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Frequent consumption of diet drinks was associated with oocyte dysmorphism, decreased embryo quality, and an adverse effect on pregnancy rate. We investigated the harmful effects of aspartame and potential mechanisms through which it increases infertility risk through clinical observations and in vivo and in vitro studies. Methods: We established a cohort of 840 pregnant women and retrospectively determined their time to conceive. We assessed the estrus cycle, the anti-Mullerian hormone level, ovarian oxidative stress, and ovarian mitochondrial function in an animal study. We also evaluated mitochondria function, mitochondrial biogenesis, and progesterone release with in vitro studies. Aspartame consumption was associated with increased infertility risk in the younger women (Odds ratio: 1.79, 95% confidence interval: 1.00, 3.22). The results of the in vivo study revealed that aspartame disrupted the estrus cycle and reduced the anti-Mullerian hormone level. Aspartame treatment also suppressed antioxidative activities and resulted in higher oxidative stress in the ovaries and granulosa cells. This phenomenon is caused by an aspartame-induced decline in mitochondrial function (maximal respiration, spare respiratory capacity, and ATP production capacity) and triggered mitochondrial biogenesis (assessed by examining the energy depletion signaling-related factors sirtuin-1, phosphorylated adenosine monophosphate-activated protein kinase, peroxisome proliferator-activated receptor-gamma coactivator-1α, and nuclear respiratory factor 1 expression levels). Aspartame may alter fertility by reserving fewer follicles in the ovary and disrupting steroidogenesis in granulosa cells. Hence, women preparing for pregnancy are suggested to reduce aspartame consumption and avoid oxidative stressors of the ovaries.

Introduction Although an array of maternal and child-centered risks have been researched, considerably less is known about the effects of paternal influences on child's birth outcomes and early development. This longitudinal study thus examined the effects of paternal influences (parental stress, partner support, childcare and nursing, and father–child interaction) from early pregnancy to 2 years postpartum on pregnancy outcomes and toddlerhood development, with a simultaneous consideration of maternal depression. Methods Pregnant women together with their partners were recruited from 2011 to 2016 at five selected hospitals in Taipei, Taiwan. In total, 440 families completed seven assessments from early pregnancy to 2 years postpartum. Self-reported data were analyzed using logistic regression and generalized estimating equation models. Results The increment in parental stress from early to late pregnancy was independently and significantly associated with higher risks of low birthweight (adjusted odds ratio [aOR] = 5.3, 95% confidence interval [CI] = 1.0–27.7). In the postpartum years, paternal poorer childcare and nursing (aOR = 1.7, 95% CI = 1.0–3.0) and father–child interaction (aOR = 1.8, 95% CI = 1.2–2.9) were significantly associated with increased risks of child's suspected developmental delay up to 2 years postpartum, particularly among children of nondepressed mothers’ children. Limitations Selecting both parents in metropolitan areas with higher socioeconomic status may compromise the generalizability of the study. Conclusions We suggested the essential role of longitudinal paternal influences from early pregnancy on birth outcomes and child's development during infancy and toddlerhood. Maternal depression remains critical to concern.

To evaluate the effects of an integrated childbirth education intervention on reducing childbirth fear, anxiety, and depression, and improving dispositional mindfulness.A two-arm parallel, single-blind randomised controlled trial.A teaching hospital in Northern Taiwan.Pregnant women ≥ 20 years of age with a singleton pregnancy (12-24 weeks gestation) and their support partners were recruited. All women included in the study had a score of ≥ 7 points on a fear of childbirth visual analogue scale.The intervention group (n = 53) received an 8-week course in a childbirth education programme, which included (1) childbirth education using simulation-based learning that highlighted coping with labour pain and (2) instruction in mindfulness breathing, body scans, stretching, sitting meditation, and mindfulness walking. Support partners were invited to participate. The control group (n = 53) received the usual standard prenatal care.The primary outcome of fear of childbirth was assessed using the Wijma Delivery Expectancy/Experience Questionnaire. The secondary outcomes of anxiety, depression, and dispositional mindfulness were assessed with the Edinburgh Postpartum Depression Scale, State-Trait Anxiety Inventory Scale, and the Mindful Attention Awareness Scale, respectively. Repeated data were collected at baseline, 36 weeks gestation, and 1 week postpartum.Ninety-one mothers completed the study, with a mean age of 33.9 years (SD = 4.4), and most were primipara (n = 83). The baseline measurements did not differ between the groups. Compared with the control group, there were significant differences in all measures from baseline for the intervention group: the scores were significantly lower for fear of childbirth (mean difference (MD) =-14.8 ∼ -23.7, p.01), symptoms of anxiety (MD =-7.4 ∼ -6.4, p.01), and depression (MD =-3.7 ∼ -3.5, p.01); the levels of dispositional mindfulness were significantly higher (MD =4.9 ∼ 5.7, p.01) at 36 weeks gestation, and 1 week postpartum.The 8-week integrated childbirth education intervention was effective in reducing the fear of childbirth in pregnant women. The mindfulness techniques were easily learnt and applied by the participants. Using these techniques during pregnancy and labour enhanced participants' mental health and coping. The integrated childbirth education which includes pregnant women and their support partners could be easily taught by midwives in other contexts.

Background Mental distress patterns in first-time or experienced mothers and fathers during the transition to parenthood have been inadequately studied. This longitudinal study thus investigated changes in depression, anxiety, and health-related quality of life in both parents from early pregnancy until 1 year postpartum. Parity effects were specifically examined. Methods In total, 531 pregnant women and their partners were recruited in Taiwan during early prenatal visits from 2011 to 2015, with five follow-ups from midpregnancy to 1 year postpartum. The participants’ self-reported data were collected and analyzed using generalized estimating equation models. Results Maternal mental distress levels were highest at 1 month postpartum. During postpartum periods, depression scores increased and social relations domain scores decreased in men. Although mental distress levels were higher in mothers than in fathers, parity evidently affected men. Experienced fathers were independently associated with a 70% higher risk of perinatal depression (odds ratio [OR] = 1.7, 95% confidence interval [CI] = 1.2–2.3) and anxiety (OR = 1.7, 95% CI = 1.2–2.6). Experienced fathers also exhibited significantly lower perinatal scores than first-time fathers in the physical health and social relations domains. Limitations Selection of both parents in metropolitan areas with higher socioeconomic status may restrict the generalizability of our findings. Conclusions In addition to maternal mental distress during the transition to parenthood, we highlighted experienced fathers’ psychological difficulties throughout perinatal periods. Such trends may indicate unsatisfied needs and could guide timely intervention to prevent adverse consequences.

