Rola Turki

Effects of increased paternal age on sperm quality, reproductive outcome and associated epigenetic risks to offspring

Over the last decade, there has been a significant increase in average paternal age when the first child is conceived, either due to increased life expectancy, widespread use of contraception, late marriages and other factors. While the effect of maternal ageing on fertilization and reproduction is well known and several studies have shown that women over 35 years have a higher risk of infertility, pregnancy complications, spontaneous abortion, congenital anomalies, and perinatal complications. The effect of paternal age on semen quality and reproductive function is controversial for several reasons. First, there is no universal definition for advanced paternal ageing. Secondly, the literature is full of studies with conflicting results, especially for the most common parameters tested. Advancing paternal age also has been associated with increased risk of genetic disease. Our exhaustive literature review has demonstrated negative effects on sperm quality and testicular functions with increasing paternal age. Epigenetics changes, DNA mutations along with chromosomal aneuploidies have been associated with increasing paternal age. In addition to increased risk of male infertility, paternal age has also been demonstrated to impact reproductive and fertility outcomes including a decrease in IVF/ICSI success rate and increasing rate of preterm birth. Increasing paternal age has shown to increase the incidence of different types of disorders like autism, schizophrenia, bipolar disorders, and childhood leukemia in the progeny. It is thereby essential to educate the infertile couples on the disturbing links between increased paternal age and rising disorders in their offspring, to better counsel them during their reproductive years.

Prevalence of human papillomavirus in women from Saudi Arabia.

BACKGROUND Human papillomavirus (HPV) infection is the main causes of cervical cancer in women worldwide. The goal of the present study was to determine the prevalence and distribution of HPV genotypes in women from Saudi Arabia. Recently, several HPV detection methods have been developed, each with different sensitivities and specificities. METHODS In this study, total forty cervical samples were subjected to polymerase chain reaction and hybridization to BioFilmChip microarray assessment. RESULTS Human papillomavirus (HPV) infections were found in 43% of the specimens. The most prevalent genotypes were HPV 16 (30%) HPV 18 (8.0%) followed by type HPV 45, occurring at 5.0%. CONCLUSION Our finding showed the HPV infection and prevalence is increasing at alarming rate in women of Saudi Arabia. There was no low risk infection detected in the tested samples. The BioFilmChip microarray detection system is highly accurate and suitable for detection of single and multiple infections, allowing rapid detection with less time-consumption and easier performance as compared with other methods.

Endocrine Disruption: Computational Perspectives on Human Sex Hormone-Binding Globulin and Phthalate Plasticizers.

Phthalates are a class of high volume production chemicals used as plasticizers for household and industrial use. Several members of this chemical family have endocrine disrupting activity. Owing to ubiquitous environmental distribution and exposure of human population at all stages of life, phthalate contamination is a continuous global public health problem. Clinical and experimental studies have indicated that several phthalates are associated with adverse effects on development and function of human and animal systems especially the reproductive system and exposures during pregnancy and early childhood are by far of utmost concern. Sex hormone-binding globulin (SHBG) is a plasma carrier protein that binds androgens and estrogens and represents a potential target for phthalate endocrine disruptor function in the body. In the present study, the binding mechanism of the nine phthalates i.e. DMP, DBP, DIBP, BBP, DNHP, DEHP, DNOP, DINP, DIDP with human SHBG was delineated by molecular docking simulation. Docking complexes of the nine phthalates displayed interactions with 15–31 amino acid residues of SHBG and a commonality of 55–95% interacting residues between natural ligand of SHBG, dihydrotestosterone, and the nine phthalate compounds was observed. The binding affinity values were more negative for long chain phthalates DEHP, DNOP, DINP, and DIDP compared to short chain phthalates such as DMP and DBP. The Dock score and Glide score values were also higher for long chain phthalates compared to short chain phthalates. Hence, overlapping of interacting amino acid residues between phthalate compounds and natural ligand, dihydrotestosterone, suggested potential disrupting activity of phthalates in the endocrine homeostasis function of SHBG, with long chain phthalates expected to be more potent than the short chain phthalates.

