Reproductive Sciences最新文献

Assisted reproduction techniques for infertile men with non-obstructive azoospermia require a sufficient number of functional germ cells produced in vitro. Understanding the mechanisms that allow the resumption of spermatogenesis outside the testicular environment is crucial for fertility preservation in these patients. A review of the literature was conducted using databases such as PubMed, Scopus and Web of Science, with keywords including "spermatogonial stem cell," "germ cells," "male factor infertility," and "enrichment and propagation of SSCs in vitro." Currently, two models-"in vivo" and "in vitro"-have been developed for producing haploid germ cells. The "in vivo" models include spermatogonial stem cell transplantation and testicular xenograft techniques. In contrast, the "in vitro" models consist of conventional culture systems, organ culture, and three-dimensional culture systems, all designed to induce spermatogenesis in vitro. These culture systems enable the simulation of the seminiferous epithelium in vitro, which facilitates better regulation of cell-signaling pathways that control the self-renewal and differentiation of SSCs. This review provides up-to-date information on the organization of SSCs, focusing on the identification, proliferation, and differentiation of spermatogonia in vitro.

Hypoxia is one of the main reasons causing male reproductive damage for people living in high altitude. Pathological evidences have been presented both in humans and animal models. Spermatogenesis disruption, worse sperm parameters, hormone disorder and erectile dysfunction are emblematic of male reproductive impairments brought by hypoxia. Among many mechanisms impairing male reproductive systems, oxidative stress is always a field of interest to explore. Although previous reviews have discussed about hypoxia or oxidative stress and antioxidants on male fertility respectively, no one has elucidated the concrete role of oxidative stress in hypoxia and correlating antioxidants that can ameliorate the negative effects. In this review, we firstly introduce hypoxia etiology and describe specific damage of hypoxia on male reproductive functions. Then, we emphasized interplays between hypoxia and oxidative stress as well as negative influences brought by oxidative stress. Finally, we listed antioxidants for oxidative stress and hypoxia-induced reproductive damage and discussed their controversial experimental effects for male infertility.

Alterations in the microbiome composition have been identified in common gynecologic pathologies such as endometriosis carving a new frontier in diagnosis and treatment. We aimed to examine the existing literature on perturbations in the reproductive tract microbiome of individuals with adenomyosis informing future therapeutic targets. To examine the association between the reproductive tract microbiome composition among individuals with adenomyosis when compared to controls that can lead to new research evaluating novel mechanisms of action and treatment modalities. A systematic literature search identified studies that compared differences in microbiome composition using culture-independent microbiome analysis between individuals with adenomyosis when compared to controls. Five observational cross-sectional studies characterizing the lower and upper reproductive tract in humans were included. The diagnostic criteria of adenomyosis included surgical and imaging-based criteria. All studies used a 16S rRNA sequencing method. All individuals were recruited from either China or Thailand. An association between adenomyosis and alterations in the microbiome composition included relative deficiencies in Lactobacillus and relative enrichment of anaerobic and gram-negative bacteria when compared to control participants. Comparative studies suggest that there are significant perturbations in the microbiota composition of individuals with adenomyosis when compared with controls. Limiting conclusions include relative small sample sizes, a homogeneous population, and scant clinical phenotypic data. This systematic review identified significant alterations in the bacterial composition of adenomyosis cases that can be leveraged to design mechanistic studies and future innovative approaches to diagnose and manage this pathology. Trial registration: PROSPERO (CRD42023494563). Registered December 28, 2023.

