Unveiling the role of chronic inflammation in ovarian aging: insights into mechanisms and clinical implications.

Ovarian aging, a natural process in women and various other female mammals as they age, is characterized by a decline in ovarian function and fertility due to a reduction in oocyte reserve and quality. This phenomenon is believed to result from a combination of genetic, hormonal, and environmental factors. While these factors collectively contribute to the shaping of ovarian aging, the substantial impact and intricate interplay of chronic inflammation in this process have been somewhat overlooked in discussions. Chronic inflammation, a prolonged and sustained inflammatory response persisting over an extended period, can exert detrimental effects on tissues and organs. This review delves into the novel hallmark of aging-chronic inflammation-to further emphasize the primary characteristics of ovarian aging. It endeavors to explore not only the clinical symptoms but also the underlying mechanisms associated with this complex process. By shining a spotlight on chronic inflammation, the aim is to broaden our understanding of the multifaceted aspects of ovarian aging and its potential clinical implications.

[Impacts of ODF2 gene knockdown on the sperm motility and fertility of male mice].

OBJECTIVE: To investigate the knockdown of the outer dense fiber protein 2 (ODF2) gene on the sperm motility and fertility of male mice. METHODS: We constructed three knockdown vectors with the target gene ODF2 and one control vector without the target gene. After infecting ICR mice, we determined the vector with the best knockdown effect by RT-PCR and Western blot and reinfected the mice with it. Then we obtained and analyzed the sperm motility parameters, pathological changes of the testis issue, and the litter size of the mice with gene knockdown. RESULTS: Compared with the normal controls, the mice infected with the vector with the best knockdown effect showed significantly decreased sperm motility parameters, pathomorphological abnormalities of the testis, and a reduced litter size (10.86 ± 1.28 vs 12.72 ± 2.05, P = 0.001). CONCLUSION: Decreased expression of the ODF2 gene deceases sperm motility parameters, impairs the morphology of the testis and affects the fertility of male mice.

[Expressions of ODF2 mRNA and protein are down-regulated in the sperm of asthenospermia patients].

OBJECTIVE: To investigate the mRNA and protein expressions of outer dense fiber 2 (ODF2) in the sperm of the asthenospermia patient and their differences from those in normal healthy men. METHODS: According to the WHO criteria, we collected semen samples from 45 asthenozoospermia patients and 15 normal healthy volunteers. Using computer-assisted sperm analysis (CASA), we divided the semen samples from the asthenospermia patients into a mild, a moderate and a severe group, and determined the mRNA and protein expressions of ODF2 in different groups by RT-PCR and Western blot. RESULTS: Compared with the normal healthy men, the expression of the ODF2 gene showed no statistically significant difference in the mild asthenospermia group (1.112 0 ± 0.525 5 vs 0.688 0 ± 0.372 0, P >0.05) but remarkably decreased in the moderate (0.483 3 ± 0.186 3, P <0.05) and severe asthenospermia patients (0.448 3 ± 0.340 8, P <0.01). The OD value (ODF2/ß-actin) of the ODF2 protein in the normal men exhibited no statistically significant difference from that in the mild asthenospermia group (0.458 7 ± 0.052 1 vs 0.326 1 ± 0.071 4, P >0.05), but markedly lower than in the moderate (0.145 4 ± 0.053 6, P <0.05) and severe asthenospermia patients (0.122 7 ± 0.045 7, P <0.01), which was consistent with the results of RT-PCR. CONCLUSIONS: Decreased mRNA and protein expressions of ODF2 in the sperm are positively correlated with declined sperm motility of the asthenospermia patient, which is suggestive of the involvement of the ODF2 gene in the regulation of sperm motility.

A novel SNP in HUWE1 promoter confers increased risk of NOA by affecting the RA/RARα pathway in Chinese individuals.

