Reproductive Biology and Endocrinology最新文献

Background: Levonorgestrel (LNG) acts as an emergency contraceptive mainly by inhibiting or postponing ovulation. We carried out this study to investigate whether LNG at concentration relevant for emergency contraception (EC) affect ciliary beat frequency and muscular contraction of the human Fallopian tube, which might contribute additional actions for EC.

Methods: This was an in vitro experimental study on human Fallopian tube tissue collected from ten women undergoing hysterectomy. The tubal explants were cultured in vitro, primed with oestradiol and progesterone at concentrations resembling the physiological early luteal phase, and treated with LNG at 0, 1, 10 and 100 ng/ml concentrations. Ciliary beat frequency was measured from the tubal epithelial strips, and the basal tone, amplitude and frequency of contractions were recorded from longitudinal smooth muscle strips. These parameters at different LNG concentrations were compared against the control (LNG 0 ng/ml).

Results: Treatment of tubal tissue strips with LNG at all concentrations studied did not significantly alter the ciliary beat frequency nor basal muscle tone (p > 0.05 for both) compared with control. Significant reduction in the amplitude and frequency of tubal muscular contractions was shown after treatment with LNG only at 100 ng/ml (p < 0.05 for both) but not lower concentrations (p > 0.05) compared with control.

Conclusion: LNG did not significantly inhibit ciliary beat frequency and muscular contraction of the human Fallopian tube at the doses used for EC, suggesting that the Fallopian tube is unlikely a target for the EC action of LNG.

Background: Diminished ovarian reserve (DOR) is clinically characterized by a decrease in the number of available ovarian follicles and a decline in the quality of oocytes, accompanied by hormonal changes. Low quality of DOR oocyte leads to impaired embryo development, an increased risk of aneuploid pregnancies and miscarriages. However, the specific pathogenic mechanism remains unclear, posing a significant challenge for assisted reproductive technology.

Methods: For the first time, our study employed single-cell RNA sequencing to reveal the altered transcriptomic landscape of DOR oocytes at GV stage after ovarian stimulation. Differentially expressed genes analysis (DEGs), functional enrichment analysis, weighted gene co-expression network analysis (WGCNA) and protein-protein interactions network analysis were performed.

Results: We found 132 up-regulated genes and 466 down-regulated genes in DOR oocytes, with the down-regulated genes primarily enriched in mitochondrial function and translation. Hub genes, identified through integrated analysis of WGCNA and DEGs, were further validated in DOR and control oocytes using RT-qPCR. By utilizing hub genes and employing transcription factor enrichment tools, it had been predicted that pleomorphic adenoma gene 1 (PLAG1) played a crucial role as a transcriptional regulatory factor in DOR oocytes. Additionally, we conformed the PLAG1-IGF2 axis was dysregulated in DOR oocytes.

Conclusions: Transcriptome analysis revealed that DOR oocytes exhibited mitochondrial dysfunction and translational defects, and the PLAG1-IGF2 axis might be a potential contributor for the low quality of DOR oocytes.

Contemporary societies exhibit delayed reproductive age and increased life expectancy. While the male reproductive system demonstrates relatively delayed aging compared to that of females, increasing age substantially impacts its function. A characteristic manifestation is age-induced testosterone decline. Testosterone, a crucial male sex hormone, plays pivotal roles in spermatogenesis and sexual function, and contributes significantly to metabolism, psychology, and cardiovascular health. Aging exerts profound effects on the hypothalamic-pituitary-gonadal axis and Leydig cells, precipitating testosterone reduction, which adversely affects male health. Exogenous testosterone supplementation can partially ameliorate age-related testosterone deficiency; however, its long-term safety remains contentious. Preserving endogenous testosterone production capacity during the aging process warrants further investigation as a potential intervention strategy.

Background: Obesity and adverse lipid profile leads to female infertility. The cardiometabolic index (CMI) is a promising indicator for predicting obesity-related diseases. The correlation between CMI and female infertility merits further investigation.

Methods: The data for this study were acquired from the 2013-2020 National Health and Nutrition Examination Survey (NHANES), with 2333 women enrolled. The cardiometabolic index (CMI) of each participant was calculated as the ratio of triglycerides and high-density lipoprotein cholesterol multiplied by waist-to-height ratio. Weighted multivariate logistic regression models were used to assess the independent correlation between the log-transformed CMI and infertility. Subgroup analyses were carried out to assess the reliability of the findings. Interaction tests were employed to determine whether variables affected infertility by interacting with log CMI.

