Saad H.E.S.,University Paris Diderot |
Saad H.E.S.,French Institute of Health and Medical Research |
Meduri G.,French Institute of Health and Medical Research |
Phrakonkham P.,French National Institute for Agricultural Research |
And 7 more authors.
Reproductive Toxicology | Year: 2011
The impact of early exposure to endocrine disruptor mixtures on mammary gland development is poorly known. Here, we identify the effects of a conception to weaning exposure of rats to the phytoestrogen genistein (G) and/or the antiandrogen vinclozolin (V) at 1. mg/kg-d, alone or in association. Using several approaches, we found that G- and GV-exposed rats displayed significantly greater epithelial branching and proliferation, wider terminal end buds than controls at PND35, as well as ductal hyperplasia and periductal fibrosis. Focal branching defects were present in V-exposed rats. An increased ER and AR expression was observed in G- and GV- as compared to V-exposed rats at PND35. Surprisingly, a significant number of GV- and to a lesser extent, V-exposed animals displayed abnormal hyperplasic alveolar structures at PND50. Thus, gestational and lactational exposure to low doses of genistein plus vinclozolin may seriously affect peripubertal development of the rat mammary gland. © 2011 Elsevier Inc.
Kouidhi W.,Tunis el Manar University |
Kouidhi W.,French National Institute for Agricultural Research |
Desmetz C.,French National Institute for Agricultural Research |
Nahdi A.,Tunis el Manar University |
And 5 more authors.
Toxicologic Pathology | Year: 2012
It has been suggested that hormonally controlled submandibular salivary gland (SSG) development and secretions may be affected by endocrine disruptor compounds. We investigated the effects of oral gestation-lactation exposure to 1 mg/kg body weight daily dose of the estrogenic soy-isoflavone genistein and/or the anti-androgenic food contaminant vinclozolin in female rats. The SSGs of female offspring were collected at postnatal day 35 to study gland morphogenesis and mRNA expression of sex-hormone receptors and endocrine growth factors as sex-dependent biomarkers. Because of high expression in neonatal SSG, mRNA expression of transforming growth factor α was also studied. Exposure to genistein, vinclozolin, or a genistein+vinclozolin mixture resulted in significantly lower numbers of striated ducts linked to an increase in their area and lower acinar proliferation (Ki-67-positive nuclei). Exposure to the mixture had the highest significant effects, which were particularly associated with repression of epidermal growth factor, nerve growth factor, and transforming growth factor α expression. In conclusion, early exposure to low doses of genistein and vinclozolin can affect glandular structure and endocrine gene mRNA expression in prepubertal SSG in female rats, and the effects are potentialized by the genistein+vinclozolin mixture. Our study provides the first evidence that SSG are targeted by both estrogenic and anti-androgenic disrupting compounds and are more sensitive to mixtures. © 2012 by The Author(s).
Fauque P.,Service dHistologie Embryologie |
Fauque P.,University of Paris Descartes |
Fauque P.,French Institute of Health and Medical Research |
Mondon F.,University of Paris Descartes |
And 21 more authors.
PLoS ONE | Year: 2010
Background: Assisted Reproductive Technologies (ART) are increasingly used in humans; however, their impact is now questioned. At blastocyst stage, the trophectoderm is directly in contact with an artificial medium environment, which can impact placental development. This study was designed to carry out an in-depth analysis of the placental transcriptome after ART in mice. Methodology/Principal Findings: Blastocysts were transferred either (1) after in vivo fertilization and development (control group) or (2) after in vitro fertilization and embryo culture. Placentas were then analyzed at E10.5. Six percent of transcripts were altered at the two-fold threshold in placentas of manipulated embryos, 2/3 of transcripts being down-regulated. Strikingly, the X-chromosome harbors 11% of altered genes, 2/3 being induced. Imprinted genes were modified similarly to the X. Promoter composition analysis indicates that FOXA transcription factors may be involved in the transcriptional deregulations. Conclusions: For the first time, our study shows that in vitro fertilization associated with embryo culture strongly modify the placental expression profile, long after embryo manipulations, meaning that the stress of artificial environment is memorized after implantation. Expression of X and imprinted genes is also greatly modulated probably to adapt to adverse conditions. Our results highlight the importance of studying human placentas from ART. © 2010 Fauque et al.