BACKGROUND: The ubiquitin ligase HECT, UBA, and WWE domain-containing E3 ubiquitin protein ligase 1 is essential for the establishment and maintenance of spermatogonia. However, the role of HECT, UBA, and WWE domain-containing E3 ubiquitin protein ligase 1 in regulating germ cell differentiation remains unclear, and clinical evidence linking HECT, UBA, and WWE domain-containing E3 ubiquitin protein ligase 1 to male infertility pathogenesis is lacking. OBJECTIVE: This study aims to investigate the role of HUWE1 in germ cell differentiation and the mechanism by which a HUWE1 single nucleotide polymorphism increases male infertility risk. MATERIALS AND METHODS: We analyzed HUWE1 single nucleotide polymorphisms in 190 non-obstructive azoospermia patients of Han Chinese descent. We evaluated HECT, UBA, and WWE domain-containing E3 ubiquitin protein ligase 1 regulation by retinoic acid receptor alpha using chromatin immunoprecipitation assays, electrophoretic mobility shift assays, and siRNA-mediated RARα knockdown. Using C18-4 spermatogonial cells, we determined whether HECT, UBA, and WWE domain-containing E3 ubiquitin protein ligase 1 participated in retinoic acid-mediated retinoic acid receptor alpha signaling. We performed luciferase assays, cell counting kit-8 assays, immunofluorescence, quantitative real-time polymerase chain reaction, and western blotting. We quantified HUWE1 and retinoic acid receptor alpha in testicular biopsies from non-obstructive azoospermia and obstructive azoospermia patients using quantitative real-time polymerase chain reaction and immunofluorescence. RESULTS: Three HUWE1 single nucleotide polymorphisms were significantly associated with spermatogenic failure in 190 non-obstructive azoospermia patients; one (rs34492591) was in the HUWE1 promoter. Retinoic acid receptor alpha regulates HUWE1 gene expression by binding to its promoter. HECT, UBA, and WWE domain-containing E3 ubiquitin protein ligase 1 participates in retinoic acid/retinoic acid receptor alpha signaling pathway and regulates the expression of germ cell differentiation genes STRA8 and SCP3 to inhibit cell proliferation and reduce γH2AX accumulation. Notably, significantly lower levels of HUWE1 and RARα were detected in testicular biopsy samples from non-obstructive azoospermia patients. CONCLUSIONS: An HUWE1 promoter single nucleotide polymorphism significantly downregulates its expression in non-obstructive azoospermia patients. Mechanistically, HECT, UBA, and WWE domain-containing E3 ubiquitin protein ligase 1 regulates germ cell differentiation during meiotic prophase through its participation in retinoic acid/retinoic acid receptor alpha signaling and subsequent modulation of γH2AX. Taken together, these results strongly suggest that the genetic polymorphisms of HUWE1 are closely related to spermatogenesis and non-obstructive azoospermia pathogenesis.

Effect of sequential embryo transfer on in vitro fertilization and embryo transfer outcomes: a systematic review and meta-analysis.

Background: Sequential embryo transfer has been recognized as a strategy to increase pregnancy rates in women undergoing in vitro fertilization and embryo transfer (IVF-ET). However, its impact on assisted reproductive outcomes remains to be substantiated by robust evidence. This systematic review aims to summarize and analyze the available evidence to investigate the effect of sequential embryo transfer on assisted reproductive outcomes. Methods: A comprehensive literature search was executed across the Pubmed, Cochrane Library, Web of Science, and Scopus databases in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data were aggregated utilizing a random effects model, and the resultant outcomes were articulated as odds ratios (ORs) along with their 95% confidence intervals (CIs). Results: The pooled results revealed a statistically significant enhancement in reproductive outcomes for infertile patients undergoing sequential embryo transfer as evidenced by elevated rates of chemical pregnancy (OR = 1.67, 95% CI = 1.23-2.27), clinical pregnancy (OR = 1.78, 95% CI = 1.43-2.21), and ongoing pregnancy (OR = 1.54, 95% CI = 1.03-2.31). Compared with cleavage-stage embryo transfer, sequential transfer yielded superior outcomes in terms of chemical pregnancy rate (OR = 2.08, 95% CI = 1.35-3.19) and clinical pregnancy rate (OR = 1.78, 95% CI = 1.37-2.31). Furthermore, among the repeated implantation failure (RIF) cohort, sequential embryo transfer surpassed blastocyst-stage transfer, delivering a heightened chemical pregnancy rate (OR = 1.66, 95% CI = 1.19-2.53) and clinical pregnancy rate (OR = 1.65, 95% CI = 1.19-2.27). Conclusion: Our meta-analysis indicates that sequential transfer may enhance clinical pregnancy rate in a small subgroup of well-selected women. While promising, further evidence from prospective studies is needed.

