The testis-specific gene 1700102P08Rik is essential for male fertility.

Male infertility is a rising problem around the world. Often the cause of male infertility is unclear, and this hampers diagnosis and treatment. Spermatogenesis is a complex process under sophisticated regulation by many testis-specific genes. Here, we report the testis-specific gene 1700102P08Rik is conserved in both the human and mouse and highly expressed in spermatocytes. To investigate the role of 1700102P08Rik in male fertility, knockout mice were generated by CRISPR-Cas9. 1700102P08Rik knockout male mice were infertile with smaller testis and epididymis, but female knockout mice retained normal fertility. Spermatogenesis in the 1700102P08Rik knockout male mouse was arrested at the spermatocyte stage, and no sperm were found in the epididymis. The deletion of 1700102P08Rik causes apoptosis in the testis but did not affect the serum concentration of testosterone, luteinizing hormone, and follicle-stimulating hormone or the synapsis and recombination of homologous chromosomes. We also found that 1700102P08Rik is downregulated in spermatocyte arrest in men. Together, these results indicate that the 1700102P08Rik gene is essential for spermatogenesis and its dysfunction leads to male infertility.

The expression of the new epididymal luminal protein of PDZ domain containing 1 is decreased in asthenozoospermia.

Spermatozoa are not mature until they transit the epididymis where they acquire motility and the ability to fertilize an egg through sequential modifications. The epididymis has three functional regions, caput, corpus, and cauda, and the luminal proteins of the epididymis play important roles in the above modifications. However, the proteins with differential enrichment between the caput and cauda are still largely unknown. To reveal the functions of the caput and cauda during sperm maturation, luminal proteins from caput and cauda of mice were analyzed by isobaric tag for relative and absolute quantitation (iTRAQ). Overall, 128 differentially enriched proteins were found, of which 46 were caput enriched and 82 were cauda enriched. Bioinformatic analysis showed that lipid metabolism was active in the caput; while anion- and cation-binding activity and phosphorus and organophosphate metabolism were active in the cauda. A new epididymal luminal protein, the caput-enriched PDZ domain containing 1 (Pdzk1), also named Na+/H+ exchange regulatory cofactor 3 (NHERF3), which plays a critical role in cholesterol metabolism and carnitine transport, was found in the lipid metabolism. Western blotting and immunofluorescence analyses showed that Pdzk1 was expressed in the epididymis but not in the testis, and localized at the middle piece of the sperm tail. Pdzk1 protein level was also reduced in the spermatozoa in case of asthenozoospermic patients compared with that in normozoospermic men, suggesting that Pdzk1 may participate in sperm maturation regulation and may be associated with male infertility. These results may provide new insights into the mechanisms of sperm maturation and male infertility.

Dysregulation and functional roles of miR-183-96-182 cluster in cancer cell proliferation, invasion and metastasis.

Previous studies have reported aberrant expression of the miR-183-96-182 cluster in a variety of tumors, which indicates its' diagnostic or prognostic value. However, a key characteristic of the miR-183-96-182 cluster is its varied expression levels, and pleomorphic functional roles in different tumors or under different conditions. In most tumor types, the cluster is highly expressed and promotes tumorigenesis, cancer progression and metastasis; yet tumor suppressive effects have also been reported in some tumors. In the present study, we discuss the upstream regulators and the downstream target genes of miR-183-96-182 cluster, and highlight the dysregulation and functional roles of this cluster in various tumor cells. Newer insights summarized in this review will help readers understand the different facets of the miR-183-96-182 cluster in cancer development and progression.

Effect of high ovarian response on the expression of endocrine gland-derived vascular endothelial growth factor (EG-VEGF) in peri-implantation endometrium in IVF women.

