Human Genetics & Embryology

Cancer and developmental biology scientists realized over a century ago that genes and pathways relevant to cancer overlap with embryonic development as reflected in the reactivation of embryonic genes during tumor progression. Consequently the question was raised of whether tumors could arise from transformation of tissue stem cells or “retro-differentiation” of more differentiated cells. Nearly 40 years later, these ideas and questions are still hot spots in cancer research. The “retrodifferentation” concept can be now translated as cellular plasticity, a process by which non-stem differentiated cells can spontaneously acquire stem cell like characteristics . This phenomenon has important implications for cancer therapy and a big impact on our current view of the cancer stem cell hypothesis.

Recently, I had in my hands an interesting and highly recommended review from Jueng Soo You and Peter Jones entitled “Cancer Genetics and Epigenetics: Two Sides of the Same Coin?” which was published in Cancer Cell. In this review, the authors discuss the role and the weight of genetics and epigenetics in tumorigenesis. According to them “intriguing evidences have emerged showing that genetic and epigenetic mechanism are not separate events in cancer” and “alterations in epigenetic mechanisms can lead to genetic mutations, and genetic mutations in epigenetic regulators lead to an altered epigenome”. Here, I develop this theme based on this last statement.

Objective: To report a successful pregnancy after transfer of embryos derived from oocytes activated by calcium ionophore after intracytoplasmic sperm injection (ICSI) with round-headed sperms and aneuploid screening using a- CGH. Design: Case report Setting: Private IVF clinic. Patient: A 28-year-old patients and her 31-year-old husband, diagnosed with 100% globozoospermia, underwent ICSI, oocyte activation and chromosome screening using a-CGH. Intervention: Ten metaphase II oocytes were injected with round-headed sperms. After ICSI, the oocytes were treated with 10 μM calcium ionophore solution for 20 minutes at 37◦C in 6% CO2. The fertilization was checked 18 hours later. On morning of day 3, one blastomere was biopsied from embryos which had at least 6 cells and sent to the genetic lab for aneuploid screening using a-CGH. Two euploid embryos were transfer on the fifth day after oocyte retrieval. Supernumerary normal embryos were vitrified for future use. Main Outcome Measure: Ongoing pregnancy after transfer of embryos after calcium ionophore activation and a- CGH screening. Results: This couple experienced only 12% fertilization after ICSI in their first cycle. On the second cycle, 8 out of 10 metaphase II oocytes were fertilized after ICSI and calcium ionophore activation immediately after ICSI. 6 out of 8 embryos were diagnosed as euploid. Two normal blastocysts were chosen for transfer. Clinical pregnancy was confirmed at 7 weeks of gestation with two heartbeats. Two healthy babies were born. Conclusion: Artificial oocyte activation using calcium ionophore is beneficial in patients with globozoospermia. This study showed that the method of oocyte activation does not affect chromosome constitution and the normal growth of preimplantation embryos. Further studies are needed to confirm the safety of oocyte activation in born babies.

Objectives: Hypogonadism is the clinical manifestation of the impaired function of the testes and the ovaries, and is either due to endocrinological problems or chromosomal abnornlalities (CA). Chromosomal analysis is one important piece in the hypogonadism individuals, and becomes essential from the clinical point of view. Design: To determine the frequency, types of CAs in a hypogonadism population. Materials and method: The current study was a retrospective analysis to examine the CAs and prevalence in 64 cases with unexplained hypogonadism problem. The samples were cultured routinely for the karyotype analysis using G banding. Results: A total of 64 individuals with infertility was analysed. The karyotype results were normal in 52 (81.2%) of 64 individuals. However, CAs were detected in 12 (18.8%) of all individuals. The 15.6% of these CAs was numerical aberrations, and also structural CA was 3.1%. Specifically, Klinefelter syndrome (KS) was the most common karyotype (14.1%,9 cases) among the all cases, followed by 46,XX,anoploidy; 46,Xi(Xq) and 46,XY,robt(14;15). Conclusion: We found a high rate CAs (18.8%) in patients with hypogonadism. Therefore, cytogenetic analysis can be strongly recommended in hypogonadism individuals, and should be performed routinely in both the male and female with hypogonadism.

We use genetic screening to establish the genes which are responsible for the production of specific proteins. When this technique was developed it was heralded as the ultimate solution: 'the answer to life, the universe and all that'; but as time has gone on we have come to recognise that it is extremely rare to be able to link one particular gene to the production of one particular protein because the expression of proteins involves the influence of many genes.