The implicated role of GDF15 in gastrointestinal cancer.

BACKGROUND: Growth differentiation factor 15 (GDF15), a stress-responsive cytokine from transforming growth factor superfamily, is highly expressed in mammalian tissues, including pancreas, stomach and intestine under pathological conditions. In particular, elevated levels of GDF15 might play an important role in the development and progression of various gastrointestinal cancers (GCs), suggesting its potential as a promising target for disease prediction and treatment. METHODS: In this review, systematic reviews addressing the role of GDF15 in GCs were updated, along with the latest clinical trials focussing on the GDF15-associated digestive malignancies. RESULTS: The multiple cellular pathways through which GDF15 is involved in the regulation of physiological and pathological conditions were first summarized. Then, GDF15 was also established as a valuable clinical index, functioning as a predictive marker in diverse GCs. Notably, latest clinical treatments targeting GDF15 were also highlighted, demonstrating its promising potential in mitigating and curing digestive malignancies. CONCLUSIONS: This review unveils the pivotal roles of GDF15 and its potential as a promising target in the pathogenesis of GCs, which may provide insightful directions for future investigations.

Ultra-Fast Vitrification: Minimizing the Toxicity of Cryoprotective Agents and Osmotic Stress in Mouse Oocyte Cryopreservation.

Globally, women have been adopting oocyte cryopreservation (OC) for fertility preservation for various reasons, such as inevitable gonadotoxic treatment for specific pathologic states and social preferences. While conventional vitrification (C-VIT) has improved the success rate of OC, challenges of possible toxicities of high-concentration cryoprotective agents and osmotic stress persist. To overcome these challenges, we evaluated the ultra-fast vitrification (UF-VIT) method, which reduces the equilibration solution stage exposure time compared to C-VIT by observing mouse oocyte intracellular organelles and embryonic development. Consequently, compared to fresh mouse oocytes, UF-VIT presented significant differences only in endoplasmic reticulum (ER) intensity and mitochondrial (MT) distribution. Meanwhile, C-VIT showed substantial differences in the survival rate, key ER and MT parameters, and embryonic development rate. UF-VIT exhibited considerably fewer negative effects on key MT parameters and resulted in a notably higher blastocyst formation rate than C-VIT. Meiotic spindle (spindle and chromosomes) morphology showed no significant changes between the groups during vitrification/warming (VW), suggesting that VW did not negatively affect the meiotic spindle of the oocytes. In conclusion, UF-VIT seems more effective in OC owing to efficient cytoplasmic water molecule extraction, osmotic stress reduction, and minimization of cell contraction and expansion amplitude, thus compensating for the drawbacks of C-VIT.

Risk factors related to the recurrence of endometrioma in patients with long-term postoperative medical therapy.

OBJECTIVES: The purpose of this study was to identify clinical risk factors for the recurrence of ovarian endometrioma after ovarian cystectomy in Korean women with long-term postoperative medical therapy. MATERIAL AND METHODS: A total of 134 patients who were surgically treated for endometriotic cysts at Pusan National University Hospital were included in this retrospective study. All patients received long-term postoperative medical treatment for at least 12 months after the first-line conservative surgery. Several epidemiologic variables were analyzed as possible risk factors for recurrence. Endometrioma recurrence was considered when a cystic mass was observed on transvaginal or transrectal sonography. Statistical analysis was performed using independent t-tests for parametric continuous variables. RESULTS: The mean follow-up period for the 134 patients was 56.5 ± 14.3 months (range, 36-120 months) and the mean duration of the medical therapy was 17.9 ± 17.3 months (range, 12-120 months). The overall recurrence rate was 35/134 (26.12%). Our univariate analysis showed statistically significant differences between the recurrent and non-recurrent groups in terms of weight (P = 0.013), body mass index (P = 0.007), age at the time of surgery (P = 0.013), the diameter of the largest cyst (P = 0.001), the presence of dysmenorrhea (P < 0.0001), and postoperative pregnancy (P = 0.016). Multivariate analysis showed that body mass index (OR 1.153, 95% CI 1.003-1.326, P = 0.046), age at the time of surgery (OR 0.924, 95% CI 0.860-0.992, P = 0.029), and presence of dysmenorrhea (OR 12.226, 95% CI 3.543-42.188, P < 0.0001) were significantly correlated with the recurrence of endometrioma. CONCLUSIONS: We found that patients with dysmenorrhea after surgery, and a younger age of the patient at the time of surgery were the highest risk factors associated with the recurrence of endometrioma, despite long-term postoperative medication.