Low self-efficacy affects new mothers' ability to sustain breastfeeding. Interventions that increase self-efficacy could improve sustained breastfeeding.To develop an integrated breastfeeding education program based on self-efficacy theory, and evaluate the effect of the intervention on first-time mothers' breastfeeding self-efficacy and attitudes.A single-blind, randomised controlled trial.A prenatal clinic of a teaching hospital.First-time mothers with a singleton pregnancy (12-32 weeks' gestation) and their support partners were selected by convenience sampling (N = 104) and allocated by block-randomization to an intervention or control group.A 3-week breastfeeding intervention program was developed based on self-efficacy theory. The intervention group received the breastfeeding program; the control group received standard care. Data between groups were compared for scores on breastfeeding self-efficacy, infant feeding attitude, and breastfeeding practice, which were assessed using the Breastfeeding Self-Efficacy Scale-Short Form, the Iowa Infant Feeding Attitude Scale, and a structured questionnaire, respectively. Repeated data measurements were collected at baseline, 36-weeks' gestation, and postpartum at 1-week, and 1-, 3-, and 6-months.Ninety-three mothers completed the study. Data were compared for the self-efficacy intervention group (n = 50) with the control group (n = 43). Baseline measures did not differ between groups. The intervention group had significantly higher breastfeeding self-efficacy at 36 weeks' gestation (mean difference (MD): 7.3, p.001), and postpartum at 1-week (p.001), 1-month (p.001) and 3-months (p.01) with MD: 6.7, 7.9, and 8.1, respectively; differences in scores from baseline were also significantly greater from 36 weeks' gestation to 3-months (MD from 9.1~9.9, p.001) and 6-months postpartum (MD: 7.0, p.05). Infant feeding attitude scores significantly improved from 36 weeks' gestation to 6-months postpartum for the intervention group (MD from 3.5~7.4, p.05). Rates for exclusive and predominant breastfeeding postpartum were significantly higher for the intervention group vs control (p.02) at 1-week (98% vs. 86%), 1-month (100% vs. 90.7%), and 3-months (94% vs. 76.7%). Odds ratio (OR) postpartum for exclusive and predominant breastfeeding was greater for the intervention group at 3-months (OR = 4.7, 95% Confidence interval (CI), 1.2 -18.6; p = .05) and for exclusive breastfeeding at 6-months (OR: 2.82, 95% CI 1.0-8.1; p = .05).The breastfeeding education intervention improved breastfeeding self-efficacy, infant feeding attitudes, and exclusive breastfeeding rates. The breastfeeding education program could be effective for sustaining breastfeeding in new mothers.Registered with www.clinicaltrials.gov (NCT03807726).

Objective To determine whether Cesarean scar defect (CSD) parameters assessed by transvaginal sonography (TVS) might affect the outcome of early termination of pregnancy (TOP) with mifepristone–misoprostol. Methods This was a retrospective review of 183 women with previous Cesarean delivery who received oral mifepristone and misoprostol for TOP. A successful TOP was defined by the absence of an intrauterine gestational sac, with no need for surgical intervention. CSD was diagnosed by TVS in the presence of a hypoechogenic indentation within the myometrium of the lower uterine segment at the site of a previous Cesarean incision. Women were analyzed in three subgroups according to size of defect (ratio of residual myometrial thickness over the defect to adjacent myometrial thickness 70%). Results Of the 183 women, 43 (23.5%) had failure of TOP. Fifty-nine (32.2%) had CSD detectable at TVS, and these women had a higher failure rate of TOP than did those without CSD (38.9% vs 16.1%; P = 0.001). CSD was associated significantly with failure of TOP (odds ratio, 3.32 (95% CI, 1.64–6.75)). The TOP failure rates in relation to defect size in the myometrial thickness ratio 70% subgroups were 57.1%, 25.0% and 18.2%, respectively. There was a linear trend in failure rate across these ratios (Cochran–Armitage trend test; P = 0.015). Conclusions Women with CSD are at increased risk of failed TOP. Women with a defect in which the residual myometrial thickness was < 30% of the adjacent myometrial thickness tended to have a greater chance of failed TOP. CSD detected at TVS is of clinical relevance in counseling women with a history of Cesarean delivery who are considering TOP. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Summary Hypoxia cooperates with endocrine signaling to maintain the symmetric self-renewal proliferation and migration of embryonic germline stem cells (GSCs). However, the lack of an appropriate in vitro cell model has dramatically hindered the understanding of the mechanism underlying this cooperation. Here, using a serum-free system, we demonstrated that hypoxia significantly induced the GSC mesenchymal transition, increased the expression levels of the pluripotent transcription factor OCT4 and migration-associated proteins (SDF-1, CXCR4, IGF-1, and IGF-1R), and activated the cellular expression and translocalization of the CXCR4-downstream proteins ARP3/pFAK. The underlying mechanism involved significant IGF-1/IGF-1R activation of OCT4/CXCR4 expression through HIF-2α regulation. Picropodophyllin-induced inhibition of IGF-1R phosphorylation significantly suppressed hypoxia-induced SDF-1/CXCR4 expression and cell migration. Furthermore, transactivation between IGF-1R and CXCR4 was involved. In summary, we demonstrated that niche hypoxia synergistically cooperates with its associated IGF-1R signaling to regulate the symmetric division (self-renewal proliferation) and cell migration of alkaline phosphatase-positive GSCs through HIF-2α-OCT4/CXCR4 during embryogenesis., Graphical Abstract, Highlights • Hypoxia regulated AP+GSC self-renewal and cell migration via IGF-1R and CXCR4 • Hypoxia increased IGF1/IGF-1R and SDF-1/CXCR4 to promote AP+GSC migration • Crosstalk of IGF-1/IGF-1R and SDF-1/CXCR4 signaling in AP+GSCs under hypoxia • Inhibition of IGF-1R phosphorylation suppressed hypoxia-induced cell migration, In this article, Huang and colleagues demonstrate that niche hypoxia promotes symmetric self-renewal proliferation and migration of PGC-like CD49f+AP+GSCs through IGF-IR regulation. Using a serum-free culture system, the crosstalk between IGF-1R and CXCR4 signaling was discovered. This work demonstrated that embryonic hypoxia synergistically cooperated with IGF-1R signaling to regulate the symmetric self-renewal and migration of PGC-like GSCs through a HIF-2α–OCT4/CXCR4 loop.

