Intracytoplasmic sperm injection (ICSI) is widely used to treat human infertility, yet its effects on offspring fertility remain unclear. As infertile gametes are used in human ICSI procedures, it has remained unclear whether the procedure per se influences fertility of the resulting offspring. Here, we report on increased abortion rates and the induction of immunotolerance breakdown in mice following ICSI. Although sperm concentration was normal, sperm from ICSI-derived males showed higher curvilinear velocity and greater amplitude of lateral head displacement, suggesting a potentially increased fertilization capacity. However, when ICSI-produced males were naturally mated with wild-type females, 27.1% of the fetuses were aborted, compared to a loss of 7.5% of fetuses in control pregnancies, despite identical H2 haplotypes. Analysis of the placenta revealed infiltrating macrophages and granulocytes, as well as increased levels of 8-oxoguanine. This was accompanied by activation of innate immunity and significant downregulation of microRNAs located in the Dlk1-Dio3 microRNA cluster. Several organs of the grand-offspring exhibited inflammation. Therefore, ICSI procedure using wild-type gametes impairs the fertility of ICSI-derived male offspring by activating innate immunity during pregnancy.

Introduction. Vulvovaginal candidiasis (VVC) is a common fungal infection that has a significant impact on global public health. Although studies associate VVC with male infertility, its influence on the female reproductive system, particularly uterine involvement, remains unknown.Gap statement. While recent animal studies propose that Candida albicans migration from the vaginal tract to the uterus in VVC could lead to infertility, the underlying histopathological alterations that support this connection are not well understood.Aim. To investigate possible changes in the uterine tissue of BALB/c mice infected experimentally with C. albicans, by analysing the progression and effects of infection on the uterus.Methodology. Female BALB/c mice were divided into two groups (infected and control). Vaginal infection was induced by C. albicans, and vaginal and uterine tissues were collected at different intervals (1, 3, 5, 7 and 10 days). Analyses included fungal burden (c.f.u. g-1), histopathology stained with Grocott-Gomori and macroscopic and microscopic evaluation (haematoxylin-eosin staining) of uterine tissue.Results. Vaginal infection was confirmed by a consistent presence of yeast in vaginal tissue. C. albicans migration was observed in the uterus, with a significant increase in fungal burden on day 3, followed by macroscopic alterations such as oedema and hyperaemia. Histologically, inflammatory infiltrates, epithelial necrosis and progressive degeneration were identified until day 7, with signs of resolution by day 10.Conclusion. The results demonstrate that vaginal infection by C. albicans was able to cause significant uterine alterations with self-limiting progression. These findings suggest that VVC may have direct implications for female fertility, warranting future investigations into its influence on infertility cases.

COVID-19 vaccine uptake remains low in several parts of Ghana. Therefore, this study assessed prior exposure to SARS-CoV-2 by detecting immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies among unvaccinated adults in the Wassa Amenfi East District, and examined socio-demographic determinants of vaccine hesitancy and potential motivators for future vaccine acceptance. This cross-sectional study was conducted at Bethany Memorial Hospital, Wassa Akropong, Ghana, where unvaccinated adults aged ≥ 18 years were randomly selected. Blood samples were tested for SARS-CoV-2 IgG and IgM antibodies, and a structured questionnaire captured demographic characteristics, reasons for vaccine refusal, and factors influencing future acceptance. Data were analysed using descriptive statistics and Chi-square or Fisher's exact tests, with statistical significance set at p < 0.05. Seroprevalence rates for IgG, IgM, and combined IgG/IgM were 85% (142/166), 9.0% (15/166), and 7.8% (13/166), respectively. Antibody prevalence did not differ significantly by age, gender, or pregnancy status. Gender-specific patterns of hesitancy were observed: females more frequently reported fears of side effects, infertility, and pregnancy-related concerns, whereas males more commonly cited reduced productivity, impotence, and a perceived lack of need for vaccination (p < 0.05). Older adults were more likely to doubt vaccine efficacy, while younger adults reported fertility-related fears. Across all groups, credible evidence of vaccine safety and efficacy emerged as the strongest motivators for future acceptance. These findings indicate widespread prior exposure to SARS-CoV-2 among unvaccinated adults and highlight the need for gender-responsive, evidence-based community engagement to address vaccine hesitancy in low-coverage settings.