Results: A total of 2333 participants aged 18-45 years were enrolled, 274 of whom were infertile. Log CMI of the infertility group was significantly higher than that of the non-infertility group (P < 0.001). After adjustment for potential confounders, women with higher CMI were at an increased risk of infertility (OR = 2.411, 95% CI: 1.416-4.112), and this correlation was still consistent in subgroups aged under 35 years (P < 0.001). Furthermore, restricted cubic spline analysis showed a positive non-linear relationship between log CMI and infertility.

Conclusions: Cardiometabolic index levels are positively correlated with increased risk of infertility in American females. Our study demonstrates the predictive capacity of CMI for female infertility.

Background: Sperm capacitation is a prerequisite for natural or in vitro fertilization. After capacitation, sperm become hyperactivated and undergo an acrosome reaction, which helps them penetrate the oocyte. Cordycepin, a bioactive compound first isolated from Cordyceps militaris, is an adenosine analog with numerous physiological activities. However, its effects on sperm capacitation remain unclear. This study aims to elucidate the effects and mechanisms of cordycepin on human sperm capacitation.

Methods: During in vitro capacitation culture, healthy human sperm were treated with cordycepin (20, 100, 500 µM). Sperm motility and hyperactivation were detected using a computer-assisted sperm analyzer. Sperm acrosome reaction was measured using fluorescein isothiocyanate-conjugated Pisum sativum agglutinin. Sperm protein kinase A (PKA) activity was analyzed using an ELISA kit. The levels of sperm protein tyrosine phosphorylation were detected by western blotting. Sperm DNA damage was detected by a sperm chromatin dispersion assay. Reactive oxygen species (ROS) were measured using the fluorescence probe 2',7'-dichlorodihydrofluorescein diacetate. The expression and localization of adenosine receptors were analyzed by western blotting and immunofluorescence. The specific inhibitors of adenosine receptors were used to confirm their effects on cordycepin-induced sperm capacitation. Finally, molecular docking was performed to analyze the interaction between cordycepin and adenosine receptors.

Results: Cordycepin improved hyperactivated sperm motility, acrosome reaction, PKA activity, and protein tyrosine phosphorylation during capacitation while having no obvious effects on sperm ROS or DNA damage. Four adenosine receptor subtypes were expressed in human sperm, but their localizations differed. Inhibition of adenosine receptors significantly decreased cordycepin-induced sperm hyperactivation and the acrosome reaction. Molecular docking showed that cordycepin can bind to the four subtypes of adenosine receptors.

Conclusion: Cordycepin may promote human sperm capacitation through adenosine receptor-mediated signaling pathways. These findings may be useful for assisted reproductive technology and animal breeding.

The female reproductive system can face serious disorders and show reproductive abnormalities under the influence of environmental pollutants. Microplastics (MPs) and nanoplastics (NPs) as emerging pollutants, by affecting different components of this system, may make female fertility a serious challenge. Animal studies have demonstrated that exposure to these substances weakens the function of ovaries and causes a decrease in ovarian reserve capacity. Also, continuous exposure to micro/nano plastics (MNPs) leads to increased levels of reactive oxygen species, induction of oxidative stress, inflammatory responses, apoptosis of granulosa cells, and reduction of the number of ovarian follicles. Furthermore, by interfering with the hypothalamic-pituitary-ovarian axis, these particles disturb the normal levels of ovarian androgens and endocrine balance and delay the growth of gonads. Exposure to MNPs can accelerate carcinogenesis in the female reproductive system in humans and animal models. Animal studies have determined that these particles can accumulate in the placenta, causing metabolic changes, disrupting the development of the fetus, and endangering the health of future generations. In humans, the presence of micro/nanoplastics in placenta tissue, infant feces, and breast milk has been reported. These particles can directly affect the health of the mother and fetus, increasing the risk of premature birth and other pregnancy complications. This review aims to outline the hazardous effects of micro/nano plastics on female reproductive health and fetal growth and discuss the results of animal experiments and human research focusing on cellular and molecular pathways.

Implantation is the key initial complex stage of pregnancy. Several factors are involved in implantation, but acute and controlled inflammation has been shown to play as a key role. On the other hand, the role of viral infections in directly infecting blastocyst and trophoblast and inducing chronic and uncontrolled inflammation and disrupting microRNAs expression can make this review strongly attractive and practical. We aim to provide an overview of viral infections as the potential etiology of unsuccessful implantation pathophysiology through alteration of the cellular and molecular endometrial microenvironment. Based on our search, this is the first review to discuss the role of inflammation associated with viral infection in implantation failure.