We aimed to define endometrial pattern and endometrial thickness in predicting the outcome of early medical abortion.While blinded to outcomes of abortion, we retrospectively reviewed the ultrasound scan performed 14-21 days after medical abortion. We assessed the endometrial pattern and endometrial thickness. A total of 943 women at or before 56 days of gestation who underwent medical abortions were included. Abortion was induced with mifepristone (600 mg) orally followed 48 h later with oral misoprostol (600 mcg). A successful medical abortion was defined as complete abortion without surgical intervention. Three sonographic patterns (homogenous, heterogeneous and multilayered) were devised to correlate with the outcome.Of the 940 women, 92 (9.8%) had failed medical abortions. Eighty-seven (94.6%) patients with failed treatment outcomes had a heterogeneous pattern, while no patients with failed treatments had a multilayered pattern. Based on multivariable logistic regression, women who had an endometrial thickness in the range of 10-15 or15 mm were more likely to have failed outcomes than those with a thickness10 mm, with ORs of 3.69 (p=.001) and 8.82 (p.001). Compared to those with a homogenous pattern, women with a heterogeneous endometrial pattern were more likely to have failed outcomes (OR 4.5, p=.003). In addition, an endometrial thickness10 mm in combination with a heterogeneous pattern had the highest balanced accuracy in the prediction of failed outcome (81.9%; 95% CI, 77.6-86.3).Women with a multilayered pattern could be reassured that they have successful medical abortion, while those with a heterogeneous pattern and/or endometrium10 mm may need follow-up. Sonographic endometrial pattern and endometrial thickness may serve as objective criteria in the management of early medical abortions.

Objective— Recent clinical evidence has failed to demonstrate the benefits of elevation of serum high-density lipoprotein (HDL), suggesting potential loss of protective effects of HDL at high concentrations. This study aimed to investigate the concentration-related effects of HDL on in vitro and in vivo functions of human endothelial progenitor cells (EPCs) and related angiogenesis. Methods and Results— Early and late outgrowth EPCs were generated from human circulating mononuclear cells. Oxidized low-density lipoprotein reduced viability of late outgrowth EPCs, which was reversed dose dependently by HDL. In the absence of oxidized low-density lipoprotein, HDL at low concentrations (5–50 μg/mL, equal to 0.5–5 mg/dL in human) enhanced EPC tube formation by activating phosphatidylinositol-3 kinase/Akt/endothelial NO synthase pathways. Moderate to high concentrations (400–800 μg/mL) of HDL paradoxically enhanced EPC senescence and impaired tube formation by activating Rho-associated kinase (ROCK) and inhibiting phosphatidylinositol-3 kinase/Akt and p38 mitogen-activated protein kinase pathways. Rho-associated kinase inhibitors, either Y27632 or statins, prevented high HDL–induced EPC senescence and improved in vitro tube formation, as well as in vivo capacity of angiogenesis of EPCs. Conclusion— While protecting EPCs from the injury of oxidized low-density lipoprotein, moderate to high concentrations of HDL paradoxically impaired EPCs and related angiogenesis in the absence of oxidized low-density lipoprotein by activating Rho-associated kinase pathways, providing mechanistic evidence of potential hazard effects of HDL.

Objective: To present molecular cytogenetic characterization of a prenatally detected duplication of 15q26.2 / q26.3 in a fetus with overgrowth. Case Report: A 34-year-old para 0 woman underwent amniocentesis at 18 weeks of gestation because of advanced maternal age. Amniocentesis revealed a derivative chromosome 15, or der(15), with additional material at the end of the long arm of one chromosome 15. Parental karyotypes were normal. Fetal overgrowth was first noted at 21 weeks of gestation. Repeated amniocentesis was performed at 22 weeks of gestation. Array comparative genomic hybridization revealed a 4.71-Mb duplication from 15q26.2 to 15q26.3 encompassing the IGF1R gene. Fluorescence in situ hybridization analysis using the bacterial artificial chromosome clone probes specific for 15q26.2-q26.3 and the subtelomeric region of 15q showed a direct duplication and no terminal deletion in the der(15). Polymorphic DNA marker analysis determined a paternal origin of the duplication of 15q. Level II ultrasound at 23 weeks of gestation revealed a fetal biometry equivalent to 26 weeks. The pregnancy was subsequently terminated, and a 1062-g (>99 th centile) malformed fetus was delivered at 24 weeks of gestation with craniofacial dysmorphism, craniosynostosis, and overgrowth. Conclusion: The present case provides evidence for prenatal overgrowth, craniosynostosis, and characteristic facial dysmorphism in association with a duplication of 15q26.2 / q26.3 and a duplication of the IGF1R gene. Prenatal diagnosis of fetal overgrowth should include a differential diagnosis of the chromosome 15q overgrowth syndrome. Copyright 2011, Taiwan Association of Obstetrics & Gynecology. Published by Elsevier Taiwan LLC. All rights reserved.

Endometriosis is an estrogen-dependent inflammatory disease that affects up to 10% of women of reproductive age and accounts for up to 50% of female infertility cases. It has been highly associated with poorer outcomes of assisted reproductive technology (ART), including decreased oocyte retrieval, lower implantation, and pregnancy rates. A better understanding of the pathogenesis of endometriosis-associated infertility is crucial for improving infertility treatment outcomes. Current theories regarding how endometriosis reduces fertility include anatomical distortion, ovulatory dysfunction, and niche inflammation-associated peritoneal or implantation defects. This review will survey the latest evidence on the role of inflammatory niche in the peritoneal cavity, ovaries, and uterus of endometriosis patients. Nonhormone treatment strategies that target these inflammation processes are also included. Furthermore, mesenchymal stem cell-based therapies are highlighted for potential endometriosis treatment because of their immunomodulatory effects and tropism toward inflamed lesion foci. Potential applications of stem cell therapy in treatment of endometriosis-associated infertility in particular for safety and efficacy are discussed.

