Etude de l'empreinte parentale de quatre gènes MEST, SNRPN, H19 et IGF2 dans des populations de spermatozoïdes éjaculés

PARIS-BIUP (751062107) / SudocSudocFranceF

Intégrines spermatiques et échanges membranaires entre les gamètes (implications dans l'interaction gamétique chez la souris)

LE KREMLIN-B.- PARIS 11-BU Méd (940432101) / SudocSudocFranceF

Epigenetic disorders and male subfertility

Abstract: Objective: To provide a link between epigenetics and male subfertility at the DNA, histone-protamine, and RNA levels and its consequences on fertilization and embryo development. Design: Review of the relevant literature. Setting: University-based clinical and research laboratories. Patient(s): Fertile and infertile men. Intervention(s): None. Main Outcome Measure(s): Critical review of the literature. Result(s): Epigenetic markers can be modified in infertile patients. Epigenetic modifications include methylation loss or gain on the global level and on imprinted genes, high levels of histone retention in spermatozoa, and deficiencies in some transcripts involved in spermatogenesis. Interestingly, these abnormalities are all linked together, because DNA methylation maintenance depends on DNA histone-protamine configuration which itself is stabilized by spermatozoal RNAs. Conclusion(s): The paternal genome has long been considered to be silent and passive in embryo formation. The epigenetic processes associated with the paternal DNA genome highlights its importance in male fertility as well as for embryo development

Post-treatment sperm cryopreservation practices in childhood and young adult cancer survivors

International audienceResearch question: What are current practices of post-treatment fertility preservation in male childhood cancer survivors (CCS) who have not benefitted from pre-therapeutic fertility preservation in France and other European countries?Design: A survey was conducted of all fertility preservation centres in France (n = 30) and European fertility specialists (n = 9) in five European countries. Eight clinical cases and 40 questions were included to assess the effect of age at diagnosis, type of treatment (alkylating-agents, orchidectomy, testicular radiotherapy) and sperm parameters on the probability of a post-treatment fertility preservation proposal. Demographic characteristics of the responding practitioner were also collected.Results: Post-treatment sperm cryopreservation was proposed by 100% of fertility specialists in cases of severe oligoasthenoteratozoospermia, 77-88% in cases of moderate oligoasthenoteratozoospermia and in 65-77% in cases of sperm motility and vitality impairment. In cases of normal sperm parameters, 27-54% of fertility specialists would propose post-treatment sperm cryopreservation. These results did not differ significantly according to the type of treatment received or to responder-related factors. Practices of European specialists were also guided by sperm parameter results; 44-67% of specialists responding that they would propose sperm cryopreservation in cases of moderate to severe sperm parameter alterations.Conclusion: Post-treatment semen analysis could be widely proposed to CCS who have not benefitted from pre-therapeutic fertility preservation. Post-treatment fertility preservation could be proposed in cases of persistent moderate to severe sperm parameter alterations. Guidelines would be important to homogenize practices and to encourage oncologists to refer CCS for fertility assessments

Partial Sperm beta1 Integrin Subunit Deletion Proves Its Involvement in Mouse Gamete Adhesion/Fusion

We have previously shown, using antibodies, that the sperm alpha6beta1 integrin is involved in mouse gamete fusion in vitro. Here we report the conditional knockdown of the sperm Itgb1 gene. It induced a drastic failure of sperm fusogenic ability with sperm accumulation in the perivitelline space of in vitro inseminated oocytes deleted or not for the Itgb1 gene. These data demonstrate that sperm, but not oocyte, beta1 integrin subunit is involved in gamete adhesion/fusion. Curiously, knockdown males were fertile in vivo probably because of the incomplete Cre-mediated deletion of the sperm Itgb1 floxed gene. Indeed, this was shown by Western blot analysis and confirmed by both the viability and litter size of pups obtained by mating partially sperm Itgb1 deleted males with females producing completely deleted Itgb1 oocytes. Because of the total peri-implantation lethality of Itgb1 deletion in mice, we assume that sperm that escaped the Itgb1 excision seemed to be preferentially used to fertilize in vivo. Here, we showed for the first time that the deletion, even partial, of the sperm Itgb1 gene makes the sperm unable to normally fertilize oocytes. However, to elucidate the question of the essentiality of its role during fertilization, further investigations using a mouse expressing a recombinase more effective in male germ cells are necessary