Cederroth C.R.,University of Geneva |
Auger J.,Service dHistologie Embryologie |
Zimmermann C.,University of Geneva |
Eustache F.,Service dHistologie Embryologie Cytogenetique |
Nef S.,University of Geneva
International Journal of Andrology | Year: 2010
There is growing interest in the possible health threat posed by the effects of endocrine disruptors on reproduction. Soy and soy-derived products contain isoflavones that mimic the actions of oestrogens and may exert adverse effects on male fertility. The purpose of this review was to examine the evidence regarding the potential detrimental effects of soy and phyto-oestrogens on male reproductive function and fertility in humans and animals. Overall, there are some indications that phyto-oestrogens, alone or in combination with other endocrine disruptors, may alter reproductive hormones, spermatogenesis, sperm capacitation and fertility. However, these results must be interpreted with care, as a result of the paucity of human studies and as numerous reports did not reveal any adverse effects on male reproductive physiology. Further investigation is needed before a firm conclusion can be drawn. In the meantime, caution would suggest that perinatal phyto-oestrogen exposure, such as that found in infants feeding on soy-based formula, should be avoided. © 2009 European Academy of Andrology.
Rolland A.D.,French Institute of Health and Medical Research |
Lavigne R.,French Institute of Health and Medical Research |
Dauly C.,Thermo Fisher Scientific |
Calvel P.,French Institute of Health and Medical Research |
And 7 more authors.
Human Reproduction | Year: 2013
Study Question Can protein biomarkers of the male genital tract be identified in human seminal plasma? Summary Answer We identified potential biomarkers for each of the organs participating in the secretions of the human seminal plasma. What is Known Already The seminal plasma fulfills critical functions for fertility by providing spermatozoa with a protective milieu, promoting their final maturation and modulating the immune responsiveness of the female reproductive tract. It is also considered to be a promising source of biomarkers of male infertility and/or pathologies of the male genital tract. Study Design, Size, Duration This study combines proteomic analyses of normal seminal plasma together with transcriptomic gene expression profiling of human healthy tissues.MATERIALS, SETTING, Methods Non-liquefied seminal plasma proteins from a healthy donor were prefractionated using two sequential Proteominer™ libraries. Eight subproteome fractions were collected, trypsin digested and subjected to three successive mass spectrometry analyses for peptide characterization. The list of identified proteins was compared with and merged with other available data sets of the human seminal plasma proteome. The expression of corresponding genes was then investigated using tissue transcriptome profiles to determine where, along the male reproductive tract, these proteins were produced. Finally, tissue specificity of a selected subset of biomarker candidates was validated on human tissues. Main Results AND THE ROLE OF CHANCEWe first performed a proteomic analysis of the human seminal plasma and identified 699 proteins. By comparing our protein list with other previous proteomic data sets, we found that 2545 unique proteins have been described so far in the human seminal plasma. We then profiled their expression at the gene level and identified 83 testis, 42 epididymis, 7 seminal vesicle and 17 prostate candidate protein markers. For a subset of testis-specific candidates, i.e. TKTL1, LDHC and PGK2, we further validated their germ cell expression and demonstrated that such markers could distinguish between semen from fertile and infertile men. Limitations, Reasons for Caution While some of the markers we identified are well-known tissue-specific products, further dedicated studies to validate the biomarker status of new candidates will be required. Additionally, whether or not the abundance of these proteins is indeed decreased in some specific pathological situations remains to be determined. Wider Implications of the Findings Using an integrative genomics approach, we identified biomarker candidates for each of the organs participating in the seminal plasma production. In this study, we essentially focused on germ cell markers and their potential application for the diagnosis of male infertility. Other types of markers also deserve a focused attention given their potential predictive value for various reproductive disorders, notably for prostate cancers. Study Funding/Competing Interest (S)This work was supported by the Proteomics Core Facility at Biogenouest and was funded by Conseil Régional de Bretagne, IBiSA and Agence de la Biomédecine grants. The authors declare that there exists a competing financial interest in this work that is related to a patent application on the use of identified germ cell-specific proteins in an antibody-based assay (Fertichip™) to predict the successful testicular biopsy outcomes in human non-obstructive azoospermia. © 2012 The Author.
