Rôle des protéases et de leurs inhibiteurs dans la placentation et la vascularisation endométriale

Le rôle important joué par les protéases dans plusieurs processus physiologiques (reproduction, cicatrisation et régénération tissulaire) n’exclut pas leurs contributions parfois primordiales dans divers pathologies, telles que la croissance tumorale et les métrorragies dysfonctionnelles. Lors de ce travail, nous nous sommes intéressés à l’étude des protéases et de l’angiogenèse au niveau de deux aspects distincts de la reproduction :1)Une situation physiologique qu’est la placentation par le biais d’un modèle murin ;2)Une situation pathologique chez les femmes souffrant de métrorragies dysfonctionnelles suite à l’utilisation d’un système intra-utérin à libération de progestatif comme moyen de contraceptio

Crónica pictórica de viajes: Recopilación paisajística, escénica y cultural a lo largo del itinerario

[ES] A raíz de los viajes llevados a cabo por el norte de India, Colombia y actualmente por España, el proyecto a realizar pretende recopilar parte de las historias, escenas y vivencias experimentadas durante el recorrido; Todo ello manifestándose a través de lo pictórico, forjando finalmente una crónica o diario de viajes.[EN] As a result of the trips made by the north of India, Colombia and currently by Spain, the project that will be carried out aims to compile part of the stories, scenes and experiences lived during the tour; All this is manifested through the pictorial, finally achieving a chronicle or travel diary.Labied Ochoa, N. (2019). Crónica pictórica de viajes: Recopilación paisajística, escénica y cultural a lo largo del itinerario. http://hdl.handle.net/10251/131789TFG

Les expérimentations de logements sociaux en terre crue au Maroc dans les années 1960 : modernisation et transmission des savoirs

La relance de la filière de construction en terre en France date de la fin des années 1970, mais elle a été précédée par une période encore mal connue, sans laquelle cet essor n’aurait pas eu lieu. Au Maroc, dès les années 1960, des milliers de logements sociaux en terre ont été réalisés par un ingénieur français et un architecte belge, qui ont modernisé le matériau, l’outillage et l’organisation des chantiers. Nous allons montrer par l’étude de deux sites (Daoudiate, Marrakech, 1962 ; Ouarzazate, 1967) comment les concepteurs européens se sont approprié les savoir-faire anciens transmis par la tradition vernaculaire, et comment ils les ont rationalisés grâce à de nouvelles techniques. Ainsi des coopérants européens ont révélé les savoirs locaux, tout en transmettant leur propre savoir d’industrialisation de la construction, dans le contexte particulier de la décolonisation et de l’émergence de mouvements de retour vers le vernaculaire

Differential elevation of matrix metalloproteinase expression in women exposed to levonorgestrel-releasing intrauterine system for a short or prolonged period of time

peer reviewedBACKGROUND: The levonorgestrel-releasing intrauterine system (LNG-IUS) is an effective contraceptive and has many non-contraceptive health benefits. However, it is commonly associated with irregular endometrial bleeding. Metalloproteinases contribute to extracellular matrix (ECM) remodelling and regulate bleeding during the menstrual cycle. Enhanced metalloproteinase expression participates in the pathogenesis of breakthrough bleeding. Thus the objective of this study was to compare matrix metalloproteinase (MMP) expression in endometrium during luteal phase and in short-term (1 month) and long-term (> or =6 months) LNG-IUS users. METHODS: MMP expression was analysed by semi-quantitative RT-PCR and immunohistochemistry. Gelatinase activity was determined by gelatin zymography. RESULTS: MMP-1, -2, -3, -7, -9 and -12 mRNAs levels were increased, whereas that of MMP-26 was decreased in the endometrium of LNG-IUS users. MMP-1, -2, -3, -7 and -9 were localized by immunohistochemistry in all biopsies in the short-term group but in only 0-27% in the control group. The incidence of positive immunostaining for MMP-2 and -3 decreased significantly in the long-term compared with short-term LNG-IUS users. MMP-26 was localized in all biopsies from the control group but in only 14 and 25% from the short- and long-term LNG-IUS groups, respectively. In both LNG groups, the numbers of macrophages (the major source of MMP-12) was increased. CONCLUSIONS: MMP-1, active MMP-2, MMP-3, MMP-7, MMP-9 and MMP-12 are more prevalent in the short-term LNG-IUS group, suggesting their important contribution to ECM breakdown and transient bleeding. The decrease in the percentage of women expressing MMP-2 and -3 might contribute to the decreased occurrence of unwanted spotting and bleeding in long-term LNG-IUS users

