Reproductive Medicine and Biology最新文献

Background: Müllerian duct anomalies (MDAs) are developmental malformations of the female genital tract that present as a series of abnormalities within the reproductive tracts of females. The etiology of MDAs is complex and heterogeneous, especially genetic factors.

Methods: We conducted a comprehensive literature search in PubMed to identify relevant research articles and reviews. The search primarily targeted English-language publications from January 1978 to June 2025. Key search terms included Müllerian duct anomalies, Müllerian duct development, candidate gene, genetic, epigenetic, whole-exome sequencing, DNA methylation, chromosome, and related keywords.

Results: This review provides a comprehensive overview of the genetic factors and mechanisms underlying human Müllerian duct development. It systematically examines the genetic mutations and other mechanisms contributing to Müllerian duct anomalies (MDAs), including candidate genes and epigenetic abnormalities. Furthermore, the review summarizes recent advances in MDAs research and the digenic mode of inheritance.

Conclusion: We summarized the current genetic status of MDAs and discussed the research progress of relevant candidate genes in recent years in detail, and reviewed the reasons hindering progress in the field of MDAs.

Piezo-intracytoplasmic sperm injection (piezo-ICSI) is increasingly used to reduce mechanical damage during sperm injection. In the recent study by Ashibe et al., placing the first polar body (PB) at the 2 or 4 o'clock position ("para-PB piezo") improved immediate oocyte survival versus conventional 6/12 o'clock orientation, without negatively affecting blastocyst formation or chromosomal integrity in bovine oocytes. The proposed mechanism is that drilling through the wider perivitelline gap reduces oolemma perturbation and secondary Ca²⁺ influx. We comment herein on: (1) the need for reporting effect sizes with confidence intervals; (2) the imperfect correspondence between PB orientation and spindle location and the value of combining para-PB with spindle imaging; (3) mechanistic studies combining Ca²⁺ imaging, cortical cytoskeleton labeling, and standardized pulse logging; and (4) a recommended path toward human randomized trials with usable-blastocyst yield and euploidy as endpoints. With these refinements, para-PB orientation could be a low-complexity improvement to piezo-ICSI protocols.

Purpose: The influence of culture media used during in vitro fertilization (IVF) on offspring phenotype remains controversial. However, specific effects of short exposure time after fertilization remain underexplored. By evaluating Ca²⁺ oscillations as a readout of the first response of eggs to their microenvironment, we aim to investigate if early differences correlate with later adult phenotypes.

Methods: Oocytes fertilized by ICSI were cultured for 4 h in three different media (Cook and Vitrolife, used in human IVF, and KSOM, used for mouse embryos). They were either measured for Ca²⁺ oscillations or transferred into pseudo-pregnant females. After birth, growth curves of pups were measured up to adulthood and various organs were weighed.

Results: Culture media significantly modulate Ca²⁺ oscillations during oocyte activation. ICSI-fertilized oocytes cultured in Cook and Vitrolife exhibited fewer oscillations, lower frequency, and reduced variability compared to KSOM. These early differences correlated with long-term developmental outcomes: females from Cook and Vitrolife cultures were heavier throughout growth and had larger adult organ sizes compared to those from KSOM.

Conclusions: Brief exposure to media immediately after ICSI shapes Ca²⁺ dynamics and adult phenotypes. Optimizing embryo culture protocols in assisted reproductive technologies may improve IVF outcomes by modulating metabolic pathways linked to development.

Purpose: We demonstrated that briefly treating ovaries with collagenase before exposure to a hyperosmotic solution preserved secondary follicles. However, preserving antral follicles remained difficult. We investigated whether the absence of lipids in warming (thawing) solution is a limiting factor.

Methods: Frozen ovary was thawed in a lipid-containing solution and investigated for the effect on the structure, function, and viability of granulosa cells, which are important for antral follicle function.

Results: Lipids incorporated into the granulosa cell membrane protected the distribution of actin structures lining the cell membrane and maintained the expression of paxillin, actin-related adapter proteins, and YAP, which induces genes critical for granulosa cell function, to support the survivability of granulosa cells in antral follicles. It also preserved the function of frozen ovaries for 3 months after transplantation into the ovarian bursa of recipient hosts, significantly increasing the total number of viable offspring.