Quantitative Assessment of Endometrial Volume and Uterine Vascularity and Pregnancy Outcome in Frozen-Thawed Embryo Transfer Cycles.

OBJECTIVE: To investigate the usefulness of the endometrial volume and vascular indices in the endometrial region as an effective predictor for pregnancy outcome in frozen-thawed embryo transfer (FET). STUDY DESIGN: We evaluated 131 embryo transfer cycles in 73 infertile women. After controlled ovarian stimulation all embryos were cultured to blastocyst stage, and the blastocysts with good quality were vitrified for elective FET. On the day of FET, endometrial thickness, endometrial volume, pulsatility index (PI), and resistance index of uterine artery and endometrial-subendometrial vessels (ESVs) with zonal discrimination were evaluated by transvaginal ultrasonography in each patient. These variables were compared between pregnant and nonpregnant cycles. RESULTS: The endometrial volume was significantly higher in the pregnant group (2.32 ± 0.86, 1.96 ± 0.62 mL, p = 0.007). Also, PI of ESVs was significantly higher in the pregnant cycle (2.58 ± 1.32 and 2.05 ± 1.08, p = 0.016). The other variables were not different between the 2 groups. CONCLUSION: This study suggested that endometrial volume and the vascular indices measured in endometrial region are useful predictors of pregnancy outcome.

Gut microbiota-generated metabolites: missing puzzles to hosts' health, diseases, and aging.

The gut microbiota, an intricate community of bacteria residing in the gastrointestinal system, assumes a pivotal role in various physiological processes. Beyond its function in food breakdown and nutrient absorption, gut microbiota exerts a profound influence on immune and metabolic modulation by producing diverse gut microbiota-generated metabolites (GMGMs). These small molecules hold potential to impact host health via multiple pathways, which exhibit remarkable diversity, and have gained increasing attention in recent studies. Here, we elucidate the intricate implications and significant impacts of four specific metabolites, Urolithin A (UA), equol, Trimethylamine N-oxide (TMAO), and imidazole propionate, in shaping human health. Meanwhile, we also look into the advanced research on GMGMs, which demonstrate promising curative effects and hold great potential for further clinical therapies. Notably, the emergence of positive outcomes from clinical trials involving GMGMs, typified by UA, emphasizes their promising prospects in the pursuit of improved health and longevity. Collectively, the multifaceted impacts of GMGMs present intriguing avenues for future research and therapeutic interventions. [BMB Reports 2024; 57(5): 207-215].

Frankincense ameliorates endometriosis via inducing apoptosis and reducing adhesion.

Background: Frankincense, a resin derived from trees of the Boswellia genus, has been used as an incense and a type of herbal medicine for treating inflammatory diseases such arthritis, chronic bowel illness, and asthma. While endometriosis is a well-known inflammatory gynecological illness caused by the ectopic attachment and development of uterine tissue over the menstrual cycle, the impact of frankincense on this illness is poorly understood. The purpose of this study was to explore the effects of frankincense on endometriosis. Methods: We used a network pharmacological assessment, in vitro and in vivo investigations with a human endometriotic cell line as well as a syngeneic uterine transfer mouse model. High-performance liquid chromatographic analysis was used to compare water-extracted frankincense (Fr) to its reference compounds and validate the sample. Results: A network pharmacological analysis suggested a positive effect of Fr on endometriosis. Fr relieved endometriosis by reducing ectopic endometrial adherence and development, according to both in vivo and in vitro models. We suggested that the ER stress/p53-apoptosis and chemokine-migration/adhesion pathways underlie Fr's anti-endometriotic action using RNA sequencing and bioinformatic analysis. Conclusion: This study revealed the potential effect of Fr on endometriosis using an experimental investigation. Fr may have the potential to be an effective and safe treatment for endometriosis.