Alter L.,Service dHistologie Embryologie |
Boitrelle F.,Service dHistologie Embryologie |
Sifer C.,Service de Biologie de la Reproduction
Gynecologie Obstetrique Fertilite | Year: 2014
Multiple pregnancies stand as the most common adverse outcome of assisted reproduction technologies (ART) and the dangers associated with those pregnancies have been reduced by doing elective single embryo transfers (e-SET). Many studies have shown that e-SET is compatible with a continuously high pregnancy rate per embryo transfer. Yet, it still becomes necessary to improve the selection process in order to define the quality of individual embryos - so that the ones we choose for transfer are more likely to implant. First, analysis of embryo morphology has greatly helped in this identification and remains the most relevant criterion for choosing the embryo. The introduction of time-lapse imaging provides new criteria predictive of implantation potential, but the real contribution of this system - including the benefit/cost ratio - seems to be not yet properly established. In this context, extended culture until blastocyst stage is an essential practice but it appears wise to keep it for a population showing a good prognosis. Then, the failure of aneuploid embryos to implant properly led to achieve preimplantation genetic screening (PGS) in order to increase pregnancy and delivery rates after ART. However, PGS by fluorescence in situ hybridization (FISH) at day 3 is a useless process - and may even be harmful. Another solution involves using comparative genomic hybridisation (CGH) and moving to blastocyst biopsy. Finally, it is envisaged that morphology will also be significantly aided by non-invasive analysis of biomarkers in the culture media that give a better reflection of whole-embryo physiology and function. © 2014 Elsevier Masson SAS. All rights reserved.
Auger J.,Service dHistologie Embryologie
Asian Journal of Andrology | Year: 2010
The assessment of the percentage of spermatozoa having an 'ideal' morphology using so-called strict method is the method recommended in the latest edition of the World Health Organization (WHO) laboratory manual for semen analysis. This recommendation is a result of the statistical association between 'ideal' sperm morphology and fertility, and of the current general belief that sperm morphology assessment should be used primarily as a fertility tool. The notion of an 'ideal' sperm morphology has persisted despite the very low percentage of such spermatozoa in the semen of fertile men, a subject of intense controversy. The detailed categorization of each abnormal spermatozoon has thus, for a long time, been considered optional and partially redundant, an idea which is reflected in the earlier editions of the WHO manual. However, several recent studies have shown the importance of carefully assessing abnormal sperm morphology for use in the diagnosis of infertility, to determine fertility prognosis, and for basic or public health studies. One approach, which combines videomicroscopy and computer vision, and is the only approach able to assess the continuum of sperm biometrics, has been used successfully in several recent clinical, basic and toxicology studies. In summary, the visual assessment of detailed sperm morphologyincluding the categorization of anomalies allowing arithmetically derived indices of teratozoospermiaand the more modern computer-based approaches, although often considered to be redundant, are in fact complementary. The choice of the most appropriate method depends on the field of investigation (clinical, research, toxicology) and the problem being addressed. Each approach has advantages as well as certain limitations, which will be discussed briefly herein. © 2010 AJA, SIMM & SJTU.
