Cleland K.,Princeton University |
Zhu H.,Shanghai JiaoTong University |
Goldstuck N.,Reproduction Research South Africa |
Cheng L.,Shanghai Institute of Planned Parenthood Research |
And 2 more authors.
Human Reproduction | Year: 2012
Background Intrauterine devices (IUDs) have been studied for use for emergency contraception for at least 35 years. IUDs are safe and highly effective for emergency contraception and regular contraception, and are extremely cost-effective as an ongoing method. The objective of this study was to evaluate the existing data to estimate the efficacy of IUDs for emergency contraception. Methods The reference list for this study was generated from hand searching the reference lists of relevant articles and our own article archives, and electronic searches of several databases: Medline, Global Health, Clinicaltrials.gov, Popline, Wanfang Data (Chinese) and Weipu Data (Chinese). We included studies published in English or Chinese, with a defined population of women who presented for emergency contraception and were provided with an IUD, and in which the number of pregnancies was ascertained and loss to follow-up was clearly defined. Data from each article were abstracted independently by two reviewers. Results The 42 studies (of 274 retrieved) that met our inclusion criteria were conducted in six countries between 1979 and 2011 and included eight different types of IUD and 7034 women. The maximum timeframe from intercourse to insertion of the IUD ranged from 2 days to 10 or more days; the majority of insertions (74 of studies) occurred within 5 days of intercourse. The pregnancy rate (excluding one outlier study) was 0.09. Conclusions IUDs are a highly effective method of contraception after unprotected intercourse. Because they are safe for the majority of women, highly effective and cost-effective when left in place as ongoing contraception, whenever clinically feasible IUDs should be included in the range of emergency contraception options offered to patients presenting after unprotected intercourse. This review is limited by the fact that the original studies did not provide sufficient data on the delay between intercourse and insertion of the IUD, parity, cycle day of intercourse or IUD type to allow analysis by any of these variables. © The Author 2012. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved.
Xie S.,CAS Shanghai Institutes for Biological Sciences |
Shen B.,Nanjing University |
Zhang C.,CAS Shanghai Institutes for Biological Sciences |
Huang X.,Nanjing University |
And 2 more authors.
PLoS ONE | Year: 2014
Although the CRISPR/Cas9/sgRNA system efficiently cleaves intracellular DNA at desired target sites, major concerns remain on potential "off-target" cleavage that may occur throughout the whole genome. In order to improve CRISPR-Cas9 specificity for targeted genome editing and transcriptional control, we describe a bioinformatics tool "sgRNAcas9" , which is a software package developed for fast design of CRISPR sgRNA with minimized off-target effects. This package consists of programs to perform a search for CRISPR target sites (protospacers) with user-defined parameters, predict genome-wide Cas9 potential off-target cleavage sites (POT), classify the POT into three categories, batch-design oligonucleotides for constructing 20-nt (nucleotides) or truncated sgRNA expression vectors, extract desired length nucleotide sequences flanking the on- or off-target cleavage sites for designing PCR primer pairs to validate the mutations by T7E1 cleavage assay. Importantly, by identifying potential off-target sites in silico, the sgRNAcas9 allows the selection of more specific target sites and aids the identification of bona fide off-target sites, significantly facilitating the design of sgRNA for genome editing applications. sgRNAcas9 software package is publicly available at BiooTools website (www.biootools.com) under the terms of the GNU General Public License. © 2014 Xie et al.
Zhao S.,CAS Shanghai Institutes for Biological Sciences |
Gou L.-T.,CAS Shanghai Institutes for Biological Sciences |
Zhang M.,CAS Shanghai Institutes for Biological Sciences |
Zu L.-D.,CAS Shanghai Institutes for Biological Sciences |
And 8 more authors.
Developmental Cell | Year: 2013
The PIWI/PIWI-interacting RNA (piRNA) machinery has been well documented to maintain genome integrity by silencing transposons in animal germ cells. Recent studies have advanced our understanding of the biogenesis and function of this machinery; however, its metabolism has remained largely unexplored. Here, we show that murine PIWI (MIWI) is degraded through the APC/C-26S proteasome pathway and that piRNAs play an indispensable role in this process by enhancing MIWI interaction with an APC/C substrate-binding subunit. Interestingly, piRNA-triggered MIWI destruction occurs in late spermatids, which in turn leads to piRNA elimination, suggesting a feedforward mechanism for coordinated removal of the MIWI/piRNA machinery at a specific developmental stage. Importantly, the proper removal of MIWI/piRNA is essential for sperm maturation. Together, our results reveal a role for piRNAs in regulating the clearance of the MIWI/piRNA machinery via the ubiquitin-proteosome pathway and demonstrate the critical importance of proper temporal regulation of MIWI/piRNA in male germ cell development.
