Reproductive Sciences最新文献

Polycystic ovarian syndrome (PCOS) is a leading cause of infertility due to chronic anovulation. Letrozole is the first-line treatment for ovulation induction, but combination therapy with clomiphene citrate (CC) may enhance outcomes. We conducted a systematic search of three databases until October 2024, including randomized controlled trials (RCTs). Bias was assessed using the Revised Cochrane risk of bias tool (RoB 2). Six RCTs with 619 PCOS patients were included. The combination of Letrozole and CC resulted in a higher, though non-significant, ovulation rate (53.74%) vs. Letrozole alone (40.08%) (OR 1.22, 95% CI [0.88, 1.69], P = 0.23). Lower-dose combination therapy (50 mg CC + 2.5 mg Letrozole) significantly improved ovulation (OR 4.45, 95% CI [2.19, 9.08], P < 0.001), whereas higher-dose therapy (100 mg CC + 5 mg Letrozole) had no effect. Pregnancy rates were higher with combination therapy (26.25% vs. 22.18%) but not significant (OR 1.26, 95% CI [0.84-1.88], P = 0.26). Miscarriage rates were lower (OR 0.32, 95% CI [0.12-0.88], P = 0.03). Lower-dose combination therapy also increased the proportion of follicles > 15 mm (OR 4.09, 95% CI [1.94, 8.60], P < 0.001), with no significant differences in endometrial thickness, follicular size, or progesterone levels. Side effects were similar, though hot flushes were more common with combination therapy (OR 2.99, 95% CI [1.23, 7.23], P = 0.02). Our results support lower-dose combination therapy for improved ovulation, follicle count, and pregnancy outcomes while reducing miscarriage risk.

The effect of polycystic ovary syndrome (PCOS) on the fatty acid (FA) content of follicular fluid (FF) is not fully understood. The present study aimed to determine whether the FA composition of FF phospholipids (PLs) and triglycerides (TGs) undergoes alterations in women with PCOS. A total of 40 subjects, including 20 PCOS patients and 20 controls, were enrolled. Thin-layer chromatography followed by gas chromatography was carried out to isolate FF lipid fractions and measure relative concentrations of their FAs, respectively. Percentages of individual FAs in FF PLs and TGs did not statistically differ between the control and PCOS groups (p > 0.05), other than palmitoleic acid, which significantly decreased and increased in PLs and TGs of women with PCOS, respectively (p < 0.05). There were positive correlations between intrafollicular levels of androgens and PL levels of several n-6 polyunsaturated FAs in the PCOS group (r > 0.4, p < 0.05). In addition, relative concentrations of eicosapentaenoic acid in both PL and TG fractions were inversely correlated with the fertilization rate (r < -0.4, p < 0.05). PCOS women with positive pregnancy outcomes also had higher PL and TG stearic acid with concomitant lower docosahexaenoic acid and peroxidizability index in PL and TG fractions, respectively (p < 0.05). It could be concluded that PCOS was associated with minor alterations in the FA composition of FF PLs and TGs. Furthermore, there were differential fraction-dependent associations between FF FA profile and biochemical and reproductive parameters in women with PCOS.

Bidirectional embryo-endometrial communication is critical for embryo implantation. As a bio-sensor of embryos, the human endometrium is capable of mounting a response tailored to individual embryos, but how embryos signal their development potential remains an unresolved question. Emerging evidence showed that embryo-released miRNAs could mediate the interaction between the embryos and endometrium. In our previous study, miR-519d-3p was detected in the spent embryo culture medium with notably higher levels from implantation-failed blastocysts. To explore the role of miR-519d-3p at the maternal-fetal interface, human endometrial stromal cells (hESCs) were isolated and cultured in vitro. The miRNA uptake assay revealed that blastocyst-derived miR-519d-3p could be internalized by hESCs. miR-519d-3p overexpression significantly promoted cell apoptosis while suppressing cell viability and the migration of hESCs, as demonstrated by flow cytometry, CCK-8, and wound-healing assay. Furthermore, miR-519d-3p downregulated the expression of MMP-2, MMP-9, and VEGF-key proteins involved in hESC motility, uterine vascular permeability, and angiogenesis. HIF1α was a target of miR-519d-3p. With HIF1α overexpression, the biological effects of miR-519d-3p on hESCs were partially reversed. Taken together, blastocyst-secreted miR-519d-3p might contribute to the regulation of endometrial receptivity by targeting HIF1α, potentially offering a new perspective on embryo-maternal communication.