MicroRNAs (miRNAs) are a type of specific molecules that control the activities of the uterus, such as the process of cellular maturing and evolution. A lot of substances like growth factors, cytokines, and transcription factors play a role in embryo-endometrial interaction. MiRNAs could regulate various these factors by attaching to the 3' UTR of their mRNAs. Moreover, current research show that miRNAs participate in formation of blood vessels in endometrium (miR-206, miR-17-5p, miR-16-5p…), decidualization (miR-154, miR-181, miR-9…), epithelial-mesenchymal transition (miR-30a-3p), immune response (miR-888, miR-376a, miR-300…) embryo attachment (miR-145, miR-27a,451…) and pinopod formation (mir-223-3p, mir-449a, mir-200c). In this study, the focus is on the role of miRNAs in managing the uterus' receptivity to an embryo and its ability to facilitate attachment. More specifically, we are exploring the mechanisms by which miRNAs regulate the presence of specific molecules involved in this crucial physiological process.

Background: 46,XX complete gonadal dysgenesis (46,XX-CGD) is a rare disorder of sexual development (DSD) characterized by primary amenorrhea and a lack of spontaneous pubertal development in individuals with a 46,XX karyotype despite the presence of female internal and external genitalia due to failure of bilateral ovarian development. The condition is genetically heterogeneous, and in most cases, its etiology is unknown. Determining the genetic cause would provide insights into potential targets for genetic diagnosis and counseling.

Methods: To clarify the molecular mechanisms of 46,XX complete gonadal dysgenesis in the population of China, whole-exome sequencing (WES) was performed on DNA samples from patients with 46,XX-CGD. In silico analysis was conducted to predict the pathogenicity of the variants.

Results: We recruited 20 patients with 46,XX-CGD and identified 8 variants in 6 genes, including three homozygous variants in MCM9, POF1B, and PSMC3IP; compound heterozygous variants in TWNK; and three heterozygous variants in TP63 and INSRR, from 7 patients. These variants included 3 recurrent variants and 5 novel variants.

Conclusions: This study identified several novel variants, broadening the variant spectrum of 46,XX-CGD. 46,XX-CGD is a genetically heterogeneous condition, and WES is a powerful tool for determining its genetic etiology. The results of this study will aid researchers and clinicians in genetic counseling and suggest that WES is valuable for detecting 46,XX-CGD, which may lead to early interventions for patients.

Background: Advanced maternal age is associated with decreased oocyte quantity and quality and in vitro fertilization (IVF) success rates. This study aimed to investigate whether melatonin supplementation can improve IVF outcomes in women of advanced maternal age by modulating cuproptosis and ferroptosis.

Methods: This prospective cohort study included 161 women aged 35-45 years undergoing IVF-frozen embryo transfer cycles. Participants were assigned to either melatonin (n = 86, 2 mg daily for ≥ 8 weeks) or control (n = 75) groups. Cumulus cells were analyzed for cuproptosis and ferroptosis-related gene expression. Additional experiments were conducted on the HGL5 human granulosa cell line to assess mitochondrial function and metabolic reprogramming.

Results: Melatonin supplementation significantly improved IVF outcomes in women aged ≥ 38 years, increasing clinical pregnancy rates (46.0% vs. 20.3%, P < 0.01), ongoing pregnancy rates (36.5% vs. 15.3%, P < 0.01), and live birth rates (33.3% vs. 15.3%, P < 0.05). In cumulus cells from patients, gene expression analysis revealed that melatonin modulated cuproptosis and ferroptosis-related genes, including ATP7B and GPX4, with more pronounced effects in the ≥ 38 years group. This suggests melatonin enhances cellular resilience against oxidative stress and metal-induced toxicity in the ovarian microenvironment. In vitro studies using HGL5 cells showed melatonin reduced oxidative stress markers, improved mitochondrial function, restored expression of glycolysis and TCA cycle-related genes and modulated cuproptosis and ferroptosis-related gene expression. These findings provide mechanistic insight into melatonin's protective effects against regulated cell death in ovarian cells, potentially explaining the improved IVF outcomes observed.

Conclusions: Melatonin supplementation significantly improved IVF outcomes in women of advanced maternal age, particularly those ≥ 38 years old, likely by modulating cuproptosis and ferroptosis and enhancing mitochondrial function in cumulus and granulosa cells. These results suggest that melatonin could be a promising adjuvant therapy for improving IVF success rates in older women.