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Abstract Background In 15–49 years-old men, the main cancers are testicular cancer (TC) and lymphomas (L): freezing of ejaculated sperm is primarily used for male fertility preservation (FP) before cancer treatment. Our objective was to analyze the French FP rate in 15–49 years-old men diagnosed with TC or L in 2018. We designed a national descriptive cross-sectional study of sperm banking rate in men with a diagnosis of TC, Hodgkin L (HL) or non-Hodgkin L (NHL). From the French National Cancer Institute (INCa) 2018 data, we extracted the estimated incidence of TC and L in metropolitan France. From the 2018 activity report of CECOS network (Centers for Study and Banking of Eggs and Sperm), we extracted the number of men with TC or L who banked ejaculated sperm. We estimated the proportion of 15–49 years-old men diagnosed with TC or L who banked sperm. Results Among 15–49 years-old men, INCa estimated 38,048 new cancer diagnoses in metropolitan France in 2018: 2,630 TC and 3,913 L (943 HL and 2,970 NHL). The CECOS network provided data from 26/27 metropolitan centers (96% response rate): 1,079 sperm banking for men with TC, 375 for HL and 211 for NHL. We estimated that the 2018 sperm banking rate in France was 41% for TC, 40% for HL, and 7% for NHL. Conclusions To our knowledge, our paper is the first cross-sectional study with multicenter and national data analyzing FP rate in cancer men: it suggests an efficient pathway for men to FP before cancer treatment, compared to previously published studies. Although sperm banking rate in 15–49 years-old men could definitely be improved, further studies should evaluate the information given to patients before gonadotoxic treatments, the factors associated with the absence of sperm banking and whether this lack of referral induces a loss of chance for these men.

Résumé Contexte La mise en évidence d’une mosaïque germinale est. un événement rare mais probablement sous-estimé du fait de l’accès limité aux cellules germinales. Les variations génomiques caractéristiques de ce phénomène peuvent être des single nucleotide polymorphismes (SNPs), des copy number variations (CNVs) ou des aneuploïdies. Dans le cas des CNVs, les délétions sont plus fréquentes dans la lignée germinale paternelle tandis que les duplications sont plus fréquemment d’origine maternelle. Le risque de mosaïcisme germinal augmente avec l’âge paternel de part une augmentation du risque de SNPs associée à la division constante des cellules germinales pendant toute la vie d’un homme. Nous rapportons ici un cas de mosaïque germinale chez un donneur de spermatozoïdes ayant entraîné la survenue d’une grossesse pathologique. Résultats Les paillettes d’un même donneur de spermatozoïdes ont été attribuées à sept couples receveurs permettant l’obtention de quatre grossesses évolutives. Pour l’une d’entre elle, l’échographie du deuxième trimestre a permis d’identifier chez le fœtus des pieds bots associés à un retard de croissance intra utérin. L’analyse par hybridation génomique comparative (CGH)-array après amniocentèse a révélé une délétion de 4 MB dans la région 7q32.1q33. Les caryotypes sanguins et les analyses par CGH-array étaient normaux chez la mère et le donneur. Cependant les profils de microsatellites ont montré une origine paternelle du chromosome délété. Une analyse par fluorescent in situ hybridization (FISH) des spermatozoïdes du donneur a révélé la présence de la même délétion dans 12% des spermatozoïdes étudiés. Etant donné le risque de retard mental associé à des remaniements chromosomiques dans cette même région, le couple a préféré interrompre la grossesse. Une amniocentèse a été réalisée pour les autres grossesse en cours et n’a retrouvé aucune anomalie. Conclusions Plusieurs cas de mosaïques germinales ont été rapportés mais leur fréquence réelle reste probablement sous-estimée. En effet, un mosaïcisme germinal ne peut être détecté par les techniques de cytogénétique conventionnelle sur sang. Ce cas illustre la nécessité d’un suivi en temps réel des grossesses obtenues par don de spermatozoïdes étant donné que la survenue d’une grossesse pathologique peut avoir un retentissement sur les autres grossesses issues du même donneur.

