Systems Biology in Reproductive Medicine最新文献

Despite the significant morphological changes that occur in the seminal vesicles with aging, the transcriptomic characteristics remain largely unexplored. To address this, we performed bulk RNA sequencing on seminal vesicle samples from mice aged 3, 13, and 21 months to uncover transcriptomic alterations. Our findings reveal that aged seminal vesicles display cystic dilatation, epithelial hypoplasia, disordered muscle layers, fibrosis, and reduced proliferation capability. A comparison between 3-month-old and 21-month-old mice indicated that leukocyte-mediated immunity and leukocyte migration were the most significantly upregulated biological processes among differentially expressed genes (DEGs). Notably, several DEGs associated with "leukocyte migration," such as Vcam1, Cxcl13, and Ccl8, exhibited an increasing trend in transcriptomic and protein expression at three different time points in the seminal vesicles of mice. Additionally, we identified multiple aging-associated DEGs, including P21 and Tnfrsf1b. Two genes (Cd209f and Ccl8) were consistently upregulated across all six regions of the male reproductive glands (testis, epididymis, and seminal vesicle) in the comparison of bulk RNA datasets from 3-month-old and 21-month-old mice. These analyses highlight an enhanced state of immune and inflammatory response in aged seminal vesicles. This study represents the first exploration of the overall transcriptome landscape of seminal vesicles in a murine model of natural aging, offering new insights into the mechanisms underlying aging-related seminal vesicle dysfunction.

Polyamines are polycationic molecules which contains two or more amino groups (-NH₃⁺) highly charged at physiological pH, and among them we found spermine, spermidine, putrescine, and cadaverine. They interact with proteins, nucleic acids, modulate Ca²⁺, K⁺, and Na⁺ channels, and protect sperm from oxidative stress. In this work, we evaluate the effect of spermine, spermidine, and putrescine on the total, progressive and kinematic parameters of motility, capacitation, acrosome reaction, also in presence and absence of the dbcAMP, an analogue of the cAMP, and the IBMX, a phosphodiesterase inhibitor. In addition, we evaluated the intracellular concentrations of cAMP [cAMP]i, and performed an in silico analysis between polyamines and the sAC from mouse to predict the possible interaction among them. Our results showed that all polyamines decrease drastically the total, progressive and the kinetic parameters of sperm motility, decrease the capacitation, and only spermidine and putrescine impeded the acquisition of acrosome reaction. Moreover, the effect of polyamines was attenuated but not countered by the addition of db-cAMP and IBMX, suggesting a possible inhibition of the sAC. Also, the presence of polyamines induced a decrease of the [cAMP]i, and the in silico analysis predicted a strong interaction among polyamines and the sAC. Overall, the evidence suggests that probably the polyamines interact and inhibit the activity of the sAC.

Effective treatments for nonobstructive azoospermia (NOA), which affects 1% of all men globally, are limited by undefined pathogenic mechanisms, especially in idiopathic NOA (iNOA). Here, we tried to identify the functional ferroptosis-related genes and phenotypes involved in iNOA. Differentially expressed ferroptotic genes were identified from iNOA mRNA microarray datasets by bioinformatic analyses, and these ferroptotic genes were subsequently filtered by various algorithms. Then, receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic ability of the abovementioned genes for iNOA. Generally, 11 differentially expressed ferroptotic genes were downregulated, and five genes were upregulated in iNOA samples. Four genes, including DUSP1, GPX4, HSD17B11, and SLC2A8, were technically selected and determined to be potential biomarkers for iNOA. Subsequently, similar expression levels were validated at both the RNA and protein levels in the iNOA specimens. Finally, morphologic and biochemical assays were applied to define the ferroptotic phenotypes in testes. The ferroptotic features, like shrunken mitochondria with electron-dense membranes and a reduction in cristae were observed across various cell types within iNOA patients, accompanied by the overload of ferrous ions and increased lipid peroxidation production. Our findings demonstrated that these ferroptosis genes could be involved in the underlying pathogenesis mechanisms of iNOA by regulating ferroptosis and serve as potential diagnostic biomarkers. Also, the ferroptotic phenotypes were identified in iNOA patients.

Cervical cancer (Cacx) is the second and endometrial cancer (Ec) is the third most common gynecological cancer worldwide. The present study aims to understand the complex and unexplored conditions occurring in cervix and endometrium of the female genital tract caused due to the infection of the human papilloma viruses (HPVs) and Chlamydia trachomatis (CT). A total of 300 tissue biopsy samples of cervix and endometrium were included in the present study and tested for the presence of HPV and CT deoxyribonucleic acid (DNA) by using polymerase chain reaction (PCR) technique. The odds ratios and 95% confidence interval were considered for the calculation of the association of HPV and CT infection with the risk of cervical or Ec. Among endometrial patients, samples were 5% positive for HPV and 5% positive for CT infection. Among endometrial control group, no sample was found positive for either HPV or CT infection. Among cervical patients, 72% samples were positive for only HPV infection and 1% samples were positive for only CT infection. Among control group, 7% of samples were positive for only HPV infection and 3% were positive for only CT infection. The co-infection of CT with HPV in 9% of Cacx cases and in 2% of cervical control samples was also observed. This is the first study in Indian women to detect the prevalence of HPV and CT infections in endometrium cases and control. An updated estimate regarding the HPV and CT prevalence in cervix cases and control samples was also provided.