BACKGROUND: Precise sperm-oocyte interaction is a critical event for successful fertilization. However, the identity of molecules involved in this process in humans remains largely unknown. This report describes the identification and characterization of a novel cell-surface protein and its potential role in human sperm-oocyte interaction. METHODS AND RESULTS: We previously identified an orphan guanylyl cyclase receptor (mouse GC-G) highly enriched in mouse testis and involved in sperm activation. By using a comparative genomic approach, we found the homologue gene in human (hGC-G) composed of 2I exons, spanning a minimum of 48 kb on chromosome I0q25. Real-time RT-PCR analysis revealed hGC-G mRNA selectively expressed in testis but with low or no expression in all other tissues examined. Compared with mGC-G, the hGC-G transcript contains three I-bp deletions and two in-frame termination codons, which results in a short putative receptor-like polypeptide. Western blot analysis with an anti-hGC-G-specific antibody confirmed the protein expression of hGC-G in human sperm lysate. Flow cytometry and confocal immunofluorescence analysis demonstrated the localization of hGC-G protein on the acrosome cap and equatorial segment of mature human sperm. In addition, an integrin-binding Arg-Gly-Asp (RGD) motif was found in the extracellular domain of hGC-G. Pre-incubation of the hGC-G RGD peptide with zona pellucida-free oocytes greatly decreased the binding of human sperm to hamster oocytes, which suggests a role for hGC-G role in sperm-oocyte interaction. CONCLUSIONS: hGC-G is a novel surface protein on human sperm and potentially mediates sperm-oocyte interaction through its RGD-containing motif.

Several cases in which uteruses have been preserved in women with placenta percreta have been reported. We herein report a 38-year-old woman with a history of previous cesarean section who was admitted with lower abdominal pain and vaginal bleeding at 31 weeks of gestation. An urgent exploratory laparotomy revealed active bleeding from the uterine rupture on the posterior uterine wall. A female infant weighing 1560 g, with Apgar scores of 1, 1, and 3 at 1, 5, and 10 min, respectively, was delivered, and the placenta was removed. We performed bilateral uterine vessel occlusion, followed by wedge resection of the ruptured uterine wall with the aid of an intrauterine muscle injection of 20 IU oxytocin, a local injection of diluted vasopressin (1:60) into the myometrium around and into the rupture site, and an intramuscular injection of 0.2 mg methylergonovine, primary repair of the defect, and an additional 24-h postoperative oxytocin infusion (30 IU in 5% dextrose 500 mL) to preserve the uterus successfully. Although the overall blood loss was 3700 mL, no disseminated intravascular coagulopathy occurred after the patient had received adequate blood transfusion. The postoperative pathological diagnosis was placenta percreta with uterine rupture. The patient and her baby were discharged uneventfully. In some cases of spontaneous uterine rupture secondary to placenta percreta, we can preserve the uterus by performing bilateral uterine vessel occlusion and wedge resection of the ruptured uterine wall.

Reported herein is the case of a 35-year-old multipara woman diagnosed (on sonography) with total placenta previa that had ruptured through the myometrium of the uterus, invading the wall of the urinary bladder. In the 32nd week of gestation the patient underwent an emergency cesarean section due to profuse vaginal bleeding. Due to possible intraoperative massive bleeding during removal of the placenta it was decided to preserve the uterus and placenta temporarily. The patient underwent superselective trans-uterine embolization through the bilateral anterior branches of the hypogastric arteries, using gelfoam cubes and coils. Two days later cesarean hysterectomy was performed, and the placenta was successfully removed from the invaded urinary bladder. The whole procedure went smoothly and the estimated blood loss was only 1300 mL.

Introduction Considerable concern persists on tobacco use during perinatal periods. No study has simultaneously investigated the longitudinal association of paternal smoking with maternal and paternal depressive and anxiety symptoms during perinatal periods. Methods In this prospective study, 533 couples (pregnant women and their husbands) completed 5 self-report instruments from early pregnancy until 6 months postpartum. Generalized estimating equations were used for the analyses. Results We found that fathers who smoked in the mother’s presence had higher depressive (regression coefficient=1.0, 95% confidence interval (CI) 0.3–1.8) and anxiety symptoms (3.0, 95% CI=1.2–4.7) during perinatal periods compared with nonsmoking fathers. Paternal smoking in the mother’s presence also increased maternal disturbances, especially for depression during pregnancy (1.2, 95% CI=0.1–2.3) and anxiety during the postpartum period (3.4, 95% CI=0.6–6.3). No significant association was found between paternal smoking but not in the mother’s presence and maternal emotional disturbances. Paternal smoking but not in the mother’s presence affected only paternal anxiety, especially in the postpartum period (regression coefficient 2.7, 95% CI 0.7–4.7) compared with nonsmokers. Limitations Self-report measures were used. The effects of maternal smoking could not be estimated because of the small sample of pregnant women who disclosed their smoking status. Conclusions These findings imply a necessity to combine strategies for smoking cessation with interventions for affective disturbances in fathers. We also stress the importance of at least restricting the father’s smoking in the presence of the pregnant wife during perinatal periods if smoking cessation is tentatively unattainable.

This study evaluated the effectiveness of cold-gel packing on episiotomy pain among postpartum women who had normal spontaneous deliveries.A quasi-randomised control trial was conducted in a maternity ward of a regional teaching hospital in northern Taiwan. Seventy postpartum women were recruited, choosing to be in either the experimental or control group (35 women per group). Subjects in the experimental group received at least six interventions of cold-gel packing applied to the perineal wound and were provided oral analgesics routinely. The subjects in the control group received oral analgesics routinely.Pain intensity, pain interference on daily activities and satisfaction levels with pain management were assessed using Brief Pain Inventory (BPI) and pain management questionnaire, respectively. The results showed that women in the experimental group reported significantly lower mean pain intensity score, pain interference on daily activities scores at 48 hours post-delivery, and higher level of satisfaction with pain management at 24 and 48 hours post-delivery than the control group after adjusting for demographic and obstetric data.Cold-gel packing on the perineum is a cost-effective, convenient, easy-to-deploy and non-pharmacologic approach to pain reduction, with an overall positive impact on postpartum recovery for parturients.