Effects of 17ß-estradiol on the release of monocyte chemotactic protein-1 and MAPK activity in monocytes stimulated with peritoneal fluid from endometriosis patients.

AIM: Hormones and inflammation have been implicated in the pathological process of endometriosis; therefore, we investigated the combined effects of 17ß-estradiol (E2) and peritoneal fluid obtained from patients with endometriosis (ePF) or a control peritoneal fluid (cPF) obtained from patients without endometriosis on the release of monocyte chemotactic protein-1 (MCP-1) by monocytes and the role of signaling pathways. METHODS: Monocytes were cultured with ePF and cPF in the presence of E2; the MCP-1 levels in the supernatants were then measured by ELISA. In addition, mitogen activated protein kinase (MAPK) activation was measured by Western blotting of phosphorylated proteins. RESULTS: E2 down-regulated MCP-1 release by lipopolysaccharide- or cPF-treated monocytes, but failed to suppress its release by ePF-treated monocytes. The release of MCP-1 by ePF- and cPF-treated monocytes was efficiently abrogated by p38 mitogen activated protein kinase (MAPK) inhibitors; however, the MCP-1 release by cPF-treated monocytes, but not by ePF-treated monocytes, was blocked by a MAPK kinase inhibitor. In addition, ePF and cPF induced the phosphorylation of extracellular stress regulated kinase (ERK)1/2, p38 MAPK and c-Jun N-terminal kinase (JNK). E2 decreased the phosphorylation of p38 MAPK, but not ERK1/2 in ePF-treated monocytes; however, E2 decreased the phosphorylation of p38 MAPK, ERK1/2 and JNK in cPF-treated monocytes. CONCLUSIONS: The ability of E2 to modulate MCP-1 production is impaired in ePF-treated monocytes, which may be related to regulation of MAPK activity. These findings suggest that the failure of E2 to suppress ePF-treated production of MCP-1 may be involved in the pathogenesis of endometriosis.

Decreased expressions of vascular endothelial growth factor and visfatin in the placental bed of pregnancies complicated by preeclampsia.

AIM: The aim of the present study was to examine the expression of vascular endothelial growth factor (VEGF) and visfatin in the third trimester placental bed of pregnancies with and without preeclampsia (PE). MATERIAL AND METHODS: The study group consisted of placental bed biopsy tissues obtained from pregnancies with (n = 20) and without (n = 20) PE. The normotensive controls without PE were matched for gestational age at delivery with patients with PE. The expression of VEGF and visfatin in the placental bed tissues were evaluated using reverse transcriptase-polymerase chain reaction (RT-PCR), real-time polymerase chain reaction (PCR), immunohistochemistry and Western blot. RESULTS: There was no statistical difference between the PE group and the normotensive control group in age and body mass index (BMI). The expression of VEGF and visfatin was significantly decreased in the PE group compared with the normotensive control group (P < 0.05). CONCLUSION: This study showed decreased expressions of VEGF and visfatin in the third trimester placental bed of pregnancies with PE compared with the normotensive controls. This result suggests that decreased expression of these angiogenic factors in placental bed may be associated with the pathogenesis of PE.

The effect of long zona dissection using ICSI pipettes for mechanical assisted hatching in vitrified-thawed blastocyst transfers.

