Search Results (1,349)

Toxoplasma gondii, an obligate intracellular protozoan infecting approximately one-third of the global population, poses a significant yet underappreciated threat to reproductive health in both sexes. Although this parasite has long been linked to birth defects caused by infection during pregnancy, new research shows that it also reduces fertility in both sexes through different but related mechanisms. This review synthesizes knowledge on T. gondii-induced reproductive pathology across females and males, examining shared mechanistic themes while respecting tissue-specific differences, and evaluates emerging therapeutic strategies. In females, the parasite establishes persistent uterine reservoirs, triggers decidual immune dysregulation characterized by NK cell cytotoxicity, M1 macrophage polarization, Treg apoptosis, and inflammasome-mediated pyroptosis, while disrupting estrogen and progesterone signaling through both host receptor modulation and intrinsic parasite steroidogenic enzymes (TgCYP450mt, TgMAPR, Tg-HSD). In males, T. gondii breaches the blood–testis barrier, induces germ cell and Leydig cell apoptosis via ER stress and caspase pathways, impairs sperm quality parameters across acute and chronic infection, and disrupts the hypothalamic–pituitary–gonadal axis. Conserved molecular mechanisms—including NLRP3 inflammasome activation, PERK/eIF2α/ATF4/CHOP-mediated ER stress, and oxidative stress—operate in both reproductive tissues. The parasite’s intrinsic steroidogenic capability and bidirectional hormonal manipulation represent a paradigm shift in understanding host–parasite interactions. Conventional antiparasitics face limitations due to poor reproductive sanctuary penetration. Immunomodulatory approaches targeting Trem2, Tim-3, and the NLRP3 inflammasome show promise, along with natural products including Inonotus obliquus polysaccharide and ginseng polysaccharide. Nanomedicine platforms and mRNA vaccine candidates offer new directions for overcoming tissue barrier limitations. Toxoplasma gondii represents a fundamental threat to fertility and pregnancy outcomes rather than merely a risk for congenital infection. Integrated therapeutic strategies addressing direct parasitism, immunopathology, and endocrine disruption are needed. Longitudinal cohort studies, strain-specific mechanistic comparisons, and clinical trials of immunomodulatory adjuncts are urgently required. Full article

Background/Objectives: Infertility affects about 17.5% of people globally, with higher rates in women. Despite advances in assisted reproductive technologies, success remains limited. Endometrial scratching (ES) is proposed to enhance implantation by altering cytokines and gene expression, but evidence is conflicting. Methods: A systematic search of the PubMed, Cochrane Library, and Scopus databases was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Eight randomized controlled trials (RCTs) involving women undergoing in vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI), with ES performed in the luteal phase of the cycle preceding IVF or ICSI, were included. Results: The meta-analysis included 3210 patients and 1445 clinical pregnancies (754 in the ES group and 691 in the control group). In the ES group, a significantly higher clinical pregnancy rate (CPR) (RR 1.09, 95% CI 1.01–1.18, p = 0.02) was revealed. Pooled data from six studies reporting live birth rates (1268 births) showed a significant increase in the LBR after ES (RR 1.12, 95% CI 1.03–1.22, p = 0.01). The ongoing pregnancy rate (OPR) was also statistically significant in the ES group (RR 1.13, 95% CI 1.01–1.26, p = 0.03). Conclusions: This meta-analysis shows a small but statistically significant and consistent positive effect of ES on the LBR, CPR, and OPR in women undergoing IVF or ICSI, with a modest but measurable absolute benefit of approximately 4–5 additional events per 100 individuals. This procedure may particularly benefit patients with impaired endometrial receptivity, potentially enhancing reproductive outcomes while reducing the time and cost required to achieve a successful pregnancy. Further research is warranted to optimize its use and identify patients most likely to benefit. Full article

