Does the Use of a Uterine Manipulator or Intracorporeal Colpotomy Confer an Inferior Prognosis in Minimally Invasive Surgery-Treated Early-stage Cervical Cancer?

STUDY OBJECTIVE: To identify whether the use of a uterine manipulator (UM) or intracorporeal colpotomy conferred inferior short-term survival among patients treated for early-stage cervical cancer. DESIGN: Retrospective cohort study. SETTING: Tertiary university-based hospital. PATIENTS: 1169 patients with stage IB1 to IB2 cervical cancer. INTERVENTIONS: All patients underwent minimally invasive radical hysterectomy and pelvic lymphadenectomy. MEASUREMENTS AND MAIN RESULTS: A total of 1169 patients diagnosed with preoperative stage IB1 to IB2 cervical cancer were primarily treated with surgery from 2018 to 2019. The eligible patients had a median age of 48 years (range, 23-76 years), and the median follow-up time was 34 months (range, 3.57-50.87 months). The 2-year overall survival rate of the patients with pathologic stage IB1 and IB2 was 99.8% and 98.8%, respectively, according to the 2018 International Federation of Gynecology and Obstetrics staging system. Univariable analysis revealed that the UM group had a 7.6-times higher risk of death than that of the manipulator-free group (p = .006), but multivariable analysis clarified that only tumor size (p = .016; hazard ratio, 2.285; 95% confidence interval, 1.166-4.479) and parametrial involvement (p = .003; hazard ratio, 3.556; 95% confidence interval, 1.549-8.166) were independent risk factors for overall survival. There was no statistically significant difference in survival between patients who underwent intracorporeal and protective colpotomy. CONCLUSION: Short-term survival outcomes in women undergoing minimally invasive radical hysterectomy for treatment of early-stage cervical cancer did not differ when a UM was avoided or when a protective colpotomy was performed.

Inactivation of Yes-Associated Protein Mediates Trophoblast Dysfunction: A New Mechanism of Pregnancy Loss Associated with Anti-Phospholipid Antibodies?

Pregnancy morbidity induced by anti-phospholipid antibodies (aPL+/PM+) is mainly thought to arise from placental abnormalities. We attempted to investigate the effect of aPL on the activity of Yes-associated protein (YAP) in the trophoblast and how YAP regulated human trophoblasts function. Thus, HTR-8 cells were treated with IgG purified from aPL+/PM+ women or normal controls. We found that aPL+/PM+ IgG impacted YAP activity via abrogating YAP expression. Further investigation of the anti-ß2GPI-IgG/ß2GPI complex showed an inhibition of nuclear YAP level and translocation in a dose-dependent manner, which might be rescued by progesterone in HTR-8 cells. YAP overexpression or knockdown HTR-8 cells were established for the evaluation of cell function and related gene expression in vitro. Loss of YAP arrested cell cycles in the G2/M phase, accelerated cell apoptosis by increasing the ratio of Bax/Bcl2, and disrupted MMP2/9-mediated cell migration and angiogenesis tube formation by VEGF. These findings support a new mechanism of PM associated with aPL through which YAP inactivation induced by aPL perturbs the trophoblast cell cycle, apoptosis, migration, and angiogenesis, finally developing into pregnancy failure.

Exploring a Better Adjuvant Treatment for Surgically Treated High-Grade Neuroendocrine Carcinoma of the Cervix.