Fuss S.H.,Rockefeller University |
Fuss S.H.,Bogazici University |
Zhu Y.,Max Planck Institute of Biophysics |
Zhu Y.,Shanghai Institute of Planned Parenthood Research |
And 2 more authors.
Molecular and Cellular Neuroscience | Year: 2013
In the mouse, a mature olfactory sensory neuron (OSN) of the main olfactory epithelium (MOE) expresses one allele of one of the 1200 odorant receptor (OR) genes in the genome. The mechanisms that underlie the one receptor-one neuron rule remain poorly understood. A popular experimental paradigm for OR gene choice is to delete an OR coding region by gene targeting or in a transgene. Here we have applied this incrementOR paradigm to SR1, also known as MOR256-3 or Olfr124. This gene is expressed in OSNs of the MOE, and in ~. 50% of the OSNs of the septal organ. In heterozygous incrementSR1 mice, we observe an unprecedented biallelic expression rate of 30% at the SR1 locus. In homozygous incrementSR1 mice, we find a significant increase in the number of septal organ OSNs that undergo apoptosis. As a population, incrementSR1 OSNs project their axons to 81-85 glomeruli in each half of the OB, and coexpress at least 77 OR genes as evaluated by single-cell molecular analysis. There are no obvious or simple rules for the set of OR genes that are coexpressed with the incrementSR1 allele. The frequencies of coexpression are different for incrementSR1 OSNs in the septal organ compared to those in the MOE. We propose that there are as many as five scenarios for the fate of individual incrementSR1 OSNs. © 2013 Elsevier Inc.
Zhang X.Z.,Shanghai Institute of Planned Parenthood Research
Zhonghua nan ke xue = National journal of andrology | Year: 2013
To identify the proteins that could improve the resistance of human sperm to cryopreservation using comparative proteomics. A total of 31 semen samples from 10 donors were divided into a high recovery and a low recovery group. Differentially expressed proteins in sperm and seminal plasma were detected and compared between the two groups by two-dimensional differential gel electrophoresis and mass spectrometry. Totally, 22 differentially expressed proteins were found in the two groups, 12 seminal plasma proteins, 9 sperm proteins, and 1 belonging to both. These identified proteins were involved in the maturation, movement, energy metabolism, DNA repair and other activities of spermatozoa. Many proteins were identified in sperm and seminal plasma that might influence the resistance of human sperm to cryopreservation.
Wu J.Q.,Shanghai Institute of Planned Parenthood Research
Zhonghua liu xing bing xue za zhi = Zhonghua liuxingbingxue zazhi | Year: 2012
To explore the effect and heaviness of smoking on the routine parameters of semen quality. A total of 727 eligible subjects including 421 smokers and 306 nonsmokers were selected in 2004 - 2006 in Hebei, Shanxi, Guizhou, Zhejiang and Shandong provinces. Data on background information, general demographic characteristics, exposure to smoking and related confounding factors were obtained through a questionnaire survey. Semen samples of all the subjects were collected during the period of study. Parameters of semen were examined according to the manual recommended by WHO. Four models from the multiple logistic regression regarding the semen routine parameters were used as the dependent variables to be fitted in descending order respectively, while six confounders including area, age, abstinence time, education level, history of alcohol intake and the exposure to pesticides etc., were adjusted. showed that smoking could affect the sperm viability, with significantly higher proportion of abnormal sperm viability seen in the smoking group (OR = 1.77, 95% CI: 1.12 - 2.80). Proportions regarding the abnormal mobility and morphology of sperms in the smoking group were also significantly higher than in the control group, with OR values as 1.51 (95%CI: 1.00 - 2.27) and 2.55 (95%CI: 1.68 - 3. 88) respectively. The density of sperms was significantly decreased in the smoking groups who smoked more than 20 cigarettes per day (OR = 1.70, 95%CI: 1.05 - 2.76) or the total numbers of cigarette consumption exceeding 150 000 (OR = 1.84, 95% CI: 1.03 - 3.29). Smoking showed adverse effects on the quality of semen, especially for heavy or long-term smokers.
Zhu Q.X.,Shanghai Institute of Planned Parenthood Research
Zhonghua nan ke xue = National journal of andrology | Year: 2011
Endocrine disrupting chemicals (EDCs) are natural or man-made agents that interfere in some way with human or animal normal endocrine function, and even influence the endocrine function of their offspring. There are many kinds of EDCs, which are widely present in soil, water, and even food. This review elaborates the impact of EDCs on human and animal semen quality from the viewpoint of epidemiology and biology by focusing on pesticides, plasticizers and detergents.