Single Cell Proteomics Profiling Reveals That Embryo-Secreted TNF-α Plays a Critical Role During Embryo Implantation to the Endometrium.

It has been long-known that endometrium-secreted cytokines play a critical role during embryo implantation. However, whether cytokines secreted from the embryo are relevant to the process of embryo implantation remains unclear. The concentration of cytokines in embryo culture medium was tested using a newly developed, high-sensitivity single-cell proteomic platform and evaluated in comparison to embryo quality and clinical outcome. The effect of TNF-α on embryo and endometrium Ishikawa cells was investigated using immunofluorescence staining, CCK-8 assay, TUNEL staining, and RT-qPCR. Of the 10 cytokines measured, only TNF-α concentration was significantly higher in the group with embryo implantation failure. Immunofluorescence staining showed that the expression of TNF-α was unevenly distributed in blastocysts, and the expression level was significantly correlated with the blastocyst inner cell mass (ICM) quality score. Gene profiling showed that addition of TNF-α led to increased expression of tumor necrosis factor receptor 1 (TNFR1) and apoptosis-related genes and that this could be inhibited by the TNF-α receptor inhibitor etanercept (ETA). In addition, an increased expression of water and ion channels, including AQP3, CFTR, ENaCA, and CRISP2 was also observed which could also be inhibited by ETA. Our results show that higher embryo-secreted TNF-α levels are associated with implantation failure through activation of TNF-α receptor, and TNF-α may be an independent predictor for pre-transfer assessment of the embryo development potential in IVF patients.

CEP128 is involved in spermatogenesis in humans and mice.

Centrosomal proteins are necessary components of the centrosome, a conserved eukaryotic organelle essential to the reproductive process. However, few centrosomal proteins have been genetically linked to fertility. Herein we identify a homozygous missense variant of CEP128 (c.665 G > A [p.R222Q]) in two infertile males. Remarkably, male homozygous knock-in mice harboring the orthologous CEP128R222Q variant show anomalies in sperm morphology, count, and motility. Moreover, Cep128 knock-out mice manifest male infertility associated with disrupted sperm quality. We observe defective sperm flagella in both homozygous Cep128 KO and KI mice; the cilia development in other organs is normal-suggesting that CEP128 variants predominantly affected the ciliogenesis in the testes. Mechanistically, CEP128 is involved in male reproduction via regulating the expression of genes and/or the phosphorylation of TGF-ß/BMP-signalling members during spermatogenesis. Altogether, our findings unveil a crucial role for CEP128 in male fertility and provide important insights into the functions of centrosomal proteins in reproductive biology.

Granulocyte Colony-Stimulating Factor Combined With Transcutaneous Electrical Acupoint Stimulation in Treatment of Unresponsive Thin Endometrium in Frozen Embryo Transfer Cycles.

Objective: This trial was designed to assess the treatment effects of granulocyte colony-stimulating factor (G-CSF) and transcutaneous electrical acupoint stimulation (TEAS) on thin endometrium in frozen-thawed embryo transfer (FET) cycles. Methods: Ninety-nine patients with previous cancellations of embryo transfer were included, 56 of whom were prospectively treated with intrauterine perfusion of G-CSF in subsequent FET cycles. The selected patients were randomized into the G-CSF perfusion only group and the G-CSF perfusion combined with TEAS group. The other 43 patients were retrospectively included as controls. Results: Compared to previous cycles, endometrial thickness was statistically significantly increased in the two treatment groups (5.97 ± 0.60, 7.52 ± 0.56, 6.14 ± 0.52, and 7.66 ± 0.44; P = 0.00 and 0.00, respectively). The increases in endometrial thickness suggested that no statistically significant difference was found between the two treatment groups. The G-CSF with TEAS group suggested a higher embryo implantation rate than the G-CSF perfusion only and control groups (33.33 and 29.1% and 33.33 and 17.39%; P = 0.412 and 0.091, respectively). The G-CSF combined with TEAS group demonstrated nominally higher clinical and ongoing pregnancy rates than the G-CSF perfusion-only group and controls, though, the difference was not statistically significant. Conclusion: G-CSF has a potential role in improving endometrium thickness in patients with thin unresponsive endometrium in FET treatment cycles. In addition, when combined with TEAS, G-CSF perfusion treatment also improves the embryo implantation rate; however, randomized controlled trials are highly demanded to provide high-grade evidence regarding clinical pregnancy rate after G-CSF perfusion treatment.