OBJECTIVES: The objective of this study was to explore a better adjuvant treatment for patients with high-grade (HG) neuroendocrine cervical carcinomas (NECC) who had undergone surgery as a primary treatment. DESIGN: A retrospective cohort study, which involved women diagnosed as HG-NECC, was conducted in the Obstetrics and Gynecology Hospital of Fudan University. All patients had undergone radical surgery and pelvic lymphadenectomy with a laparotomy or a minimally invasive surgery. An analysis was made of the prognosis of HG-NECC. METHODS: Overall survival (OS) and progression-free survival (PFS) curves were drawn using the Kaplan-Meier method to be compared via log-rank tests. A Cox proportional hazards model was used to estimate the independent prognostic factors. RESULTS: A number of 110 patients diagnosed as HG-NECC at the pathological stage IA2 to IIIC2 according to the International Federation of Gynecology and Obstetrics (FIGO) 2018 staging system were initially treated with a primary surgery between 2008 and 2020. The eligible patients had the median age of 42.5 years (range: 22-76), with the median follow-up period of 39.6 months (range: 1.0-156.6). The 5-year OS of the patients at pathological stage I, II, and III accounted for 84.9%, 85.7%, and 60.9%, respectively. The Kaplan-Meier survival curves revealed no significant differences in OS and PFS between postoperative chemoradiotherapy and chemotherapy alone (OS: p = 0.77; PFS: p = 0.41). Etoposide plus platinum therapy did not improve OS when compared with platinum plus paclitaxel therapy after surgery (p = 0.71). The univariable analysis showed that chemotherapy with cycles ≥4 presented a better prognosis than with cycles <4 (OS: p = 0.01; HR = 6.71; PFS: p = 0.02; HR = 5.18). The multivariate analysis indicated that the cycles of chemotherapy (p = 0.02; HR 0.29) were a prognostic factor for PFS. LIMITATIONS: A retrospective design and the absence of partial follow-up data are limitations of the study. CONCLUSIONS: In initially surgically treated HG-NECC, postoperative chemotherapy alone showed no inferiority when compared with chemoradiotherapy for HG-NECC, and 4+ cycles of chemotherapy tended to produce a better prognosis than 4-ones.

Rapamycin maintains the primordial follicle pool and protects ovarian reserve against cyclophosphamide-induced damage.

Any abnormal activation of primordial follicles and subsequent depletion can irreversibly diminish the ovarian reserve, which is one of the major chemotherapy-induced adverse effects in young patients with cancer. Herein, we investigated the effects of rapamycin on the activation and development of ovarian follicles to evaluate its fertility-sparing therapeutic value in a cyclophosphamide (CTX)-treated mouse model. Based on ovarian histomorphological changes and follicle counting in 50 SPF female C57BL/6 mice, daily administration of 5 mg/kg rapamycin for 30 days was deemed an ideal dosage and duration for administration in subsequent experiments. Compared with the control group, rapamycin treatment inhibited the activation of quiescent primordial follicles, with no obvious side effects observed. Finally, 48 mice were randomly divided into four groups: control, rapamycin-treated, cyclophosphamide-treated, and rapamycin intervention. Body weight, ovarian histomorphological changes, number of primordial follicles, DDX4/MVH expression, apoptosis of follicular cells, and expression of apoptosis protease-activating factor (APAF)-1, cleaved caspase 3, and caspase 3 were monitored. Co-administration of rapamycin reduced primordial follicle loss and the development of follicular cell apoptosis, thereby rescuing the ovarian reserve after CTX treatment. On analyzing the mTOR signaling pathway, we observed that rapamycin significantly decreased CTX-mediated overactivation of mTOR and its downstream molecules. These findings suggest that rapamycin exhibits potential as an ovarian-protective agent that could maintain the ovarian primordial follicle pool and preserve fertility in young female patients with cancer undergoing chemotherapy.

CD55 is upregulated by cAMP/PKA/AKT and modulates human decidualization via Src and ERK pathway and decidualization-related genes.