Preservation of female fertility: The current therapeutic strategy.

peer reviewedBACKGROUND: Preservation of female fertility is a relatively new field in medicine that has grown very rapidly in recent decades. At the beginning, embryo freezing remained the most effective technique. Thereafter, cryopreservation of oocytes and ovarian tissue was considered a secure tool in human fertility preservation. Storage of cortical ovarian tissue is moreover relevant for children, prepubertal girls, and adult patients who cannot benefit from cryopreservation of oocytes. OBJECTIVE: To analyze and review recent and relevant scientific literature on medical and social reasons for preservation of fertility. METHODS: The review was conducted based on articles identified from PubMed databases using keywords. MAIN RESULTS: Oocyte vitrification allows women to preserve their fertility without the need for fertilization. Nowadays, thousands of healthy children have been born from this procedure. Occurrence of pregnancy depends on two main factors: the number of mature oocytes in storage and the age of the patient at the time of vitrification. Numerous adaptations have been developed to suit the ovarian stimulation regiments to patients with cancer. In young prepubertal girls, freezing of ovarian tissue remains the best and only option. CONCLUSION: Oocyte vitrification therefore appears to be the gold standard technique of preserving fertility in young women

Influence of mouse strain on ovarian tissue recovery after engraftment with angiogenic factor.

BACKGROUND: For women facing gonadotoxic treatment, cryopreservation of ovarian tissue with subsequent retransplantation during remission is a promising technique for fertility preservation. However, follicle loss within grafted ovarian tissue can be caused by ischemia and progressive revascularization. Several xenograft models using different immunodeficient rodent lines are suitable for studying ovarian tissue survival and follicular viability after frozen-thawed ovarian cortex transplantation. SCID mice, which are deficient for functional B and T cells, are the most commonly used mice for ovarian xenograft studies. However, due to incomplete immunosuppression, NOD-SCID mice displaying low NK cell function and an absence of circulating complement might be more appropriate. The present study aims to define the most appropriate immunodeficient mouse strain for ovarian tissue xenotransplantation by comparing ovarian graft recovery in SCID and NOD-SCID mice following engraftment in the presence of isoform 111 of vascular endothelial growth factor. METHODS: Sheep ovarian cortex fragments were embedded in a collagen matrix, with or without VEGF111, before being stitched onto the ovaries of SCID and NOD-SCID mice. Transplants were recovered after 3 days to study early revascularization or after 3 weeks to evaluate follicle preservation and tissue fibrosis through histological analyses. RESULTS: At day 3, vessels were largely reorganized in the ovarian grafts of both mouse strains. After 3 weeks, the cortical tissue was clearly identifiable in SCID mice but not in NOD-SCID mice. Upon VEGF111 treatment, vascularization was significantly improved 3 days after transplantation in SCID mice. This increase in vessel density was correlated with better follicular preservation in SCID mice 3 weeks after transplantation. Fibrosis was not decreased by VEGF treatment in either mouse strain. CONCLUSIONS: Tissue architecture and follicular morphology were better preserved in ovarian tissues grafted in SCID mice in comparison with NOD-SCID mice. Moreover, tissue revascularization was improved in SCID mice by VEGF111 graft treatment. Thus, we consider SCID mice to be the best murine model for studying ovarian tissue xenografts

Development of an animal experimental model to study the effects of levonorgestrel on the human endometrium