MgB2 superconducting whiskers synthesized by using the hybrid physical-chemical vapor deposition.

In this work, MgB(2) whiskers were fabricated on a copper substrate by using the hybrid physical-chemical vapor deposition, which was one of the most effective ways to make high quality pure MgB(2) films, with the possible growth mechanism discussed. The whiskers are hexagonal and conelike and grow along the [0001] direction with a single-crystal structure. The onset transition temperature is approximately 39 K, which is among the best in the published nanostructure MgB(2) papers. Fabrication of nanoscale MgB(2) whiskers provides the fundamental understanding of the effect of dimensionality and size on superconductivity.

Electronic and Mechanical Coupling in Bent ZnO Nanowires.

A red shift of the exciton of ZnO nanowires is efficiently produced by bending strain, as demonstrated by a low-temperature (81 K) cathodoluminescence (CL) study of ZnO nanowires bent into L- or S-shapes. The figure shows a nanowire (Fig. a) with the positions of CL measurements marked. The corresponding CL spectra-revealing a peak shift and broadening in the region of the bend-are shown in Figure b.

Whispering gallery modes in single triangular ZnO nanorods.

Whispering gallery modes in ZnO nanorods with equilateral triangular cross sections were studied for the first time, to our knowledge. Photoluminescence following excitation with 325 nm radiation was observed at discrete wavelengths and thereby indicated the excitation of whispering gallery modes of triangular ZnO nanorod resonators. These resonances extended over both the visible emission band and the ultraviolet emission band of ZnO. The refractive index of ZnO between 2 eV and 3.2 eV was calculated assuming a "folded" whispering gallery mode and a simple plane-wave model. Our analysis shows that the plane-wave model produces a dispersion curve that agrees well with that of bulk ZnO for large nanorods but shows small deviations when the size of the nanorod resonator approaches the wavelength of the emitted light.

In situ study of epitaxial growth of ZnO nanowires at the junctions of nanowall networks on zinc particles.

The authors show the real-time growth of ZnO nanowalls and nanowires on zinc particles via in situ observation in an environmental scanning electron microscopy. It was observed that a ZnO polycrystalline film is first deposited on zinc particles. The nanowires started to grow when the nanowalls had just formed and they grew epitaxially on the junctions of the nanowalls. The nanowalls and the nanowires grew together until the source of zinc was exhausted. The vapor-solid mechanism is deemed to be the growth mechanism as it quantitatively accounts for the growth speed of the nanowalls and nanowires observed in the experiment. Cathodoluminescence reveals that the growth at low zinc concentration leads to blue emission from defects, which may be zinc vacancies.

Solution Grown Se/Te Nanowires: Nucleation, Evolution, and The Role of Triganol Te seeds.

We have studied the nucleation and growth of Se-Te nanowires (NWs), with different morphologies, grown by a chemical solution process. Through systematic characterization of the Se-Te NW morphology as a function of the Te nanocrystallines (NCs) precursor, the relative ratio between Se and Te, and the growth time, a number of significant insights into Se-Te NW growth by chemical solution processes have been developed. Specifically, we have found that: (i) the growth of Se-Te NWs can be initiated from either long or short triganol Te nanorods, (ii) the frequency of proximal interactions between nanorod tips and the competition between Se and Te at the end of short Te nanorods results in V-shaped structures of Se-Te NWs, the ratio between Se and Te having great effect on the morphology of Se-Te NWs, (iii) by using long Te nanorods as seeds, Se-Te NWs with straight morphology were obtained. Many of these findings on Se-Te NW growth can be further generalized and provide very useful information for the rational synthesis of group VI based semiconductor NW compounds.