The utilization of cytoplasmic male sterility (CMS) is essential in hybrid seed production; however, its operational value in eggplant is insufficiently documented under practical conditions. This study compared CMS-based and conventional (non-CMS) hybridization systems with respect to flower production, flower functionality, and hybrid seed production efficiency, quantified as seed and viable seedling output per unit time, in three eggplant cultivars (‘Emi’, ‘Langada’, and ‘Tsakoniki’) in intra- and interspecific crosses. CMS did not affect total flower production or inflorescence architecture, which were primarily genotype-dependent. However, it altered flower opening, resulting in genotype- and position-dependent proportions of semi-opened and closed flowers at anthesis. Despite this effect, sufficient flowers suitable for hybridization remained available across all genotypes. CMS substantially simplified the hybridization process by eliminating emasculation, reducing flower manipulation time by approximately 55%, and increasing crossing rate by nearly twofold. Importantly, CMS did not negatively affect female fertility, as indicated by comparable percentages of successful crosses and high seed germination rates across cytoplasmic backgrounds. Seed production per fruit was moderately but significantly increased in intraspecific crosses, while it remained comparable between CMS and non-CMS systems for the interspecific crosses. As a result, CMS significantly increased hybrid seed output and effective seedling production per unit time in intraspecific crosses, while similar trends were observed in interspecific crosses, with gains ranging from 86% to 184% depending on genotype and pollen parent. Overall, this study demonstrates, from an operational perspective, that CMS enhances the efficiency of eggplant hybrid seed production by reducing labor requirements and increasing output per unit time without compromising reproductive performance. These findings highlight the practical value of CMS as a tool for improving hybrid seed production systems, including applications in both commercial hybrid development and rootstock breeding. Full article

Novel brominated flame retardants (NBFRs), including 1,2-bis(2,4,6-tribromophenoxy)ethane (BTBPE), are emerging endocrine-disrupting chemicals, though their direct effects on female gamete maturation remain insufficiently characterized. In this study, we used a refined zebrafish oocyte in vitro maturation (IVM) model integrating germinal vesicle breakdown (GVBD) assessment with real-time, image-based oocyte diameter quantification. The workflow incorporated donor-condition optimization and diameter-based quality control during sorting. Oocytes from donors 4 to 5 months post-fertilization (mpf) showed more consistent diameter dynamics at the dish level than those from donors 3 to 4 mpf. Mixed-sex co-housing was associated with higher GVBD and larger Δdiameter than separated housing, although this comparison should be considered preliminary. Under DHP induction, BTBPE (1–1000 nM) consistently suppressed GVBD and attenuated maturation-associated diameter increases, with a non-monotonic-like response pattern. These findings indicate that BTBPE impairs oocyte maturation competence in vitro and supports real-time morphometric tracking as a practical QC component for zebrafish IVM workflows. Full article

Background: Fertility preservation aims to maintain reproductive potential in patients undergoing potentially gonadotoxic treatments, increasingly relying on centralized cryobanks requiring ovarian tissue transport. Ovarian tissue cryopreservation is a widely implemented, evidence-based procedure for young women (age 18–35) with a regular ovarian reserve. The ovaries of patients are typically transported overnight to a centralized cryobank for freezing and storage, using a certified hypothermic organ preservation solution such as histidine-tryptophan-ketoglutarate (HTK) at 4–8 °C. The molecular effects of transport on ovarian tissue remain unclear. Methods: In this prospective study of 36 breast cancer patients, we compared whole-transcriptome RNA (RNA-seq) expression in 18 frozen–thawed ovarian biopsies after overnight hypothermic transport followed by slow-freezing versus 18 direct slow-freezing within ≤2 h under FertiPROTEKT-standard conditions. Results: The RNA-seq analysis identified 6 significantly upregulated genes (Bonferroni < 0.05, fold change > 1.5), including histone H2B and mitochondrial NADH dehydrogenase subunit 6 (MT-ND6). The small number of differentially expressed genes suggests only limited transcriptional changes between the two transport conditions. H2B upregulation was confirmed by qPCR, while MT-ND6 showed only moderate levels in RNA-seq but remained stable in qPCR. Immunohistochemical analysis confirmed protein presence and localization in formalin-fixed tissue from four samples, constituting, to our knowledge, the first report of MT-ND6 protein expression in human ovarian tissue. Conclusions: Overall, these results are consistent with subtle changes in chromatin organization and mitochondrial energy metabolism. Since RNA-seq revealed only modest differences in gene expression, with no appreciable up- or downregulation of apoptosis- or damage-related genes after ≤24 h, this indicates tissue stability under the studied combined conditions (transport + cryopreservation). These findings are consistent with the feasibility of the workflow under the studied conditions of centralized ovarian tissue cryobanking combined with overnight transportation and hypothermic HTK solution. Full article