Analysis of chromosomal and genetic disorders in patients with recurrent miscarriages in Saudi Arabia

BackgroundRecurrent spontaneous abortion has been reported tooccur in 15-20% of all clinically recognizable pregnancies.Numerous studies have reported a clear relationshipbetween the chromosomal abnormalities in parents andrecurrent miscarriages and infertility [1-3], however lim-ited data is available from Arabian Peninsula. The maingoal of this study was to determine the prevalence ofchromosomal abnormalities and correlate them with clini-cal characteristics of couples with recurrent spontaneousabortions (RSA) in Saudi Arabia.Materials and methodsCytogenetic analysis of 171 consent patients with sponta-neous recurrent abortions was performed by the standardmethod of 72-hour lymphocyte culture and GTG banding.

Genomic answers for recurrent spontaneous abortion in Saudi Arabia: An array comparative genomic hybridization approach

To study the genomics/genetic factors associated with recurrent spontaneous abortion (RSA), as ∼50% of RSA are unexplained. However, chromosome abnormalities have been reported to play major role in RSA. We performed whole genome array-CGH based genomic analysis of forty four Saudi RSA patients to identify potential molecular and chromosomal abnormalities. We identified a total of 845 alterations, usually not detected by classic cytogenetic methods, in different genomic regions using a cut off value of -0.25 and 0.25 for structural loss and gain, whereas -1.0 and 0.58 were used for single copy number deletion and duplication respectively. We identified frequent (present at least in 10% of patients) alterations including three macro-alteration at 8p23.1, 10q11.21-q11.22 and 15q11.2 as well as large numbers of micro-deletions/amplifications with affected genes including 22q11.23 (GSTT1), 3p22.2 (CTDSPL), 6p21.32 (HLA), and 8p22 (MSR1). Pathway analysis of genes located in detected CNVs regions revealed the allograft rejection signaling, IL-4 signaling, and autoimmune thyroid disease signaling as the most significant canonical pathways associated with RSA. Whole genome array CGH technique can be used to identify potential genes, biofunctions and chromosomal abnormalities associated with RSA which is supported by our findings of a number of novel CNVs/genes (22q11.23/GSTT1, 3p22.2/CTDSPL, 6p21.32/HLA, 8p22/MSR1, and 14q32.33/AKT1) and pathways in patients affected with RSA. To improve diagnosis and treatment of RSA, a comprehensive procedure is needed for identification and validation of causative genes.

Genetic diversity and phylogenetic analysis of HPV 16 & 18 variants isolated from cervical specimens of women in Saudi Arabia

Human papillomavirus (HPV) are well known to be associated with the development of cervical cancer. HPV16 and HPV 18 are known as high-risk types and reported to be predominantly associated with cervical cancer. The prevalence and genetic diversity of HPV have been well documented globally but, in the Kingdom of Saudi Arabia, data on HPV genetic diversity are lacking. In this study, we have analyzed the genetic diversity of both HPV16 and HPV18 based on their L1 gene sequence because L1 gene is a major capsid protein gene and has been utilized to develop a prophylactic vaccine. In January 2011–2012, a total of forty samples from cervical specimens of women in Saudi Arabia were collected. The association of HPV16, HPV18 was detected by polymerase chain reaction, sequenced and submitted to GenBank. The sequences identity matrix and the phylogenetic relationship were analyzed with selected HPVs. The highest sequence identity (99.5%) for HPV16 and (99.3%) for HPV was observed with selected HPVs. The phylogenetic analysis results showed that HPVs from Saudi Arabia formed a closed cluster with African, Asian, East Asian as well as American HPVs distributed into multiple linages from various geographical locations. The results provided the valuable information about genetic diversity, but there is an urgent need to generate full genome sequence information which will provide a clearer picture of the genetic diversity and evolution of HPVs in Saudi Arabia. In conclusion, the generated data will be highly beneficial for developing molecular diagnostic tools, analyzing and correlating the epidemiological data to determine the risk of cervical cancer and finally to develop a vaccine for Saudi Arabian population.