The physiological changes in endometriosis involving multiple steps of matrix remodeling include abnormal tissue growth, invasion, and adhesion formation. Endometriosis-associated abnormal matrix remodeling is affected by several molecular factors including proteolytic enzymes and their inhibitors, which mediate tissue turnover throughout the reproductive tract to maintain the integrity of the endometrium, and ovarian steroids, which normally regulate reconstruction and breakdown of endometrium in the menstrual cycle. In addition, various growth factors, such as platelet-derived growth factor, transform growth factor β, and epidermal growth factor, direct modulation of growth, activation, and chemotaxis which may facilitate endometrial cell adhesion onto the peritoneal mesothelium during the development of endometriosis. Furthermore, cell adhesion molecules are believed to be critically involved in most cellular-level processes including cellular differentiation, motility, and attachment with the extracellular matrix. The present review focuses on the abnormal matrix remodeling process and its possible regulatory mechanism in association with endometriosis development. As a greater understanding of the cause of endometriosis is achieved, better treatment of the disease and its prevention become possible.

The rearrangement of mitochondrial DNA in luteinized granulosa cells was determined in order to evaluate the fertilization capacity of oocytes and the development of embryos. Multiple deletions of mtDNA were found in luteinized granulosa cells from in vitro fertilization (IVF) patients. The 4977-base pair (bp) deletion was the most frequent deletion found in human granulosa cells. No significant difference was noted between mtDNA deletions of granulosa cells based on the fertilization capacity of oocytes and the development of embryos. To determine the relationship of proportions of mtDNA rearrangements with the aging process, granulosa cells were grouped into three different cohorts according to maternal age: younger than 32 years, between 32 and 37 years, and older than 37 years. No statistical correlation was noted between patient age and the frequency of occurrence of multiple mtDNA deletions. However, an increase in granulosa cell apoptosis was associated with an increase in mtDNA deletions. Accumulation of mtDNA deletions may contribute to mitochondrial dysfunction and impaired ATP production. We concluded that the accumulation of rearranged mtDNA in granulosa cells might not interfere with fertilization of human oocytes and further embryonic development; it was, however, associated with apoptosis processes.

Endometriosis is a benign but aggressive disease. It occurs when shed endometrium from the female reproductive tract grows at a site outside the uterus. The physiological changes in endometriosis-abnormal tissue growth, invasion, and adhesion phenomena-are similar to those seen in tumorous tissues. Although the etiology of endometriosis is not well understood, the disease is widely accepted to result from the ectopic implantation of refluxed menstrual tissues. In addition, immunologic changes, genetic factors, and environmental factors might also affect a woman's susceptibility to develop endometriosis. Thus far, laparoscopic examination is required to confirm the presence of endometriosis; there is no reliable marker for its diagnosis. Many studies are therefore focusing on identifying markers for the diagnosis and follow-up of endometriosis. This chapter provides a systematic review of these studies, including recent findings from our group on the identification of molecules, in serum and/or endometrium, which are associated with the development of endometriosis at different stages. From this research, we hope to be able to suggest how to approach the potential markers. The identification of highly sensitive and specific markers of endometriosis should facilitate the development of accurate and non-invasive techniques for diagnosis and prognosis.

This study investigated the effect of supplementation with chicken extract on plasma and colostrum protein compositions in lactating women. Thirty healthy pregnant women were evenly divided into the control (n = 15) or chicken extract (CE) group (n = 15). The CE group was given one bottle (70 mL/bottle) of chicken extract three times a day to provide 18 g protein from the 37th week pregnancy to 3 days postpartum. All women in the CE group consumed chicken extract at least for 2 weeks (18 +/- 5 days). High protein supplement was restricted in the control group. Blood samples were collected during the 37th week pregnancy and 3-day postpartum, and milk was collected during 3-day postpartum. The results showed that plasma total protein was significantly lower by 14% in the CE group compared with that in the control group during 3-day postpartum. Plasma epidermal growth factor (EGF) significantly elevated by 236% during 3-day postpartum compared with those during the 37th week pregnancy in the CE group. The levels of lactoferrin, EGF, and transforming growth factor-beta2 (TGF-beta2) in colostrum significantly increased by 34%, 62%, and 196%, respectively, in the CE group compared with those in the control group. However, the levels of total protein, casein, lactalbumin, and secretory immunoglobulin A in colostrum did not significantly differ between two groups. Therefore, supplementation with chicken extract increased colostrum levels of lactoferrin, EGF, and TGF-beta2, which are important for the growth and immune functions of the infants, in lactating women.

Objective To identify the impact of the pluripotent transcription factor OCT4 in endometrial cell migration and endometriosis. Design The OCT4 expression and cell migration study. Setting Research institution and reproductive medical clinic. Patient(s) Nine subjects with normal endometrium, 3 subjects with normal myometrium, 36 patients with hyperplastic endometrium, and 58 patients with endometriosis. Intervention(s) The expression of OCT4 messenger RNA in normal endometrium, normal myometrium, hyperplastic endometrium, and ectopic endometriotic tissues was analyzed using reverse transcription and quantitative real-time polymerase chain reaction (PCR). The effect of OCT4 expression on the migration activity of the endometrial cells was examined. Main Outcome Measure(s) Reverse transcription and quantitative real-time PCR, Western blotting, and wound closure and transwell assays. Result(s) The expression of OCT4 and NANOG messenger RNA was significantly higher in ectopic endometriotic tissues, compared with that of the normal endometrium, the normal myometrium, and the hyperplastic endometrium. The level of OCT4 messenger RNA in endometriotic tissues was positively correlated with the expression of genes associated with cell migration. Overexpression of the OCT4 protein in primary human endometriotic stromal cells and human RL95-2 and HEC1A endometrial carcinoma cell lines resulted in decreased levels of E-CADHERIN, the increased expression of the VIMENTIN, TWIST, and SLUG proteins, and an increase in the migration activity of endometrial cells in transwell and wound closure assays. Conclusion(s) The transcription of the OCT4 gene is significantly up-regulated in human ectopic endometriotic tissues. The expression of OCT4 may contribute to the pathology of ectopic endometrial growth by stimulating the migration activity of endometrial cells.