BACKGROUND: This study was designed to develop an animal model to test the response of endometrium to local progestin delivery. METHODS: Proliferative human endometrium was subcutaneously grafted in two groups of SCID mice that received, 2 days before, a subcutaneous estradiol (E2) pellet and, for half of them, an additional implant of levonorgestrel (LNG). Mice were sacrificed 1, 2, 3 or 4 weeks after endometrial implantation and grafts were histologically analysed. Proliferation, steroid hormone receptors, blood vessels and stromal decidualization in both groups (E2 and LNG) were immunohistologically evaluated and compared with proliferative endometrium and endometrium from women with an LNG intrauterine device. RESULTS: Grafts presented normal morphological endometrial characteristics. The expression of progesterone receptors was significantly decreased in glands and stroma of the LNG group as compared with the E2 group at all times. A significant decrease was also observed in the stromal expression of estrogen receptor- in the LNG group. At 4 weeks, the mean cross-sectional area of vessels was significantly higher after LNG treatment. CONCLUSIONS: These morphological and immunohistochemical characteristics are similar to those observed in women treated with local LNG. This mouse model might facilitate further investigations needed to understand the mechanisms responsible for the breakthrough bleeding frequently observed in progestin users

Oocyte Cryopreservation in Patients with Endometriosis: Current Knowledge and Number Needed to Treat.

peer reviewedThe rise of oocytes cryopreservation (OOC) in assisted reproductive techniques allows fertility preservation (FP) in an increasing number of indications. Endometriosis, a highly prevalent disease, potentially impairing ovarian reserve, seems, therefore, an interesting indication for it. The purpose of this study is to summarize the available evidence concerning FP by OOC in women with endometriosis and to calculate the number needed to treat (NNT). In total, 272 articles related to this topic were identified in PubMed. Eight studies were eligible for the review. In order to shed some light, a SWOT analysis was performed and the argument pros and cons were developed. The NNT calculated of OOC was 16, meaning that 16 women need to perform an OOC for one of them to have a child that she would not have had without this technique. In conclusion, OOC must be discussed with patients who suffer from endometriosis since it is an effective technique of FP, which can allow these patients to succeed a pregnancy that they otherwise would not have achieved. Nevertheless, it should not be performed in all patients as there is still a lack of robust socio-economic and risk-benefit data

HoxA-11 and FOXO1A Cooperate to Regulate Decidual Prolactin Expression: Towards Inferring the Core Transcriptional Regulators of Decidual Genes

During the menstrual cycle, the ovarian steroid hormones estrogen and progesterone control a dramatic transcriptional reprogramming of endometrial stromal cells (ESCs) leading to a receptive state for blastocyst implantation and the establishment of pregnancy. A key marker gene of this decidualization process is the prolactin gene. Several transcriptional regulators have been identified that are essential for decidualization of ESCs, including the Hox genes HoxA-10 and HoxA-11, and the forkhead box gene FOXO1A. While previous studies have identified downstream target genes for HoxA-10 and FOXO1A, the role of HoxA-11 in decidualization has not been investigated. Here, we show that HoxA-11 is required for prolactin expression in decidualized ESC. While HoxA-11 alone is a repressor on the decidual prolactin promoter, it turns into an activator when combined with FOXO1A. Conversely, HoxA-10, which has been previously shown to associate with FOXO1A to upregulate decidual IGFBP-1 expression, is unable to upregulate PRL expression when co-expressed with FOXO1A. By co-immunoprecipitation and chromatin immunoprecipitation, we demonstrate physical association of HoxA-11 and FOXO1A, and binding of both factors to an enhancer region (−395 to −148 relative to the PRL transcriptional start site) of the decidual prolactin promoter. Because FOXO1A is induced upon decidualization, it serves to assemble a decidual-specific transcriptional complex including HoxA-11. These data highlight cooperativity between numerous transcription factors to upregulate PRL in differentiating ESC, and suggest that this core set of transcription factors physically and functionally interact to drive the expression of a gene battery upregulated in differentiated ESC. In addition, the functional non-equivalence of HoxA-11 and HoxA-10 with respect to PRL regulation suggests that these transcription factors regulate distinct sets of target genes during decidualization