Decidualization is an essential process for embryo implantation and maintenance of pregnancy, and abnormal decidualization contributed to several pregnancy disorders like a miscarriage. The objective of this study was to explore the regulation and function of CD55 in human decidualization. By immunohistochemical staining, it was found that CD55 expression was higher in first-trimester decidua than in the endometrium. In both primary endometrial stromal cells and immortalized cell line T-hESCs, CD55 was upregulated by induction of in vitro decidualization with medroxyprogesterone acetate (MPA) and 8-Br-cAMP. During decidualization in vitro, CD55 was stimulated by 8-Br-cAMP in a time- and concentration-dependent manner, which was reversed by a PKA inhibitor H89 and partially by an AKT activator SC79. Knocking down CD55 expression diminished the expression of decidualization markers prolactin (PRL) and insulin-like growth factor-binding protein 1 (IGFBP1), accompanied by inhibition of Src, aberrant activation of ERK and decreased expression of several decidualization-related genes, including FOXO1, EGFR, and STAT3. Furthermore, the decidua of unexplained miscarriage women and the endometrium of unexplained infertile women both exhibited decreased CD55 expression. Collectively, these findings revealed that 8-Br-cAMP promotes CD55 expression via PKA activation and AKT dephosphorylation, and decreased CD55 impairs decidualization by inactivation of Src, aberrant activation of ERK pathway, and compromised expression of decidualization-related genes, indicating that CD55 deficiency may contribute to the pathogenesis of spontaneous miscarriage and infertility.

Luteal phase deficiency during the early trimester in a case with secondary hypopituitarism following craniopharyngioma resection.

A 31-year-old woman, who had been diagnosed with craniopharyngioma (CP) at the age of 13, suffered secondary hypopituitarism after two surgical resections of CP, receiving supplement of levothyroxine, cortisone, and sequential estrogen and progesterone because of primary amenorrhea. She managed to conceive after ovulation induction with human menopausal gonadotropin. Luteal phase deficiency (LPD) was found during the first trimester, as the progesterone stayed at a low level between 0.07 and 1.63 ng/ml within seven gestational weeks, followed by a gradual rise from 4.01 up to 34.70 ng/ml in the 11th week, which was mainly secreted by the placenta. Estrogen and progesterone were administered to the patient as luteal support until the 12th week, who succeeded in delivering a healthy baby at term. In conclusion, the patient with hypopituitarism who develops severe LPD during the early pregnancy may need luteal support until 12th week.

Identification of predictors of the ovarian response to clomiphene citrate in infertile women with polycystic ovary syndrome: a prospective cohort study.

OBJECTIVE: To identify predictors of the ovarian response to clomiphene citrate (CC) in infertile patients with polycystic ovary syndrome (PCOS). METHODS: We performed a prospective cohort study of infertile patients with PCOS. The participants underwent assessments of their physical, endocrine, and metabolic characteristics, and treatment with CC at an initial dose of 50 mg/day and a maximum of 100 mg/day between days 3 and 7 of their menstrual cycles. Participants who ovulated were identified as responders and those who did not as non-responders. RESULTS: Of the 72 participants, 48 (66.7%) were identified as responders and 24 as non-responders. Sex hormone-binding globulin (SHBG) (odds ratio 1.022, 95% confidence interval: 1.000-1.045) was found to be associated with the ovarian response to CC using logistic multivariate regression analysis. Receiver operating characteristic analysis also showed that SHBG was a significant predictor of the response to CC (area under the curve 0.799). CONCLUSION: We have shown that SHBG is the best prognostic indicator of an ovulatory response to CC. However, larger prospective studies, in which more variables are assessed, are required to confirm this finding and to identify appropriate cut-off values.

Toll-Like Receptor 4 Inhibits Estradiol Secretion via NF-κB Signaling in Human Granulosa Cells.