Conclusions: Lipids-key components of serum-protected the granulosa cell membrane during warming by preventing the efflux of fatty acids for maintenance of proper localization of the actin cytoskeleton and membrane proteins, supporting normal antral follicle function. The novel method combining collagenase pretreatment with a lipid-containing warming solution offers a promising approach to maintaining the function of cryopreserved ovaries.

Purpose: To identify risk factors that predict the persistence of noncyclical pelvic pain in patients with endometriosis despite receiving hormone therapy.

Methods: This retrospective study examined 164 patients with histopathologically confirmed deep infiltrating endometriosis (DE) and/or ovarian endometrioma (OV). Clinical data obtained through preoperative face-to-face interviews were analyzed to identify risk factors for persistent pain despite receiving hormonal treatment (defined as visual analog-scale score [VAS] score > 30). All patients received preoperative hormonal treatment with progestins, combined oral contraceptives, or gonadotropin-releasing hormone agonists for at least three months prior to surgery.

Results: Multivariable analysis identified several risk factors: OV (odds ratio [OR]: 4.11, 95% confidence interval [CI]: 1.67-10.1, p = 0.002) versus no OV, noncyclical chronic pelvic pain (VAS score ≤ 60: OR: 12.0, 95% CI: 4.17-34.6; VAS score > 60: OR: 7.03, 95% CI: 2.25-21.9, p < 0.001) versus no pain, severe dyspareunia (VAS score > 60) (OR: 6.73, 95% CI: 4.17-34.6, p = 0.002) versus no dyspareunia, and a previous cesarean section (OR: 9.53, 95% CI: 1.54-59.0, p = 0.02) versus no previous cesarean section.

Conclusions: Patients with ovarian endometrioma, noncyclical chronic pelvic pain, severe dyspareunia, and a history of cesarean section are at an increased risk for persistent pain despite hormonal treatment.

Purpose: To explore how intimate hygiene practices and related products-such as feminine washes, wipes, and lubricants-affect the vaginal microbiome.

Methods: Vaginal bacterial communities of 96 non-pregnant Western Australian women were characterised via full-length 16S rRNA gene sequencing. Participants completed an online questionnaire capturing demographics, intimate health, hygiene and sexual practices, to compare these with microbial composition.

Results: Beta diversity varied significantly across multiple variables, particularly in relation to Lactobacillus spp. abundance. Compared to women with no partners or two or more sexual partners, monogamous women had lower L. crispatus (p = 0.002 and p = 0.04, respectively), higher L. iners (p = 0.017 and p = 0.044, respectively), and were least likely to cluster into CST I (p < 0.001). Postmenopausal women showed reduced L. crispatus (p = 0.009), increased levels of L. iners (p = 0.037), and were most likely to cluster into CST IV (p = 0.029) compared with women who did not report menopause. Regular perineal washing was associated with fewer reported infections (p = 0.029), whereas internal washing correlated with recurrent thrush (p = 0.017).

Conclusions: Sexual practices and menopause status are key factors influencing L. crispatus and L. iners colonisation. Most hygiene practices had minimal impact on Lactobacillus dominance, although behaviours associated with significant microbiome disruption were uncommon in this cohort.

Purpose: Considering the immune-related etiology of RIF, administration of an immunomodulatory approach such as autologous PBMCs seems to be helpful in modifying the dysregulated immune responses.

Methods: 100 RIF women were divided into the PBMC receiving and the control group. Blood sampling was conducted 48 h before and 2 weeks after PBMC administration. The frequency of Th17, Treg, and NK cells, the expression level of related transcription factors and miRNAs, and the concentration of inflammatory and anti-inflammatory cytokines were evaluated pre- and post-treatment. Pregnancy outcome including pregnancy, live birth, and miscarriage rates were also evaluated.

Results: PBMC therapy significantly elevated the frequency of Th17 and NK cells (p = 0.0035 and 0.0013, respectively) and the expression of RORγt (p < 0.0001), in comparison with pre-treatment, while the frequency of Treg cells (p = 0.0063) and the expression of FoxP3 and PTEN were decreased post treatment. The serum concentration of IL-1β, IL-17, and TNF-α was increased, while IL-10 and TGF-β were reduced post-treatment when compared to pre-treatment. Pregnancy and live birth rates were significantly higher in the PBMC-treated group in comparison with routine treatment.

Conclusion: Intrauterine administration of autologous PBMCs may be helpful in treating RIF patients, especially those with decreased inflammatory cells and mediators in the implantation process.