Congenital anomalies of the reproductive system represent a heterogeneous group of structural and functional abnormalities affecting both male and female genital organs. These anomalies typically arise during embryogenesis and may remain asymptomatic until they are incidentally identified during evaluation for infertility, recurrent pregnancy loss, or disorders of sexual development. In females, abnormalities include Müllerian duct anomalies and congenital malformations of the uterus, cervix, vagina, and ovaries, such as Mayer–Rokitansky–Küster–Hauser syndrome, septate, unicornuate, bicornuate, and didelphys uteri, and ovarian agenesis and undescended ovaries. In males, congenital conditions such as anorchia, cryptorchidism, hypospadias, ejaculatory duct obstruction, and ejaculatory dysfunction may be associated with impaired spermatogenesis and reduced fertility. Early recognition of these conditions may facilitate timely clinical evaluation and individualized management, which can include surgical correction, hormonal therapy, and reproductive counseling. When appropriate, early diagnosis may support multidisciplinary care, with the aim of optimizing sexual development, preserving reproductive potential, and reducing long-term morbidity associated with congenital anomalies. However, the clinical impact of early detection varies depending on the type and severity of the anomaly. A systematic and multidisciplinary approach may contribute to improved reproductive outcomes and better overall reproductive health in affected individuals. Further research is needed to better define the optimal timing and clinical utility of systematic evaluation strategies in this patient population. Full article

Although the ATP-binding cassette (ABC) transporter superfamily of proteins typically facilitates the movement of compounds across cellular membranes, the ABC E subfamily (ABCE) influences protein synthesis via non-transporter roles in ribosome biogenesis. Despite this essential role, our understanding of the impact that ABCE proteins have on insect physiology is limited. Here, we identified and characterized the ABCE gene from Lygus hesperus, a major agricultural pest of crops in North America. LhABCE transcripts were constitutively expressed throughout development and were present in all adult tissues tested. RNA interference (RNAi)-mediated knockdown of LhABCE transcripts in fifth instar nymphs resulted in high nymphal mortality and an incomplete molt. LhABCE knockdown in adults disrupted gametogenesis and reduced longevity. In females, oogenesis was impaired and oocytes did not progress beyond the pre-vitellogenic phase. In males, LhABCE knockdown reduced both spermatozoa abundance and male fertility. LhABCE knockdown, however, had little to no impact on hemolymph protein levels or the levels of circulating vitellogenin. Taken together, the results indicate that LhABCE is critical for the normal progression of processes like molting and gametogenesis that require coordinated bursts of protein synthesis and suggest that ABCE may play an important role in the mechanisms underlying those bursts. Full article

