Project description:<p>The purpose of this study is to provide a reference profile of small extracellular RNAs in body fluids. These samples were originally obtained in a study that had a different purpose. The purpose of the original study was to establish a data and biological specimen repository to advance future research into male reproductive health and urologic health. Semen from semen analyses, as part of standard of care at the Center for Reproductive Health, was collected and stored in a tissue bank for future research purposes. These samples and associated clinical data (including age, race, education level, medical history and diet, environmental exposures and laboratory values, fertility diagnosis and infertility treatments) will help researchers understand any urological disorders and male reproductive health issues.</p>
Project description:RATIONALE: Learning about the amount of information on fertility and infertility by patients before they received treatment for cancer in a comprehensive cancer center may help doctors plan the best treatment.
PURPOSE: This clinical trial is studying the amount of information on fertility and infertility received by patients before treatment of cancer in patients who have finished treatment.
Project description:A majority of the cases of primary male infertility are idiopathic with the underlying molecular mechanisms contributing to the pathophysiology as yet unknown. Effects of the environment can alter the sperm epigenome thereby impacting male reproduc-tive health. Epigenetic mechanisms are crucial to understanding health and disease, and methylome alterations are now known to have far-reaching clinical implications. Here, we report the results from our pilot study, a first of its kind analysis of the ef-fect of the traditional practice of yoga on human sperm quality. We find marked im-provement in sperm characteristics in patients of idiopathic male infertility following asupervised21-dayyogaregimen.Furthermore,next-generationsequencing-basedmethylome analysis reveals alterations in the sperm epigenome of these patients. We find that the practice of yoga is associated with DNA methylation changes at nearly 400 genes, 147 of which were hypermethylated while 229 were hypomethyl-ated. These included promoters of several genes linked to maintenance of fertility and genomic integrity. This novel piece of work draws a direct link between positive lifestyle practices and male reproductive health.
Project description:We investigated the miRNA cluster miR-106b~25 as potential candidate causing male infertility. We analized single and double KO mice. Single KO show derregulation of multiple molecular pathways and disrupted early spermatogenesys, but retain fertility. Double KO show severely disrupted testicular histology and significantly reduced fertility.
Project description:To assess the relations of infertility causes and treatment to cancer risk, we will conduct a retrospective cohort study of approximately 12,000 women evaluated for infertility between 1965-1988. These women will be ascertained from several large infertility clinics and private practices in various geographic locations in the United States: Boston, Chicago, Detroit, New York, and Palo Alto. These practices were selected on the basis of their having large number of patients who received ovulation stimulating drugs many years in the distant past. Abstractors reviewed clinic medical records to identify eligible study participants and abstract data needed to classify causes of infertility and document therapies employed. Using a variety of tracing sources (including the National Death Index, credit bureaus, and postmasters), the vital status and location of the study subjects were determined. Subjects who were traced and identified as alive are being sent a detailed questionnaire that requests information on their health status as well as on a number of lifestyle practices. For subjects who report a cancer, medical verification is being sought from the diagnosing physicians and/or facilities. Death certificates are being sought for deceased subjects.
Project description:The product of the Bmal1 locus is an essential component of the circadian clock that plays important roles in various aspects of reproductive biology,and when disrupted results in infertility. In an effort to establish the identity of the tissue specific clock that is responsible for this infertility, we used the steroidogenic factor-1 (Sf1) promoter to drive Cre-mediated recombination and genetically delete Bmal1 within cells of the reproductive axis. We show that Bmal1 within the reproductive axis of females is essential for normal fertility through its role in maintaining implantation, but is not required for normal estrous cycling. At the root of this biology appears to be a defect in the ovaries, including regulation of ovarian lipid biosynthetic or metabolic processes and their roles in maintaining progesterone synthesis. This conclusion is based upon three observations. First, that deletion of Bmal1 within the reproductive axis reducesleads to affected transcripts in steroidogenic pathways for the LH receptor , and lowers progesterone levels. Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants rescues fertility. Our study demonstrates the significance of ovarian Bmal1 as an overriding influence in experimental models of infertility. A time series was performed in time-mated C57Bl/6J mice to identiy oscillating transcripts. During the peak and trough of the majority of transcripts (ZT0 and ZT12) samples from Bmal1fx/fx Sf1Cre mice and control litermates as well and global Bmal1 nulls were also analyzed. The tissue types (ovary, pituitary) are not comparable.
Project description:The product of the Bmal1 locus is an essential component of the circadian clock that plays important roles in various aspects of reproductive biology, and its disruption results in infertility. In an effort to identify the identity of the tissue specific clock that is responsible for this infertility, we used the steroidogenic factor-1 (Sf1) promoter to drive Cre-mediated recombination and genetically delete Bmal1 within cells of the reproductive axis. We show that Bmal1 within the reproductive axis of females is essential for normal fertility through its role in maintaining implantation, but is not required for normal estrous cycling. At the root of this biology appears to be a defect in the regulation of ovarian steroidogenic acute regulator (StAR) and its role in maintaining progesterone synthesis. This conclusion is based upon three observations. First, that deletion of Bmal1 within the reproductive axis leads to lower levels of StAR mRNA, and lower progesterone levels. Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants results in 100% fertility. Our study suggests that ovarian Bmal1 is an essential peripheral clock governing implantation and fertility in female mice. Ten week old female Bmal1fxfx mice positive or negative for Cre-recombinase driven by the sf-1 promoter, housed in 12 hour light:12 dark, ad lib feeding and drinking conditions were sacrificed at ZT12 on 3.5dpc (3.5 days post copulation). For each array analysis, a pool of 3 RNA samples from 3 individual Bmal1fx/fxCresf-1 ovaries labeled with cy3 were co-hybridized with a pool of 3 RNA samples from Bmal1fx/fx ovaries labeled with cy5, according to Agilent protocols.
Project description:The product of the Bmal1 locus is an essential component of the circadian clock that plays important roles in various aspects of reproductive biology, and its disruption results in infertility. In an effort to identify the identity of the tissue specific clock that is responsible for this infertility, we used the steroidogenic factor-1 (Sf1) promoter to drive Cre-mediated recombination and genetically delete Bmal1 within cells of the reproductive axis. We show that Bmal1 within the reproductive axis of females is essential for normal fertility through its role in maintaining implantation, but is not required for normal estrous cycling. At the root of this biology appears to be a defect in the regulation of ovarian steroidogenic acute regulator (StAR) and its role in maintaining progesterone synthesis. This conclusion is based upon three observations. First, that deletion of Bmal1 within the reproductive axis leads to lower levels of StAR mRNA, and lower progesterone levels. Second, that progesterone supplementation of these conditional mutants rescues implantation. Third, transplantation of wild type ovaries into Bmal1 reproductive axis mutants results in 100% fertility. Our study suggests that ovarian Bmal1 is an essential peripheral clock governing implantation and fertility in female mice.