Saira Amir

Sperm epigenome undergoes age-dependent changes increasing risks of adverse conditions in offspring conceived by fathers of advanced age. The mechanism(s) linking paternal age with epigenetic changes in sperm remains unknown. The sperm epigenome is shaped in a compartment protected by the blood-testes barrier (BTB) known to deteriorate with age. Permeability of the BTB is regulated by the balance of two mTOR complexes in Sertoli cells. We hypothesized that this balance is also responsible for age-dependent changes in the sperm epigenome. Experiments with transgenic mice demonstrate that the shift of the balance in favor of mTOR complex two rejuvenates sperm DNA-methylome while the shift in favor of mTOR complex one accelerates aging of the sperm DNA-methylome and results in a reproductive phenotype concordant with older age.One-Sentence SummaryThe balance between mTOR complexes in Sertoli cells regulates sperm methylome aging.

The human microbiota is recognized as a vital “virtual” organ of the human body that influences human health, metabolism, and physiology. While the microbiomes of the gut, oral cavity, and skin have been extensively studied in the literature, relatively little work has been done on characterizing the microbiota of the human reproductive tract organs, and specifically on investigating its association to fertility. Here, we implemented a 16S ribosomal RNA (rRNA) amplicon sequencing approach to sequence and characterize the gut and genital tract microbiomes from several married Pakistani couples. The recruited individuals included 31 fertile and 35 infertile individuals, with ages ranging from 19–45 years. We identified several fluctuations in the diversity and composition of the gut and genital microbiota among fertile and infertile samples. For example, measures of α-diversity varied significantly between the genital samples donated by fertile and infertile men and there was overall ...

The study was carried to find out the distributional pattern of blood groups of a random population samples from the area of Danyore and Gilgit, Pakistan. The blood samples were taken randomly from population .This study is aimed to determine and find significance valve of blood groups with gender and location. The total of 150 limited blood groups were taken and studied, comprising by 56 males population (37.4%) and 94 females population (62.6%). Among 08 blood groups A+ve has highest count in the total of 150 Population of district Gilgit while Blood Group B-ve and AB-ve has least. The total number of observation for Blood Group A+ve were 34 (22.7%), among these 8 was males and remaining 26 females. This shows that among A+ve Blood Group female were dominate as camper to male. The total number of observation for the Blood Group A-ve were 24 (16%),among these 13 were male and 11 were females. The number of observation for the Blood group B+ve were 28 (18.7%), among these 12 was mal...

The Gilgit Baltistan of Pakistan spans an area of 72,496 square kilometers, bordering China, Afghanistan, AJK and India. Gilgit Baltistan is connection of three greatest mountain ranges of the world; the Karakorum, the Hindukush and the Himalayas. As a result of its politically sensitive location, the Gilgit Baltistan has been accorded special territorial status; the area was administered directly by the Federal Government, through the “Ministry of Kashmir affairs & Northern Areas (Gilgit Baltistan).

The goal of this project is to identify molecular mechanisms and disease categories sensitive to chemical exposures in an unbiased way. Results of this project are published on preprints.org (doi: 10.20944/preprints202006.0261.v1). The data-files described below represent major steps of our analysis: 1. Annotated chemical-gene interactions.xlsx The data on chemical-gene interactions obtained from high-throughput toxicological genomic experiments with human, mouse, or rat cells and tissues was extracted from Comparative Toxicogenomic Database (CTD, http://ctdbase.org/) on 08.24.2018. Genes of olfactory receptors were removed from resulting database as these genes have different names in different mammalian species. Chemical compounds were annotated for major uses with information from Wikipedia, PubChem, and PubMed. Based on textual annotation every compound was assigned one to three annotation terms out of the following list: pharmaceutical, recreational drug, research, warfare, endobiotic, agricultural, cosmetics, environment, food components, industrial, and pollutant. All contributors annotated an equal numbers of chemicals, and AS checked every annotation to insure consistency of approaches. The resulting dataset includes 641,516 individual chemical-gene interactions. 2. Number of chemical-gene interactions per gene.xlsx The dataset created at the previous step was used to determine number of chemical-gene annotations for every gene, including total number as well as number of activating and suppressive chemical-gene annotations. We hypothesize, that number of chemical gene interactions can be used as a measure of the gene sensitivity to chemical exposures. 3. Enrichment of molecular pathways with genes sensitive to chemical exposures.xlsx The list of genes with the total number of chemical-gene interactions for every gene was used as an input for the Gene-Set Enrichment Analysis (GSEA, https://www.gsea-msigdb.org/gsea/index.jsp) against Hallmark, KEGG, and Reactome datasets, to identify molecular pathways highly enriched with genes sensitive to chemical exposures. We suggest, that normalized enrichment score (NES) for every enriched pathway is a measure of the pathway's sensitivity to chemical exposures. 4. Predicted adverse outcomes_KEGG.xlsx and Predicted adverse outcomes_Reactome.xlsx After identification of the most sensitive pathways (see previous paragraph) we inquired, what adverse outcomes may be associated with perturbation of these pathways. To do so we uploaded lists of the most sensitive KEGG and Reactome pathways (NES > 2.5, FDR < 0.1) to CTD and conducted an association analysis between pathway terms and disease terms. Many disease terms occurred more than one time in the output of this analysis as they were associated with multiple sensitive pathways. We suggest that the number of occurrences is and indicator of the susceptibility of the corresponding health condition to chemical exposures