Gut microbiota plays a critical role in maintaining reproductive homeostasis, and mounting evidence highlights probiotic supplementation as a promising therapeutic candidate owing to its immunomodulatory potentials. Neurotensin (NTS), a tridecapeptide neuropeptide, has been shown to link with the regulation of inflammation and reproductive processes. This study aims to evaluate the possible simultaneous ameliorative effect of NTS receptor 1 agonist PD149163 co-administration with multi-strain probiotics in lipopolysaccharide/LPS induced ovarian dysfunction. Female Swiss albino mice (8 weeks old) were randomly assigned to seven groups: control, LPS (1 mg/kg bw), LPS + PD149163 (50 µg/kg bw), LPS + probiotics (0.6 gm/kg bw/day), LPS + PD149163 + probiotics, PD149163, and probiotics. After 32 days, plasma and ovarian samples were collected for biochemical and histological analyses. Additionally, an in-silico approach was employed to assess the potential interaction of probiotic-derived metabolites (butyrate and propionic acid) with the key proteins of TLR4/MyD88/NF-κB signalling pathway (TLR4/MD-2 complex, MyD88 and NF-κB). Co-administration of PD149163 with multi-strain probiotics attenuated inflammatory markers (NF-κB, TNF-α, IL-6), restored anti-oxidant enzyme activity (SOD, CAT), reduced lipid peroxidation (LPx), normalized hormonal levels (NTS, LH, FSH, E2) and improved ovarian histopathological features. Co-supplementation of probiotics with PD149163 as an adjunct therapy has shown superior efficacy in mitigating the ovarian dysfunction compared to employing single treatment approach. This ameliorative effect is presumably mediated by suppressing TLR4/MyD88/NF-κB signalling pathway, thereby dampening inflammatory cascade and alleviating ovarian dysfunction. Therefore, further investigations are warranted to unravel the underlying mechanisms of probiotic action on reproductive physiology, thereby providing therapeutic insights for the management of sepsis-related reproductive dysfunction.

Polycystic ovary syndrome (PCOS) is a complex and heterogeneous disorder in reproductive-aged women and adolescents. Vitamin D deficiency (VDD) and genetic variations in the vitamin D receptor (VDR) pronouncedly influence its manifestations. The interplay between VDD and VDR polymorphisms has an umbrella effect on the endocrine and metabolic milieu of PCOS, underscoring the importance of vitamin D (VD) in its management. This study tried to find out the association between VDD and single-nucleotide polymorphisms (SNPs) in the VDR gene in the differential pathophysiological manifestations of PCOS in the ethnic population of West Bengal, India. The case-control study was conducted involving 170 PCOS women (ages 17-36 years) and 150 of their gender, and age and ethnicity-matched healthy controls. VDD was assessed along with the association of VDR polymorphisms [BsmI (rs1544410) and FokI (rs2228570)] with the nutritional and biochemical indices. Bioelectrical impedance (anthropometric indices), structured questionnaires (sociodemographic characteristics, solar-UVB exposure and nutritional status), haematological estimation (VD and other necessary parameters) and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP, VDR-SNPs) were employed in this study. In the PCOS population, the BsmI-VDR-based VD cutoff level was 19.17 ng/ml [asymptotic sig.: 0.000, with area under the curve (AUC): 0.894, sensitivity: 0.950, and specificity: 0.657] and the FokI-VDR-based VD cutoff level was 17.67 ng/ml [asymptotic sig.: 0.000, with AUC: 0.947, sensitivity: 0.875, and specificity: 0.732] derived by receiver operating characteristic (ROC) curve analysis. VDR-SNPs were further stratified by performing Sanger sequencing. Significant correlations were found between VDR variants and hyperandrogenism (HA), insulin resistance (IR), inflammatory markers, and obesity indices of PCOS patients. Mutant (BsmI-bb/Bb and FokI-ff/Ff) VDR genotypes were found to be influential upon the metabolic and cutaneous features of PCOS patients, suggesting a genetic basis for VD-related disturbances in PCOS. This study accentuates the need for personalised therapeutic strategies, particularly VD supplementation, based on genetic profiles to manage the severity and prevalence of PCOS and its associated metabolic deregulations.