Fluoxetine is used in the management of depression, anxiety and other mood disorders by increasing serotonin levels in the brain and can cause sexual side effects by changing the homeostasis of sex hormones and increasing oxidative stress. Since many men who take fluoxetine are of reproductive age and sperm are exposed to fluoxetine for a considerable time, this study aimed to examine the in vitro effects of fluoxetine on human sperm biochemical markers and sperm parameters. Semen samples from 30 fertile men were divided into three groups: a positive control group, a negative control group and a fluoxetine-treated group. We investigated sperm parameters, mitochondrial membrane potential (MMP), acrosome reaction, DNA fragmentation, chromatin integrity, and the expression of CASPASE8, CASPASE9, BAX, and BCL2 genes and proteins. Data were analyzed using repeated measures analysis. The results showed that the average percentage of motility, viability, MMP, acrosome and chromatin integrity, total antioxidant capacity (TAC) level, and BCL2 gene and protein expression in the fluoxetine group were significantly reduced compared to the positive and negative control groups. While the average percentage of non-progressive motility, sperm DNA fragmentation, malondialdehyde (MDA) level, reactive oxygen species (ROS), gene and proteins expression of CASPASE8, CASPASE9 and BAX increased significantly. This study suggests that fluoxetine may impair sperm quality by increasing the expression of apoptotic genes, proteins, and oxidative stress. Therefore, careful management of fluoxetine in treating depression is crucial, especially in men of reproductive age, due to its potential sexual side effects. HIGHLIGHTS: • Fluoxetine reduces the quality of human sperm by inducing oxidative stress. • Fluoxetine lowers the total antioxidant capacity in human sperm by increasing ROS. • Fluoxetine increases the expression of apoptosis genes in human sperm.

Fetal growth restriction (FGR) affects between 5-10% of all live births. Placental insufficiency is a leading cause of FGR, resulting in reduced nutrient and oxygen delivery to the fetus. Currently, there are no effective in utero treatment options for FGR, or placental insufficiency. We have developed a gene therapy to deliver, via a non-viral nanoparticle, human insulin-like 1 growth factor (hIGF1) to the placenta as a potential treatment for placenta insufficiency and FGR. Using a guinea pig maternal nutrient restriction (MNR) model of FGR, we aimed to understand the transcriptional changes within the placenta associated with placental insufficiency that occur prior to/at initiation of FGR, and the impact of short-term hIGF1 nanoparticle treatment. Using RNAsequencing, we analyzed protein coding genes of three experimental groups: Control and MNR dams receiving a sham treatment, and MNR dams receiving hIGF1 nanoparticle treatment. Pathway enrichment analysis comparing differentially expressed genelists in sham-treated MNR placentas to sham-treated Control revealed upregulation of pathways associated with degradation and repair of genetic information and downregulation of pathways associated with transmembrane transport. When compared to sham-treated MNR placentas, MNR + hIGF1 placentas demonstrated changes to genelists associated with transmembrane transporter activity including ion, vitamin and solute carrier transport. Overall, this study identifies the key signaling and metabolic changes occurring in the placenta contributing to placental insufficiency prior to/at initiation of FGR, and increases our understanding of the pathways that our nanoparticle-mediated gene therapy intervention regulates.

This study aimed to determine the protective role of boric acid in a pregnant rat model of high fructose corn syrup consumption. Consumption of high fructose corn syrup has been associated with adverse health outcomes in humans and animals. Twenty-eight healthy female Wistar albino rats (250-300 g weight and 16-24 weeks old) were randomly distributed into four equal groups (n = 7): Control, Boric acid (BA), High Fructose Corn Syrup (HFCS), HFCS + BA. Boric acid (20 mg/kg) was administered to pregnant rats via oral gavage every day during pregnancy. The prepared 30% HFCS (F30) solution (24% fructose, 28% dextrose) was added to the drinking water throughout pregnancy. At the end of pregnancy (day 19), blood, placenta, uterus, and fetuses were collected from rats. The results indicated that HFCS increases oxidative stress by increasing the level of MDA and decreasing GSH, SOD, and CAT activity in the blood of maternal. However, BA administration significantly decreased MDA levels and increased GSH levels, SOD, and CAT activity (p < 0.05). In addition, HFCS consumption significantly increased plasma TNF-α, IL-6, and leptin levels compared to control, BA, and HFCS + BA groups (p < 0.05). However, BA administration significantly decreased plasma TNF-α, IL-6, and leptin levels (p < 0.05). Furthermore, BA (20 mg/kg) significantly decreased HFCS-induced histopathological and immunohistochemical alterations in the placenta, uterus, and fetal tissue. In conclusion, BA may prevent HFCS toxicity in maternal and fetal tissues, as it regulates oxidative imbalance in pregnant rat and alleviates histopathological and immunohistochemical changes. The findings indicate a need for further studies to assess the potential of boron in preventing or mitigating the effects of HFCS during pregnancy.