Cannabis sativa is a multipurpose dioecious species whose crop performance is governed by sex expression. Although sex is genetically determined by an X/Y chromosome system, plants can develop flowers of the opposite sex through sex reversion, commonly induced by manipulating endogenous hormone levels using plant growth regulators (PGRs). Here, we evaluated the effectiveness of PGRs that promote or inhibit major hormone pathways implicated in plant sex expression. Male and female clones from two accessions were treated with foliar applications of nine PGRs and four combinatory treatments to assess sex- and genotype-specific responses. Floral biomass and the proportion of each sex were recorded at harvest to assess treatment effectiveness. Ethylene emerged as the primary regulator of chemically modulated sex reversion in C. sativa, with its inhibition by silver thiosulfate inducing strong female-to-male reversion and its promotion by ethephon inducing equally strong male-to-female reversion in the inflorescences. Gibberellin promotion on its own resulted in female-to-male reversion at the axial nodes only, while its inhibition showed no reciprocal effects. The combination of silver thiosulfate and gibberellic acid resulted in the most complete female-to-male reversion, and all sex-reverted flowers were fertile. Together, the results indicated that flowers at axial nodes and at the terminal ends of inflorescences are under different hormonal control. Cytokinins, auxins, and jasmonates were found to exert minimal influence on sex reversion. All treatments exhibited pleiotropic effects, particularly gibberellic acid and paclobutrazol, which altered resource allocation, shifting biomass away from and towards floral tissue, respectively. These findings advance our understanding of the hormonal regulation of sex expression in C. sativa and identify optimized approaches for its manipulation. Full article

Conventional hormonal and clinical models inadequately clarify the complex and diverse aspects of female infertility, resulting in poor reproductive outcomes and reduced egg viability. A growing body of research indicates that female reproductive failure is mostly due to disruptions in cellular homeostasis, especially concerning organelle quality control. Oxidative stress has emerged as a crucial mediator connecting metabolic, inflammatory, and ageing-related processes to ovarian failure, however its downstream impacts on intracellular organelle turnover remain insufficiently clarified. Our narrative review encapsulates the existing data for a unified pathogenic concept focused on the redox-regulated mitochondria–lysosome axis. We examine the interaction of oxidative stress, mitochondrial malfunction, compromised mitophagy, and lysosomal deficiency in granulosa cells and oocytes. Prolonged oxidative stress may disrupt this equilibrium, leading to defective mitochondria accumulation and impaired mitophagy. This self-perpetuating cycle may ultimately jeopardises reproductive viability and oocyte integrity. The integrated axis offers a shared molecular foundation for various infertility-related diseases, such as inadequate ovarian response, obesity-associated infertility, polycystic ovary syndrome, and ovarian ageing. Ultimately, we analyse new findings suggesting that specific antioxidant chemicals modify mitophagy and lysosomal function while also neutralising reactive oxygen species, highlighting their potential use in precision fertility treatments. Our research redefines female infertility as a condition of redox-dependent organelle quality control, thereby introducing novel avenues for identifying biomarkers, categorising patients, and targeting treatments in assisted reproduction. Full article

Proteostasis, defined as the coordinated regulation of protein synthesis, folding, trafficking, and degradation, is essential for maintaining cellular integrity and supporting normal development. During reproduction and early life stages, efficient proteostasis is crucial for gamete quality, successful fertilization, embryonic development, and neurodevelopmental outcomes. Increasing evidence suggests that impaired proteostasis contributes to infertility and may be intertwined with biological vulnerabilities associated with assisted reproductive technologies [ARTs]. This review provides an integrative perspective on the role of disrupted proteostasis in infertility, ART procedures, and neurodevelopmental differences [NDD]. We review epidemiological and molecular findings indicating proteostasis failure in both male and female infertility, with particular emphasis on molecular chaperones. Among these, heat shock protein 60 [Hsp60] is discussed as a central mediator linking mitochondrial function, protein quality control, and reproductive competence. We further highlight that ART procedures coincide with sensitive periods of epigenetic reprogramming and proteostasis regulation during early embryogenesis, indicating that disturbances in proteostasis may affect epigenetic stability and subsequent neurodevelopmental outcomes. In addition, this review emphasizes the importance of proteoforms and proteome complexity as critical determinants of reproductive success and neurodevelopmental robustness in the context of ART. Finally, we discuss the potential of proteomic and chaperone-based biomarkers as emerging tools to optimize ART strategies, improve gamete and embryo selection, and enhance risk assessment and clinical outcomes. The current review underscores proteostasis as a fundamental yet underrecognized mechanism linking reproductive biology, ART outcomes, and long-term neurodevelopment while highlighting future directions for translational investigations. Full article