Identifying treatments for male infertility has received limited focus, partly because of the success of assisted reproductive techniques (ART), where only few spermatozoa are needed to fertilise the oocyte in vitro. The successful development of ART has created a paradox because we now initiate treatment of the woman even when male-factor infertility is the cause of the couple's inability to conceive. Increased awareness of lower fertility rates, focus on reproductive problems, and the MeToo movement have stimulated interest in male infertility, although neither researchers, governments, nor the pharmaceutical industry are investing sufficient resources to revolutionise infertility treatment by developing innovative therapies for male infertility. This review summarises the challenges we face in developing novel treatment options for male infertility, highlights prior efforts and presents several considerations for future studies. Hopefully, in the near future, we will be able to offer treatment options for subsets of infertile men rather than solely relying on their healthy partners undergoing hormone treatment and subsequent ART, but this requires that authorities, funding bodies, researchers, the pharmaceutical industry and the infertile men themselves prioritise efforts to achieve this.

Primary ovarian insufficiency (POI) and related infertility, early menopause, and endocrine disorders due to hormonal deficiency are major side effects in young female cancer patients undergoing cancer therapy. Current strategies preserving the fertility and hormonal functions of the ovary remain imperfect due to concerns of feasibility, efficacy, or safety. Herein, we identified c-Jun N-terminal kinase (JNK) as a pivotal regulator of the DNA damage response (DDR) signaling in oocytes of primordial follicles in response to DNA-damaging cancer therapy. Using pharmacological JNK inhibition and a genetically modified mouse model with oocyte-specific JNK deletion, together with histological, bioinformatic, and molecular approaches, we demonstrated that JNK inhibition prevented chemotherapy-induced oocyte apoptosis and POI, and preserved long-term reproductive cycles and fertility. Mechanistically, JNK was activated in response to chemotherapy-induced DNA damage in oocytes of primordial follicles, causing activation of transcription factor TAp63α and subsequent oocyte apoptosis, ultimately resulting in diminished ovarian reserve and POI. A more clinically relevant breast cancer-bearing mouse model revealed that JNK inhibition preserved the ovarian reserve without compromising anti-cancer efficacy of chemotherapy. Together, our study identifies oocyte-intrinsic JNK as a promising target for developing ovarian protectants and safeguarding reproductive health and fertility in young female cancer survivors.

Maintaining the primordial follicle pool and precisely regulating folliculogenesis are critical for female fertility. Despite advances in understanding ovarian development, the molecular mechanisms safeguarding follicle survival and oocyte maturation remain incompletely defined. Here, we identify YPEL5 as an essential regulator of folliculogenesis and oocyte development. Using an oocyte-specific conditional knockout (cKO) mouse model, we demonstrate that Ypel5 deletion causes complete female infertility, characterized by accelerated depletion of the primordial follicle pool, defective antral follicle formation, and impaired oocyte maturation. Loss of Ypel5 results in increased DNA damage, disrupted mitochondrial homeostasis, elevated oxidative stress, and ultimately triggers apoptotic depletion of primordial follicle oocytes. Moreover, Ypel5-deficient oocytes exhibit severe abnormalities in spindle organization and mitochondrial distribution, culminating in defective oocyte maturation. Collectively, these findings establish YPEL5 as a critical regulator of follicle development and oocyte maturation, and provide mechanistic insights into the molecular basis of female infertility.

Mammalian oogenesis is a precisely orchestrated developmental process, which depends on accurate chromatin remodeling and transcriptional regulation in the absence of DNA replication. The histone variant H2A.Z is required for oogenesis and embryogenesis, yet the chaperone directing its deposition has not been well characterized in mammalian oocytes. Here, we identify Znhit1, a core subunit of the SRCAP chromatin remodeling complex, as the essential factor mediating H2A.Z deposition in oocytes. Oocyte specific depletion of Znhit1 impairs H2A.Z incorporation and leads to severe ovarian phenotype, characterized by follicle loss, homologous chromosome segregation defects and meiotic arrest, which ultimately leads to female infertility. On molecular level, integrated Smart-seq2 and H2A.Z CUT&Tag analyses demonstrate that Znhit1 depletion severely reduces genome-wide H2A.Z deposition, particularly at promoter regions of key meiotic genes such as Aurkb, Tpm3, and Zar1, resulting in transcriptional dysregulation and aberrant meiotic gene expression. Our findings pinpoint Znhit1 as the histone chaperone essential for accurate deposition of histone variant H2A.Z ensuring meiotic progression and oocyte development in mice.