Toll-like receptor 4 (TLR4) may play a critical role in regulating follicular development. Data are scarce on the role of TLR4 in the follicle. This study investigated the effects of TLR4 on steroidogenesis in human granulosa cells. Immunohistochemical analysis revealed stage-specific expression of TLR4 in the mouse ovarian cycle, and immunofluorescence showed TLR4 expression in the human granulosa-like tumor cell line (KGN). TLR4 agonist lipopolysaccharides (LPS) significantly inhibited follicular development and synthesis of estradiol (E2) in mice. In KGN cells, TLR4 activation significantly inhibited CYP19A1, FSHR and StAR, and TLR4 inhibition reversed these effects. TLR4 activation also inhibited forskolin-induced secretion of E2 by inhibiting CYP19A1, with no effect on progesterone. Further studies showed activation of p38, JNK and NF-κB signaling after TLR4 activation. Subsequent analyses showed that an NF-κB antagonist reversed the inhibitory effects on CYP19A1 expression and E2 secretion. Together, our results suggest that TLR4 activation may suppress CYP19A1 expression and E2 secretion via NF-κB signaling in human granulosa cells, with important implications for the regulation of ovarian pathophysiology.

Dydrogesterone treatment for menstrual-cycle regularization in abnormal uterine bleeding - ovulation dysfunction patients.

BACKGROUND: Dydrogesterone has shown significant efficacy in treatment of irregular menstrual cycle due to abnormal uterine bleeding - ovulation dysfunction (AUB-O), but there were few relevant studies. This observational study was designed to evaluate the effectiveness of dydrogesterone for the treatment of Chinese patients with AUB-O. AIM: To evaluate the effects of dydrogesterone on menstrual-cycle (MC) regularization and metabolism in the patients with AUB-O. METHODS: A prospective, non-interventional, single-arm, post-marketing observational study was conducted. Chinese women aged 16 years or above with AUB-O who had been prescribed dydrogesterone were enrolled. The patients were treated with dydrogesterone 10 mg from day 16 to day 25 of each cycle, consecutively for at least 3 cycles. The main outcome was defined as the percentage of patients whose MCs returned to normal (defined as 21 d < menstrual cycle ≤ 35 d) after three cycles of dydrogesterone treatment. RESULTS: One hundred and fourteen women with AUB-O were enrolled in the present study. Of 89 patients who completed treatment, 72 (80.9%) achieved a regular MC at the end of the 3rd circle. The level of androgen, including testosterone and dehydroepiandrosterone sulfate, declined significantly (P = 0.01 and 0.031, respectively), whereas other hormone levels remained steady. During the treatment, 44/80 (55.0%) subjects in the per-protocol set had reported biphasic basal body temperature. CONCLUSION: Dydrogesterone therapy was effective in achieving MC regularization for Chinese patients with AUB-O.

Promotion of the occurrence of endometrioid carcinoma by S100 calcium binding protein P.

BACKGROUND: Endometrial cancer, one of the most common malignant tumors, is a serious threat to women's health. Endometrial hyperplasia is a precursor of endometrial cancer. S100 calcium binding protein P (S100P) has been found to play important roles in many types of cancer. The present study aimed to investigate the expression of S100P in endometrial cancer and its precursor lesions, and to explore the possible mechanisms. METHODS: We collected paraffin sections of normal endometrium, simple and complex non-atypical hyperplasia, atypical hyperplasia, and endometrioid carcinoma. The expression of S100P in endometrial cancer and its precancerous lesions was observed using immunohistochemistry. We also cultured primary endometrial cells and endometrial cancer cell lines (Ishikawa and RL95-2), and observed the expression of S100P in these cells. Laser confocal microscopy was used to observe the co-localization of S100P and its interacting protein Ezrin in RL95-2 cells. We employed lentiviruses to knockdown and overexpress S100P and then detected the F-actin distribution and cell invasion using phalloidin staining and Transwell assays. RESULTS: There was a gradual increase in the S100P signal as the disease progressed from normal endometrium and simple non-atypical hyperplasia, to complex non-atypical hyperplasia, atypical hyperplasia, and then to endometrial cancer. S100P was mainly distributed in the cytoplasm and co-localized with Ezrin in endometrial cancer cells. After knocking down S100P, F-actin aggregated in the nucleus or to the local cell membrane. Furthermore, knockdown of S100P in Ishikawa cells decreased their cell invasion capability. Meanwhile, S100P overexpression in endometrial stromal cells increased cell invasion. CONCLUSIONS: These data suggested that S100P might be involved in the occurrence and development of endometrial cancer via interaction with Ezrin and re-organization of F-actin to promote cell invasion.