We explore the interaction between estrogen and PCSK9 and their collective impact on lipid metabolism, especially concerning the regulation of low-density lipoprotein receptor levels. Utilizing both animal and cellular models, including ovariectomized mice and HepG2 cell lines, we demonstrate that estrogen deficiency leads to a disruption in lipid metabolism, characterized by elevated levels of total cholesterol and LDL-C. The study commences with mice undergoing ovariectomy, followed by a diet regimen comprising either high-fat diet or normal feed for a four-week duration. Key assessments include analyzing lipid metabolism, measuring PCSK9 levels in the bloodstream, and evaluating hepatic low-density lipoprotein receptor expression. We will also conduct correlation analyses to understand the relationship between PCSK9 and various lipid profiles. Further, a subset of ovariectomized mice on high-fat diet will undergo treatment with either estrogen or PCSK9 inhibitor for two weeks, with a subsequent re-evaluation of the earlier mentioned parameters. Our findings reveal that estrogen inhibits PCSK9-mediated degradation of low-density lipoprotein receptor, a process crucial for maintaining lipid homeostasis. Through a series of experiments, including immunohistochemistry and western blot analysis, we establish that PCSK9 is involved in lipid metabolism disorders caused by estrogen deficiency and that estrogen regulates PCSK9 and low-density lipoprotein receptor at post-transcriptional level. The study provides a mechanism for the involvement of PCSK9 in elucidating the disorders of lipid metabolism caused by estrogen deficiency due to perimenopause and ovarian decline.

Recent research has proven that peripheral (PS) and central sensitization (CS), mental health, and myofascial dysfunction all play a role, alongside nociception, in the genesis and in the perpetuation of endometriosis' symptoms. However, such components of pain are still largely ignored in clinical practice, although not considering such contributors may entail serious consequences on women's health, including the choice of unnecessary surgery and leaving the real causes of pain untreated. At the present time, we are facing a paradox by which 25-40% of women who undergo laparoscopic surgery for pelvic pain do not have an obvious diagnosis, while the percentage of women with endometriosis who have signs of CS, of depressive or anxiety disorders, or who have an increased pelvic muscle tone ammounts to 41-55%, 15-88% and 28-73%, respectively. Moving from the widely-accepted stepwise approach suggested for endometriosis management, which consists in the initial prescription of low-dose combined oral contraceptives (COCs) or of a progestin monotherapy, followed by GnRH analogues and, ultimately, by surgery, when COCs and progestins have proven ineffective or are not tolerated or contraindicated, we propose an integration of such model which takes into account the identification and the simultaneous treatment of all pain contributors. Our objective is to encourage physicians' awareness of the need of a multidisciplinary, multimodal approach to endometriosis-related pain, and ultimately to promote a reduction in the number of unnecessary surgeries.

Polycystic ovarian syndrome (PCOS) is a complex endocrine-metabolic disorder, and multiple factors contribute to its pathophysiology. The current study assessed a PCOS-like animal model induced by consuming a high-fat sugar (HFHS) diet and compared the treatment outcome of mitochondrial-targeted antioxidants versus heat therapy. Sixty rats were divided into the following study groups: three control groups (negative and positive for the treatments used), HFHS, hot tub therapy (HTT) treatment, and MitoQ10 treatment (500 µmol/L MitoQ10 in clean drinking water daily, from week fourteen till week twenty-two of the study). At week fourteen, PCOS was confirmed by vaginal smear examination; measurements of blood testosterone (T), anti-Mullerian hormone (AMH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), glucose, and insulin; and determination of the homeostatic model assessment of IR (HOMA-IR). At week 22, blood samples were collected for measurement of the serum LH, FSH, AMH, T, insulin, glucose, lipid profile, kisspeptin, ADAM metallopeptidase with thrombospondin type 1 motif 19 (ADAMTS19), S100 calcium-binding protein B (S100B), fibulin 1 (FBLN1), immunoglobulin free light chains (FLCs), kappa and lambda. Ovaries were examined for morphological changes; for the levels of glutathione (GSH), catalase, SOD, malondialdehyde (MDA), and nitric oxide (NO); and the expression of FK506 binding protein 52 (FKBP52) and the androgen receptor (AR). The consumption of HFHS diet-induced PCOS-like features, which have been ameliorated by both HTT and mitoQ10 as potential therapies, with MitoQ10 showing a superior effect over HTT.