Cheng L.,Shanghai Institute of Planned Parenthood Research
Cochrane database of systematic reviews (Online) | Year: 2012
Emergency contraception (EC) is using a drug or copper intrauterine device (Cu-IUD) to prevent pregnancy shortly after unprotected intercourse. Several interventions are available for EC. Information on the comparative effectiveness, safety and convenience of these methods is crucial for reproductive healthcare providers and the women they serve. To determine which EC method following unprotected intercourse is the most effective, safe and convenient to prevent pregnancy. The search included the Cochrane Controlled Trials Register, Popline, MEDLINE, PubMed, Biosis/EMBASE, Chinese biomedical databases and UNDP/UNFPA/WHO/World Bank Special Programme on Human Reproduction (HRP) emergency contraception database (July 2011). Content experts and pharmaceutical companies were contacted. Randomised controlled trials and controlled clinical trials including women attending services for EC following a single act of unprotected intercourse were eligible. Data on outcomes and trial characteristics were extracted in duplicate and independently by two review authors. Quality assessment was also done by two review authors independently. Meta-analysis results are expressed as risk ratio (RR) using a fixed-effect model with 95% confidence interval (CI). In the presence of statistically significant heterogeneity a random-effects model was applied. One hundred trials with 55,666 women were included. Most trials were conducted in China (86/100). Meta-analysis indicated that mid-dose mifepristone (25-50 mg) (20 trials; RR 0.64; 95% CI 0.45 to 0.92) or low-dose mifepristone (< 25 mg) (11 trials; RR 0.70; 95% CI 0.50 to 0.97) were significantly more effective than levonorgestrel (LNG), but the significance was marginal when only high-quality studies were included (4 trials; RR 0.70; 95% CI 0.49 to 1.01). Low-dose mifepristone was less effective than mid-dose mifepristone (25 trials; RR 0.73; 95% CI 0.55 to 0.97). This difference was not statistically significant when only high-quality trials were considered (6 trials; RR 0.75; 95% CI 0.50 to 1.10). Ulipristal acetate (UPA) appeared more effective (2 trials; RR 0.63) than LNG at a marginal level (P = 0.09) within 72 hours of intercourse.Regarding effectiveness in relation to the time of administration, women who took LNG within 72 hours of intercourse were significantly less likely to be pregnant than those who took it after 72 hours (4 trials; RR 0.51; 95% CI 0.31 to 0.84). It was not evident that the coitus-treatment time affected the effectiveness of mifepristone and UPA.Single-dose LNG (1.5 mg) showed similar effectiveness as the standard two-dose regimen (0.75 mg 12 h apart) (3 trials; RR 0.84; 95% CI 0.53 to 1.33). This conclusion was not modified by the time elapsed from intercourse to treatment administration.Mifepristone (all doses) (3 trials; RR 0.14; 95% CI 0.05 to 0.41) and LNG (5 trials; RR 0.54; 95% CI 0.36 to 0.80) were more effective than the Yuzpe regimen in preventing pregnancy. One trial compared gestrinone with mifepristone. No significant difference of effectiveness was identified in this trial (996 women; RR 0.75; 95% CI 0.32 to 1.76).All methods of EC were safe. Nausea and vomiting occurred with oestrogen-containing EC methods and progestogen and anti-progestogen methods caused changes in subsequent menses. LNG users were more likely to have a menstrual return before the expected date, but UPA users were more likely to have a menstrual return after the expected date. Menstrual delay was the main adverse effect of mifepristone and seemed to be dose-related. Intermediate-dose mifepristone (25-50 mg) was superior to LNG and Yuzpe regimens. Mifepristone low dose (< 25 mg) may be more effective than LNG (0.75 mg two doses), but this was not conclusive. UPA may be more effective than LNG. LNG proved to be more effective than the Yuzpe regimen. The copper IUD was the most effective EC method and was the only EC method to provide ongoing contraception if left in situ.