Preeclampsia (PE), a severe pregnancy complication, arises from placental hypoxia-induced mitochondrial and endoplasmic reticulum (ER) oxidative stress, contributing to inadequate spiral artery remodeling and endothelial dysfunction. Calpastatin, a mitochondrial protective protein, mitigates oxidative stress-related pathologies, but its role in PE remains unclear. This study investigated the effects of Calpastatin on trophoblast cellular proliferation, migration, invasion, apoptosis, and the expression of autophagy protein (PINK1), mitochondrial dynamics protein (Mfn2), ER stress protein (GRP78), ATP, Ca²⁺, and mitochondrial membrane potential under hypoxia using transfected HTR8-SVneo cells. Calpastatin overexpression significantly enhanced proliferation, migration, and invasion while reducing apoptosis (P < 0.05); knockdown inversely affected these parameters under normoxic conditions. Under hypoxia, overexpression further amplified proliferation and migration (P < 0.01), whereas knockdown reduced migration at 48 h (P = 0.04) but not proliferation. Invasion decreased and apoptosis increased in both groups (P < 0.05). Calpastatin overexpression upregulated PINK1, downregulated Mfn2/GRP78, increased ATP and mitochondrial membrane potential, and reduced Ca²⁺. Conversely, knockdown suppressed Pink1/Parkin, elevated Mfn2/Drp1/GRP78, decreased ATP, and increased Ca²⁺ and mitochondrial depolarization (P < 0.05). These findings demonstrate calpastatin promotes trophoblast function by maintaining mitochondrial-ER contact sites stability and ATP production, Ca²⁺ homeostasis, and mitophagy mechanism, suggesting its critical role in PE pathogenesis.

It is thought that decreased HERC2 expression increases the sensitivity to ferroptosis in ovarian cancer cells and may increase the VEGF pathway in porcine endothelium by inhibiting LKB1. Based on these data, we aimed to determine whether HERC2 expression may have a positive prognostic significance in patients receiving anti-VEGF based therapy in ovarian cancer patients. The study used public databases and has a retrospective design. Following web tools or datasets were used: TCGA TARGET GTEX study (n = 427 cancer vs. 88 normal ovarian tissue) at UCSC Xena and CPTAC at UALCAN for expression, Kaplan-Meier plotter for overall survival (OS) (n = 1207 for serous histology and n = 37 for endometrioid histology in gene chip), progression-free survival (PFS) (n = 1104 for serous histology in gene chip), TIMER2.0 for correlation of PDCD1, CTLA4, CD274 (PDL1), GEPIA2 for immune gene signatures, OncoLnc, DoSurvive and OncomiR for miRNA and OS associations, CancerSEA for functional status analyses. HERC2 expression levels were lower in ovarian serous cystadenocarcinoma (OV). Lower HERC2 expression was also seen in CPTAC ovarian cancer cohort. In the overall ovarian cancer cohort, decreased HERC2 expression was associated with longer OS. In the serous histology cohort, decreased HERC2 expression was associated with shorter PFS in those receiving bevacizumab-containing chemotherapy. PDL1 and HERC2 expressions were positively correlated. hsa-miR-500a-3p was negatively correlated with HERC2 in OV, and increased expression of this miRNA was associated with better OS. There was a positive association between HERC2 expression and angiogenesis and EMT, and a negative association with invasion. Decreased HERC2 expression is associated with a favorable prognosis in overall ovarian cancer cohort, but is associated with a worse PFS in patients receiving bevacizumab with serous ovarian cancer.