Obesity is associated with menstrual dysfunction, anovulation, and infertility, particularly in women with polycystic ovary syndrome (PCOS). This narrative review summarizes evidence on the effects of bariatric surgery [focusing on sleeve gastrectomy (SG) Roux-en-Y gastric bypass (RYGB)] on female reproductive function and fertility outcomes. Developed according to SANRA (Scale for the Assessment of Narrative Review Articles) principles, a structured search of PubMed, Scopus, and Web of Science (English language; inception–30 September 2025) was conducted, using fertility-related terms (e.g., fertility, ovulation, IVF/ART, AMH, PCOS, pregnancy, live birth, time to conception) combined with bariatric surgery terms (SG/VSG, RYGB, metabolic/bariatric surgery, and weight loss surgery). Guidelines from IFSO, BOMSS, and ASMBS were also reviewed. Findings were synthesized narratively. Across mainly observational studies, bariatric surgery is associated with improved menstrual regularity, increased ovulation, reduced hyperandrogenism, and improved insulin sensitivity, with higher conception rates reported after substantial weight loss. AMH responses are inconsistent across studies and their clinical significance remains uncertain. SG and RYGB appear to improve fertility-related outcomes in women with obesity. Programming of pregnancy and nutritional monitoring are critical. In conclusion, long-term, standardized reproductive endpoints are needed to clarify bariatric surgery-associated effects during pregnancy. Full article

Date palm (Phoenix dactylifera L.) production relies on the availability of viable and physiologically active pollen during female flowering, making pollen storage an important strategy to overcome flowering asynchrony and ensure effective artificial pollination. In this study, we systematically reviewed and quantitatively synthesized the effects of pollen storage conditions on pollen physiological quality and reproductive performance in date palm. Following PRISMA guidelines, 22 experimental studies were identified in the qualitative synthesis, and comparable quantitative datasets were used for meta-analysis. Acetocarmine staining, the most commonly used method for assessing pollen stainability across studies, was selected as the standardized indicator of pollen stainability. Multilevel random-effects meta-regression models were applied to evaluate temporal deterioration patterns over storage periods of up to 24 months, while standardized forest plot meta-analyses were used to estimate pooled effects after 12 months of storage. The results revealed a strong temperature-dependent decline in pollen physiological quality. Acetocarmine stainability declined by −6.41, −3.10, −2.62, and −2.24% month⁻¹ under ambient, refrigerated, mild freezing, and moderate freezing conditions, respectively, whereas germination declined by −6.77, −1.86, −3.14, −1.09, and −1.05% month⁻¹ under ambient (23–25 °C), refrigerated (4–5 °C), mild freezing (−5 °C), moderate freezing (−20 °C), and deep freezing (−80 °C) conditions, respectively. After 12 months of storage, stainability, germination, and fruit set were significantly reduced relative to fresh pollen. In contrast, pollen storage had no significant effect on final fruit weight, suggesting that pollen deterioration primarily affects fertilization success rather than subsequent fruit development. The available evidence suggests that low-temperature storage represents the most effective strategy for preserving date palm pollen functionality. Refrigerated storage around 4 °C appears to provide a reliable and accessible option for short- to medium-term pollen preservation, whereas freezing conditions may be advantageous for longer storage periods when moisture control and thawing procedures are properly managed. Full article