Female fertility relies on tightly regulated mitochondrial bioenergetics to support oocyte maturation, fertilization, and early embryonic development. Beyond ATP generation, mitochondria orchestrate redox signaling, calcium homeostasis, metabolic-epigenetic coupling, and nuclear-mitochondrial communication, thereby shaping oocyte competence and ovarian longevity. Aging, obesity, metabolic stress, and genetic perturbations disrupt these regulatory networks, leading to redox imbalance, impaired oxidative phosphorylation, altered mitochondrial dynamics, and mitochondrial DNA instability. These changes compromise granulosa cell support, impair meiotic progression, and accelerate ovarian aging, contributing to female infertility disorders such as polycystic ovary syndrome. This review integrates therapeutic strategies that actively reprogram ovarian mitochondrial function rather than merely counteracting damage. Mitochondria-targeted antioxidants-including melatonin, resveratrol, N-acetylcysteine, mitochondria-directed scavengers, and coenzyme Q10 restore redox balance, stabilize mitochondrial dynamics, and enhance oocyte bioenergetics. In parallel, metabolic modulators such as metformin, dapagliflozin, and glucagon-like peptide-1 receptor agonists reprogram ovarian bioenergetics by reshaping substrate utilization, suppressing inflammatory and oxidative signaling, and improving mitochondrial efficiency within the ovary. Collectively, these interventions demonstrate that, positioning mitochondria-centered therapies as promising strategies to preserve fertility and extend the female reproductive health span.

Congenital dysfibrinogenemia is a qualitative fibrinogen disorder with phenotypes ranging from isolated laboratory abnormalities to bleeding or thrombosis. Transvaginal ultrasound-guided oocyte retrieval is minimally invasive but may cause pelvic bleeding, and peri-procedural management in patients with congenital dysfibrinogenemia is not standardized. We report a 34-year-old woman with tubal-factor infertility and persistently low functional fibrinogen who pursued in vitro fertilization. Targeted sequencing of coagulation-related genes identified a heterozygous fibrinogen gamma chain gene (FGG) variant (NM_021870.3:c.902G>A, p.Arg301His), which was considered potentially contributory to the laboratory phenotype. She had no personal history of abnormal bleeding or thrombosis and had previously tolerated laparoscopic salpingotomy without transfusion or fibrinogen supplementation. A multidisciplinary team involving reproductive medicine, anesthesia, laboratory medicine, transfusion medicine, and internal medicine implemented a conservative, trigger-based plan without routine prophylactic transfusion, with prearranged availability of fibrinogen-containing products and predefined escalation criteria based on symptoms, hemodynamics, hemoglobin trends, and ultrasound findings. Controlled ovarian stimulation was performed using a gonadotropin-releasing hormone antagonist protocol, and oocyte retrieval was completed under standard intravenous sedation by an experienced operator. Ten oocytes were retrieved with an estimated blood loss of <5 mL. Postprocedure monitoring with serial vital signs, complete blood counts, coagulation tests, and transvaginal ultrasound showed hemodynamic stability and no clinically significant hemoperitoneum. This case illustrates the feasibility of transvaginal oocyte retrieval in a carefully selected, low-risk patient with congenital dysfibrinogenemia and provides a practical framework for individualized, risk-stratified peri-procedural management.

PCOS is the most common disorder encompassing reproductive, metabolic, and endocrine abnormalities, and has an increased risk of adverse pregnancy and neonatal complications, such as miscarriage, gestational diabetes mellitus, and preterm birth. Many studies suggested that oocyte quality is compromised in patients with PCOS compared to those without PCOS. To systematically characterize the follicular fluid (FF) proteomic landscape and identify potential biomarkers for oocyte quality assessment, we conducted a label-free proteomics analysis between patients with and without PCOS.