Premature ovarian insufficiency (POI) is a condition in which the ovarian function decreases beyond the extent of the normal range of young adults' age. This can be a consequence of cancer treatments like doxorubicin, leading to reproductive deterioration that hormonal replacement therapy cannot fully address. Flaxseed lignans are weak phytoestrogens that can mimic the effects of estrogen and alleviate POI-associated symptoms. Therefore, this study aimed to evaluate the potential of flaxseed lignans to improve the recovery from doxorubicin-induced POI in adult mice. Thirty-six regularly-cycling virgin female mice were randomly allocated into: normal, POI, and lignans-treated POI groups. These mice were assigned to either experiment I to assess cyclicity, ovarian hormones, ovarian histomorphometry, and immunohistochemistry; or to experiment II, where the females were mated to assess pregnancy rates, and embryos quantity and quality. Exposure to doxorubicin resulted in irregular estrous cycles, and significant decrease in body and ovarian weights, estradiol, follicular count, and pregnancy rate; while showed a significant increase in FSH and follicular atresia. Lignans treatment improved body and ovarian weights, and significantly ameliorated the decrease in estradiol levels, viable follicular count, as well as the pregnancy rate. Lignans have been also observed to reduce elevated FSH levels and the number of atretic follicles, while also helping to normalize estrous cycle regularity. In conclusion, flaxseed lignans, due to their estrogen-like effects, can help mitigate reproductive deteriorations caused by cancer treatments, which suggests their potential use in treating premature ovarian insufficiency.

Despite broad consensus on the oncological criteria for the inclusion of patients in conservative therapy for endometrial cancer (EC), several prognostic factors affecting patients' subsequent oncological and reproductive outcomes have yet to be explored. To assess the prognostic factors influencing remission, pregnancy and recurrence in conservative therapy of endometrial hyperplasia (EH) and EC. Following the PRISMA statement and the Cochrane Handbook, the search for relevant studies was conducted in PubMed, Embase, Web of Science, Wan fang and China National Knowledge Infrastructure from the inception of the databases to 1 March 2024. Studies that met the inclusion criteria were evaluated for quality using the Newcastle-Ottawa Scale and subsequently analyzed for data extraction. This meta-analysis included 3815 patients with EC or EH treated with conservative therapy in 35 studies. The analysis revealed the overall remission rate of 92.0% (95% CI, 87.0-96.0%), pregnancy rate of 34.0% (95% CI, 32.0-36.0%), and recurrence rate of 27.0% (95% CI, 25.0-29.0%). Four study characteristics, including obesity, pathology type, lesion size, and insulin resistance were associated with remission rate. A total of 8 study characteristics were found to be associated with pregnancy rate, including obesity, pathology type, time to complete response (CR), mode of conception, intrauterine adhesion, the number of uterine manipulations, endometrial thickness and recurrence before pregnancy. Seven study characteristics were found to be associated with recurrence rate, including age over 35.0 years, obesity, family history of cancer, pathological type, abnormal menstruation, pregnancy and maintenance treatment after CR. Common prognostic factors affecting remission, pregnancy and recurrence of endometrial cancer and endometrial hyperplasia are obesity and type of pathology. Patient characteristics, medical factors, and pathological features significantly influence oncological and reproductive outcomes in patients with EH and EC undergoing conservative therapy. Consequently, careful clinical selection and individualized assessment of each candidate for conservative therapy are essential to optimally balance short-term oncological and reproductive outcomes with long-term survival prognosis.