OBJECTIVE: To investigate the effect of long zona dissection (LZD) compared with partial zona dissection (PZD) using ICSI pipettes for mechanical assisted hatching (AH) in vitrified-thawed blastocyst transfers. DESIGN: Prospective study. SETTING: University IVF clinic. PATIENT(S): A total of 120 women ≦ 38 years old undergone vitrified-thawed blastocyst transfers with LZD or PZD. INTERVENTION(S): The culture of all pronucleate embryos to the blastocyst stage and the selection of blastocysts ≧ grade 3BB (Gardner and Schoolcraft score), followed by vitrified-thawed blastocyst transfers with LZD (n = 60) or with PZD (n = 60) MAIN OUTCOME MEASURE(S): Complete hatching rates, implantation rates, pregnancy rates. RESULT(S): At 5 h after thawing, complete hatching rates of blastocysts were significantly higher in LZD group compared with PZD group, 52.4 % vs. 31.8 % (P = 0.001). Implantation and clinical pregnancy rates were significantly higher in LZD group compared with PZD group, 40.9 % vs. 25.7 % and 63.0 % vs. 40.0 %, respectively (P = 0.010, P = 0.011). CONCLUSION(S): LZD using ICSI pipettes for mechanical AH improves significantly complete hatching, implantation and pregnancy rates in vitrified-thawed blastocyst transfers.

Identification and analysis of novel endometriosis biomarkers via integrative bioinformatics.

Endometriosis is a gynecological disease prevalent in women of reproductive age, and it is characterized by the ectopic presence and growth of the eutopic endometrium. The pathophysiology and diagnostic biomarkers of endometriosis have not yet been comprehensively determined. To discover molecular markers and pathways underlying the pathogenesis of endometriosis, we identified differentially expressed genes (DEGs) in three Gene Expression Omnibus microarray datasets (GSE11691, GSE23339, and GSE7305) and performed gene set enrichment analysis (GSEA) and protein-protein interaction (PPI) network analyses. We also validated the identified genes via immunohistochemical analysis of tissues obtained from patients with endometriosis or healthy volunteers. A total of 118 DEGs (79 upregulated and 39 downregulated) were detected in each dataset with a lower (fold change) FC cutoff (log2|FC| > 1), and 17 DEGs (11 upregulated and six downregulated) with a higher FC cutoff (log2|FC| > 2). KEGG and GO functional analyses revealed enrichment of signaling pathways associated with inflammation, complement activation, cell adhesion, and extracellular matrix in endometriotic tissues. Upregulation of seven genes (C7, CFH, FZD7, LY96, PDLIM3, PTGIS, and WISP2) out of 17 was validated via comparison with external gene sets, and protein expression of four genes (LY96, PDLIM3, PTGIS, and WISP2) was further analyzed by immunohistochemistry and western blot analysis. Based on these results, we suggest that TLR4/NF-κB and Wnt/frizzled signaling pathways, as well as estrogen receptors, regulate the progression of endometriosis. These pathways may be therapeutic and diagnostic targets for endometriosis.

Effects of peritoneal fluid from endometriosis patients on the release of monocyte-specific chemokines by leukocytes.

PURPOSE: Chemokines have been implicated in the pathological process of endometriosis. We compared the effects of peritoneal fluid obtained from patients with endometriosis (ePF) and controls without endometriosis (cPF) on the release of monocyte-specific CC chemokines such as monocyte chemotactic protein-1 (MCP-1), regulated upon activation normal T cell expressed and secreted (RANTES), and macrophage inflammatory protein-1α (MIP-1α) by neutrophils, monocytes, and T cells. Moreover, we evaluated the correlation between the levels of chemokines in ePF and their release by these cells. METHODS: Cells were obtained from healthy young volunteers and cultured with ePF (n = 12) or cPF (n = 8). The chemokine levels in the ePF and the supernatants of cultured cells with ePF were then measured by ELISA. RESULTS: There was a positive correlation between the levels of MCP-1 and MIP-1α in ePF. The addition of ePF to the cell cultures failed to increase the release of MCP-1, RANTES, and MIP-1α when compared to cPF, but the levels of RANTES in ePF were positively correlated with the release of RANTES by ePF-treated monocytes and T cells. Moreover, there was a positive correlation between the levels of RANTES and MIP-1α released by neutrophils and between the levels of MCP-1 and MIP-1α released by T cells. Finally, the levels of RANTES released by monocyte-derived macrophages and monocytes cultured with ePF were positively correlated. CONCLUSIONS: These findings suggest that monocytes, neutrophils, and T cells release differential levels of MCP-1, RANTES, and MIP-1α in response to stimulation with ePF.

