Reproductive Sciences最新文献

Mono-butyl phthalate (MBP), the metabolite of dibutyl phthalate (DBP), is the most abundant phthalate metabolite found in Chinese women. Extracellular vesicles (EVs) are nanoscale lipid bilayer particles produced by extensive kinds of cells, serving a key role in intercellular communication. Extracellular vesicle miRNAs (EV-miRNAs) in follicular fluid (FF) have been evidenced to be associated with female reproductive health. The objective of this study was to investigate the associations of EV-miRNAs expressed profile with DBP exposure in FF of female participants and expose its potential mechanism in impaired oocyte development. Based on participants' FF MBP concentrations and fertilization status, we compared the miRNA expression between the FF-EVs of group A (high DBP exposure and impaired fertilization) and group B (low DBP exposure and normal fertilization). Compared with group B, miR-1246, miR-3679-5p, miR-423-5p, miR-5585-3p, miR-116-5p, miR-172-5p were upregulated, while miR-34b-3p was downregulated in group A. Target genes of the differently expressed miRNAs were predicted, and the functional analysis was performed. Furthermore, we exposed human ovarian granulosa tumor cell line (KGN) to MBP (4ug/L) to isolate the EVs from the culture medium and validated the expression levels of different miRNAs. We found that MBP exposure was significantly associated with increased levels of miR-116-5p (P = 0.01). In addition, we demonstrated that the most different miRNA, miR-116-5p regulated oocyte fertilization by inhibiting FOXO3a. Our findings suggested that EV-miRNAs in the FF might mediate MBP toxicity in oocytes.

Premature ovarian insufficiency (POI) is one of the leading causes of female infertility. To date, the genetic etiology of POI has been elucidated in approximately 20-25% of the total cases. The human zona pellucida (ZP) plays an important role in the organization and differentiation of granulosa cells, follicle formation, and sperm recognition. Mutations in ZP1, ZP2, and ZP3 have been reported to cause female infertility due to oocyte degeneration, empty follicle, or in vitro fertilization failure. In this study, we identified three novel missense mutations in ZP3 (NM_001110354.2): c.643G > A (p.Asp215Asn), c.215 C > T (p.Thr72Ile), and c.152T > C (p.Leu51Pro) in three sporadic Han Chinese POI patients through whole-exome sequencing. These variants are absent from population databases and were predicted to be deleterious by multiple in silico tools. Structure prediction analysis showed that the affected amino acid altered the ZP3 protein structure. Western blot further confirmed that these ZP3 variants reduced the expression and secretion of ZP components. In summary, this study reports three novel deleterious variants in ZP3 associated with POI, thereby broadening the mutation spectrum of ZP3 in POI patients.

This study aimed to systematically review existing randomized clinical trials on the effect of dietary interventions on endometriosis. A search was performed on the Cochrane Central Register of Controlled Trials (CENTRAL), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Clinical Trials, EMBASE, PubMed, Lilacs, and Cielo databases. The search terms were used: "endometriosis", "endometrioma", "diet", "supplements" and "nutrition". Electronic literature searches through databases yielded 866 publications. Two authors performed The study selection independently (and blinded), and disagreements were discussed. Eleven RCTs were included in the systematic review, with 716 women randomized. Most studies reported a positive effect on endometriosis pain scores; however, they were characterized by moderate or high-risk bias. Of these, six RCTs, including 457 women with endometriosis, were included in the meta-analysis. Compared with Placebo, antioxidant use was associated with a reduction in dysmenorrhea (mean difference - 1.95 [CI 95%, -3.78 to -0.13]. Supplementation was not significant for reducing chronic pelvic pain (mean difference - 2.22 [95% CI, -4.99 to 0.55] and dyspareunia (MD - 2.56 [95% CI, - 5. 22 to 0.10]. Both analyses showed a high degree of heterogeneity. Moreover, studies with low risk of bias did not show significant results compared to those on Placebo. The effects of nutrient compounds seem to have the potential to reduce pain in women with endometriosis, mainly to reduce dysmenorrhea. However, the available studies present high heterogeneity and moderate/high risk of bias. More randomized clinical trials are needed to accurately determine dietary interventions' short- and long-term efficacy and safety in managing endometriosis pain.