Recently, endometrial hyperplasia was identified as presenting a higher risk for progressing to endometrial carcinoma more readily than adenomyosis. The Lcn-2 gene encodes neutrophil gelatinase-associated lipocalin (NGAL), which promotes cell proliferation and serves as a cancer marker in some cancers. In our current study, we investigated the relationship between the expression of NGAL and that of pathogenic cytokines and cancer-related genes including cyclooxygenase-2 (COX-2), E-cadherin, β-catenin, and vimentin in patients with endometrial disorders. NGAL expression was examined by Western blotting, immunohistochemistry, and reverse-transcription polymerase chain reaction (RT-PCR) in hyperplasia and adenomyosis biopsy samples. Immunohistochemistry demonstrated the occurrence of NGAL in glandular epithelial cells but not in the stromal cells of hyperplasia biopsy samples. NGAL protein and mRNA expression were significantly greater in endometrial hyperplasia than in endometrial adenomyosis. Although our data showed no difference in pathogenic cytokines between patients with endometrial hyperplasia and endometrial adenomyosis, we observed high expression levels of COX-2, β-catenin, vimentin, and E-cadherin in patients with endometrial hyperplasia. NGAL mRNA expression correlated positively with COX-2 and E-cadherin mRNA expression (r = 0.41 and r = 0.57, respectively), but correlated negatively with vimentin and β-catenin mRNA expression (r = −0.42 and r = −0.61, respectively). Our data suggest that NGAL is up-regulated in patients with endometrial hyperplasia to prevent the transition from hyperplasia to carcinoma.

Successful fertilization is tightly regulated by capacitation and decapacitation processes. Without appropriate decapacitation regulation, sperm would undergo a spontaneous acrosome reaction which leads to loss of fertilization ability. Seminal plasma is known to negatively regulate sperm capacitation. However, the suppressive mechanisms still remain unclear. In this study, we demonstrate the decapacitation mechanism of mouse seminal vesicle autoantigen (SVA) might target membrane sphingomyelin (SPM) and regulate plasma membrane Ca 2þ ATPase (PMCA) activity. The SVA was shown to suppress sperm capacitation induced by a broad panel of capacitation factors (bovine serum albumin (BSA), PAF, and cyclodextrin (CD)). Furthermore, SVA significantly decreased [Ca 2þ ]i and NaHCO3-induced [cAMP]i. Cyclic AMP agonists bypassed the SVA’s suppressive ability. Importantly, the SVA may regulate PMCA activity which was evidenced by the fact that the SVA decreased the [Ca 2þ ]i and intracellular pH (pHi) of sperm; meanwhile, a PMCA inhibitor (carboxyeosin) could reverse SVA’s suppression of [Ca 2þ ]i. The potential target of the SVA on membrane SPM/lipid rafts was highlighted by the high binding affinity of SPM‐SVA (with a Kd of � 3 mM) which was close to the IC50 of SVA’s suppressive activity. Additionally, treatment of mink lung epithelial cells with the SVA enhanced plasminogen activator inhibitor (PAI)-1 expression stimulated by tumor growth factor (TGF)-b and CD. These observations supported the membrane lipid-raft targeting of SVA. In summary, in this paper, we demonstrate that the decapacitation mechanism of the SVA might target membrane sphingolipid SPM and regulate PMCA activity to lower [Ca 2þ ]i, thereby decreasing the [cAMP]i level and preventing sperm pre-capacitation. J. Cell. Biochem. 111: 1188‐1198, 2010. 2010 Wiley-Liss, Inc.

Objective The aim of this study was to investigate the in vitro effect of polyphenols in purple sweet potato leaves (PSPLs) on angiogenesis in human umbilical vascular endothelial cells (HUVECs). The ex vivo effect was test in human serum collected from the subjects who consumed 200 g of PSPL in a low polyphenol diet versus a low polyphenol diet. Methods Methanolic extract from PSPLs and human sera from subjects were treated with HUVECs and the effects of cell proliferation, migration, tube formation, and matrix metalloproteinase activity were investigated. Results The PSPL polyphenols at 0.2 to 0.6 mM gallic acid equivalents inhibited proliferation, migration, and tube formation of vascular endothelial growth factor–treated HUVECs. Further, the activity of secreted matrix metalloproteinase-2 was decreased by at least 13.8%. However, 5% PSPL serum increased migration and tube formation of HUVECs by 110% and 56.9%, respectively, compared with serum from subjects on the low polyphenol diet. Further, the activity of matrix metalloproteinase-9 was increased by 128% in the PSPL serum. Conclusion These results suggest that PSPL polyphenols inhibited in vitro angiogenesis, but PSPL constituents might shift serum biochemistries to be more proangiogenic.

To clarify the relationship between mitochondria and embryo development, we collected human unfertilized oocytes, early embryos, and arrested embryos. Unfertilized oocytes and poor-quality embryos were collected, and the ultrastructure of mitochondria was determined by transmission electron micrography. Four criteria for determining the mitochondrial state were mitochondrial morphology, cristae shape, location, and number of mitochondria. In mature oocytes, mitochondria were rounded with arched cristae and a dense matrix and were distributed evenly in the ooplasm. In pronuclear zygotes, the size and shape of mitochondria were similar to those in mature oocytes; however, mitochondria appeared to migrate and concentrate around pronuclei. In this study, 67% of examined unfertilized oocytes had fewer mitochondria in the cytoplasm. A decreased number of mitochondria located near the nucleus was also demonstrated in 60% of arrested embryos. Fewer differentiated cristae were determined in all three arrested blastocyst stages of embryos. The relative expressions of oxidative phosphorylation genes in oocytes and embryos were also determined. These data imply that inadequate redistribution of mitochondria, unsuccessful mitochondrial differentiation, or decreased mitochondrial transcription may result in poor oocyte fertilization and compromised embryo development.

Granulosa cells are known to contribute to maturation of oocytes, and most of the growth factors exert their action via granulosa cells. It has been established that granulosa cell death during follicular atresia and luteolysis results from apoptosis. However, the precise mechanistic pathways of granulosa cell apoptosis have not yet been defined. In this study, we determined the proportions of apoptosis in granulosa cells treated with two kinds of gonadotrophin-releasing hormone agonists (GnRHa): buserelin and leuprorelin depot. The incidences of DNA fragmentation of human granulosa cells treated with buserelin and leuprorelin were 54.33% and 39.02%, respectively. The proportions of apoptotic bodies were 6.04% and 4.29%, respectively. There was a significant difference in the proportions of DNA fragmentation between the two kinds of GnRHa-treated granulosa cells. The apoptosis pathway and associated protein expression in granulosa cells treated with GnRHa were also determined. The Bax molecule, a pro-apoptosis protein, was expressed in granulosa cells undergoing apoptosis. In contrast, Bcl-2, an anti-apoptosis protein, could not be detected in the same group of granulosa cells. The distribution of cytochrome c determined via immunostaining showed a diffuse pattern, which most likely indicated that cytochrome c was translocated from mitochondria into the cytoplasm. Western blotting showed the expressions of caspase-9 and caspase-3 in patients' granulosa cells. The GnRHa effects on granulosa cells indicated a higher incidence of DNA fragmentation and apoptotic bodies in the buserelin-treated than in the leuprorelin depot-treated group. The granulosa cells go through the mitochondria-dependent apoptosis pathway; the indicated pro-apoptosis protein Bax was expressed and induced cytochrome c release from mitochondria, which then activated caspase-9 and caspase-3 until cell death occurred.