OBJECTIVE: To investigate the effect of ovarian stimulation on the expression of EG-VEGF mRNA and protein in peri-implantation endometrium in women undergoing IVF and its relation with endometrial receptivity (ER). DESIGN: Prospective laboratory study. SETTING: University hospital. PATIENTS: Eighteen women in stimulated cycles (SC) as study subjects and 18 women in natural cycles (NC) as controls. Women in SC group were classified with two subgroups, high ovarian response (SC1, n=9) with peak serum E2>5,000 pg/mL and moderate ovarian response (SC2, n=9) with peak serum E2 1,000-5,000 pg/mL. INTERVENTION(S): Endometrial biopsies were collected 6 days after ovulation in NC or after oocyte retrieval in SC. MAIN OUTCOME MEASURE(S): Endometrium histological dating was observed with HE staining. EG-VEGF mRNA expression levels determined by real-time polymerase chain reaction analysis, and protein levels by immunohistochemistry. RESULTS: All endometrial samples were in the secretory phase. The endometrial development in SC1 was 1 to 2 days advanced to NC, and with dyssynchrony between glandular and stromal tissue. Immunohistochemistry analysis showed that EG-VEGF protein was predominantly expressed in the glandular epithelial cells and endothelial cells of vessels, and also presented in the stroma. The image analysis confirmed that both the gland and stroma of endometrium in SC1 had a significantly lower EG-VEGF protein expression than that in SC2 and NC endometrium. Moreover, EG-VEGF mRNA levels were significantly lower in SC1 than in NC. Both EG-VEGF protein and mRNA levels had no significant difference between SC2 and NC. CONCLUSION: Decreased expression of EG-VEGF in the peri-implantation is associated with high ovarian response, which may account for the impaired ER and lower implantation rate in IVF cycles.

The regulation network and network motif analysis in ovarian cancer.

OBJECTIVE: Several gene alterations have been identified associated with ovarian cancer (OC) development. However, how these genetic elements are coordinated in transcription network during OC initiation and progression is poorly understood. Thus, the objective of this study was to interpret the transcription regulation network of OC. MATERIALS AND METHODS: The GSE14407 microarray data was used for analysis of the transcription regulation network of OC. RESULTS: The results showed that the TP53 (tumor protein p53) was the most crucial transcription factor in the transcriptome network. P53 could down-regulate CDC14A (CDC14 cell division cycle 14 homolog A [S. cerevisiae]) and FAS (TNF receptor superfamily, member 6) expression, but up-regulate SFN (stratifin) and THBS1 (thrombospondin 1) expression to involve in pathways in cancer, cell cycle, p53 signaling pathway, and apoptosis pathway. CONCLUSION: This transcriptional regulation may provide a better understanding of molecular mechanism and some potential therapeutic targets in the treatment of OC.

[A multi-center study to evaluate the dynamic changes of uterine artery and umbilical artery flow in a normal pregnancy and hypertensive disorders in pregnancy].