Research into innovative non-pharmacological therapeutic routes via the utilization of natural elements like zinc (Zn) has been motivated by the discovery of new severe acute respiratory syndrome-related coronavirus 2 (SARS-COV2) variants and the ineffectiveness of certain vaccination treatments during COVID-19 pandemic. In addition, research on SARS-COV-2's viral cellular entry and infection mechanism has shown that it may seriously harm reproductive system cells and impair testicular function in young men and adolescents, which may lead to male infertility over time. In this context, we conducted a narrative review to give an overview of the data pertaining to Zn's critical role in testicular tissue, the therapeutic use of such micronutrients to enhance male fertility, as well as in the potential mitigation of COVID-19, with the ultimate goal of elucidating the hypothesis of the potential use of Zn supplements to prevent the possible harmful effects of SARS-COV2 infection on testis physiological function, and subsequently, on male fertility.

Varicocele causes infertility. The current study has investigated the impact of experimental varicocele on DNA methylation, demethylation, and damage in the germ cells, TESE-derived and epididymal spermatozoa. Moreover, the results were compared between epidydimal and TESE-derived spermatozoa. Finally, the varicocele-induced effect on active DNA demethylation (ADD) of male pronucleus and pre-implantation embryo development was assessed. The mature male rats were divided into control, control-sham (undergone simple laparotomy), and experimental varicocele-induced groups (n = 6/each group). The left renal vein semi-ligation was considered to induce varicocele. The expression levels of DNA methyltransferase 1 (DNMT1) and ten-eleven-translocation proteins (TET1, 2, 3), and global DNA methylation in testicular tissue, TESE, and epididymis-derived spermatozoa, and the ADD in zygotes male pronucleus as well as pre-implantation embryo development were assessed. The expression levels of DNMT1 and TET1, 2, 3 in testicles, TESE, and epididymis-derived spermatozoa were decreased in the varicocele group compared to the control and control-sham groups. The TESE-derived spermatozoa exhibited higher DNMT1, higher DNMT1, and TET 1, 2, and no change in TET3 expression compared to epididymis-derived spermatozoa. The varicocele group represented lower DNA methylation in the testicles, TESE-derived and epididymal spermatozoa, higher 5mC⁺ signal in male pronucleus, and a lower pre-implantation embryo development compared to control and control-sham rats. The TESE-derived spermatozoa exhibited higher 5mC protein expression compared to epididymal spermatozoa. In conclusion, varicocele can negatively impact the DNA methylation/demethylation processes impairing spermatogenesis and leading to fertilization failure, which may ultimately result in a decrease in embryo development by increasing susceptibility to DNA damage.

The aim of this study was to evaluate which frozen embryo transfer (FET) strategy benefits the recurrent implantation failure (RIF) population. A retrospective study of 336 women with RIF was performed from July 2020 to October 2023. The patients were divided into three groups according to the FET protocol. The three FET protocols included transferring a blastocyst on both days 5 and 6 (Group 1, n = 138); transferring a cleavage-stage embryo on day 3 and a blastocyst on day 5 (Group 2, n = 55); and transferring double blastocysts on day 5 (Group 3, n = 143).The sequential day 5 and day 6 blastocyst ET strategy significantly improved in vitro fertilization success rates compared with those of both the traditional double-blastocyst day 5 transfer strategy and the strategy involving one cleavage-stage embryo transfer on day 3 and one blastocyst transfer on day 5 in RIF patients. Compared with those observed in Day 5 double-blastocyst transfer, the rates of clinical pregnancy and implantation increased (51.75% vs. 64.49%, P < 0.001 and 37.06% vs. 41.3%, P = 0.005, respectively), while the rates of biochemical pregnancy and multiple gestation decreased (18.18% vs. 12.32%, P = 0.006 and 43.24% vs. 28.09%, P = 0.044, respectively) with the new protocol.Blastocysts from sequential embryo transfer on day 5 and day 6 were more effective than those from the traditional FET protocol at improving pregnancy outcomes and lowering the multiple pregnancy rate in RIF patients. When only one or zero good-quality blastocysts are available, sequential blastocyst ET on days 5 and 6 should be considered.

