Patients with severe β-thalassemia face not only lifelong dependence on blood transfusions but also the management of serious and potentially life-threatening complications. The pathophysiology of this disorder is largely attributed to a defective transition from γ-globin to β-globin gene expression, a process essential for normal hemoglobin production after birth. This developmental transition involves the silencing of fetal γ-globin and coordinated activation of adult β-globin gene transcription. Central to this regulation are transcription factors that directly bind to the γ-globin promoter. This review synthesizes recent advances in understanding the γ-to-β-globin switch, focusing on four principal transcription factors—GATA1, BCL11A, ZBTB7A, and NFY—and partner proteins including GATA2 and KLF1. In addition, we propose a competitive binding model in which the GATA1/NFY and ZBTB7A/BCL11A protein complexes compete for promoter occupancy. This model provides a useful framework that may inform future strategies for the prevention, diagnosis, and treatment of β-thalassemia.

Objective: To evaluate the clinical efficacy of vaginal repair as a salvage treatment for cesarean scar defects in patients with previously failed repair surgery. Methods: This retrospective cohort study included 16 patients with cesarean scar defects who underwent vaginal repair as salvage therapy after prior repair surgery failure between March 2019 and September 2022 at the Department of Obstetrics and Gynecology, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine. The previous failed procedures included vaginal repair, hysteroscopic repair, and laparoscopic repair. A control group of 108 patients who underwent primary vaginal repair during the same period was also analyzed. Perioperative outcomes and post-operative repair efficacy were compared. The length, width, and depth of the cesarean scar defect, as well as the thickness of the residual myometrium, were measured by transvaginal ultrasonography. Results: No significant differences were observed between the two groups in demographic characteristics. In both groups, the duration of menstruation significantly decreased after vaginal repair (from 12.8 ± 5.3 to 6.75 ± 1.8 days in the salvage therapy group, and from 13.5 ± 3.8 to 7.1 ± 1.7 days in the primary surgery group), while the thickness of the residual myometrium significantly increased (from 3.0 ± 2.0 to 7.7 ± 2.6 mm in the salvage therapy group, and from 2.6 ± 1.2 to 7.7 ± 2.5 mm in the primary surgery group). Post-operatively, there were no significant differences between the two groups in either menstrual duration (6.8 ± 1.8 vs . 7.1 ± 1.7 days) or residual myometrial thickness (7.7 ± 2.6 vs . 7.7 ± 2.5 mm). The data also indicated that performing salvage therapy within ≤21 months of the initial surgery was associated with a better prognosis. Conclusions: Vaginal repair as salvage therapy is a feasible and effective option for patients with cesarean scar defects after failed repair surgery.

Objective: Cisplatin (Cis) is an anticancer agent used to treat several types of cancers, including testicular cancer. However, despite its therapeutic efficacy, it increases the levels of reactive oxygen species (ROS), which damage healthy tissues and cells, resulting in tissue toxicity. This study aimed to examine the healing effect of selenium (Se) on Cis-induced testicular injury in male rats by evaluating testicular weight and monitoring the levels of oxidative stress and reproductive function markers in testicular homogenates. Methods: A total of 38 male rats were divided into four distinct groups. The control group was administered an isotonic solution as the solvent for the active ingredients, while the Se group was administered 1 mg/kg Se dissolved in an isotonic solution via gastric gavage. The Cis group was administered 7.5 mg/kg Cis dissolved in an isotonic solution. The Cis + Se group received both the treatments. Reproductive function and oxidative stress markers in testicular homogenates were analyzed using enzyme-linked immunosorbent assay (ELISA). Results: Compared to the control group, the Cis group exhibited significantly lower testicular weight, antioxidant activity (superoxide dismutase [SOD]; total antioxidant status [TAS], P < 0.001), and reproductive function activity (follicle-stimulating hormone [FSH]; inhibin B, P < 0.001; luteinizing hormone [LH], P < 0.01), and significantly higher oxidant levels (malondialdehyde [MDA], P < 0.01; total oxidant status [TOS], P < 0.01). The Cis + Se group exhibited significantly higher TAS ( P < 0.04) and testosterone ( P < 0.01) levels than the control group. Conclusion: Administration of Se ameliorated the toxic effects of Cis. Owing to its antioxidant effects, Se may be useful in preventing Cis-induced toxicity in the testicles by alleviating oxidative stress.