Number of Removed Pelvic Lymph Nodes as a Prognostic Marker in FIGO Stage IB1 Cervical Cancer with Negative Lymph Nodes.

STUDY OBJECTIVE: To investigate whether the number of removed lymph nodes (RLNs) influences the clinical outcome of stage IB1 cervical cancer on the premise of uniform pelvic lymphadenectomy. DESIGN: Retrospective cohort study. SETTING: Obstetrics and Gynecology Hospital of Fudan University. PATIENTS: Women (n = 782) with stage IB1 cervical cancer. INTERVENTIONS: Laparoscopic radical hysterectomy and uniform pelvic lymphadenectomy (common iliac, external iliac, internal iliac, obturator) for stage IB1 cervical cancer. The median time of follow-up was 64.7 months (range, 4.3-102.8). MEASUREMENTS AND MAIN RESULTS: Of 782 patients with stage IB1 cervical cancer, the median number of pelvic RLNs was 19 (range, 7-49). Twenty-one patients (2.7%) had RLNs ≤ 10, 461 (59.0%) had 11 to 20, 263 (33.6%) had 21 to 30, and 37 (4.7%) had RLNs ≥ 31. The differences were not statistically significant in the clinicopathologic characteristics between the 4 groups (p >.05). In the multivariate analysis, pelvic RLN number became an independent prognostic factor for progression-free survival (PFS) and cancer-specific survival (CSS) in stage IB1 cervical cancer (p = .029; .015 for CSS and PFS). After the stratified analysis by lymph node metastasis, RLN number remained an independent predictive value (p = .026 for CSS, p = .012 for PFS) in patients with negative pelvic lymph nodes. Moreover, patients with RLN number ≤ 10 carried a 5.550-fold higher risk for progression (p <.001) and 5.596-fold greater likelihood of death (p = .001) than those with RLN number > 10 in case of no lymph node metastasis. CONCLUSION: With uniform pelvic lymphadenectomy, the total pelvic RLN number could be a valuable predictor of outcome in stage IB1 cervical cancer without lymph node metastasis during a follow-up of at least 5 years.

Follicle loss and PTEN/PI3K/mTOR signaling pathway activated in LepR-mutated mice.

Female mice (Y123F) with substitution mutations introduced through homologous gene targeting, replacing the three tyrosine residues of LepR, Tyr985, Tyr1077, and Tyr1138 with phenylalanine, could induce infertility. This study aimed to describe the reproductive alteration and to explore its mechanism. We compared the reproductive characteristics in the female homozygous (HOM) Y123F mice and wild-type (WT) littermates, analyzing the expression of downstream molecules of LepR, like protein kinase B (Akt)/mammalian target of rapamycin (mTOR), phosphatase and tensin homolog deleted on chromosome 10 (PTEN) and insulin receptor substrate (IRS) in the ovaries. The results showed that 10-week old female Y123F HOM exhibited no reproductive periods, declined anti-mullerian hormone (AMH) levels in the serum and ovaries, reduced primordial follicles, primary follicles, secondary follicles, antral follicles and hardly no corpus lutea (all p < .05). The phosphorylation of downsream Akt, mTOR, S6K1 and eIF4B of LepR were all elevated in the ovaries of the mutated female mice. They also presented a decreased phosphorylation of IRS-1, IRS-2, and PTEN, and a strengthened phosphorylation of FOXO-3A in the ovaries. In conclusions, LepR mutation could result in follicle loss and activation of PTEN/PI3K/Akt/mTOR pathway in adult female mice, independent of insulin signaling pathway.

