The Impact of Methylenetetrahydrofolate Reductase (MTHFR) Sperm Methylation and Variants on Semen Parameters and the Chance of Recurrent Pregnancy Loss in the Couple.

BACKGROUND: Recurrent pregnancy loss (RPL) defined as three or more consecutive spontaneous miscarriages before the 20th week of gestation is caused by different factors including genetic and epigenetic background. However the involvement of paternal background on RPL is an interesting novel argument, which is not well studied. The main focus of the present study was to investigate for the association of paternal methylenetetrahydrofolate reductase (MTHFR) epigenotypes with sperm parameters and RPL. Moreover, the frequency of two of MTHFR Single Nucleotide Polymorphisms (SNPs) in males was assessed. METHODS: This is a case-control study. Methylation Specific PCR (MSP) was used to evaluate the methylation status of MTHFR promoter on sperm DNA of 25 male partners of RPL and 25 male partners of non-RPL couples. PCR-RFLP method was used to analyze 1,298 A>C (rs1801131) and 677 C>T (rs1801133) polymorphisms. RESULTS: No significant difference was observed in frequency of methylated MTHFR epigenotype between RPL and non-RPL males. Furthermore, methylated MTHFR epigenotype was more frequent (but not statistically significant) among men with abnormal sperm parameters compared to normal-sperm men. Among studied polymorphisms, only the mutated allele of C677T showed statistically higher prevalence among RPL males. CONCLUSIONS: Although our results do not establish any connection between MTHFR epigenotypes and RPL they do highlight the impact of C677T in the pathology.

Clinical and genetic-epignetic aspects of recurrent hydatidiform mole: A review of literature.

Hydatidiform Mole (HM) is the most common form of Gestational Trophoblastic Disease (GTD), defined by hyper-proliferation of trophoblastic cells. HM is typified as abnormal proliferation of extraembryonic trophoblastic (placental) tissues and failure of embryonic tissues development and is the only GTD with Mendelian inheritance, which can reoccur in different pregnancies. Moles are categorized into Complete Hydatidiform Moles (CHM) or Partial Hydatidiform Moles (PHM) and a rare familial trait, which forms a CHM and despite having androgenetic pattern, shows normal biparental inheritance, conceived from one sperm and egg. Recessive maternal-effect mutations in NLRP7 (NACHT, leucine rich repeat and PYD containing 7) and KHDC3L (KH Domain Containing 3-Like) genes have been shown to be responsible for Recurrent Hydatidiform Moles (HYDM1 MIM# 231090 when is caused by mutation in the NLRP7 gene and HYDM2 MIM#614293 when is caused by mutation in the KHDC3L gene). Methylation aberration in multiple maternally imprinted genes is introduced as the cause of Recurrent HYDM pathology. The current article reviews the histopathology, risk factors, and genetic and epigenetic characteristics of Recurrent HYDMs.

Proteomics of the periconception milieu.

There is increasing realisation that human health status in adulthood depends critically upon environmental conditions pertaining around the time of conception and during pregnancy. Poor maternal diet or adverse environmental conditions around the periconception period somehow induces the resultant embryo to adapt predictively in order to survive this level of stress for the whole of its life. However, if there is a mismatch between expectation and reality, where the conditions during later life are better than expected, things go wrong and the adult suffers a range of illnesses, including diabetes, heart disease, hypertension and stroke. Understanding the molecular signals that direct the early embryo to adopt appropriate adaptations to suit its future life would be extremely valuable. However, although it appears to be an ideal task for proteomic applications, there are technical, ethical and practical limitations to what can be achieved with the current framework of proteomic technology. Here, we review what has been achieved to date, explain some of the experimental problems and suggest some strategies for taking this field forward.

Heat-shock protein A8 restores sperm membrane integrity by increasing plasma membrane fluidity.

The constitutive 70  kDa heat-shock protein, HSPA8, has previously been shown to contribute to the long-term survival of spermatozoa inside the mammalian female reproductive tract. Here, we show that a recombinant form of HSPA8 rapidly promotes the viability of uncapacitated spermatozoa, the ability of spermatozoa to bind to oviductal epithelial cells, enhances IVF performance, and decreases sperm mitochondrial activity. Fluorescence recovery after photobleaching revealed that the repair of membrane damage is achieved by an almost instantaneous increase in sperm membrane fluidity. The ability of HSPA8 to influence membrane stability and fluidity, as well as its conserved nature among mammalian species, supports the idea that this protein protects sperm survival through membrane repair mechanisms. Free Persian abstract A Persian translation of the abstract is freely available online at http://www.reproduction-online.org/content/147/5/719/suppl/DC1.

Attenuation of cardiovascular responses and upper airway events to tracheal extubation by low dose propofol.

BACKGROUND: Hemodynamic changes and respiratory tract complications are often followed by tracheal extubation. These events may be dangerous in neurosurgical patients and those with cardiovascular disease or at an old age. OBJECTIVES: The aim of this study is to investigate the attenuation of cardiovascular responses and upper airway events resulting from tracheal extubation by low dose propofol. MATERIALS AND METHODS: 80 patients with ASA physical status I, undergoing an elective surgery in a double blind manner received 0.5mg/kg propofol or normal saline 2 minutes before extubation. Heart rate and blood pressure and quality of tracheal extubation were recorded. RESULTS: Heart rate and blood pressure in patients receiving propofol were less than the control group (P < 0.05) at the time of injection of propofol, but there were no differences between the two groups at the time of extubation. CONCLUSIONS: We concluded that propofol can reduce SBP, DBP, MAP, HR & cough production at the time of injection but there were no significant changes in these parameters after extubation.