Objectives: African giant rats (AGRs) exhibit low reproductive performance in captivity due to infertile copulation or lack of mating. In this study, we investigated the effects of Zingiber officinale aqueous extract (ZOAE) on libido, sperm cell kinetics, and reproductive organ development in AGRs. Methods: Twenty-four animals weighing 861.20 ± 65.44 g were individually housed in concrete cages with ad libitum access to water and food. The animals were randomly assigned to four treatment groups. G 0 was the control group, whereas G 250 , G 500 , and G 1000 , which received 250, 500, and 1000 mg/kg of ZOAE daily, respectively, mixed with 10 g of avocado paste. After 49 days of treatment, the animals were sacrificed for data collection. Results: The results showed that ZOAE supplementation significantly ( P <0.05) enhanced libido, as indicated by a reduced reaction time. Additionally, testosterone levels increased with higher ZOAE concentrations. Sperm cell count was nearly twice as high ( P <0.05) in the treated groups compared with the control. Sperm kinetic parameters (overall mobility, progressive motility, path velocity, and linear motility) were significantly greater in the ZOAE-treated groups than in the control ( P <0.05). However, the weights of the reproductive organs (testes, vas deferens, and accessory glands) were not significantly affected ( P >0.05). Conclusion: In conclusion, ZOAE effectively enhances libido, sperm count, and sperm kinetics in AGRs.

Despite impressive progress being made in investigating the mechanisms underlying endometriosis, the pathophysiology of this disease remains unclear. Although typical methods used for diagnosing endometriosis such as ultrasound, magnetic resonance imaging, and blood tests are available, these are also inefficient, and effective noninvasive diagnostic methods are lacking. The advances in high-throughput omics techniques have enabled metabolomics to become an effective approach for discovering promising biomarkers. The aberrant metabolism associated with serious symptoms of endometriosis in women has been revealed in recent years. Analyzing the global metabolic patterns in patients with endometriosis may help deepen the understanding of the disease mechanism and have a significant impact on future diagnostic and treatment methods for endometriosis. Herein, we reviewed relevant studies on metabolic changes in patients with endometriosis and discussed the changes in metabolites both in biological fluids and endometriosis tissues. The findings discussed in this review have potential diagnostic implications and will enhance the understanding of the pathophysiological processes underlying the disease.

Objective: Progesterone (P4) is the optimal agent for luteal support in assisted reproductive technologies. Despite the availability of various formulations, the impacts of P4 treatment administered through different routes on offspring growth remain unevaluated. This study aimed to investigate and compare the effects of P4 administration through three different routes in pregnant rats during the teratogenesis-sensitive period on fertility outcomes and the behavior, plasma P4 and pregnenolone levels, and alterations in gut microbiota in the filial generation (F1) of offspring. Methods: Female rats that mated successfully were randomly classified into four groups: Group 1, the normal control group; Group 2, the IG group, in which utrogestan was administered via intragastric gavage; Group 3, the IM group, in which P4 was administered via intramuscular injection; and Group 4, the VAGIN group, in which P4 sustained-release vaginal gel was administered through the vagina. Except for the control group, P4 was administered in other groups through their respective routes for 13 consecutive days daily during the teratogenic-sensitive gestation period (days 6–18). The fertility outcomes of the maternal rats were observed, and open-field and three-chamber social preference tests were conducted to assess anxiety and social behavior, along with an exhaustive swimming experiment to evaluate the motor endurance of the offspring. Plasma P4 and pregnenolone levels in the offspring were measured, and fecal samples were assessed using gut microbiota sequencing and subsequent bioinformatics analysis. Results: No significant alterations in fertility outcomes were observed through three P4 administration routes—intragastric gavage, intramuscular injection, and vaginal administration—in rats. However, in behavioral experiments in offspring, a significant increase was observed in swimming time in the IG group than in the control group (P = 0.013). Furthermore, the offspring in the IG group exhibited a marked decrease in non-social behaviors compared with the control group (P = 0.030). No significant behavioral changes were observed in the F1 offspring in the open-field test. Additionally, the offspring in the IG group exhibited a significant elevation in plasma pregnenolone levels compared with the control group (P = 0.019) 30 days after birth. No notable differences in the α-diversity of gut microbiota were observed among the groups. However, significant differences in β-diversity were observed in both the IG and IM groups compared with the control group, indicating that P4 treatment via the two routes exhibited a significant impact on the gut microbiota composition of F1 offspring. Distinct differences were observed in the gut microbiota of the offspring among the three P4 treatment groups, with 22, 28, and 33 differential bacterial taxa identified in the IG, IM, and VAGIN groups, respectively, using linear discriminant effect size analysis, whereas Olivella appeared exclusively in the control group rather than in the P4 treatment groups. Conclusion: Oral administration of P4 to maternal rats during the teratogenesis-sensitive period enhanced motor endurance and plasma pregnenolone levels and altered the composition of the gut microbiota in the offspring. Our findings demonstrated different effects on offspring growth when P4 is administered orally, intramuscularly, or vaginally.