Auger J.,Service dHistologie Embryologie |
Eustache F.,Service dHistologie Embryologie
International Journal of Andrology | Year: 2011
Second- to fourth-digit length ratio, 2D:4D, is a marker of testosterone level during foetal life that was found associated with sperm concentration or testosterone levels in some studies, but not in others, a difference possibly related to the way the ratio is assessed. In this study, 2D:4D was assessed in 122 men partners of pregnant women and in 71 testicular cancer patients using a new method based on direct measurements of finger lengths. In addition, we investigated the association between 2D:4D, birth weight, testicular volume, semen quality and time to pregnancy. A validation study of the method demonstrated high reliability and reproducibility. Neither digit lengths nor 2D:4D significantly differed in both groups of men. We found a significant negative association between 2D:4D and birth weight in testicular cancer patients. In fertile men, 2D:4D was associated with testicular volume (r=-0.36, p<0.001), total sperm number (r=-0.18, p=0.04) and time to pregnancy (r=0.24, p<0.02). In addition, participants with a history of epididymal cyst had a significantly higher 2D:4D than those without cysts. In conclusion, all significant findings indicate that the human male reproductive function is negatively related to 2D:4D. However, 2D:4D for testicular cancer patients does not point to a hormonal imbalance during foetal life as the common cause for developing germ-cell cancer. Such results obtained, thanks to an easy, direct and reliable method for measuring finger lengths, suggest the usefulness of this new tool in fertility studies as well as for studying men with developmental disorders of the reproductive tract. © 2010 The Authors. International Journal of Andrology © 2011 European Academy of Andrology.
Are abnormalities of male reproductive function becoming increasingly common? Facts and controversies, possible causative factors: An up to date analysis of the literature and of disease registers [Les différentes anomalies de la reproduction masculine sont-elles en augmentation? Faits et controverses, possibles facteurs en cause:une analyse actualisée des données de la littérature et des registres]
Auger J.,Service dhistologie embryologie
Andrologie | Year: 2011
In recent decades, numerous observations in wildlife of various anomalies of the male reproductive functions-some being reminiscent of experimental toxicology data-have raised questions about the possible role of environmental pollutants. A number of studies suggest an increased prevalence of reproductive disorders in adult humans in recent decades in many (but not all) Western countries. The best documented data concern testicular cancer, its increasing rate suggesting that environmental factors and/or changes in lifestyle may come into play. However, considerable regional and ethnic differences exist in absolute incidence rates, suggesting in turn the concomitant role of the genetic background. Finally, several studies suggest that semen quality has declined in many countries. In the early 2000's, Skakkebæk's group in Copenhagen postulated a common origin to these different abnormalities - the so-called testicular dysgenesis syndrome (TDS) - all possibly related to abnormal testis development during gestation. Is there a causal link between these different conditions and deleterious environmental and/or lifestyle factors? The answer is far from being unequivocal, and the subject, a potential major public health problem, remains a source of hot debate both within the scientific community and in the media. The present review aims to provide an updated synthesis of these complex issues. © 2010 Springer.
PubMed | Service dhistologie embryologie and Service de biologie de la reproduction
Type: Journal Article | Journal: Gynecologie, obstetrique & fertilite | Year: 2014
Multiple pregnancies stand as the most common adverse outcome of assisted reproduction technologies (ART) and the dangers associated with those pregnancies have been reduced by doing elective single embryo transfers (e-SET). Many studies have shown that e-SET is compatible with a continuously high pregnancy rate per embryo transfer. Yet, it still becomes necessary to improve the selection process in order to define the quality of individual embryos - so that the ones we choose for transfer are more likely to implant. First, analysis of embryo morphology has greatly helped in this identification and remains the most relevant criterion for choosing the embryo. The introduction of time-lapse imaging provides new criteria predictive of implantation potential, but the real contribution of this system - including the benefit/cost ratio - seems to be not yet properly established. In this context, extended culture until blastocyst stage is an essential practice but it appears wise to keep it for a population showing a good prognosis. Then, the failure of aneuploid embryos to implant properly led to achieve preimplantation genetic screening (PGS) in order to increase pregnancy and delivery rates after ART. However, PGS by fluorescence in situ hybridization (FISH) at day 3 is a useless process - and may even be harmful. Another solution involves using comparative genomic hybridisation (CGH) and moving to blastocyst biopsy. Finally, it is envisaged that morphology will also be significantly aided by non-invasive analysis of biomarkers in the culture media that give a better reflection of whole-embryo physiology and function.