CYP1B1 C4326G polymorphism and susceptibility to cervical cancer in Chinese Han women.

Cytochrome P450 1B1 (CYP1B1) is a key P450 enzyme, which could catalyze the formation of 4-hydroxy estrogen metabolites and play a role in estrogen-dependent cancers. We hypothesized that genetic variant in CYP1B1 may modify individual susceptibility to cervical cancer. The aim of this study was to evaluate the association between CYP1B1 C4326G polymorphism and cervical cancer risk in Chinese women. We extracted the peripheral blood samples in 250 patients with cervical cancer and 250 female controls. The matrix-assisted laser desorption ionization time-of-flight mass spectrometry method and direct DNA sequencing were performed to detect the polymorphism. The frequencies of CC, CG, and GG genotypes of CYP1B1 C4326G in cases and controls were 66.0, 26.8, 7.2% and 75.2, 21.6, and 3.2%, respectively, and there was a significant difference between the two groups (P = 0.034). Compared with the wild-type CC genotype, the variant GG genotype was associated with a significantly increased risk of cervical cancer (adjusted OR = 2.30; 95% CI = 1.02, 5.50). Moreover, stratification analysis by age, smoking, drinking, human papillomaviruses (HPV) 16 or 18 carrier status, and family history of cervical cancer, we found that the variant genotypes containing the G allele were associated with a significantly increased risk of cervical cancer among HPV 16 or 18-positive individuals (adjusted OR = 2.85; 95% CI = 1.45, 5.62) and among women younger than 45 years old (adjusted OR = 1.87; 95% CI = 1.03, 3.37). These results suggest that CYP1B1 C4326G polymorphism may increase risk of cervical cancer in Chinese women, especially among young individuals with high-risk HPV infection.

FOXO1 expression and regulation in endometrial tissue during the menstrual cycle and in early pregnancy decidua.

AIMS: To determine FOXO1 (forkhead box O1) expression in the human endometrium during the menstrual cycle and decidua of early pregnancy, as well as FOXO1 regulation in endometrial stromal cells (ESC). METHODS: Immunohistochemistry, RT-qPCR, and Western blot analyses evaluated cellular localization and altered FOXO1 expression in the endometrium during the menstrual cycle and decidua of early pregnancy (proliferative phase, n = 12; early-secretory phase, n = 7; mid-secretory phase, n = 10; late-secretory phase, n = 10; early pregnancy, n = 12). Using RT-qPCR and Western blot, we studied the regulation of FOXO1 by 8-bromo-cAMP, 4-pregnene-3,20-dione, 17ß-estradiol, and human chorionic gonadotrophin in ESC (n = 5). RESULTS: The expression level of FOXO1 in human endometrial tissue fluctuated with the menstrual cycle. If pregnancy occurred, the expression of FOXO1 was further increased (p < 0.05) and cAMP regulated FOXO1 expression in ESC. In addition, 4-pregnene-3,20-dione cooperatively stimulated FOXO1 expression with cAMP. We also observed FOXO1 expression during in vitro cAMP-induced decidualization. CONCLUSIONS: The pattern of FOXO1 expression suggests a potential role for FOXO1 in implantation and decidualization.

[Impact of controlled ovarian hyperstimulation delayed, which occurs after functionally pituitary downregulation by depot GnRH agonist, on the outcome of in vitro fertilization and embryo transfer].