Spermatozoa undergo regulation of their functions along their lifespan through exchanges via vesicles or interactions with epithelial cells, in the epididymis, in the seminal fluid and in the female genital tract. Two different ways of oocyte membrane transfer to spermatozoa have been described: trogocytosis and exosomes.We here report an analysis of in vitro exchanges between the membranes of unfertilised oocytes and capacitated spermatozoa.We showed that optimum conditions are fulfilled when unfertilised oocytes interact with acrosome-reacted spermatozoa, a scenario mimicking the events occurring when the fertilising spermatozoon is inside the perivitelline space. Although CD9 tetraspanin is an essential molecule for fertilisation, exosome and trogocytosis transfer persists in Cd9-null oocytes in spite of their dramatic fusion failure. These exchanges are CD9 tetraspanin independent. We also confirm that mice sperm express CD9 tetraspanin and that when Cd9-null oocytes were inseminated with sperm covered with oocyte membrane materials, including CD9 tetraspanin, no rescue of the oocytes' fertilisability could be obtained. Thus, the existence of two ways of exchange between gametes during fertilisation suggests that these events could be of a physiological importance in this process. [ABSTRACT FROM AUTHOR]

Oocyte integrins have been described as essential for fertilization. But this concept has been challenged by deletion experiments. Recently, we have shown that sperm integrin α6β1 plays a determinant role in mouse gamete interaction. In this study, we demonstrate the presence of αvβ3 integrin by Western blot and immunofluorescence on the sperm membrane. Oocytes and/or sperm preincubations with anti-αv or anti-β3 antibodies were performed before in vitro fertilization on cumulus-intact and zona-free egg assays. We observed inhibitory effects on the fusion process mostly by means of sperm function. An antibody directed against vitronectin inhibited gametes fusion, whereas the presence of exogenous vitronectin increased its efficiency. We suggest that vitronectin (on multimeric forms) can play a first nonspecific link corresponding to loosely bound spermatozoa to oocyte and that this link could be mediated by means of oocyte proteoglycans or integrins, and sperm αvβ3 integrin. Developmental Dynamics 239:773-783, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

DNA methylation marks, a key modification of imprinting, are erased in primordial germ cells and sex specifically re-established during gametogenesis. Abnormal epigenetic programming has been proposed as a possible mechanism compromising male fertility. We analysed by pyrosequencing the DNA methylation status of 47 CpGs located in differentially methylated regions (DMRs), the DMR0 and DMR2 of the IGF2 gene and in the 3rd and 6th CTCF-binding sites of the H19 DMR in human sperm from men with normal semen and patients with teratozoospermia (T) and/or oligo-astheno-teratozoospermia (OAT). All normal semen samples presented the expected high global methylation level for all CpGs analysed. In the teratozoospermia group, 11 of 19 patients presented a loss of methylation at variable CpG positions either in the IGF2 DMR2 or in both the IGF2 DMR2 and the 6th CTCF of the H19 DMR. In the OAT group, 16 of 22 patients presented a severe loss of methylation of the 6th CTCF, closely correlated with sperm concentration. The methylation state of DMR0 and of the 3rd CTCF was never affected by the pathological status of sperm samples. This study demonstrates that epigenetic perturbations of the 6th CTCF site of the H19 DMR might be a relevant biomarker for quantitative defects of spermatogenesis in humans. Moreover, we defined a methylation threshold sustaining the classification of patients in two groups, unmethylated and methylated. Using this new classification of patients, the observed intrinsic imprinting defects of spermatozoa appear not to impair significantly the outcome of assisted reproductive technologies. [ABSTRACT FROM AUTHOR]

Significant 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. Copyright © 2003 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Oocyte integrins have been described as essential for fertilization. But this concept has been challenged by deletion experiments. Recently, we have shown that sperm integrin alpha6beta1 plays a determinant role in mouse gamete interaction. In this study, we demonstrate the presence of alphavbeta3 integrin by Western blot and immunofluorescence on the sperm membrane. Oocytes and/or sperm preincubations with anti-alphav or anti-beta3 antibodies were performed before in vitro fertilization on cumulus-intact and zona-free egg assays. We observed inhibitory effects on the fusion process mostly by means of sperm function. An antibody directed against vitronectin inhibited gametes fusion, whereas the presence of exogenous vitronectin increased its efficiency. We suggest that vitronectin (on multimeric forms) can play a first nonspecific link corresponding to loosely bound spermatozoa to oocyte and that this link could be mediated by means of oocyte proteoglycans or integrins, and sperm alphavbeta3 integrin., (Copyright (c) 2010 Wiley-Liss, Inc.)