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Abstract Background SERPINE2, one of the potent serpins belonging to the plasminogen activator (PA) system, is involved in the tissue remodeling. We previously demonstrated the expression patterns of Serpine2 in the mouse placenta and uterus, indicating that Serpine2 is a major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation. In this study, we further investigated the expression pattern of SERPINE2 in the human placenta and explored possible functional roles of SERPINE2 in regulating trophoblast activity. Methods Placental tissues from various trimesters were collected for real-time reverse-transcription polymerase chain reaction quantification. Immunohistochemical staining was performed in placental tissues to assure localization of SERPINE2. SERPINE2 small interfering (si) RNA was applied to suppress its expression in villous explants and extravillous trophoblast-like 3A cells. Subsequent experiments to evaluate SERPINE2 levels, villous outgrowth, trophoblast invasion, and tube formation were performed. Results SERPINE2 messenger RNA was detected in the human placenta during pregnancy with the highest levels in the third trimester. The SERPINE2 protein was present in villous syncytiotrophoblasts and trophoblasts of chorionic villi for anti-SERPINE2 immunostaining. Extravillous trophoblasts in the chorionic plate and basal plate confronting the invasive face of anchoring villi were also positive. In most decidual cells, SERPINE2 was observed in the cytoplasm. In addition, fibrinoid deposit was weakly immunoreactive. Introduction of SERPINE2 siRNA into villous explants and trophoblast cells led to significantly reduced villous outgrowth, and trophoblastic migration and invasion. Moreover, capillary-like network formation of 3A cells in Matrigel was greatly attenuated by SERPINE2 siRNA and SERPINE2 antiserum. Conclusions These data identify the temporal and spatial SERPINE2 distribution in the human placenta and suggest its possible role in modulating tissue remodeling of extravillous trophoblasts in the placenta during pregnancy.

Abstract Background Serum anti-Müllerian hormone (AMH) had been proposed as a marker of ovarian reserve. The aim of this study was to evaluate the impact of endometrioma and laparoscopic cystectomy on ovarian reserve as measured by serum AMH levels. Methods A total of 1,642 patients were recruited in this retrospective analysis. Control group (group 1) included 1,323 infertility patients without endometrioma. Endometrioma group (group 2) included 141 patients with ovarian endometrioma. Previous cystectomy group (group 3) included 147 patients who underwent unilateral or bilateral laparoscopic cystectomy due to ovarian endometrioma more than 6 months before enrollment. Current cystectomy group (group 4) included 31 patients who underwent cystectomy during study period. Serum anti-müllerian hormone (AMH) levels were measured upon enrollment with all patients. For patients in group 4, AMH levels were measured before and 3 months after cystectomy. Results Mean AMH level of patients in control group was significantly higher than that of endometrioma group or previous cystectomy group in each age subgroup, while the mean serum AMH level of the endometrioma group was also significantly higher than that of the previous cystectomy group in each age subgroup. The mean AMH level was significantly lower in patients with previous bilateral cystectomy compared to that of patients with unilateral cystectomy. The mean serum AMH level was also significantly lower in patients with bilateral endometrioma compared to that of patients with unilateral endometrioma. In group 4, mean AMH level significantly decreased from 3.95 +/- 0.42 preoperation to 2.01 +/- 0.21 ng/ml at 3-month postoperation. Conclusions Both ovarian endometrioma and cystectomy are associated with a significant reduction on ovarian reserve. Bilateral endometrioma exerts a more profound negative impact on ovarian reserve than unilateral endometrioma, regardless of either conservative or surgical intervention.

Abstract Background SERPINE2, also known as protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily. It is one of the potent SERPINs that modulates the activity of plasminogen activators (PAs). PAs and their SERPIN inhibitors, such as SERPINB2 and SERPINE1, were expressed in the human endometrium and were implicated in implantation. However, expression data about SERPINE2 in the human endometrium is still unknown. Thus, we conducted an investigation to reveal the spatiotemporal and cellular expression of SERPINE2 in the human uterus during the menstrual cycle. Methods Seven patients who underwent a hysterectomy and samples of 120 archived patients' endometrial curettage or parts of the uterus that were formalin-fixed and embedded in paraffin. Western blotting was performed to evaluate the specificity and sensitivity of the antibody. Immunohistochemistry was conducted to localize the SERPINE2 expression site. Quantitative analysis was conducted to evaluate expression levels of SERPINE2 in various sub-phases of the menstrual cycle. Results The SERPINE2 protein was primarily detected in the uterine fluid during the mid- and late-secretory phases of the menstrual cycle. It was predominantly expressed in the luminal and glandular epithelium, less in the myometrium, and only dispersedly in certain stromal cells throughout the menstrual cycle. A quantitative analysis of expression levels of SERPINE2 in the glandular epithelium revealed that it was highly expressed in the endometrium during the secretory phase compared to the proliferative phase. Conclusions The SERPINE2 protein is highly expressed in the endometrium during the secretory phase, indicating that it may participate in tissue remodeling involved in implantation.

