impact of genetic variation and gene expression level of the follicle-stimulating hormone receptor on ovarian reserve

Objective: ovarian reserve is defined as the capacity of the ovary to provide fertile oocytes. Diminished ovarian reserve [DOR] is a disorder in which ovaries are prone to go through early menopause. Where this loss of function occurs before the age of 40, it results in the premature ovarian failure [POF] disease. Throughout folliculogenesis, the follicle-stimulating hormone receptor [FSHR] starts a signaling cascade in the granulosa cells where its inactivation leads to the arrest of follicle maturation and therefore adversely affects ovarian reserve. The aim of this study was to investigate the association of genetic variation [polymorphisms and inactivating mutations] of FSHR with POF and DOR

Materials and Methods: this case-control study comprised 84 POF, 52 DOR and 80 fertile Iranian women. To determine the presence of the 566C>T mutation and the -29G>A polymorphism in FSHR, PCR-RFLP method was used. SSCP-sequencing was used to identify any allelic variants in exon 10. The expression of human FSHR at the transcript level was also compared between DOR and fertile controls by real time-polymerase chain reaction [PCR]

Results: the 566C>T polymorphism was normal in all the cases. All genotypes of -29G>A and 919G>A [exon 10] polymorphisms were observed. Statistically significant differences were seen in the genotypic distribution of both polymorphisms when comparing the control group with the DOR patient group. A decrease was observed in FSHR expression of DOR patients compared with the control group but was not significant

Conclusion: we conclude that the -29G>A and 919G>A polymorphisms in FSHR may be associated with DOR. Although these polymorphisms had significant differences at the genic level, no significant variation was found at the transcript level

Cord blood karyotyping: a safe and non-invasive method for postnatal testing of assisted reproductive technology children

Background: To verify the hypothesis that the incidence of chromosomal abnormalities increases in babies conceived by different assisted reproduction procedures. The availability of the umbilical cord blood encouraged us to study this hypothesis via this method

Materials and Methods: This is a descriptive study, umbilical cord blood samples of assisted reproductive technology [ART] children were analyzed with standard cytogenetic techniques [G banding]. Karyotyping was possible in 109 cases

Results: The number of abnormal cases was four [3.7%], among which, three cases [2.8%] were inherited and only 1 case [0.9%] was a de novo translocation. In total, the incidence of de novo chromosomal abnormalities was in the range observed in all live births in the general population [0.7-1%]

Conclusion: No significant difference in the incidence of chromosomal abnormality was found between ART and naturally conceived babies. To date, several studies have examined the medical and developmental outcome of ART children and still have not reached a definite conclusion. Genetic counseling is recommended as an integral part of planning of treatment strategies for couples wishing to undergo ART

association between [8390G>A] single nucleotide polymorphism in APOE gene with Alzheimer's and Parkinson disease

Genetic susceptibility, is considered to be involved in neurodegenerative diseases such as Alzheimer's disease [AD] and Parkinson's disease [PD]. Despite the fact that many susceptibility genes for AD and PD have been considered, the most probable genetic risk factor which has been taken into consideration is Apolipoprotein E genotype located on chromosome 19q, APOE is the gene widely considered to be a susceptibility gene for neurodegenerative diseases. This study is to investigate the association of APOE polymorphism with AD and PD. In this case control study we examined association of an APOE gene polymorphism [rs121918398] with AD and PD in Iranian population. The study included 100 AD patients, 100 PD patients and 150 healthy volunteers. An informed consent was obtained from all participants. Genomic DNA was extracted from peripheral blood leukocyte. Genotypes were determined by PCR and restriction fragment length polymorphism [RFLP] by Hha1 restriction enzyme. Sequencing of PCR products was carried out by Fazabiotech Company according to Sanger method using ABI 3730XL Capillary Sequencer. Statistical analysis was performed using the MedCalc program. The prevalence of genotype frequencies of the APOE A/A, A/G, G/G were 16%, 34% and 50% in AD subjects, 14%, 32%, 54% in PD patients and in healthy volunteers were 15%, 39% and 96% respectively. Statistical analysis showed no significant difference between genotype frequencies of AD and those of control subjects [P < 0.05]. Moreover, according to statistical analysis, the genotype frequencies of APOE in PD subjects and control group did not significantly differ. This is the very first time that the association of this polymorphism [rs121918398] with AD is being reported nevertheless, there is no evidence that APOE variant is associated with PD. Accordingly, genotype alteration of A8390>G can't be related to AD. So, this polymorphism plays no pathogenic role in the PD and AD patients in Iranian population

rare de novo complex chromosomal rearrangement [CCR] involving four chromosomes in an oligo-asthenosperm infertile man

Complex chromosomal rearrangements [CCRs] are rare events involving more than two chromosomes and over two breakpoints. They are usually associated with infertility or sub fertility in male carriers. Here we report a novel case of a CCR in a 30-year-old oligoasthenosperm man with a history of varicocelectomy, normal testes size and normal endocrinology profile referred for chromosome analysis to the Genetics unit of Royan Reproductive Biomedicine Research Center. Chromosomal analysis was performed using peripheral blood lymphocyte cultures and analyzed by GTG banding. Additional tests such as C-banding and multicolor fluorescence in situ hybridization [FISH] procedure for each of the involved chromosomes were performed to determine the patterns of the segregations. Y chromosome microdeletions in the azoospermia factor [AZF] region were analyzed with multiplex polymerase chain reaction. To identify the history and origin of this CCR, all the family members were analyzed. No micro deletion in Y chromosome was detected. The same de novo reciprocal exchange was also found in his monozygous twin brother. The other siblings and parents were normal. CCRs are associated with male infertility as a result of spermatogenic disruption due to complex meiotic configurations and the production of chromosomally abnormal sperms. These chromosomal rearrangements might have an influence on decreasing the number of sperms

Chromosome abnormalities and viability of vitrified eight-cell mouse embryos at presence of two different cryoprotectants at different storage durations

Experiments were conducted to find the differences between post-thaw viability and chromosome aberrations in eight-cell mouse embryos at presence of dimethyl sulfoxide [DMSO] and 1, 2-propanediol [PROH] as croprotectants in different storage durations. In this case-control study, a total number of 720 mouse embryos from about 250 NMRI mice were vitrified with 30% PROH or DMSO; each diluted with a solution containing 30% ficol plus 0.5 M sucrose. Embryos were exposed to the solutions for 0.5 minute at 25[degree sign] followed by cooling in liquid nitrogen, then after appropriate storage duration, they were rapidly warmed. Besides, there were 100 mouse embryos for each cryoprotectant group [totally 200 embryos] as control. Embryo survival was assessed by in vitro development, and chromosome abnormalities were analyzed by Giemsa staining. The proportion of mitotic abnormalities in PROH/DMSO vitrified embryos was significantly higher than unfrozen control group. This was confirmed also by a reduced viability of the embryos as judged by a culture at the blastocyst stage [p<0.05 in all test groups]. It can be deduced that long term cryopreservation may result in chromosomal abnormalities and/or low viability