Gemzell-Danielsson K.,Karolinska University Hospital |
Rabe T.,Universitats Frauenklinik Heidelberg |
Cheng L.,Shanghai Institute of Planned Parenthood Research
Gynecological Endocrinology | Year: 2013
There have been numerous attempts to control fertility after unprotected sexual intercourse (UPSI). From very bizarre methods like the vaginal application of Coca Cola to the more serious attempts using calcium antagonists influencing fertility parameters in sperm to hormonal methods or intrauterine devices. So far, hormonal methods preventing or delaying ovulation have proved to be the most popular starting with the combination of ethinyl estradiol and levonorgestrel (LNG), known as the Yuzpe regimen. The first dose had to be taken within 72 hours of UPSI, a second one 12 hours later. Later on, LNG alone, at first in a regimen similar to the Yuzpe method (2×0.75mg 12 hours apart) showed to be more successful, eventually resulting in the development of a 1.5mg LNG pill that combined good efficacy with a high ease of use. Several efficacious and easy to use methods for emergency contraception (EC) are available on the market today with the most widely spread being LNG in a single dose of 1.5 mg (given as one tablet of 1.5 mg or 2 tablets of 0.75 mg each) for administration up to 3 days (according to WHO up to 5 days) after UPSI. Its limitations are the non-optimal efficacy which is decreasing the later the drug is taken and the fact that it is only approved for up to 72 hours after UPSI. This regimen has no effect on the endometrium, corpus luteum function and implantation, is not abortive and don't harm the fetus if accidentally taken in early pregnancy. It has no impact on the rate of ectopic pregnancies. It has become the standard method used up to this day in most countries. Since the mid 1970s copper IUDs have been used for EC, which show a high efficacy. Their disadvantages lie in the fact that EC is considered an off label use for most IUDs (not for the GynFix copper IUD in the European Union) and that they might not be acceptable for every patient. Furthermore IUD-insertion is an invasive procedure and it is required trained providers and sterilized facilities. Mifepristone in the dosages of 10 or 25mg is used with good results as an emergency contraceptive in China for up to 120 hours after UPSI, but has never received any significant consideration in Western countries. While high doses of mifepristone has an effect on endometrial receptivity and will inhibit ovulation if given in the follicular phase and prevent implantation if given in the early luteal phase, low doses such as 10mg has no impact on the endometrium. Mifepristone does not increase the rate of ectopic pregnancies. The most recent development is the approval of the selective progesterone receptor modulator ulipristal acetate (UPA) in the dosage of 30 mg for EC up to 5 days after UPSI, combining the safe and easy application of the single dose LNG pill with an even higher efficacy. It has shown to be more efficacious than LNG and can be used for up to 120 hours after UPSI; the difference in efficacy is highest for 0-24 hours, followed by 0-72 hours following UPSI. No VTE has been reported following UPA-administration or any progesterone receptor modulator. No effect on endometrium, corpus luteum function and implantation has been observed with doses used for EC. Independent of the substance it should be noted that, if there is a choice, the intake of an oral emergency contraceptive pill should happen as soon as possible after the risk situation. A preexsisting pregnancy must be excluded. Possible contraindications and drug interactions must be considered according to the individual special product informations. © 2013 Informa UK Ltd All rights reserved: reproduction in whole or part not permitted.
Wu Q.,Shanghai Institute of Planned Parenthood Research |
Wu Q.,East China Normal University |
Ni X.,Shanghai Institute of Planned Parenthood Research
Current Drug Targets | Year: 2015
Elevated levels of both reactive oxygen species (ROS) and DNA methylation are characteristic of various types of cancer cells. However, the relation between these two is not well understood. Here we will discuss the cause-consequence relationship between ROS and DNA methylation. Cancer research reveals that disregulation of DNA methylation results in regional CpG island hypermethylation and generalized genomic hypomethylation. ROS-induced oxidative stress is associated with both aberrant hypermethylation of tumor suppressor gene (TSG) promoter regions and global hypomethylation. The DNA oxidation structure, 8-hydroxy-2'-deoxyguanosine (8-OHdG), can induce DNA hypomethylation by inhibiting DNA methylation at nearby cytosine bases, while another DNA oxidation structure, 5-hydroxymethylcytosine (5hmC), may achieve active DNA demethylation processes, thus, causing DNA hypomethylation. Recently, it has been found that ROS can function as catalysts of DNA methylation, further accounting for TSG promoter hypermethylation. Moreover, ROS may induce site-specific hypermethylation via either the up-regulation of expression of DNA methyltransferases (DNMTs) or the formation of a new DNMT containing complex. In addition, these ROS-induced DNA methylation pattern alterations have been implicated with not only malignant transformation, but also the progression of numerous tumors. In conclusion, ROS can influence both aspects of DNA methylation changes through different mechanisms, which play an important role of epigenetic regulation in cancer cells. Therefore, the comprehension of mechanisms leading to epigenetic modifications associated with ROS may help better understand the carcinogenesis and progression, as well as aid in the development of potential biomarkers for better cancer diagnostics and novel therapeutic strategies. © 2015 Bentham Science Publishers.