Levonorgestrel-Releasing Intrauterine System Use in Perimenopausal Women.

The levonorgestrel-releasing intrauterine system (LNG-IUS) is a highly effective contraceptive method that has several noncontraceptive benefits. It has been used in various gynecological conditions, such as heavy menstrual bleeding, dysmenorrhea, and endometrial hyperplasia. During the perimenopausal period, hormonal fluctuations occur, and there is a high tendency for the development of several benign gynecologic diseases. Therefore, the use of LNG-IUS in perimenopausal women might be more beneficial than in women belonging to other age groups. Moreover, the insertion of LNG-IUS during the perimenopausal period could confer endometrial protection during estrogen replacement therapy. In this review, we discuss the use of LNG-IUS in perimenopausal women.

Autophagy as a Therapeutic Target of Natural Products Enhancing Embryo Implantation.

Infertility is an emerging health issue worldwide, and female infertility is intimately associated with embryo implantation failure. Embryo implantation is an essential process during the initiation of prenatal development. Recent studies have strongly suggested that autophagy in the endometrium is the most important factor for successful embryo implantation. In addition, several studies have reported the effects of various natural products on infertility improvement via the regulation of embryo implantation, embryo quality, and endometrial receptivity. However, it is unclear whether natural products can improve embryo implantation ability by regulating endometrial autophagy. Therefore, we performed a literature review of studies on endometrial autophagy, embryo implantation, natural products, and female infertility. Based on the information from these studies, this review suggests a new treatment strategy for female infertility by proposing natural products that have been proven to be safe and effective as endometrial autophagy regulators; additionally, we provide a comprehensive understanding of the relationship between the regulation of endometrial autophagy by natural products and female infertility, with an emphasis on embryo implantation.

Paeoniflorin Enhances Endometrial Receptivity through Leukemia Inhibitory Factor.

Despite advances in assisted reproductive technology, treatment for deficient endometrial receptivity is a major clinical unmet need. In our previous study, the water extract of Paeonia lactiflora Pall. enhanced endometrial receptivity in vitro and in vivo via induction of leukemia inhibitory factor (LIF), an interleukin (IL)-6 family cytokine. In the present study, we found that paeoniflorin, a monoterpene glycoside, is the major active compound of P. lactiflora. Paeoniflorin significantly improved the embryo implantation rate in a murine model of mifepristone (RU486)-induced implantation failure. In addition, paeoniflorin increased the adhesion of human trophectoderm-derived JAr cells to endometrial Ishikawa cells through the expression of LIF in vitro. Moreover, using the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) database of the human endometrium, we confirmed that LIF signaling is a key regulator for improving human endometrial receptivity. Therefore, these results suggest that paeoniflorin might be a potent drug candidate for the treatment of endometrial implantation failure by enhancing endometrial receptivity.

Estrogen administration during superovulation increases oocyte quality and expressions of vascular endothelial growth factor and nitric oxide synthase in the ovary.