Proper steroid hormone synthesis is essential for maintaining fertility in female animals. Tribbles pseudokinase 1 (Trib1), a member of the Tribbles pseudokinase family, exerts its functions mainly through interacting with other molecules. Numerous studies have shown that Trib1 plays a central role in regulating cell proliferation. In mammals, the proliferation of granulosa cells (GCs) is a hallmark event in follicular development, which is essential for follicular maturation and successful ovulation. However, whether Trib1 regulates ovarian steroid hormone synthesis remains largely unexplored. In this study, we found that Trib1 is predominantly expressed in ovarian GCs. Knockdown of Trib1 in GCs significantly reduced their capacity for steroid hormone synthesis. Furthermore, Trib1 KO female mice were completely infertile, exhibiting impaired transition from primary to antral follicles, increased follicle atresia, and defective steroid hormone secretion. Ovarian RNA-Seq analysis revealed that differential expressed genes (DEGs) were significantly enriched in cholesterol metabolism and steroid biosynthesis pathways following Trib1 deletion. Notably, FOSL2, a transcription factor that potentially bound to the promoters of the pivotal steroidogenic genes Star and Cyp11a1, was significantly down-regulated in Trib1 KO mice. Crucially, overexpression of FOSL2 in Trib1-deficient GCs restored Star and Cyp11a1 expression and significantly rescued the ability of steroid hormone synthesis in GCs. Our findings unveil a novel Trib1 gene governing steroidogenesis in GCs and is essential for fertility in female mice, providing profound insights into the female reproductive endocrinology and potential therapeutic targets. Full article

Halogenated derivatives of polycyclic aromatic hydrocarbons (PAHs), such as chlorinated PAHs (ClPAHs), are an emerging class of contaminants that are being detected in the environment as well as in wildlife and human populations. Previous studies have shown that chemical substitution of PAHs, including chlorination, may alter the toxicity of parent PAHs; however, whether chlorination affects their endocrine-disrupting potential remains unexplored. In this study, we examined the effects of phenanthrene (Phe), one of the most prevalent PAHs, and its chlorinated congeners, 9-chlorophenanthrene (9ClPhe) and 9,10-dichlorophenanthrene (9,10Cl₂Phe), on hormone production in granulosa cells, key hormone-secreting cells of the ovary. We observed that Phe and its chlorinated congeners differentially altered anti-Müllerian hormone (AMH), estradiol (E2), and progesterone (P4) secretion. Since mitochondria are central to steroidogenesis, we further evaluated mitochondrial function. While Phe increased ATP production, both 9ClPhe and 9,10Cl₂Phe increased ROS, decreased mitochondrial membrane potential, and reduced the expression of markers for mitochondrial dynamics and mitophagy without altering ATP levels. We further tested impacts on cell fate and found that neither Phe nor its chlorinated congeners altered granulosa cell apoptosis. Together, these results suggest that chlorination of Phe leads to dose-dependent, differential effects on hormone production and mitochondrial pathways without inducing cell death in granulosa cells. This study highlights the potential adverse impacts of ClPAH exposure on ovarian follicle development and female fertility by disrupting steroidogenesis and mitochondrial quality control. Full article

Sexual reproduction is the predominant mode of reproduction in animals, and spermatogenesis is the fundamental step in this process. As the model organism for lepidopteran, the silkworm Bombyx mori exhibits typical dichotomous spermatogenesis, producing both nucleated (eupyrene) and anucleate (apyrene) sperm. Leucylaminopeptidases (LAPs), members of the M17 metalloprotease family, are characterized by their ability to cleave leucine residues from the N-terminus of peptides. In addition to this canonical function, they have been implicated in male fertility in mammals and Diptera. Nevertheless, whether LAPs are required for dimorphic spermatogenesis in Lepidoptera remains to be clarified. Here, we demonstrated that Sperm-Leucylaminopeptidase (S-LAP) plays vital roles in the silkworm eupyrene sperm development. Similar to the testis-specific expression pattern of eight S-LAPs in Drosophila melanogaster, BmS-LAP was also predominantly expressed in testis. Depletion of BmS-LAP via CRISPR/Cas9 system resulted in male sterility, while the fertility of female mutant was unaffected. Notably, male mutants displayed severe defects in the formation and migration of eupyrene sperm, whereas apyrene sperm development appeared normal. In addition, RNA-seq and qRT-PCR analyses demonstrated that spermatogenesis defects were associated with energy metabolism and flagellar assembly. Our study provides the first evidence that LAP is necessary for dimorphic spermatogenesis in Lepidopteran, offering new insights into the molecular basis of male infertility. Full article