Valuable predictors of gestational diabetes mellitus in infertile Chinese women with polycystic ovary syndrome: a prospective cohort study.

OBJECTIVE: This study aimed to explore valuable preconception predictors of gestational diabetes mellitus (GDM) in PCOS patients. METHODS: A prospective cohort study enrolling infertile Chinese PCOS women treated with ovulation induction was performed. The endocrine, metabolic and physical features of all the patients were collected before pregnancy and then followed up to 6 weeks after delivery. The prevalence of GDM was determined during 24-28 gestational weeks. Logistic regression analysis and receiver operating characteristic (ROC) curves were applied to explore the risk factors and their predictive value for GDM. RESULTS: A total of 94 infertile PCOS women who got singleton pregnancy by ovulation induction were enrolled in the study. Logistic regression analysis showed that the preconception insulin under the curve (IAUC) and sex hormone-binding globulin (SHBG) levels were two most significant risk factors for developing GDM (p = 0.014; p = 0.042, respectively). The area of SHBG and IAUC under the ROC curve were 0.806 (p < 0.001) and 0.775 (p = 0.001), respectively. The optimal cutoff values were failed to be calculated because of the limited group size. CONCLUSIONS: Low SHBG level and hyperinsulinism were both strongly associated with the development of GDM and might be two valuable predictors in PCOS patients.

Risk factors for preeclampsia in infertile Chinese women with polycystic ovary syndrome: A prospective cohort study.

To explore preconception risk factors for preeclampsia (PE) in women with polycystic ovary syndrome (PCOS), a prospective cohort study was conducted in 92 infertile Chinese women with PCOS who had a singleton pregnancy by ovulation induction and were followed up for 6 weeks after delivery. The patients underwent assessment of physical, endocrine, and metabolic features before ovulation induction. Fifteen (16.3%) patients were diagnosed with PE. Logistic regression analysis showed that preconception sex hormone-binding globulin (SHBG), insulin level at 120 minutes, and body mass index were three independent risk factors for PE (odds ratio [OR], 0.981; 95% confidence interval [CI], 0.964-0.998 [P=.027]; OR, 1.011; 95% CI, 1.000-1.021 [P=.048]; and OR, 1.249; 95% CI, 0.992-1.572 [P=.059], respectively). Receiver operator characteristic analysis indicated the risk value of prepregnancy SHBG, insulin level at 120 minutes, and body mass index (area under the curve=.788, .686, and .697, respectively). Preconception low SHBG levels, overweight/obesity, and hyperinsulinism might be correlated with the subsequent development of PE in patients with PCOS.

Follicle Loss and Apoptosis in Cyclophosphamide-Treated Mice: What's the Matter?

With increasing numbers of young female cancer survivors following chemotherapy, chemotherapy-induced fertility loss must be considered. Menstrual disorder and infertility are of particular concern in female cancer patients. We showed that treatment with the alkylating agent cyclophosphamide (CTX) could cause severe primordial follicle loss and growing follicle apoptosis, resulting in loss of ovarian reserve. SPF C57BL/6 female mice were treated with a single dose of 120 mg/kg of CTX or saline as a control, and both sides of ovaries were collected three or seven days after injection. Following CTX treatment, the ovaries were mostly composed of collapsed oocytes and presented marked cortical fibrosis and a reduced number of follicles, especially primordial follicles. The loss of primordial follicles was confirmed by primordial follicle counting, immunohistochemistry and Western blot detection of DDx4/MVH. Follicle apoptosis was tested by a TUNEL assay and the number of TUNEL-positive follicle cells increased, as expected, in CTX-treated mice. Furthermore, expression of APAF-1 and cleaved caspase-3 was also increased after CTX treatment. Analysis of the PI3K/Akt/mTOR signaling pathway showed that CTX increased phosphorylation of Akt, mTOR and downstream proteins without affecting total levels. These results demonstrated that the CTX treatment led to the hyperactivation of the PI3K/Akt/mTOR signaling pathway in ovaries which may be related to primordial follicle loss and growing follicle apoptosis.