Recurrent spontaneous abortions (RSA) is defined as a loss of two or more consecutive clinically recognized pregnancies before the 20th week of gestation. In RSA, several causative maternal factors are known, but still, 50% of the cases remain unexplained. Evidence suggests that paternal factors are also equally important. Epigenetic phenomenon such as genomic imprinting and regulation of gene expression by miRNAs plays an important role in embryonic and placental development. Two large miRNA clusters, C14MC (Chromosome 14 microRNA cluster) and C19MC (Chromosome 19 microRNA cluster) are imprinted and expressed in the placenta during pregnancy and are known to regulate functionally important processes such as the trophoblast proliferation, adhesion, and migration. Hence, we studied the DNA methylation at the Differentially Methylated Regions (DMRs) of these clusters in spermatozoa and chorionic villi by pyrosequencing. In Spermatozoa, few Cytosine followed by Guanosine (CpG) sites at DMRs of C14MC and C19MC showed significant hypermethylation. In Chorionic villi, CpG sites showed significant hypomethylation in the RSA group as compared to control group. Semen parameters like sperm concentration, sperm motility, morphology, and chromatin compaction were comparable in control and RSA groups. The study suggests aberrant DNA methylation in spermatozoa and chorionic villi at DMRs of both miRNA coding clusters to be associated with RSA.

Here, we report on a rare case of a successful live birth in a patient with empty follicle syndrome. A 35-year-old woman with ovulatory disorder and a 4-year history of primary infertility conducted in vitro fertilization-embryo transfer (IVF-ET) treatment in our hospital. The patient experienced six controlled ovarian stimulation cycles. In the first two cycles, despite adequate ovarian response, normal development of multiple follicles, and normal serum estradiol (E2) levels, no oocytes were retrieved from these mature follicles during the aspiration procedure. The patient was diagnosed with "empty follicle syndrome". Whole exome sequencing (WES) identified a missense mutation in the luteinizing hormone/chorionic gonadotropin receptor (LHCGR). In subsequent cycles, we try to increase the trigger dosage, combine gonadotropin-releasing hormone agonists (GnRH agonist) with human chorionic gonadotropin (HCG) for a dual trigger, supplement with luteinizing hormone (LH)-like active substances during the stimulation process, and extend the time between triggering and oocyte retrieval. In the end, successful oocyte retrieval and pregnancy were achieved.

Polycystic ovary syndrome (PCOS) is a ubiquitous reproductive condition with triggering hallmarks such as glucose intolerance, hyperandrogenism, and dyslipidemia. Despite the existence of various PCOS animal models, an ideal model which could encompass all PCOS-specific phenotype is of dire need. Dehydroepiandrosterone (DHEA) induced PCOS rats are frequently employed; though, determining the superior model among pubertal and prepubertal rats, incorporation of high fat diet (HFD), and their sustainability remains uncertain. This study aims to examine the age factor, impact of HFD, and DHEA regimen in model development. Prepubertal and pubertal Sprague-Dawley rats were subcutaneously injected with DHEA (6 mg/kg and 60 mg/kg/day, respectively) with and without HFD up to 21 days. Serum testosterone, glucose, lipid profile, ovary morphology, and estrous cycle were evaluated. Following 21 days of treatment with DHEA, pubertal PCOS rats exhibited better reproductive phenotype than prepubertal rats. However, there was no significant difference in the lipid profile. Accordingly, both the age-group rats were concomitantly treated with DHEA and HFD for additional 3 weeks on alternate day basis after model development. The persistence of reproductive and metabolic features on treatment withdrawal were also simultaneously investigated by alienating the rats into continuous and stop dosing groups. The DHEA + HFD and DHEA treated pubertal rats in continuous dosing group showed significant PCOS features (p < 0.05) compared to stop dosing, prepubertal, and control groups. To conclude, continual dosing with DHEA on alternate days for 3 weeks is necessary to sustain metabolic and reproductive phenotypes of PCOS.