Human and mouse ZFY genes produce a conserved testis-specific transcript encoding a zinc finger protein with a short acidic domain and modified transactivation potential

Mammalian ZFY genes are located on the Y chromosome, and code putative transcription factors with 12–13 zinc fingers preceded by a large acidic (activating) domain. In mice, there are two genes, Zfy1 and Zfy2, which are expressed mainly in the testis. Their transcription increases in germ cells as they enter meiosis, both are silenced by meiotic sex chromosome inactivation (MSCI) during pachytene, and Zfy2 is strongly reactivated later in spermatids. Recently, we have shown that mouse Zfy2, but not Zfy1, is involved in triggering the apoptotic elimination of specific types of sex chromosomally aberrant spermatocytes. In humans, there is a single widely transcribed ZFY gene, and there is no evidence for a specific role in the testis. Here, we characterize ZFY transcription during spermatogenesis in mice and humans. In mice, we define a variety of Zfy transcripts, among which is a Zfy2 transcript that predominates in spermatids, and a Zfy1 transcript, lacking an exon encoding approximately half of the acidic domain, which predominates prior to MSCI. In humans, we have identified a major testis-specific ZFY transcript that encodes a protein with the same short acidic domain. This represents the first evidence that ZFY has a conserved function during human spermatogenesis. We further show that, in contrast to the full acidic domain, the short domain does not activate transcription in yeast, and we hypothesize that this explains the functional difference observed between Zfy1 and Zfy2 during mouse meiosis

Le témoignage des CECOS au sujet de l’accès à l’assistancemédicale à la procréation avec don de spermatozoïdes et àl’accès aux « origines »

The opening of MAP to couples of women and single women by the law of August 2nd, 2021 constitutes new stakes for the Centers for the Study and Conservation of Eggs and Sperm (CECOS), which the article echoes.L’ouverture de la PMA aux couples de femmes et aux femmes seules par la loi du 2 août 2021 constitue de nouveaux enjeux pour les Centres d’Études et de Conservation des Œufs et du Sperme (CECOS) dont l’article se fait l’écho

The Right Age to Tell?: The Insufficiency of the Age Criteria for Characterizing the Experience of French Donor Conceived Families in Disclosing to their Offspring

International audienceSecrecy was the norm for decades in donor conception, but “openness” has now become the new core value. Accordingly, in recent years information-sharing practices have shifted in donor conceived families, but a proportion of parents still appear to not inform their children about their being donor conceived. Disclosure recommendations seem difficult to apply in practice. A recurring question is: when should children be told? Age is presented as a key criteria: the younger the children are when their conception story is shared, the less of a problem it would create. The poster investigates the question of age, drawing on a interview-study with French donor conceived adults and parents who have used donor conception. It shows that although the age of donor offspring at the time of disclosure has an impact, age alone cannot describe these families’ experiences

Etude structurale et fonctionnelle de la vésicule sexuelle au cours de la méiose masculine

AIX-MARSEILLE2-BU Méd/Odontol. (130552103) / SudocPARIS-BIUP (751062107) / SudocSudocFranceF

Préservation de la fertilite feminine dans les maladies auto-immunes

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Entre lecture pragmatique et vision anxiogène : vécu de la cryoconservation embryonnaire par les patients en parcours de FIV

International audienceObjectifLe but de cette étude est d’interroger des patients inscrits en parcours de FIV sur leur ressenti face à la congélation embryonnaire, de comprendre leurs possibles réticences face à cette technique ainsi que leur difficulté à envisager le devenir de ces embryons congelés une fois leur projet parental terminé.MéthodesVingt-sept entretiens semi-directifs avec des patients inscrits en parcours de fécondation in vitro (FIV) intraconjugales ont été réalisés. Ces personnes étaient prises en charge dans deux centres d’assistance médicale à la procréation (AMP) de Marseille.RésultatsSi la totalité des personnes interrogées ont accepté la congélation embryonnaire ou ont accepté par principe, une grande majorité d’entre eux ont une attitude ambivalente. Certains partagent la vision « pragmatique » de la congélation transmise par les professionnels (biologistes, techniciens de laboratoire et gynécologues-obstétriciens), mais nombreux d’entre eux ne peuvent s’empêcher d’éprouver des craintes au sujet d’une possible détérioration de la qualité de leurs embryons, ou d’une perturbation par cette technique de l’ordre des générations. Enfin, il s’avère que ces derniers n’anticipent pas le possible devenir de leurs embryons congelés une fois désinscrits d’un projet parental.ConclusionsLe ressenti des patients face à la congélation embryonnaire est principalement marqué par de l’ambivalence. Nous voyons des rationalités différentes se hiérarchiser en fonction des enjeux et situations auxquels les patients sont confrontés

Spermatozoa in mice lacking the nucleoporin NUP210L show defects in head shape and motility but not in nuclear compaction or histone replacement

International audienceBiallelic loss‐of‐function mutation of NUP210L , encoding a testis‐specific nucleoporin, has been reported in an infertile man whose spermatozoa show uncondensed heads and histone retention. Mice with a homozygous transgene intronic insertion in Nup210l were infertile but spermatozoa had condensed heads. Expression from this insertion allele is undefined, however, and residual NUP210L production could underlie the milder phenotype. To resolve this issue, we have created Nup210l em1Mjmm , a null allele of Nup210l , in the mouse. Nup210l em1Mjmm homozygotes show uniform mild anomalies of sperm head morphology and decreased motility, but nuclear compaction and histone removal appear unaffected. Thus, our mouse model does not support that NUP210L loss alone blocks spermatid nuclear compaction. Re‐analyzing the patient's exome data, we identified a rare, potentially pathogenic, heterozygous variant in nucleoporin gene NUP153 (p.Pro485Leu), and showed that, in mouse and human, NUP210L and NUP153 colocalize at the caudal nuclear pole in elongating spermatids and spermatozoa. Unexpectedly, in round spermatids, NUP210L and NUP153 localisation differs between mouse (nucleoplasm) and human (nuclear periphery). Our data suggest two explanations for the increased phenotypic severity associated with NUP210L loss in human compared to mouse: a genetic variant in human NUP153 (p.Pro485Leu), and inter‐species divergence in nuclear pore function in round spermatids

