Vitamin B-12 and liver activity and expression of methionine synthase are decreased in fetuses with neural tube defects.

Background: The risk of neural tube defects (NTDs) is influenced by nutritional factors and genetic determinants of one-carbon metabolism. A key pathway of this metabolism is the vitamin B-12- and folate-dependent remethylation of homocysteine, which depends on methionine synthase (MS, encoded by MTR), methionine synthase reductase, and methylenetetrahydrofolate reductase. Methionine, the product of this pathway, is the direct precursor of S-adenosylmethionine (SAM), the universal methyl donor needed for epigenetic mechanisms.

Fumonisin FB1 treatment acts synergistically with methyl donor deficiency during rat pregnancy to produce alterations of H3- and H4-histone methylation patterns in fetuses.

Scope: Prenatal folate and methyl donor malnutrition lead to epigenetic alterations that could enhance susceptibility to disease. Methyl-deficient diet (MDD) and fumonisin FB1 are risk factors for neural tube defects and cancers. Evidence indicates that FB1 impairs folate metabolism.

A splicing variant leads to complete loss of function of betaine-homocysteine methyltransferase (BHMT) gene in hepatocellular carcinoma.

The remethylation of homocyteine into methionine is catalyzed either by methionine synthase (MTR) or by betaine-homocysteine methyltransferase (BHMT), in the liver. Choline/betaine deficiency and impaired BHMT pathway have been associated with hepatocellular carcinogenesis, in animal models. The molecular mechanisms that impair the BHMT pathway are unknown.

Ovarian tissue cryopreservation and subsequent spontaneous pregnancies in a patient with classic galactosemia.

Objective: To report two consecutive spontaneous pregnancies in a compound heterozygous patient with classic galactosemia and a heterozygous partner, 6 years after ovarian tissue cryopreservation.

Design: Case report.

Setting: Tertiary health care center.

Life-threatening methylenetetrahydrofolate reductase (MTHFR) deficiency with extremely early onset: characterization of two novel mutations in compound heterozygous patients.

Methylenetetrahydrofolate reductase (MTHFR) is a key enzymatic component of the folate cycle, converting 5,10-methylenetetrahydrofolate into 5-methyltetrahydrofolate, the methyl donor for remethylation of homocysteine into methionine. Severe MTHFR deficiency is a rare recessive disease leading to major hyperhomocysteinemia, homocystinuria, and progressive neurological distress within the two first decades of life. More than 50 mutations have been reported so far in affected patients but only a few cases with very early onset of symptoms during the first weeks have been described, most of them showing a particular severe clinical course.

Local lymphocytic and epithelial activation in a case of autoimmune oophoritis.

Objective: To further define the immunological tissular modifications in premature ovarian failure (POF).

Method: The patient was followed up for premature ovarian failure and mild endometriosis associated with serum antiovarian antibodies. A laparoscopic ovarian biopsy was decided on to analyze the tissue and support the onset of immunosuppressive therapy.

Impact of folate and homocysteine metabolism on human reproductive health.

Folates belong to the vitamin B group and are involved in a large number of biochemical processes, particularly in the metabolism of homocysteine. Dietary or genetically determined folate deficiency leads to mild hyperhomocysteinemia, which has been associated with various pathologies. Molecular mechanisms of homocysteine-induced cellular dysfunction include increased inflammatory cytokine expression, altered nitric oxide bioavailability, induction of oxidative stress, activation of apoptosis and defective methylation.

Corticosteroids in patients with antiovarian antibodies undergoing in vitro fertilization: a prospective pilot study.

Objective: Antiovarian autoantibodies (AOA) have been associated with reproductive failure, especially in in vitro fertilization (IVF) patients. Thus, the success rate of IVF might be improved by the use of corticosteroids. However, therapeutic trials with these drugs have yielded conflicting results, particularly because of heterogeneous inclusion criteria.

The influence of cigarette smoking on human sperm quality and DNA fragmentation.

The aim of the present study was to evaluate consequences of cigarette smoking on male gametes. In this prospective study, sperm parameters such as sperm density, motility, viability and normal morphology were measured according to the WHO criteria. In addition to these standard parameters, we analysed the degree of DNA fragmentation in spermatozoa using the TUNEL-assay with flow cytometry detection in 57 non-smokers and 51 smokers seeking for infertility counselling.

Gonadal antibodies interfering with female reproduction.

While the involvement of anti-ovarian antibodies (AOAs) is highly likely, yet still controversial, in patients with patent premature ovarian failure (POF), it is even more difficult--for several reasons--to ascertain the clinical significance of these antibodies in patients without obvious ovarian failure. First, AOAs form a heterogeneous group of antibodies recognizing several different antigenic targets such as granulosa and thecal cells, zona pellucida, oocyte cytoplasm, corpus luteum, as well as gonadotrophins and their receptors. Second, the detection of AOAs in various clinical situations does not readily imply a causal relationship between these antibodies and impaired ovarian function.