Polycystic ovary syndrome (PCOS) is a common endocrine disorder characterized by a hormonal imbalance that affects females of reproductive age. The association between advanced glycation end products (AGEs) and PCOS has attracted considerable attention in recent years, highlighting the potential of AGEs as biomarkers for this disorder. In the present systematic review and meta-analysis, we aimed to examine the association between AGEs and PCOS, evaluate their potential as biomarkers, and improve our understanding of the pathophysiology of PCOS and its associated metabolic complications. A literature search was performed using various databases from January 2000 to March 2023 to identify relevant studies investigating the association between AGEs and PCOS. Pooled effect estimates were calculated using standardized mean differences (SMD) with 95% confidence intervals (CIs). Sub-group and meta-regression analyses were performed to examine potential sources of heterogeneity. The meta-analysis included six studies with a total of 623 participants. Our results revealed a significant increase in circulating AGE levels in females with PCOS compared to healthy females (SMD = 2.35; 95% CI: 1.10–3.60; P <0.001). Significant heterogeneity was observed between the studies (I 2 = 96.37%; P <0.001), indicating the presence of several factors influencing the association. Sub-group analyses based on body mass index, age, and homeostatic model assessment for insulin resistance indicated differential effects of AGEs on specific sub-groups. This systematic review and meta-analysis support the association between elevated AGE levels and PCOS, thereby suggesting the potential role of AGEs as biomarkers in PCOS.

Objective: Duphaston is used as an alternative to gonadotropin-releasing hormone (GnRH) antagonists for suppressing premature luteinizing hormone (LH) surges. This study aimed to compare the efficacy of Duphaston protocols with that of Cetrotide in suppressing the LH surge. Methods: In this retrospective cross-sectional study, 669 infertile women (aged 25–40 years) were administered recombinant follicle-stimulating hormone (rFSH) from the third day of their menstrual cycle. After the follicular diameter reached 13 to 14 mm, Cetrotide was prescribed orally to the control subjects, also case subjects took Duphaston orally. The retrieved oocytes were fertilized by an intracytoplasmic sperm injection (ICSI). Results: The levels of FSH, LH, and estradiol did not differ significantly between the groups (P >0.05). However, the findings indicated that Duphaston led to greater oocyte retrieval than Cetrotide (P = 0.006). However, the number of mature oocytes and viable embryos in the case subjects did not reach a significant difference compared to that in the control subjects (P >0.05). The number of good-quality embryos (stage 1) was significantly higher in the case subjects (P = 0.04). In addition, there is no significant difference in the chemical, clinical pregnancy, implantation rate, and miscarriage rate between both groups (P >0.05). Conclusion: Duphaston could be utilized as a suitable medication rather than a GnRH antagonist in women subjected to controlled ovarian hyperstimulation.

Successful implantation requires concerted interactions during the apposition, adhesion, and invasion of the embryo into a receptive endometrium. However, the embryo implantation rate for assisted reproduction remains low despite the transfer of good quality embryos. Changes in endometrial transcriptomics, proteomics, lipidomics, and even microbiota all play important roles in embryo implantation. Specifically, the expression of steroid hormone-regulated adhesive and anti-adhesive molecules during the embryo implantation window is becoming an area of increasingly intense research. This review (a) summarizes the different molecules expressed in the receptive endometrium and (b) proposes the use of surface protein markers to predict pregnancy outcomes from assisted reproduction.

Autosomal reciprocal translocations represent exchanges of chromatin fragments between non-homologous chromosomes. Translocations are facilitated by the creation of quadrivalent structures during the first meiotic division, which are characterized by the length of the translocated and centric segments, asymmetry, and the presence of terminal breakpoints, all of which may impact segregation mode. Here, we report a rare case of multiple reciprocal translocations within a single family. This includes the evaluation of the translocations in each of the spouses and an analysis of their chromosome segregation patterns as determined by the constellation of universal characteristics in each of their quadrivalents. The obtained results will be of interest to fundamental biology, as they will expand the understanding of the factors affecting chromosome segregation during meiosis.