AIMS: This study investigated whether estrogen administration during superovulation enhances oocyte quality using a mice model. We also investigated whether this estrogen treatment regulates the expressions of angiogenic factors, such as vascular endothelial growth factor (VEGF) and endothelial nitric oxide synthase (eNOS), in the ovary. METHOD: Female mice were co-injected with various doses of estrogen (1 microM, 10 microM and 100 microM) and pregnant mare serum gonadotrophin during superovulation, followed by human chorionic gonadotrophin injection 48 hours later. Then they were mated with individual males. After 18 hours, zygotes were flushed and cultured to blastocyst. The expression of VEGF and eNOS in the ovary was examined using Western blot and immunohistochemistry. The control group was superovulated without estrogen. RESULTS: Both numbers of ovulated zygotes and the rate of embryo development to blastocyst were significantly increased in the 1-microM estrogen dose compared to the control group. VEGF and eNOS expressions were stimulated by estrogen treatment. In particular, VEGF expression was significantly increased at 1-microM estrogen concentration, whereas, eNOS expression was significantly increased in all estrogen concentrations compared to controls. CONCLUSIONS: The study showed that estrogen co-injection during superovulation increased the ovarian response, embryo developmental competence and expressions of VEGF and eNOS in the ovary.

The relationship of ovarian endometrioma and its size to the preoperative serum anti-Mullerian hormone level.

OBJECTIVES: The aim of this study is to evaluate the impact of ovarian endometrioma according to its size on the serum anti-Mullerian hormone (AMH) levels compared to that of other benign ovarian cysts. MATERIAL AND METHODS: The current study retrospectively evaluated preoperative serum AMH level and its association to presenting ovarian cyst size which were measured in clinical setting. Women with surgically diagnosed endometrioma or other benign ovarian cysts were included. All patients underwent transvaginal or transrectal ultrasonography to determine the size of the ovarian cysts. Preoperative serum AMH level was checked and evaluated according to histologic type of the cyst, which were endometrioma or other benign ovarian cysts, respectively. Both groups were classified into ≤ 4 cm, > 4 cm and ≤ 8 cm, > 8 cm and ≤ 12 cm, > 12 cm according to the diameter of cyst and analyzed the difference of mean AMH levels in both groups. RESULTS: There was no significant difference in preoperative serum AMH level between the two groups (3.36 ± 2.3 versus 3.76 ± 2.64, p = 0.331). The difference of preoperative AMH levels according to categorized cyst size also was not statistically significant in both groups. CONCLUSIONS: Preoperative serum AMH levels were not statistically different between endometrioma and other benign ovarian cyst groups and were not related to the size of endometrioma.

The Efficacy of Body Mass Index and Total Body Fat Percent in Diagnosis Obesity according to Menopausal Status.

OBJECTIVES: Body mass index (BMI) is commonly used in epidemiological study or clinical center. However, it is not exactly correlated with body fat composition and does not reflect sex, age, or race. The aim of this article is to evaluate the validity of BMI standards relative to total body fat (TBF) and to estimate new BMI criteria that correspond to TBF for obesity, especially for Asian postmenopausal women. METHODS: A total 3,936 patients were included in this cross-sectional study, including 1,565 premenopausal and 2,371 postmenopausal women. At the time of visit, demographic data were collected. We demonstrated the validity of BMI cut-point of 25 kg/m2 by using area under the curve (AUC), and presented the empirical optimal BMI cut-point by using Youden's index and overall accuracy in both premenopausal and postmenopausal women. RESULTS: BMI-defined obesity (≥ 25 kg/m2) represents high AUC values (> 0.9) for each TBF. In premenopausal women, TBF ≥ 38% and corresponding BMI value was 29.45 kg/m2 indicated the highest both Youden's index and overall accuracy. In comparison, postmenopausal women who were TBF ≥ 38% showed the highest Youden's index and overall accuracy, and corresponding BMI value was 26.45 kg/m2. CONCLUSIONS: We proposed new BMI criteria for obesity by using TBF reference. With application of bioelectrical impedance analysis, the diagnosis of obesity using BMI criteria may differ between premenopausal and postmenopausal women.

Amniotic fluid index, single deepest pocket and transvaginal cervical length: Parameter of predictive delivery latency in preterm premature rupture of membranes.