This study aimed to investigate the impact of mono(2-ethylhexyl) phthalate (MEHP) on the proliferation, apoptosis, and migration of human foreskin fibroblast cells (HFF-1) and the role of the JNK signaling pathway in cell migration. HFF-1 cells were randomly assigned to the control group with 0 MEHP exposure (M0) or the experimental groups with 25, 50, 100, 200, and 400 μmol/L MEHP exposure (M25, M50, M100, M200, and M400, respectively). After 24 and 48 h of MEHP exposure, the proliferation of HFF-1 cells in any group had no significant change. However, compared with the M0 group, the M200 and M400 groups presented substantially increased apoptosis of HFF-1 cells. Moreover, cell migration ability significantly decreased in all groups (p < 0.05). Additionally, the transcription and phosphorylated protein activation of JNK kinase in HFF-1 cells were substantially upregulated with the increase in MEHP exposure. Subsequently, HFF-1 cells were randomly divided into three groups: the DMSO blank control group, the 100 μM MEHP experimental group (M100), and the 100 μM MEHP plus 10 μM SP600125 (specific JNK inhibitor) experimental group (S10). The activation of JNK protein in HFF-1 cells was substantially downregulated in the S10 group. HFF-1 cells were also divided into the blank control group (M0). They were treated with 100 μM MEHP and varying concentrations of SP600125 (5, 10, and 15 μM for S5, S10, and S15, respectively). As the concentration of the antagonist increased, the migration ability of HFF-1 cells was returned to normal. Finally, the ROS in HFF-1 cells increased under MEHP exposure. This finding indicates that the regulation of cell migration by the JNK signaling pathway may be important in the occurrence of hypospadias.

The most prevalent endocrine and metabolic condition in women of reproductive age are polycystic ovary syndrome (PCOS) with significant risk factors such as circadian rhythm and melatonin disruption. The aim of this study is to assess the effect of vitamin E in combination with a combined oral contraceptive (COC) on continuous light-induced PCOS using hormonal measures, oxidative stress (OS) indicators, and the inhibin beta-A (INHBA) gene, which targets the melatonin protein kinase C (PKC) pathway. An in silico technique anticipated INHBA's binding affinity for vitamin E and COC. For the in vivo investigation (IAEC/240/2021), female SD rats were divided into six groups and subjected to a 16-week induction period, followed by a 2-month test drug treatment with drospirenone (DRSP) as a standard. Serum testosterone, FSH, melatonin, and OS were calculated as hormonal markers. The expression of the INHBA gene was studied to see if it could be linked to the circadian rhythm and OS via the melatonin PKC pathway. According to the in silico study, vitamin E and DRSP had higher binding energy for the INHBA (-8.6 kcal/mol and -8.4 kcal/mol, respectively). When compared to the control group, in vivo results showed a substantial decrease in testosterone levels (p = .05), as well as changes in FSH (p = .78) and melatonin (p = .13). IHNBA gene expression has also dramatically increased, stimulating FSH production in the pituitary gland. Vitamin E and COC concomitantly are beneficial against PCOS because it modulates OS, which in turn influences circadian rhythm and the melatonin PKC pathway.

The technique and platform used for preimplantation genetic testing for aneuploidy (PGT-A) have undergone significant changes over time. The contemporary technique utilizes trophectoderm biopsy followed by next-generation sequencing (NGS). The goal of this study was to explore the role of PGT-A using NGS technique exclusively in contemporary in vitro fertilization (IVF) practice. For this, we performed a retrospective analysis of a large dataset collected from the Shady Grove Fertility (SGF) multicentre practice. All autologous IVF cycles which were followed by at least one single embryo transfer (ET) (fresh and/or frozen) between January 2017 to July 2020, were included. Our study group included patients who had PGT-A and the control group included patients who did not proceed with PGT-A. The primary outcome was the live birth rate (LBR) per transfer. All age-adjusted LBR was higher in the PGT-A group than the non-PGT-A group (48.9% vs. 42.7%, p < 0.001), except in women <35 years old among single embryo frozen ETs. Similarly, LBR in the PGT-A group was higher in all ages except in women <35 years old (48.7% vs. 41.7%, p < 0.001) when all single embryos fresh and frozen ETs were included. In patients of decreased ovarian reserve, transfer of euploid embryo was associated with higher LBR (46.7% vs. 26.7%, p < 0.001) whereas miscarriages were lower in patients with unexplained infertility (9.3% vs. 11.3%, p = 0.007 and endometriosis (8.9% vs. 11.6%, p < 0.001) following euploid embryo transfer. To conclude, the transfer of euploid embryos tested via NGS PGT-A was associated with improved LBR per transfer in women ≥35 years old.