The anti-ovarian cancer activity by WYE-132, a mTORC1/2 dual inhibitor.

Epithelial ovarian cancer is the most common and lethal gynecological cancer in USA and around the world, causing major mortality annually. In the current study, we investigated the potential anti-ovarian cancer activity of WYE-132, a mammalian target of rapamycin (mTOR) complex 1/2 (mTORC1/2) dual inhibitor. Our results showed that WYE-132 potently inhibited proliferation of primary and established human ovarian cancer cells. Meanwhile, WYE-132 induced caspase-dependent apoptosis in ovarian cancer cells. At the molecular level, WYE-132 blocked mTORC1/2 activation and inhibited expression of mTOR-regulated genes (cyclin D1 and hypoxia-inducible factor 1α). Interestingly, introducing a constitutively active AKT (caAKT), which restored mTORC1/2 activation in WYE-132-treated ovarian cancer cells, only mitigated (but not abolished) WYE-132-mediated growth inhibition and apoptosis. Further studies showed that WYE-132 inhibited sphingosine kinase-1 (SphK1) activity, leading to pro-apoptotic ceramide production in ovarian cancer cells. Meanwhile, WYE-132-induced cytotoxicity against ovarian cancer cells was inhibited by sphingosine-1-phosphate (S1P) but was aggravated by SphK1 inhibitor SKI-II or C6 ceramide. In vivo, WYE-132 inhibited ovarian cancer cell growth, and its activity was further enhanced when co-administrated with paclitaxel (Taxol). These results demonstrate that WYE-132 inhibits ovarian cancer cell proliferation through mTOR-dependent and mTOR-independent mechanisms and indicate a potential value of WYE-132 in ovarian cancer treatment.

The clinical management and outcome of term premature rupture of membrane in East China: results from a retrospective multicenter study.

In this study, we investigated the management of term premature rupture of membranes (PROM) and maternal-fetal outcomes in East China. Between January and December 2012, the term delivery data for 111390 pregnant women was retrospectively analyzed. The subjects were divided into two groups: those women who had term PROM (PROM Group, n=13927) and those who did not (Control Group, n=94341). The general patient characteristics, the mode of delivery, and the maternal and fetal complications were recorded. Statistical analysis was completed using the Student's t-test and χ(2)-test. The incidence of term PROM in East China is approximately 12.5%. The maternal demographic and obstetric characteristics were similar between the two groups. Patients in the PROM group had a higher incidence of bacterial vaginitis (BV), chlamydia trachomatis (CT) infection, postpartum hemorrhage, and cesarean section deliveries. Infants in the PROM group experienced higher rates of infection, asphyxia, and jaundice. There was a high cesarean section rate, and further efforts are needed to increase the vaginal delivery rate for women with term PROM.

S100P expression in response to sex steroids during the implantation window in human endometrium.

BACKGROUND: S100P, a protein originally detected in the human placenta, has been found to play an important role in the development and invasion of tumors. Interestingly, we have recently discovered using data mining that S100P was considerably up-regulated during the window of implantation in the human endometrium, but little further information has been available. METHODS: Real-time PCR and immunofluorescence were performed to examine the expression and location of S100P in the human endometrium and endometrial cells. Estrogen and progesterone were added to the cultured cells to test the response of S100P to sex steroids. RESULTS: A dramatic peak, approximately a 100-fold increase in comparison with the proliferative and early- and late-secretory phases, was observed in the endometrium during the mid-secretory phase, which corresponds to the time of embryo implantation. Progesterone regulated the expression of S100P in both primary endometrial epithelial and stromal cells, but estrogen had no significant effect. CONCLUSIONS: The results indicate that S100P participates in the periodic change of the endometrium under the regulation of progesterone, may be used as a unique biomarker of the receptive endometrium and play an important role in embryo implantation.