Fertility preservation after fertility-sparing surgery in women with borderline ovarian tumours

International audienceObjective: To present a case series of women with borderline ovarian tumours (BOTs) who underwent oocyte vitrification in addition to fertility-sparing surgery.Study design: Observational study of all women referred to a French fertility preservation unit between 2015 and 2019 for counselling regarding a fertility preservation (FP) strategy after BOT fertility-sparing surgery. All eligible women underwent one or more cycles of controlled ovarian stimulation (COS) using an antagonist protocol, followed by oocyte retrieval. Metaphase II (MII) oocytes were vitrified.Results: Twenty-five women with BOTs were referred during the study period. Among them, 11 women underwent at least one cycle of COS. One hundred and seven MII oocytes were vitrified. The mean number of vitrified MII oocytes per woman was 9.7 (standard deviation 5.2). Five live births were reported during follow-up of four women with vitrified oocytes: three spontaneous pregnancies, one in-vitro fertilization cycle with fresh embryo transfer, and one live birth after return of vitrified oocytes.Conclusion: Conservative surgery for BOTs offers a high spontaneous pregnancy rate but has a higher risk of relapse than radical treatment. Furthermore, women who undergo conservative BOT surgery have a higher risk of surgery-induced premature ovarian failure. Oocyte cryopreservation after COS appears to be an effective technique after the conservative management of BOTs in women of reproductive age. Although the available short-term data are reassuring, further long-term studies evaluating the safety and cost-effectiveness of this systematic FP strategy after BOT fertility-sparing surgery are required

Heterotopic ovarian transplantation instead hormonal replacement therapy after radical hysterectomy for cervical cancer: case report and review of literature

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Less than half of men with testicular cancer or lymphomas banked sperm before gonadotoxic treatment in France in 2018

International audienceStudy questionWhat is the proportion of men treated for testicular cancer or lymphoma who banked sperm before gonadotoxic treatment in France?Summary answerIn 2018, 41% of men with testicular cancer and 28% of men with lymphoma banked sperm before gonadotoxic treatment in France.What is known alreadyCancer treatments significantly improved survival rates in men. In Europe, the 5-year survival rate is above 90% for testicular cancer (TC) and Hodgkin lymphoma (HL), which, with Non Hodgkin Lymphoma (NHL), are the most frequent cancers in men of reproductive age. However, surgery, chemotherapy and/or radiotherapy may damage male fertility: between 15% and 30% of men remain permanently infertile after treatment. Since 2011, the French bioethics law recommends and guarantees free access to fertility preservation for all patients needing gonadotoxic treatments. Few international data are available about the rate of male cancer patients who receive sperm cryopreservation before cancer treatment.Study design, size, durationWe analyzed the data of male cancer incidence in 2018 published by the French National Institute of Cancer (INCa), only available and latest French national data, estimated from cancer registers of selected metropolitan departments (Defossez et al. 2019). We organized a survey among the 27 metropolitan centers of the CECOS network (public centers for study and conservation of human eggs and sperm) to collect the annual number of sperm cryopreservations for TC, HL or NHL.Participants/materials, setting, methodsWe compared the number of 0-59 years-old men with TC, HL or NHL in metropolitan France (extracted from 2018 INCa data) and the number of sperm banking for TC, HL or NHL in metropolitan centers of the CECOS network.Main results and the role of chanceINCa estimated that 38,048 new cancers were diagnosed in metropolitan France in 2018 in men aged 0-59 years. TC accounted for 2,630 new cases and lymphomas for 3,913 new cases (943 HL and 2,970 NHL).Twenty-six out of 27 metropolitan CECOS centers answered the survey (96% participation rate): in 2018, 1,079 men banked sperm for TC, 375 for HL and 211 for NHL.In 2018, the fertility preservation rate in metropolitan France was 41% for TC and 28% for lymphomas (51% for HL, and 15% for NHL). The results of our national study are in accordance with Uçar et al. 2020, a monocentric study on 110 TC patients showing a 43% fertility preservation rate, but differ from those of Abdel-Razek et al. 2020, a monocentric study on 59 NHL and 26 HL patients, showing respectively 32% and 14% fertility preservation rates.A limit of our study is to be based on estimated cancer incidence from INCa reports without stratification on age and parenthood; sperm banking activity was measured in the CECOS network, which performs 90% of French male fertility preservation (French Biomedicine Agency 2018 data). This design may induce an underestimation of cancer incidence and of sperm banking activity.Limitations, reasons for cautionOur study did not consider patients who were informed of fertility preservation but did not want to/could not bank ejaculated sperm (azoospermia, sperm collection failure, no-show). In CECOS network, the estimated rate of such patients is 10%.French overseas regions were not studied (lack of INCa data).Wider implications of the findingsOur results suggest that despite the recommendations and facilities offered by the French bioethics law, the male patients’ pathway for fertility preservation before cancer treatments could be improved. Further study should evaluate if this suboptimal rate of fertility preservation is homogeneous on French territory or related to postal code