Mitochondrial sirtuins (SIRT3, SIRT4, SIRT5) are post-translational modifiers that regulate energy production, body homeostasis and mitochondrial activities via different substrates in response to environmental stressors. The present study aimed at assessing the expression of SIRT3, SIRT4, and SIRT5 in the semen of infertile men. Expression analysis was performed using q-RT PCR. All mitochondrial sirtuin genes were significantly down-regulated in the semen of infertile men compared to fertile men. Mitochondrial sirtuin genes expression levels were correlated with mitochondrial HSP90 expression. HSP90 expression was positively correlated with SIRT3, SIRT4 and SIRT5 expression in the semen of fertile men, while a negative correlation was observed between HSP90 in the semen of infertile men and mitochondrial sirtuin genes in the semen of fertile men. These data suggest that dysregulation of mitochondrial sirtuin genes causes mitochondrial dysfunction due to stress, which appears to be associated with human male infertility by compromising functional and structural sperm integrity.

Increasing contamination of the environment by toxic compounds such as endocrine disrupting chemicals (EDCs) is one of the major causes of reproductive defects in both sexes. Estrogen/androgen pathways are of utmost importance in gonadal development, determination of secondary sex characteristics and gametogenesis. Most of the EDCs mediate their action through respective receptors and/or downstream signaling. The purpose of this review is to highlight the mechanism by which EDCs can trigger antagonistic or agonistic response, acting through estrogen/androgen receptors causing reproductive defects that lead to infertility. In vitro, in vivo and in silico studies focusing on the impact of EDCs on estrogen/androgen pathways and related proteins published in the last decade were considered for the review. PUBMED and PUBCHEM were used for literature search. EDCs can bind to estrogen receptors (ERα and ERβ) and androgen receptors or activate alternative receptors such as G protein-coupled...

Background: Targeted methods that dominated toxicological research until recently did not allow for screening of all molecular changes involved in toxic response. Therefore, it is difficult to infer if all major mechanisms of toxicity have already been discovered, or if some of them are still overlooked. Objectives: To identify molecular mechanisms sensitive to chemical exposures in an unbiased manner. Methods: We used data on 641,516 unique chemical-gene interactions from the Comparative Toxicogenomic Database. Only data from high-throughput gene expression experiments with human, rat or mouse cells/tissues were extracted. The total number of chemical-gene interactions was calculated for every gene, and used as a measure of gene sensitivity to chemical exposures. These values were further used in enrichment analyses to identify molecular mechanisms sensitive to chemical exposures. Results: Remarkably, use of different input subsets with non-overlapping lists of chemical compounds i...

Poster Session 6 - Tumor Cell and Molecular Biology: Etiology/Carcinogenesis Abstract P6-06-04: Preliminary Studies Characterizing the Prevalence of Mouse Mammary Tumor-Like Sequences in Human Tissues of Pakistani Origin S Amir, S Bilal, W Ahmed, M Zahid, and F. Mustafa COMSATS Institute of Information Technology, Islamabad, Pakistan Background: Pakistan has the second highest rate of breast cancer in Asia after Israel with nearly 1 out of 9 women at risk of developing breast cancer at some stage in their lifetime. A potential role of viruses in human breast cancer induction/development is increasingly coming to surface. Several different groups around the world have demonstrated the presence of mousemammary tumor virus (MMTV)-like sequences in tumor but not normal breast tissue. However, these findings are controversial and seem to differ depending upon the geographic location and ethnicity of a population. Some find MMTV-like sequences in tumors of breast cancer patients only, whi...

Male infertility is a major problem with important socioeconomic consequences. It is associated with several pathological factors, including but not limited to endocrine disruption as a result of environmental pollution and the alarming decline in sperm count over the decades is indicative of involvement of many environmental and lifestyle changes around the globe. Organochlorine pollutants such as dichlorodiphenyltrichlorethanes (DDTs), polychlorinated biphenyls (PCBs) and hexachlorobenzene (HCB) disrupt male reproductive system but the exact effect of environmental exposure on semen parameters in human is still not clear. This study was designed to monitor PCBs, DDTs and HCB in hair, urine and serum samples of infertile and healthy fertile men. Solid-phase microextraction gas chromatography-mass spectrometry (SPME/GC-MS) was used to monitor analytes. All tested compounds were detected, indicating recent use/persistent accumulation. Hair samples revealed no significant association with serum/urine concentrations of the analytes, while serum/urine concentrations were significantly correlated positively. Concentrations were higher in serum compared to other samples. The levels of organochlorine pollutants were higher in infertile men compared to controls with few exceptions. Among PCBs, and DDTs, PCB-153 and pp'-DDT were detected in highest concentrations, respectively. op'-DDT and pp'-DDT levels were significantly higher in infertile men compared to controls. HCB was significantly correlated negatively with sperm motility in all samples. Serum concentrations of all compounds were higher in men with defective semen parameters compared to normospermics. Serum was the best biological sample for assessing health outcomes in relation to exposure levels.