Wangming Xu

Oxidative Stress: Placenta Function and Dysfunction

During pregnancy, the placenta is a site of active oxygen metabolism that continuously generates oxidative stress (OS). Overproduction of reactive oxygen species and reactive nitrogen species can destroy normal placental functions. Therefore, the feto‐placental unit generates abundant antioxidants to keep OS under control. Properly controlled oxidative species have been proven to serve as indispensable cellular signal messengers by regulating gene expression and downstream cellular activities. OS also plays an important immunoregulatory role during pregnancy. Oxidative disorder and immune disturbances are associated with adverse pregnancy outcomes such as spontaneous abortion, preeclampsia and intrauterine growth restriction. In this review, we introduce recent studies revealing basal functions and regulatory roles of placental OS in metabolism and immunity. The relationships between OS‐ and pregnancy‐related disorders are also discussed.

Intrauterine Administration of Peripheral Blood Mononuclear Cells (PBMCs) Improves Endometrial Receptivity in Mice with Embryonic Implantation Dysfunction

Intrauterine administration of autologous peripheral blood mononuclear cells (PBMCs) activated by HCG in vitro is reported to improve implantation rates in patients with repeated failure of IVF‐ET. In this article, the impact of intrauterine administration of PBMCs on embryo implantation, pregnancy rate and the underlying mechanisms will be investigated.

Depression and coping strategies of Chinese women undergoing in-vitro fertilization

OBJECTIVES To explore the relationship between coping strategies and depression, and the risk factors of depression among Chinese women in infertile couples undergoing in-vitro fertilization (IVF). STUDY DESIGN Two hundred and eighty-eight women undergoing IVF completed the Center for Epidemiologic Studies Short Depression Scale and the Brief COPE Inventory. Demographic data were collected, hormone levels were tested and oocyte numbers were counted. RESULTS The incidence of depression was 22.6%. The prevalence of depression was higher among women who had been married for >8 years, women who had been infertile for >6 years and women with a family income ≤3000 CNY/month. High basal follicle-stimulating hormone, oocyte number and denial score were associated with greater risk of depression. High oestradiol (basal and peak), and substance use and humour scores were associated with lower risk of depression. CONCLUSION Many women in infertile couples undergoing IVF have depression. Preventive interventions should be provided for women with risk factors of depression, such as long duration of marriage, long duration of infertility, low monthly family income, high basal follicle-stimulating hormone, low serum oestradiol, high oocyte number, and use of denial as a coping strategy.

Uterine Micro-Environment and Estrogen-Dependent Regulation of Osteopontin Expression in Mouse Blastocyst

Embryo implantation is a highly synchronized bioprocess between an activated blastocyst and a receptive uterus. In mice, successful implantation relies on the dynamic interplay of estrogen and progesterone; however, the key mediators downstream of these hormones that act on blastocyst competency and endometrium receptivity acquisition are largely unknown. In this study, we showed that the expression of osteopontin (OPN) in mouse blastocysts is regulated by ovarian estrogen and uterine micro-environment. OPN mRNA is up-regulated in mouse blastocyst on day 4 of pregnancy, which is associated with ovarian estrogen secretion peak. Hormone treatment in vivo demonstrated that OPN expression in a blastocyst is regulated by estrogen through an estrogen receptor (ER). Our results of the delayed and activated implantation model showed that OPN expression is induced after estrogen injection. While estrogen treatment during embryo culture in vitro showed less effect on OPN expression, the tubal ligation model on day 3 of pregnancy confirmed that the regulation of estrogen on OPN expression in blastocyst might, through some specific cytokines, have existed in a uterine micro-environment. Collectively, our study presents that estrogen regulates OPN expression and it may play an important role during embryo implantation by activating blastocyst competence and facilitating the endometrium acceptable for active blastocyst.

Folic acid supplementation as adjunctive treatment premature ejaculation.

Selective serotonin re-uptake inhibitors (SSRIs), has been increasingly used for the treatment of premature ejaculation over the past 5 years. It was reported that folic acid plays important roles in synthesis of 5-HT. Therefore, we hypothesize that folic acid supplementation may cures premature ejaculation by the same mechanism of interacting with monoamine neurotransmitters in brain, to be the replacement of RRSIs. Folic acid supplementation cures premature ejaculation more safely. These new views will help to understand the diagnosis and treatment methods for premature ejaculation.

Immunogenicity Study of Plasmid DNA Encoding Mouse Cysteine-Rich Secretory Protein-1 (mCRISP1) as a Contraceptive Vaccine

To examine the immunocontraceptive properties of the plasmid pcDNA‐mCRISP1 and compare them to the corresponding recombinant mCRISP1 (r‐mCRISP1).