OBJECTIVE: This study observed the influence on hormone, embryos and clinical outcomes when the starting time of controlled ovarian hyperstimulation (COH) was delayed after applying a half-dose depot gonadotropin-releasing hormone agonist (GnRHa). METHODS: A total 207 cycles were divided into 3 groups: control group (98 cycles, which performed daily low dose GnRHa during the mid-luteal phase in patients' menstrual cycles and reduced the dosage to a half at the next day 3, and added gonadotropin (Gn), conventional group (63 cycles, in which pituitary desensitization was obtained with a half-dose depot GnRHa in the mid-luteal phase, and then Gn was added at day 3) and delayed group (46 cycles, having the same usage of GnRHa to conventional group, but not adding Gn until day 7). RESULTS: The cancellation rate of cycle in conventional group was the highest (P < 0.01). At the beginning of COH, serum E2 and LH levels in delayed and control group were significantly higher than those in conventional group (P < 0.01). On the day of HCG given, serum E2 level in control group was the highest (P < 0.05). LH level in delayed and control group was higher than that in conventional group (P < 0.01). Concerning the clinical efficacy and outcome, the numbers of Gn ampoules and periods for stimulation were less in delayed group than in conventional group; the numbers of retrieved and fertilized oocytes, numbers of good quality embryos, clinical pregnancy rate and embryo implantation rate in delayed and control groups were significantly more than those in conventional group (P < 0.01). In ICSI cycles, the numbers of retrieved oocytes and metaphase II oocytes in delayed and control group were more than those in conventional group. CONCLUSIONS: A half-dose depot GnRHa may produce over suppression to pituitary gland in fertilization in vitro, appropriate delay of COH starting time can decrease ovarian stimulation period and ampoules of Gn, and increase retrieved good quality oocytes, so we could achieve a larger number of good quality embryos with a good chance of implantation.

[The affection of antigen presentation ability, which sources from the spleen macrophage of Balb/c mouse during late gestation, on maternal Th2/Th1 type of immune].

OBJECTIVE: To study the relationship between antigen presentation ability of spleen macrophage and maternal Th2>Th1 immune bias in Balb/c mice during late pregnancy. METHODS: Balb/c mice during late gestation were adopted in our study, and mice of same species in estrus were used as control. With antigen stimulation, the spleen macrophages of Balb/c mice were pulsed as antigen presentation cells (APC). T cells sensitized previously by pulsed macrophage (1 degree APC) were cultured in mixture with macrophage pulsed by same antigen (2 degrees APC). An antigen special lymphocyte transformation test in vitro was used to evaluate the antigen presentation ability of spleen macrophage from mice of late gestation, and a flow cytometry method was used to measured the ration of CD4, CD8, IL-10 and IFN-gamma positive cell in T cells which had being induced to proliferate. RESULTS: When spleen macrophage from mice during late gestation was used as 1 degree APC, the proliferation of sensitized T cell induced by macrophage from late pregnancy mice used as 2 degree APC was no more intense than that from estrous mice (P > 0.05). When spleen macrophage from mice in oestrus was used as 1 degree APC, the proliferation of sensitized T cell induced by macrophage from late pregnancy mice as 2 degrees APC was lower intense than that from estrous mice (P < 0.05). The type of 1 degree APC did not affect the ratio of IL-10 positive T cell, and macrophage from late pregnancy mice could induce more IL-10 positive T cell than that from estrous mice when they were used as 2 degrees APC (P < 0.05). The type of 1 degree or 2 degrees APC did not affect the ratio of IFN-gamma positive T cell. CONCLUSION: The spleen macrophage from mice during late gestation is not an effective APC, but can induce maternal Th2 type of immune and maintain the Th1 type immune at a lower stage during pregnancy, which means it may has some important role in pregnancy.

[The relationship between the implantation of ovarian stimulated embryos and the expression of leukemia inhibitory factor mRNA in mice metrium].

OBJECTIVE: To check the expression of leukemia inhibitory factor (Lif) mRNA, and to study the impact of ovarian stimulation on the ability of embryo implantation in mice. METHODS: Pregnancy models of mice were established. The relationship between the implantation of ovarian stimulated embryos and the expression of Lif mRNA in mice metrium was analyzed. RESULTS: The group of recipients which the transfered embryos were from stimulated cycles had lower pregnancy and implantation rate compared with the group of recipients which the transfered embryos were from non-stimulated cycles (20.00%, 8.33% vs 55.00%, 35.00%). The Lif mRNA expression was similar in the groups of recipients which the transfered embryos were from stimulated and non-stimulated cycles, so was in the groups of recipients which had single or more than one baby, but higher in the group of pregnancy recipients than in the group of unpregnancy recipients. CONCLUSION: Ovarian stimulation may reduce the ability of embryo implantation in mice. Lif mRNA expression is related to the implantation, but not parallel to the number of implantation.