Prospective analysis over time of semen parameters in spinal cord-injured patients: Results of a pilot study

International audienceBackground: Spinal cord injury often results in erectile dysfunction and an ejaculation along with impaired semen parameters. Fertility is a major concern in spinal cord injury adult males and some fear that the delay post-spinal cord injury may negatively affect sperm quality. Objectives: We aimed to (i) assess semen parameters over time in SCI patients according to age at spinal cord injury, time post-spinal cord injury, and the spinal cord injury level and completeness and (ii) measure markers in semen for inflammation and marker of oxidative stress to investigate their impact on sperm parameters. Materials and Methods: The study is a prospective, longitudinal, pilot study over 18 months. Thirty-five men with spinal cord injury from 18 to 60 years of age were enrolled. Their mean age was 29.4 ± 6.4 years. Semen retrieval was scheduled every 6 months, allowing analysis of four ejaculates, in association with measurement of granulocyte and seminal plasma elastase concentrations to assess markers in semen for inflammation and spermatozoa DNA fragmentation to assess oxidative stress. Results: Based on reference limits, a normal total sperm number, decreased motility and vitality of the spermatozoa, and increased morphological abnormalities were found. Mean round cell and granulocyte concentrations were elevated in the semen. Markers in semen for inflammation and marker of oxidative stress were elevated in several semen samples, compared to reference limits. However, neither the presence of markers in semen for inflammation or oxidative stress, the completeness or the level of the spinal cord lesion, the age or the time post-spinal cord injury had a negative impact on the semen quality over time. Discussion: There was no significant decline in semen quality in spinal cord injury patients over time within the limitations of this pilot study. Moreover, a chronic genital inflammatory status was not associated with impairment of semen quality. Conclusion: The present findings are reassuring for men with spinal cord injury and could guide the management of their reproductive ability. According to these preliminary data, not all spinal cord injury patients who are able to ejaculate require systematic freezing of their spermatozoa

Loss of parental-specific methylation at the IGF2 locus in human hepatocellular carcinoma

International audienceSignificant production of the growth factor IGF2 has been reported in human hepatocellular carcinomas (HCCs). Disturbances associated with changes in methylation at this locus or affecting the 11p15.5 imprinting domain as a whole can be postulated in HCCs. In the present study, the methylation status of differentially methylated regions of the imprinted genes TSSC5, LIT1, and IGF2, which span the 11p15 domain, was analysed in 71 liver tissues from virus-associated and non-virus-associated HCCs compared with six normal liver tissues. Altered methylation of TSSC5 and LIT1 was observed in only 6% and 8% of HCCs, respectively, compared with 89% at the IGF2 locus, suggesting that these loci were not concomitantly dysregulated. These observations suggest that loss of parental-specific methylation at the IGF2 locus may be specifically associated with HCC, whether virus-associated or non-virus-associated, and arising in cirrhotic or non-cirrhotic livers

Recommandations de l’AFU et de la SALF concernant l’ évaluation de l’homme infertile