OBJECTIVE: Prediction of delivery latency complicated with preterm premature rupture of membrane (PPROM) is crucial for reducing maternal and neonatal complications. Therefore, we investigated the correlations between latency period and cut-off values of ultrasonographic parameters, ultimately predicting delivery latency. MATERIALS AND METHODS: The retrospective study was performed on 121 PPROM patients enrolled between March 2010 and July 2015. Parameters including amniotic fluid index (AFI), single deepest pocket (SDP) and transvaginal cervical length (TVCL) were measured in 99 singleton pregnancies with PPROM. Latency was defined as the period from sonographic measurements to delivery day. The parameters were analyzed independently by Wilcoxon rank sum test and Fisher's exact test. Cut-off values were determined using a receiver operating characteristic (ROC) curve. RESULTS: In delivery latency within 3 days, AFI and SDP were decreased with significantly shorter TVCL. AFI and SDP had the highest sensitivity (82.2%) and SDP combined with TVCL showed the highest specificity (75.9%) in area under curve (AUC) value. The predicted median latency period was less than 2 days within the cutoff value of parameter (AFI ≤ 7.72, SDP ≤ 3.2 and TVCL ≤ 1.69). CONCLUSION: AFI and SDP combined with TVCL could be useful predictive parameters of the latency interval from PPROM to delivery.

Effects of three-area laser-assisted zona thinning in 8-cell human embryos on pregnancy outcomes in vitro fertilization.

OBJECTIVE: This study conducted a preliminary examination of the effects of three-area laser-assisted zona thinning (LAZT) during the cleavage stage of embryo development on the hatching process in human in vitro fertilization-embryo transfer (IVF-ET) with subjects of advanced female age or frozen-thawed (FT) embryos. METHODS: Eight-cell stage embryos were treated with LAZT in three areas of the zona pellucida at 120° intervals. The control group was embryos without LAZT. Of the 72 consecutive fresh cycles and the 28 FT embryo transfer cycles, the patients in 55 fresh cycles and 17 FT cycles declined LAZT, and those cycles were defined as the control group. RESULTS: In the fresh cycles, the pregnancy rates were similar in the LAZT and control groups. However, in the FT cycles, the pregnancy rate was significantly higher in the LAZT group than in the control group (45.5% in the LAZT group vs. 23.5% in the control group, p<0.05). CONCLUSION: These results show that multi-area LAZT resulted in significantly improved pregnancy outcomes in human 8-cell embryos compared to controls.

Leptin, leptin receptors and hypoxia-induced factor-1α expression in the placental bed of patients with and without preeclampsia during pregnancy.

The mechanism underlying the pathogenesis of preeclampsia (PE) has been previously investigated but remains to be elucidated. Among numerous biomarkers that are associated with the pathogenesis of PE, leptin is most frequently investigated. Although studies concerning the association between PE and the expression of leptin in the serum and placenta have been conducted, the results are conflicting and inconsistent. Furthermore, the expression of leptin and its receptors in the placental bed and their association with PE, to the best of our knowledge, has not been previously reported. Therefore, to determine the association between the expression of leptin and its receptor, and pathogenesis and onset period of PE, placental bed tissues were obtained from cesarean section deliveries. The mRNA and protein expression levels of leptin and its receptor were investigated in normal pregnancies (n=18), pregnancies complicated with early­onset PE (n=9) and late­onset PE (n=9) by reverse transcription­quantitative polymerase chain reaction and western blotting, respectively. The results demonstrated that the mRNA and protein expression of leptin in the placental bed was significantly increased in the PE groups compared with normal controls and was associated with the onset period of PE. Furthermore, as evidenced by immunostaining, leptin was upregulated in endothelial cells of the placental bed in the PE groups, with a particularly strong upregulation in activated endothelial cells from patients with early­onset PE. The results of the present study indicate that altered expression of leptin in the placental bed may contribute to the pathogenesis of PE.