted, simple mode, weighted mode, to test causal relationships. After observing the statistical analysis results of MR, we conducted sensitivity analysis to test robustness. After gene prediction, it was found that there was no clear causal relationship between COVID-19 and male infertility in MR analysis [OR 0.4702 (95% CI, 0.1569-1.4093), P = .178]. Moreover, COVID-19 was not associated with female infertility [OR 0.9981 (95% CI, 0.763-1.544), P = .646]. Sensitivity analysis showed that the MR results were robust [level pleiotropy, male: (MR-Egger, intercept = 0.1967434; se = 0.1186876; P = .2392406); female: (MR-Egger, intercept = -0.05902506; se = 0.05362049; P = .3211367)]. To further validate the impact of COVID-19 on infertility, we added a covariate (sex hormone binding global levels, abortion) to the MR analysis, which is a multivariate MR analysis. According to univariate and multivariate MR analyses, the evidence does not support that COVID-19 is a causal risk factor for infertility in European population. This information can provide information for doctors in reproductive centers when managing infertility patients.

[Advances in the Regulation of Follicular Development by Extracellular Vesicles and Non-Coding RNAs].

Extracellular vesicles (EV),nanoscale vesicles encapsulated by phospholipid bilayers,are rich in biological molecules such as nucleic acids,metabolites,proteins,and lipids derived from parental cells.They are mainly involved in intercellular communication,signal transmission,and material transport and affect the functions of target cells.Ovulation disorders account for a higher proportion in the factors causing infertility which demonstrates increasing incidence year by year.Non-coding RNAs participate in a series of physiological and pathological processes of follicular development,playing a key role in female infertility.This review systematically introduces the types and biological roles of EV and elaborates on the regulation of follicular development from the effects of EV and non-coding RNAs on granulosa cell function,oocyte maturation,ovulation,luteal formation,and steroid hormone synthesis,providing a new idea and a breakthrough point for the diagnosis and treatment of infertility.

A rare frameshift variant in trans with the IVS9-5T allele of CFTR in a Chinese pedigree with congenital aplasia of vas deferens.

PURPOSE: Congenital aplasia of vas deferens (CAVD) is an atypical form of cystic fibrosis (CF) and causes obstructive azoospermia and male infertility. Compound heterozygous variants of CFTR are the main cause of CAVD. However, most evidence comes from genetic screening of sporadic cases and little is from pedigree analysis. In this study, we performed analysis in a Chinese pedigree with two CAVD patients in order to determine the genetic cause of this familial disorder. METHODS: In the present study, we performed whole-exome sequencing and co-segregation analysis in a Chinese pedigree involving two patients diagnosed with CAVD. RESULTS: We identified a rare frameshift variant (NM_000492.3: c.50dupT;p.S18Qfs*27) and a frequent CBAVD-causing variant (IVS9-TG13-5T) in both patients. The frameshift variant introduced a premature termination codon and was not found in any public databases or reported in the literature. Co-segregation analysis confirmed these two variants were in compound heterozygous state. The other male members, who harbored the frameshift variant and benign IVS9-7T allele, did not have any typical clinical manifestations of CF or CAVD. CONCLUSION: Our findings may broaden the mutation spectrum of CFTR in CAVD patients and provide more familial evidence that the combination of a mild variant and a severe variant in trans of CFTR can cause vas deferens malformation.

Potential targets of TMEM176A in the growth of glioblastoma cells.

BACKGROUND: Human transmembrane protein 176A (TMEM176A) is upregulated in several tumors. Growing evidence has suggested the high clinical value of TMEM176A as a biomarker for early tumor diagnosis. However, less is known about the function of TMEM176A in glioblastomas (GBMs). METHODS: In this study, we systematically analyzed the effect of TMEM176A knockdown and overexpression in GBM cells (U87, T98G and A172) on cell proliferation, cell cycle and cell apoptosis. RESULTS: Our results indicated that TMEM176A acted as a tumor-promoting factor in GBM cells. Moreover, a specific ERK1/2 inhibitor, U0126, suppressed the function of TMEM176A in GBM cells. Therefore, we proposed that TMEM176A may be involved in a pathway including ERK1/2 in the regulation of the cell cycle. Moreover, we also found that TMEM176A affected the expression of Bcl2 and played a central role in apoptosis of GBM cells. CONCLUSION: Taken together, our results not only elucidated the multiple functions of TMEM176A in GBM cells but also provided a deep insight into the potential targets of TMEM176A in the growth of GBM cells.

Identification and expression of carbonic anhydrase 2, myosin regulatory light chain 2 and selenium-binding protein 1 in zebrafish Danio rerio: Implication for age-related biomarkers.

Proteomic study has determined age-related changes in synthesis of carbonic anhydrase 2, myosin regulatory light chain 2 and selenium-binding protein 1 in muscle of post-menopausal women. However, little information is available regarding the expression and role of these proteins in early development and life span. In this study we showed that zebrafish ca2, myl2a, myl2b and selenbp1 were highly identical to their mammalian counterparts in primary and tertiary structures as well as genomic organization and syntenic map. They displayed distinct spatiotemporal expression patterns in embryos and larvae of zebrafish. Moreover, their transcription levels in the respective tissues were obviously remodeled in an age-dependent fashion, i.e. some mRNA levels were increased, while others remained unchanged or even decreased, suggesting that CA2, MYL2a, MYL2b and SELENBP1 can be used as aging biomarkers. Our study also lays a foundation for further illumination of the functions of these genes in early development and aging processes.

Lactation-Related MicroRNA Expression in Microvesicles of Human Umbilical Cord Blood.

BACKGROUND The complex process by which lactation is initiated upon neonate delivery remains incompletely understood. Microvesicles (MVs) can transmit microRNAs (miRNAs) into recipient cells to influence cell function, and recent studies have identified miRNAs essential for mammary gland development and lactation. This study aimed to investigate the expression of lactation-related miRNAs in MVs isolated from human umbilical cord blood immediately after delivery. MATERIAL AND METHODS Umbilical cord blood samples were collected from 70 healthy pregnant women, and MVs were isolated through differential centrifugation and characterized by transmission electron microscopy, Western blotting, and nanoparticle tracking analysis. Lactation-related miRNAs were screened using bioinformatics tools for miRNA target prediction, gene ontology, and signaling pathway analyses. miRNA PCR arrays were used for miRNA expression analysis, and the results were validated by real-time PCR. Upon exposure of HBL-100 human mammary epithelial cells to MVs, MV uptake was examined by fluorescence confocal microscopy and b-casein secretion was detected by ELISA. RESULTS Spherical MVs extracted from umbilical cord blood expressed CD63 and had an average diameter of 167.0±77.1 nm. We profiled 337 miRNAs in human umbilical cord blood MVs and found that 85 were related to lactation by bioinformatics analysis. The 25 most differentially expressed lactation-related miRNAs were validated by real-time PCR. MV uptake by HBL-100 cells was after 4 h in culture, and significantly increased secretion of ß-casein was observed after 96 h from cells exposed to MVs (P<0.05). CONCLUSIONS Umbilical cord blood MVs contain many lactation-related miRNAs and can induce ß-casein production by HBL-100 cells in vitro. Thus, umbilical cord blood MVs may mediate secretion of ß-casein through miRNAs, thereby playing an important role in fetal-maternal crosstalk.