International audienceBackground. — The aim of these Association Franc ̧aise d’Urologie (AFU) and Sociétéd’Andrologie de Langue Franc ̧aise (SALF) common recommendations are to provide practiceguidelines for the French Urological and Andrological community regarding the evaluation ofinfertile men.Material and methods. — Literature search in PubMed using the keywords ‘‘male infertility’’, ‘‘diagnosis’’, ‘‘management’’ and ‘‘evaluation’’ limited to clinical articles in English and French prior to 01/01/2020. To inform the level of evidence, the HAS grading system (2013) was applied.Results. — Concerning the evaluation of infertile men, the AFU and the SALF recommend : (1)a systematic interview exploring the family history, the fertility history of the man outside thecouple, the patient’s personal history that may have an impact on his fertility, lifestyle habits,treatments, symptoms and possible sexual difficulties of the couple; (2) a general physical examination to assess signs of hypogonadism and secondary sexual characters; (3) a scrotal physical examination performed by an urologist or andrologist to assess (i) the testes for volume and consistency, (ii) vas deferens and epididymes for total or partial absence or nodules, and(iii) presence of varicoceles; (4) Performing two semen analyses, according to World HealthOrganization guidelines, if the first one has at least one abnormaly; (5) a scrotal ultrasoundas part of routine investigation, that can be completed with an endorectal pelvic ultrasound according to the clinic; (6) an endocrine evaluation with at least a Testosterone and FSH serum determination; (7) Karyotype analysis in infertile men with a sperm concentration ≤ 10 106/mL;(8) assessment of Yq microdeletions in infertile men with a sperm concentration ≤ 1 106/mL;(9) Cystic fibrosis trans membrane conductance regulator gene evaluation in case of suspicion for bilateral or unilateral congenital agenesis of vas deferens and seminal vesicles.Contexte. — Ces recommandations communes de l’Association Française d’Urologie (AFU) et de la Société d’Andrologie de Langue Franc ̧aise (SALF) ont pour objectif de fournir des directives pratiques à la communauté urologique et andrologique Française concernant l’évaluation des hommes infertiles.Matériel et méthodes. —Recherche bibliographique dans PubMed en utilisant les mots-clés «male infertility», «diagnosis», «management» et «evaluation» limitée aux articles cliniques en anglais et en français antérieurs au 01/01/2020. Pour renseigner le niveau de preuves, le système de gradation de l’HAS (2013) a été appliqué.Résultats. — Concernant l’évaluation des hommes infertiles, l’AFU et la SALF recommandent :(1) un interrogatoire systématique explorant les antécédents familiaux, les antécédents de fertilité de l’homme hors couple, les antécédents personnels du patient pouvant avoir un impact sur sa fertilité, ses habitudes de vie, ses traitements, ses symptômes et les éventuelles difficultés sexuelles du couple ; (2) un examen physique général pour évaluer les signes d’hypogonadisme et les caractères sexuels secondaires ; (3) un examen physique scrotal par un urologue ou un andrologue pour évaluer (i) le volume et la consistance des testicules, (ii)les canaux déférents et les épididymes à la recherche d’une absence totale ou partielle ou des nodules, et (iii) la présence de varicocèle ; (4) d’effectuer 2 spermogrammes, conformément aux recommandations de l’Organisation mondiale de la santé (OMS), si le premier présente au moins une anomalie ; (5) une échographie scrotale systématique, pouvant être complétée par une échographie pelvienne endorectale selon la clinique ; (6) un bilan hormonal comportant au moins une détermination de la testostérone sérique et de FSH ; si la testostérone est basse, la LH permettra de différencier hypogonadisme hypogonatrope (central) et hypogonadisme périphérique ; (7) un caryotype chez les hommes infertiles ayant une concentration de spermatozoïdes ≤ 10,106/ml ; (8) l’évaluation des micro délétions du chromosome Y chez les hommes infertiles ayant une concentration de spermatozoïdes ≤ 1,106/ml ; (9) l’évaluation du gène CFTR en cas de suspicion d’agénésie bilatérale ou unilatérale des canaux déférents et des vésicules séminales. La place de l’analyse de l’intégrité de l’ADN du sperme (SCSA, TUNEL par exemple) dans le bilan de l’homme infertile est encore en cours d’évaluation. Conclusion. — Ces recommandations peuvent être appliquées en pratique clinique en routine chez tout homme infertile

Post-transplant outcome of ovarian tissue cryopreserved after chemotherapy in hematological malignancies

International audienc