Purpose: This study aimed to identify factors influencing the accuracy and effectiveness of non-invasive preimplantation genetic testing for aneuploidy (niPGT-A) and develop clinical integration workflows to provide alternative embryo assessment and improve pregnancy outcomes.

Methods: A two-phase study analyzed 341 blastocysts and spent culture medium (SCM) from 90 IVF patients. Phase 1 assessed niPGT-A accuracy by comparing SCM/trophectoderm (TE) with whole blastocysts (100 frozen embryos). Phase 2 examined concordance, assisted hatching, and culture-duration effects, focusing on outcomes after frozen embryo transfer using 241 fresh embryos. Nineteen euploid-TE/euploid-SCM and 14 euploid-TE/aneuploid-SCM blastocysts were transferred, and a meta-analysis was conducted using data from 163 euploid embryos across four studies.

Results: The optimized niPGT-A workflow achieved a superior PPV of 92.1% and accuracy of 91.3%, outperforming conventional PGT-A. Ploidy and sex concordances were 76.5% and 98.9% among 183 fresh embryos. Assisted hatching improved amplification rates, while culture duration/ploidy did not impact concordance. Meta-analysis showed SCM-guided embryo transfer significantly improved pregnancy outcomes, compared to TE biopsy.

Conclusion: This optimized niPGT-A procedure provides a highly accurate chromosomal assessment, seamlessly integrates with IVF workflows. It supports informed embryo transfer decisions, improves outcomes, reduces embryo damage risk, and limits invasive procedures, enhancing clinical management in reproductive medicine.

Purpose: Recurrent spontaneous abortion (RSA) is an abnormal phenomenon that severely affects women's quality of life. Inhibiting Th17 cell differentiation can alleviate RSA. This research explored the mechanism by which BRD4 Inhibitor (BETi) suppressed the differentiation of Th17 cells to mitigate RSA.

Methods: PBMCs and Naive CD4⁺ T cells were induced to differentiate into Th17 and Treg cells. An abortion-prone pregnancy mouse model was constructed by intraperitoneal injection of lipopolysaccharide. The Th17/Treg ratio was determined by flow cytometry. The association between STAT3 and IL-17A promoter was investigated by ChIP and dual luciferase assays. Co-IP and yeast two-hybrid assays were used to determine BRD4 binding to STAT3. The markers of Th17/Treg cell differentiation and lipid synthesis were checked by ELISA, IHC, RT-qPCR, and Western blot.

Results: The Th17/Treg ratio and the expression levels of BRD4, STAT3, and IL-17A were elevated, while STAT5b expression was down-regulated in RSA patients. BETi or STAT3 knockdown decreased the differentiation of Th17 cells and lipid synthesis. BRD4 inhibition impaired STAT3-mediated IL-17A transcription. BETi inhibited embryo absorption in mice.

Conclusions: BETi inhibits the differentiation of Th17 cells in RSA by reducing the STAT3-mediated IL-17A expression.

Purpose: Endometrial receptivity is a critical determinant of successful embryo implantation and is intricately linked to the pathophysiology of infertility. This study aimed to elucidate the role of exosomal miR-203a-3p in regulating endometrial receptivity, thereby providing insights into potential therapeutic strategies for infertility treatment.

Methods: Transcriptomic profiling of exosomes was performed to identify factors associated with endometrial receptivity. miR-203a-3p, exhibiting high expression levels in exosomes, was selected for further investigation. Human endometrial tissues from different menstrual phases and patient groups were analyzed for miR-203a-3p expression. Functional studies using miR-203a-3p mimics and engineered exosomes were conducted in non-receptive AN3-CA cells.

Results: During the secretory phase, miR-203a-3p expression was markedly higher in the endometria of fertile women than in those of infertile women. Overexpression of miR-203a-3p, which directly targeted Snail family transcriptional repressor (SNAI1), resulted in increased E-cadherin expression and enhanced spheroid attachment in non-receptive AN3-CA cells. Consistently, delivery of miR-203a-3p mimics via engineered exosomes increased E-cadherin expression by suppressing SNAI1 and enhanced spheroid adhesion in AN3-CA cells.

Conclusions: Our data highlight the importance of the miR-203a-3p/SNAI1/E-cadherin axis in governing endometrial receptivity. Exosome-mediated delivery of miR-203a-3p mimics may represent a promising therapeutic strategy for improving embryo implantation and treating infertility.