OBJECTIVE: To investigate the dynamic changes of uterine artery and umbilical artery in the first, second, and third trimester of normal pregnancy and hypertensive disorders in pregnancy (HDP). METHODS: A multi-center prospective study was conducted on 1098 women with normal singleton pregnancies at the first prenatal visit in the Second West China Hospital of Sichuan University, First Affiliated Hospital with Nanjing Medical University, Beijing Obstetrics and Gynecology Hospital Affiliated to Capital Medical University, Wuhan Union Hospital Affiliated to Medical School of Huazhong University of Science and Technology and Renji Hospital Affiliated to Medical School of Shanghai Jiao Tong University from April 2005 to July 2006, with the average age of (28.3 ± 3.3). The pulsatility indices (PI), resistance indices (RI) and systolic to diastolic velocity ratios (S/D) of uterine artery and umbilical artery were measured for all subjects in the first (10th-14th gestational weeks), second (20th-26th gestational weeks) and third trimester (30th-36th gestational weeks), respectively. In this longitudinal study, women who developed HDP were classified into HDP group, and the rest into normal pregnancy group. RESULTS: (1) Among the 1098 pregnant women, 44 developed HDP during the index pregnancy, including 20 gestational hypertension, 15 mild pre-eclampsia and 9 severe pre-eclampsia, giving an incidence of 4.17%, and the rest 1054 were normal until delivery. (2) In the normal pregnancy group, the RI, PI and S/D of uterine artery were decreased with the progress of pregnancy (RI: 0.64, 0.57, 0.50; PI: 1.24, 0.98, 0.80; S/D: 3.26, 2.58, 2.20; P < 0.01). However, the above indices showed an increasing trend with the increase of gestations in the HDP group (RI: 0.55, 0.67, 0.64; PI: 1.22, 1.36, 1.20; S/D: 3.18, 3.41, 3.05; P < 0.01). In the second and third trimester, the RI, PI and S/D of uterine artery in the HDP group were higher than those in the normal pregnancy group (P < 0.01). (3) In the normal pregnancy group, the RI, PI and S/D of the umbilical artery decreased from the second to the third trimester (RI: 0.71 and 0.58; PI: 1.16 and 0.87; S/D: 3.58 and 2.48; P < 0.01). However, no significant difference was found in the RI, PI and S/D value of umbilical artery in the second and third trimester between the normal and HDP group (RI: 0.71 and 0.63; PI: 1.20 and 0.95; S/D: 3.71 and 2.69; P > 0.05, respectively), despite the decreasing trend in the HDP group. CONCLUSIONS: In uncomplicated pregnancies, the blood flow resistance of uterine artery decreases and the end-diastolic blood flow of uterine artery increases with the progress of pregnancy. However, in pregnant women with HDP, the blood flow resistance of uterine artery increases significantly with the increase of gestations which shows significant difference to that in normal pregnancies. The blood flow resistance of umbilical artery decreases in both normal and HDP pregnant women with the increasing gestational age.

[Pregnancy outcome in women with rheumatic heart disease].

OBJECTIVE: To evaluate the pregnancy outcome of women with rheumatic heart disease. METHODS: Clinical data of 65 cases of pregnant women with rheumatic heart disease from Jan 1993 to July 2006 were analyzed. They were divided into four groups according to the degree of mitral stenosis: normal group (> 4.0 cm(2)), slight group (2.5 - 4.0 cm(2)), moderate group (1.5 - 2.5 cm(2)) and severe group (< 1.5 cm(2)); four groups according to the degree of pulmonary hypertension: normal group, slight group (pulmonary hypertension ranging from 31 to 49 mm Hg, 1 mm Hg = 0.133 kPa) moderate group (from 50 to 79 mm Hg) and severe group (equal to and more than 80 mm Hg); two groups according to heart operation: non-operated group and operated group; and four groups according to the degree of New York heart association (NYHA) class. The perinatal mortality and morbidity of mothers and fetus were analysed. RESULTS: (1) The rate of NYHA class IV was 80% (12/15 cases) in moderate-severe group of mitral stenosis and the rate of NYHA class I and II was 80% (16/20 cases) in normal group, with a significant difference between them (P < 0.05). (2) The rate of NYHA class I and II was 73% (24/33 cases) in group of normal pulmonary pressure and the rate of NYHA class IV was 6/7 in severe group of pulmonary hypertension (P < 0.05). (3) The rate of NYHA class I and II was 71% (10/14), and NYHA class III or IV was 14% (2/14) in heart operated women (P < 0.05). (4) The delivery week was 34.6 and the birth weight was 2176 g averagely in NYHA class IV group and had significant differences from NYHA class I group (P < 0.05). There were 9 cases of abortion medically (18.9%, 9/65), 18 of preterm labor medically (28%, 18/65), 4 of fetal growth restriction (FGR) (6%, 4/65) and 3 of perinatal mortality (5%, 3/65), which all happened in groups of NYHA class III and IV. (5) The rate of NYHA class III and IV was 6/7 in atrial fibrillation women. CONCLUSION: Pregnant women with rheumatic heart disease of moderate-severe mitral stenosis, severe pulmonary hypertension and atrial fibrillation are at high risk of heart failure. The fetal outcome is not good in cases of NYHA class III and IV.