Biomedical subjects

J-P Siffroi

Publications and source records attributed to J-P Siffroi.

4 recordsLinked to original sources

PubMed2006

[Molecular anomalies of the Y chromosome: Consequences on male fertility].

Molecular anomalies of the Y chromosome leading to male infertility are mainly microdeletions of the long arm of the Y chromosome. Three recurrently deleted portions of the long arm are the AZFa, AZFb and AZFc (AZF: Azoospermia Factor) regions. Complete deletions of the AZFc region are found in 10% of cases of severe male infertility. In addition to the AZF deletions, certain classes of Y chromosome (haplogroups) may also predispose to male infertility and could be transmitted to future male descents by various Assisted Reproductive Techniques (ART). Since the first discovery of microdeletions, the sequence of the Y chromosome has become available, revealing the mechanisms underlying deletion formation and also resulting in a coherent screening strategy. Recently, partial deletions of the AZF regions have been described. The significance of these deletions in the clinical context remains to be defined.

Biological Evolution↗

PubMed2005

[Genetic risks in embryo donation].

Embryo donation is now an acceptable practice which offers new therapeutic possibilities to many infertile couples. It can be proposed for genetic reasons like the existence of hereditary diseases in the families of both members of a couple, leading to a high risk of transmission to a child, or when a male or female sterility is associated with a transmissible genetic abnormality from the other partner. Embryos eligible for donation may have been conceived by in vitro fertilization performed because of a male or female infertility of genetic origin. As a consequence, they are considered at increased risk of carrying a known or unknown genetic abnormality related to parental infertility. A consultation should be provided before donation acceptation for defining exactly the causes of the initial in vitro fertilization and checking the genetic screening in the couple. According to recent guidelines established by the Genetics Commission of the French Federation of CECOS, some embryos could be excluded from donation process.

Adult↗

PubMed2004

[Gamete donor karyotyping: between real usefulness and safety rules].

The Commission de génétique de la Fédération française des CECOS has recently sent a questionnaire to each CECOS asking for the year of activity starting, the number of karyotypes performed every year, the number and the type of chromosomal abnormalities and the consequences for the donation process. For sperm donors, 9410 karyotypes have been realized during a mean number of 21.3 years. Fifty-seven chromosomal abnormalities (0.6%) have led to the exclusion of the donors, twenty of which being directly dangerous for the offspring [eight t(13;14), three reciprocal translocations, two structural abnormalities of unknown origin and seven inversions]. Twenty-three anomalies (three supernumerary markers, five 47,XYY, five fragile sites and ten mosaicism) as well as nine other (three Y chromosome inversions and six pericentric inversions of chromosome 9), although considered either as innocuous or as chromosomal variants, have also been excluded. Lastly, five miscellaneous abnormalities have also been considered as exclusion factors. Familial data and sperm counts were known for 28 of these donors. For egg donors, only 681 karyotypes have been performed during a mean number of 7.8 years of activity. Five karyotype abnormalities have led to the exclusion of the donor: one 47,XXX, one mosaicism 45,X/47,XXX/46,XX, one case of non specific rearrangements in half of mitosis and two reciprocal translocations [t(8;20) (q13;p13) et t(3;17) (q26;p13)]. The consequences of this study on gamete donor genetic screening are discussed.

Chromosome Aberrations↗

PubMedDate not supplied

[Molecular mechanisms in sex determination: from gene regulation to pathology].

Testis determination is the complex process by which the bipotential gonad becomes a normal testis during embryo development. As a consequence, this process leads to sexual differentiation corresponding to the masculinization of both genital track and external genitalia. The whole phenomenon is under genetic control and is particularly driven by the presence of the Y chromosome and by the SRY gene, which acts as the key initiator of the early steps of testis determination. However, many other autosomal genes, present in both males and females, are expressed during testis formation in a gene activation pathway, which is far to be totally elucidated. All these genes act in a dosage-sensitive manner by which quantitative gene abnormalities, due to chromosomal deletions, duplications or mosaicism, may lead to testis determination failure and sex reversal.

Animals↗