Prospective assessment of Y-chromosome microdeletions and reproductive outcomes among infertile couples of Japanese and African origin

BACKGROUND: To compare the frequency of Y-chromosome microdeletions in Japanese and African azoospermic and oligozoospermic men and describe embryo characteristics and reproductive outcome following in vitro fertilization (IVF) with intracytoplasmic sperm injection (ICSI). METHODS: Our study was performed prospectively at two centers, a private IVF clinic and a university hospital. Japanese and African (Tanzanian) men with nonobstructive azoospermia (NOA) and oligozoospermia (concentration < 5 × 10(6 )/ml) were evaluated for Y-chromosome microdeletions (n = 162). Of the 47 men with NOA, 26 were Japanese and 21 were Africans. Of the 115 men with oligozoospermia, 87 were Japanese and 28 were Africans. Reproductive outcomes of patients with Y-chromosome microdeletions were then compared with those of 19 IVF+ICSI cycles performed on couples with Y-chromosome intact males/tubal factor infertility which served as a control group. RESULTS: Seven azoospermic and oligozoospermic patients had Y-chromosome deletions; the total number of deletions in the AZFc region was five. There was only one deletion in the AZFa region and one complete deletion involving all three regions (AZFa, b, and c) within AZF. In our study population, microdeletion frequency among Japanese men was 6.2% (95% CI, 4.25% – 14.45%), whereas no deletions were identified in the African group (95% CI, 0.0% – 7.27%). The difference between the two groups was not statistically significant, however. Embryos derived from ICSI utilizing sperm with Y-chromosome microdeletion showed reduced rates of fertilization, blastocyst development, implantation, and pregnancy compared to the Y-chromosome intact group, although these observed differences were not statistically significant. CONCLUSION: The observed frequency of Y-chromosome microdeletion was 6.2% among Japanese azoospermic and oligozoospermic males; no microdeletions were identified among our African study patients. In this population of couples undergoing IVF+ICSI, there was no statistically significant difference in embryo characteristics or pregnancy outcome between patients with Y-chromosome microdeletion and those with an intact Y-chromosome

The Tempered Polymerization of Human Neuroserpin

Neuroserpin, a member of the serpin protein superfamily, is an inhibitor of proteolytic activity that is involved in pathologies such as ischemia, Alzheimer's disease, and Familial Encephalopathy with Neuroserpin Inclusion Bodies (FENIB). The latter belongs to a class of conformational diseases, known as serpinopathies, which are related to the aberrant polymerization of serpin mutants. Neuroserpin is known to polymerize, even in its wild type form, under thermal stress. Here, we study the mechanism of neuroserpin polymerization over a wide range of temperatures by different techniques. Our experiments show how the onset of polymerization is dependent on the formation of an intermediate monomeric conformer, which then associates with a native monomer to yield a dimeric species. After the formation of small polymers, the aggregation proceeds via monomer addition as well as polymer-polymer association. No further secondary mechanism takes place up to very high temperatures, thus resulting in the formation of neuroserpin linear polymeric chains. Most interesting, the overall aggregation is tuned by the co-occurrence of monomer inactivation (i.e. the formation of latent neuroserpin) and by a mechanism of fragmentation. The polymerization kinetics exhibit a unique modulation of the average mass and size of polymers, which might suggest synchronization among the different processes involved. Thus, fragmentation would control and temper the aggregation process, instead of enhancing it, as typically observed (e.g.) for amyloid fibrillation

Chlamydia trachomatis neither exerts deleterious effects on spermatozoa nor impairs male fertility

ABSTARCT: Chlamydia trachomatis is the most prevalent sexually transmitted bacterial infection. However, whether Chlamydia trachomatis has a negative impact on sperm quality and male fertility is still controversial. Herein, we report the effects on sperm quality of the in vitro exposure of spermatozoa to Chlamydia trachomatis, and also the effects of male genital infection on male fertility using an animal model. Human and mouse sperm were obtained from healthy donors and cauda epididimys from C57BL/6 mice, respectively. Highly motile human or mouse spermatozoa were in vitro exposed to C. trachomatis (serovar E or LGV) or C. muridarum, respectively. Then, sperm quality parameters were analyzed. Moreover, male fertility of Chlamydia muridarum infected male C57BL/6 mice was assessed. Human or murine sperm in vitro exposed to increasing bacterial concentrations or soluble factors from C. trachomatis or C. muridarum, respectively, did not show differences in sperm motility and viability, apoptosis, mitochondrial membrane potential, DNA fragmentation, ROS production and lipid peroxidation levels, when compared with control sperm (p > 0.05). Moreover, no differences in fertility parameters (potency, fecundity, fertility index, pre- and post-implantation loss) were observed between control and infected males. In conclusion, our results indicate that Chlamydia spp. neither directly exerts deleterious effects on spermatozoa nor impairs male fertility

Strong fragmentation and coagulation with power-law rates

Existence of global classical solutions to fragmentation and coagulation equations with unbounded coagulation rates has been recently proved for initial conditions with finite higher order moments. These results cannot be directly generalized to the most natural space of solutions with finite mass and number of particles due to the lack of precise characterization of the domain of the generator of the fragmentation semigroup. In this paper we show that such a generalization is possible in the case when both fragmentation and coagulation are described by power-law rates which are commonly used in the engineering practice. This is achieved through direct estimates of the resolvent of the fragmentation operator, which in this case is explicitly known, proving that it is sectorial and carefully intertwining the corresponding intermediate spaces with appropriate weighted L1 spaces

The wider social environment and changes in self-reported quality of life in the transition from late childhood to early adolescence: a cohort study

<p>Abstract</p> <p>Background</p> <p>Neighbourhood socioeconomic disadvantage and social capital have been associated with adolescent well-being, but the majority of studies were cross-sectional, and the time window over which the neighbourhood may impact on development is unknown. Therefore, the contribution of the neighbourhood environment to adolescents' quality of life and the course of these effects during the period of transition from childhood to early adolescence was examined.</p> <p>Methods</p> <p>A cohort of adolescents living in Maastricht (The Netherlands), with a mean age of 11.2 years at baseline and of 13.5 years at follow-up was followed. Adolescents who responded both at baseline and at follow-up were included in the analysis (n = 475). Multilevel regression analyses estimated neighbourhood effects while controlling for individual-level effects. Neighbourhood-level socioeconomic and social capital variables, individual-level confounders, and baseline values of the outcome measures were included in the models.</p> <p>Results</p> <p>None of the neighbourhood factors was associated with changes in general health or mental health over the two-year period. However, two-year exposure to greater disparity between individual level socioeconomic status on the one hand and neighbourhood level of socioeconomic status on the other (e.g. high socioeconomic status adolescents living in deprived neighbourhoods and vice versa) negatively impacted on self-esteem and satisfaction.</p> <p>Conclusion</p> <p>The neighbourhood environment per se does not contribute to change in quality of life during the transition to early adolescence. However, adolescents living in families whose socioeconomic status deviates from the mean level of neighbourhood socioeconomic deprivation may be negatively affected.</p