Intrauterine administration of hCG-activated autologous human peripheral blood mononuclear cells (PBMC) promotes live birth rates in frozen/thawed embryo transfer cycles of patients with repeated implantation failure.

Recurrent implantation failure refers to unsuccessful implantation after repeated transfers of morphologically good quality embryos into a normal uterus. Recently, accumulating evidence has suggested that local immune cells at the implantation site have actively contributed to embryo implantation. Our aim was to study the effects of intrauterine administration of hCG-activated autologous human PBMC on clinical pregnancy, implantation rates and live birth rate of patients who received frozen/thawed embryo transfer. We observed patients with one to three failed transplantations cannot benefit from the administration, but the rate of clinical pregnancy (39.58% vs. 14.29%), live birth (33.33% vs. 9.58%) and implantation (22.00% vs. 4.88%) were significantly increased in patients with four or more failures, respectively. For patients with endometrial thickness more than 7mm and less than 8mm on day of embryo transfer, the implantation rate (22.69% vs. 14.21%) and the live birth rate significantly higher in the PBMC-treated group; For patients who had RIF and received frozen/thawed early cleavage stage embryo transfer, the live birth delivery rate (29.63% vs. 13.33%) significant higher in PBMC-treated group. These findings indicate that intrauterine administration of hCG-activated autologous PBMC effectively improves the IVF outcomes for RIF patients, especially for the RIF patients with cleavage stage embryo transfer, patients with thin endometrial thickness also benefit from this approach.

IL-17 Induces Fetal Loss in a CBA/J×BALB/c Mouse Model, and an Anti-IL-17 Antibody Prevents Fetal Loss in a CBA/J ×DBA/2 Mouse Model

Many researchers have demonstrated that the expression of interleukin‐17(IL‐17) is higher in spontaneous abortion. However, whether Th17 cells are an independent factor in inducing abortion is not known.

Temporal and spatial regulation of ezrin-radixin-moesin-binding phosphoprotein-50-kDa (EBP50) during embryo implantation in mouse uterus.

Embryo implantation is a crucial process for successful pregnancy. To date, the mechanism of embryo implantation remains unclear. Ezrin-radixin-moesin-binding protein-50-kDa (EBP50) is a scaffold protein, which has been shown to play an important role in cancer development. Embryo implantation and cancer follow a similar progression. Thus, in this article, we utilized immunohistochemical staining and western blot analyses to examine the spatiotemporal expression and regulation of EBP50 both in the mouse uterus during embryo implantation as well as in other related models. We found that EBP50 was detected in epithelial cells in all of the groups used in our study. During the peri-implantation period, EBP50 mainly localized in apical membranes. At the implantation site (IS) on day 5 (D5) of pregnancy, EBP50 was mainly expressed in the nuclei of stroma cells, whereas from day 6 to day 8 (D6–D8) of pregnancy, the expression of EBP50 was noted in the cytoplasm of decidual cells. The expression of EBP50 was not significantly different in the pseudopregnant uterus and decreased in the uteri subjected to activation of delayed implantation. Artificial decidualization also decreased EBP50 expression. Thus, the expression levels and location were affected by active blastocysts and decidualization during the window of implantation.

Dual trigger of triptorelin and HCG optimizes clinical outcome for high ovarian responder in GnRH-antagonist protocols

In this paper, a retrospective cohort study was conducted to the high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. The purpose of the study is to investigate whether dual triggering of final oocyte maturation with a combination of gonadotropin-releasing hormone (GnRH) agonist and human chorionic gonadotropin (HCG) can improve the clinical outcome compared with traditional dose (10000IU) HCG trigger and low-dose (8000IU) HCG trigger for high ovarian responders in GnRH-antagonist in vitro fertilization/intracytoplasmic sperm injection (IVF-ICSI) cycles. Our study included 226 couples with high ovarian responders in GnRH-antagonist protocols of IVF/ICSI cycles. Standard dosage of HCG trigger (10000 IU of recombinant HCG) versus dual trigger (0.2 mg of triptorelin and 2000 IU of recombinant HCG) and low-dose HCG trigger (8000IU of recombinant HCG) were used for final oocyte maturation. Our main outcome measures were high quality embryo rate, the number of usable embryos, the risk of OHSS, duration of hospitalization and incidence rate of complications. Our evidence demonstrated that dual trigger is capable of preventing severe OHSS while still maintaining excellent high quality embryo rate in in high ovarian responders of GnRH-antagonist protocols.