BACKGROUND Hatching is an important process for early embryo development, differentiation and implantation. However, little is known about its regulatory mechanisms. By integrating the technologies of RNA amplification and cDNA microarrays, it has become possible to study the gene expression profile at this critical stage. METHODS Pre-hatched and hatched ICR mouse embryos (25 blastocysts in each group were used in the triplicate experiments) were collected for RNA extraction, amplification, and microarray analysis (the mouse cDNA microarray, 6144 genes, including expressed sequence tags). RESULTS According to cDNA microarray data, we have identified 85 genes that were expressed at a higher level in hatched blastocyst than in pre-hatched blastocysts. In this study, 47 hatching-related candidate genes were verified via re-sequencing. Some of these genes have been selected and confirmed by real-time quantitative RT-PCR. These hatching-specific genes were also expressed at a lower level in the delayed growth embryos (morula or blastocyst without hatching at day 6 post hCG). These genes included: cell adhesion and migration molecules [E-cadherin, neuronal cell adhesion molecule (NCAM), lectin, galactose binding, soluble 7 (Lgals7), vanin 3 and biglycan], epigenetic regulators (Dnmt1, and SIN3 yeast homolog A), stress response regulators (heme oxygenase 1) and immunoresponse regulators [interleukin (IL)-2-inducible T-cell kinase, IL-4R, interferon-gamma receptor 2, and neurotrophin]. The immunostaining of E-cadherin and NCAM showed strong and specific localization in hatched blastocyst. CONCLUSIONS This work provides important information for studying the mechanisms of blastocyst hatching and implantation. These hatching-specific genes may have potential as new drug targets for controlling fertility.

In a retrospective university hospital-based study of spontaneously conceived (SC), intrauterine insemination (IUI), and in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) groups, this study finds maternal complications or the neonatal outcomes of twins to be similar between the groups.

Objective To evaluate the transcription and translation ability of mitochondria in terminally differentiated granulosa cells, these cells were incubated with ionic calcium. Design Prospective laboratory research. Setting In vitro fertilization laboratory in a university hospital. Patient(s) Granulosa cells were harvested from 50 female patients undergoing IVF. Intervention(s) Analysis of mitochondrial gene expression by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) and of mitochondrial-encoded proteins by Western blot. Main Outcome Measure(s) Comparison of the RNA expression levels of genes including cytochrome c oxidase subunit I (COX I), adenosine triphosphate synthase 6 (ATPase 6), flavoprotein, and succinate-ubiquinone oxidoreductase, and protein levels of COX I and flavoprotein in different calcium ion treatment groups. Result(s) There were dose-dependent increases in RNA expressions of the four genes analyzed from granulosa cells cultured in a serial concentration of calcium ions. This effect was abolished when cells were preincubated with the extracellular calcium-chelating agent, Ethylene glycol-bis (2-aminoethylether)-N,N,N′,N′-tetraacetic acid (EGTA). The effect of ionic calcium on both the nuclear- and mitochondrial-encoded subunits also was determined. Expression levels of mitochondrial transcription factor A in RNA significantly increased in granulosa cells that were exposed for 24 and 48 hours to 0.5 and 1 μM A23187. Conclusion(s) The present study is the first report to present calcium-dependent increases in the transcription and translation levels of both nuclear-encoded and mitochondrial-encoded mitochondrial respiratory enzyme subunits and also indicates that mitochondrial transcription factor A is involved in mitochondrial biogenesis.

This chapter discusses the role of mitochondria in aging ovary. Human mitochondrial deoxyribonucleic acid (mtDNA) is a maternally inherited double-stranded circular DNA molecule, which is involved in respiratory and oxidative phosphorylation. The human metaphase II oocyte is estimated to have 100,000 mitochondria; however, there is only one mitochondrial genome per organelle. The mtDNA is not protected by histones and is exposed in high concentrations of reactive oxygen species (ROS) and free radicals in the matrix of mitochondria. Thus, the aged oocytes are very vulnerable to oxidative damage and mtDNA mutation. The current study demonstrates that mtDNA 4977bp deletions in compromised human oocytes may range from 56.3% when maternal age is younger than 32 up to 73% when maternal age is older than 37. Most nondisjunction and aneuplodies take place during meiosis, which are highly energy-intensive, and increase exponentially with maternal age. Mitochondria in oocyte and early embryos are structurally immature. They are round or ovoid, with few cristae. They become more elongated with numerous transverse cristae at the blastocyst stage. Nevertheless, after ovulation the multiplication of mitochondria and the replication of mtDNA are not resumed until the gastrulation stage.

Objective To evaluate the relationship between mitochondrial gene expression of oocytes/embryos and their fertilizability in unfertilized oocytes, arrested embryos, and tripronucleate zygotes, because both nuclear and cytoplasmic factors contribute to oocyte activation, fertilization, and subsequent development. Design Prospective laboratory research. Setting In vitro fertilization (IVF) laboratory in a university hospital. Patient(s) Seventy-five unfertilized oocytes, 45 arrested embryos, and 24 tripronucleate (3PN) embryos from 45 female patients undergoing IVF. Intervention(s) Analysis of mitochondrial gene expression by semiquantitative reverse transcription polymerase chain reaction (RT-PCR). Main outcome measure(s) Comparison of the expression levels of mitochondrial genes including ND2, CO I, CO II, ATPase 6, CO III, ND3, ND6, and Cyt b in three groups. Result(s) Significantly decreased transcription levels were expressed in unfertilized oocytes and arrested embryos. The average expression levels of the eight determined genes compared with the control (GAPDH) was 4.4 ± 0.7, 6.4 ± 1.1, and 13.2 ± 1.1 in unfertilized oocytes, arrested embryos, and 3PN embryos, respectively. Significantly decreased expressions of the ATPase 6, CO III, and ND3 genes were detected from samples with 4977-bp common deletion in the mitochondrial DNA (mtDNA) compared with the non-deletion group. Conclusion(s) The present study is the first report to present globally decreased mitochondrial gene expression levels in human compromised oocytes and embryos. These data support the notion that the down-regulation of mitochondrial RNA by defective oxidative phosphorylation genes possibly affects oocyte quality including fertilization and further embryo development.