Abstract Background SERPINE2, also known as glia-derived nexin or protease nexin-1, belongs to the serine protease inhibitor (SERPIN) superfamily. It is one of the potent serpins that modulates the activity of the plasminogen activator (PA) and was implicated in tissue remodeling. In this study, we investigated the expression patterns of SERPINE2 in the mouse placenta and uterus during the estrous cycle, pregnancy, and lactation. Methods SERPINE2 was purified from mouse seminal vesicle secretion using liquid chromatography (LC) and identified by LC/tandem mass spectrometry. The antiserum against the SERPINE2 protein was raised in rabbits. To reveal the uterine and placental expression of SERPINE2, tissues at various stages were collected for real-time PCR quantification, Western blotting, and immunohistochemical staining. Results Serpine2 mRNA was the major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation, although Serpine1 mRNA had higher expression levels than Serpine2 mRNA in the placenta. Plat seemed to be the major PA in the mouse uterus and placenta. Antiserum against the SERPINE2 protein specifically recognized two forms of SERPINE2 and an extra 75-kDa protein, which was probably a complex of SERPINE2 with a certain protease, from among thousands of protein components in the tissue extract as demonstrated by Western blotting. In the uterus, SERPINE2 was primarily localized in luminal and glandular epithelial cells but it also was detected in circular and longitudinal smooth muscle cells during the estrous cycle and lactation. It was prominently expressed in decidual stroma cells, the metrial gland, and endometrial epithelium of the pregnant uterus. In the placenta, SERPINE2 was expressed in trophoblasts of the labyrinth and spongiotrophoblasts. However, its expression was remarkably reduced in giant cells which existed in the giant cell-decidual junction zone. In contrast, prominent expression of SERPINE2 seemed to be detected on clusters of glycogen cells near the junction zone. In addition, yolk sac membranes also showed high expression of SERPINE2. Conclusions These findings indicate that SERPINE2 is a major PA inhibitor in the placenta and uterus during the estrous cycle, pregnancy, and lactation. It may participate in the PA-modulated tissue remodeling process in the mouse placenta and uterus.

Abstract Background To test if early-cleavage was a strong predictor of pregnancy in patients receiving either a GnRH agonist long protocol or a GnRH antagonist protocol for in-vitro fertilization treatment (IVF) and intracytoplasmic sperm injection (ICSI). Methods This retrospective study included 534 patients undergoing a fresh cycle of oocyte retrieval and the day-3 embryo transfer (from 22 to 46 years old). Of the 534 patients treated, 331 received a GnRH agonist long stimulation protocol (GnRH agonist group) for ovarian stimulation and 203 patients received a GnRH antagonist protocol (GnRH antagonist group). In each group, patients who had at least one early-cleavage embryo transferred were designated as the 'early-cleavage' subgroup. Patients who had no early-cleavage embryos transferred were designated as the 'late-cleavage' subgroup. Results The early cleavage rate was significantly lower in the GnRH antagonist group compared with that in the GnRH agonist group (IVF cycles: 34% versus 20%; ICSI cycles: 50% versus 37.8%, respectively, P < 0.0001). In the GnRH agonist group, the pregnancy rates were significantly higher in the early-cleavage subgroup than those in the late-cleavage subgroup (53.7% vs 33.9%, P < 0.0001). In the GnRH antagonist group, the pregnancy rates were not significantly different between the early-cleavage and late-cleavage subgroups (45.9% vs 43.8%, P > 0.05). Conclusion Early cleavage of zygote is not a reliable predictor for embryo implantation potential in using the GnRH antagonist protocol. Furthermore, the implantation rates between the GnRH agonist and GnRH antagonist groups were comparable.