Objective: To investigate the correlation of blood flow detected by color Doppler sonography in the endometrial-subendometrial unit with pregnancy outcome of IVF-ET treatments. Design: Prospective clinical study. Setting: University setting. Patient(s): Six hundred twenty-three patients selected prospectively on the day of ET. Intervention(s): Transvaginal ultrasound examination was performed before ET. Main Outcome Measure(s): Association between pregnancy outcome and distribution of endometrial-subendometrial blood flow (primary outcome measure) and between pregnancy rate and endometrial measurements as well as uterine arterial blood flow (secondary outcome measures). Result(s): The overall pregnancy rate was 28.4% (177/623) per ET. The pregnancy and implantation rates of patients with the presence of both endometrial and subendometrial flow were 47.8% (64/134) and 24.2% (94/388); for patients with subendometrial flow only, 29.7% (102/343) and 15.8% (153/967); and for patients with no detectable endometrial-subendometrial flow, 7.5% (11/146) and 3.5% (13/376), respectively. The presence of both endometrial and subendometrial blood flow is indicative of good endometrial receptivity, whereas the absence of both represents a poor uterine environment. Nondetectable endometrial-subendometrial flow was associated with women who were older, had a thinner endometrium, and had higher uterine arterial resistance compared with those women who had detectable flow. Conclusion(s): Endometrial-subendometrial blood flow distribution pattern assessed by transvaginal color Doppler before ET is correlated with the implantation and pregnancy rate of IVF treatment.

Objective: To determine the rearrangement of mitochondrial DNA (mtDNA) in unfertilized human oocytes and compromised embryos to evaluate the fertilization capacity of oocytes. Design: Prospective laboratory research. Setting: IVF laboratory in a university hospital. Patient(s): One hundred twenty-four unfertilized oocytes, 98 arrested embryos, and 45 tripronucleate (3PN) embryos from 65 female patients undergoing in vitro fertilization (IVF). Intervention(s): Unfertilized oocytes and poor quality embryos were collected 48 hours after IVF. Main Outcome Measure(s): Comparison of the frequency of mtDNA deletions and fertilization rates of oocytes. Result(s): Multiple deletions of mtDNA were found in unfertilized oocytes and arrested embryos obtained from IVF patients. A 4977-bp deletion was the most frequent deletion in human oocytes and embryos. About 66.1% of the unfertilized oocytes, 34.8% of the arrested or fragmented embryos, and 21.1% of the 3PN embryos harbored the 4977-bp deletion of mtDNA. There was a significant increase in the proportion of deleted mtDNA in unfertilized oocytes. Conclusion(s): Accumulation of mtDNA deletions may contribute to mitochondrial dysfunction and impaired ATP production. We conclude that the accumulation of rearranged mtDNA may interfere with fertilization of human oocytes and further embryonic development.

BACKGROUND: The occurrence of fluid accumulation within the uterine cavity was examined in women undergoing IVF to investigate its correlation with tubal disease and impact on the pregnancy outcome. METHODS: A registry of ultrasound procedures spanning 5 years was retrospectively studied. RESULTS: Thirty five out of 746 (4.7%) IVF cycles were identified as having uterine fluid accumulation, and 15 (2.0%) persisted until the day of embryo transfer. Two of the 20 cycles of women with transient fluid accumulation were pregnant, and none of those with fluid retention on the day of embryo transfer conceived. The pregnancy rate was only 5.7% (2/35) in women with uterine fluid accumulation detected during IVF cycles. In contrast, the pregnancy rate was 27.1% (193/711) among women in whose cycles no fluid accumulation was detected (P 0.0048). Uterine fluid accumulation during IVF cycles was found in 8% (18/225) of women documented with tubal factor compared with 3.3% (17/521) with nontubal factor (P 0.005). CONCLUSIONS: Fluid accumulation within the uterine cavity during the IVF transfer treatment could be observed in patients with both tubal and non-tubal factors; however, it mainly occurred in women with tubal infertility. Although it is not a common complication of IVF cycles, excessive uterine fluid is detrimental to embryo implantation.

Endometriosis is the eutopic and/or ectopic growth of endometrial tissues. High levels of TGF-β in peritoneal fluid and increased expression of OCT4 have been well documented in endometriosis. However, the molecular mechanism between TGF-β and OCT4 expression in endometriosis still remains largely unknown. In this study, we examined the roles of OCT4 in TGF-β-induced endometrial cell migration and the progression of human ectopic endometriosis. We analyzed the plasma levels of TGF-β (n = 80) and gene expression levels of TGF-βR1 in patient tissues (n = 60) by an ELISA assay and quantitative real-time RT-PCR. The serum TGF-β and tissue TGF-βR1 expressions were significantly increased in the ectopic endometriotic tissues (n = 54, 29 for adenomyosis tissues and 25 for chocolate cysts) comparing with the normal endometrium (n = 5). The TGFβR1 transcriptional level in endometriotic tissues was positively correlated with expressions of OCT4 and genes associated with cell migration, such as VIMENTIN, TWIST, SNAIL and SLUG. TGF-β dose-dependently increased the OCT4 expression both in gene and protein levels in human endometriotic stromal cells and, at a less intensity, in HEC1A endometrial carcinoma cell line. Additionally, TGF-βincreased the expression of migration-associated genes and proteins (SNAIL and N-CAD) dose-dependently both in gene and protein levels in human endometriotic stromal cells. Knockdown of OCT4 significantly suppressed the TGF-β-induced the expressions of migration-associated genes and proteins (N-CAD and SNAIL), and promoted the migration of endometrial cells as evidenced by wound-closure and transwell assays. Conclusions: TGF-β,TGF-βRI, and OCT4 are significantly upregulated in human ectopic endometriotic tissues. The significant OCT4 expression may be involved in the pathology of ectopic endometrial growth through TGF-β-induced migration of endometrial cells. Citation Format: Te-Sheng Chang, Heng-Kien Au, Thai-Yen Ling, Ching-Chi Chi, Chii-Ruey Tzeng, Jui-Hung Chang, Yen-Hua Huang. TGF-β1 enhanced cell migration involving pluripotent transcription factor OCT4 in endometriosis. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 5580. doi:10.1158/1538-7445.AM2014-5580