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2. A partial deletion within the meiosis-specific sporulation domain SPO22 of Tex11 is not associated with infertility in mice.

Author

Ghieh, Farah, Passet, Bruno, Poumerol, Elodie, Castille, Johan, Calvel, Pierre, Vilotte, Jean-Luc, Sellem, Eli, Jouneau, Luc, Mambu-Mambueni, Hendrick, Garchon, Henri-Jean, Pailhoux, Eric, Vialard, François, and Mandon-Pépin, Béatrice

Subjects
COMPARATIVE genomic hybridization, MALE infertility, AZOOSPERMIA, HUMAN phenotype, SPERMATOGENESIS, FERTILITY, X chromosome
Abstract

Azoospermia (the complete absence of spermatozoa in the semen) is a common cause of male infertility. The etiology of azoospermia is poorly understood. Whole-genome analysis of azoospermic men has identified a number of candidate genes, such as the X-linked testis-expressed 11 (TEX11) gene. Using a comparative genomic hybridization array, an exonic deletion (exons 10–12) of TEX11 had previously been identified in two non-apparent azoospermic patients. However, the putative impact of this genetic alteration on spermatogenesis and the azoospermia phenotype had not been validated functionally. We therefore used a CRISPR/Cas9 system to generate a mouse model (Tex11Ex9-11del/Y) with a partial TEX11 deletion that mimicked the human mutation. Surprisingly, the mutant male Tex11Ex9-11del/Y mice were fertile. The sperm concentration, motility, and morphology were normal. Similarly, the mutant mouse line's testis transcriptome was normal, and the expression of spermatogenesis genes was not altered. These results suggest that the mouse equivalent of the partial deletion observed in two infertile male with azoospermia has no impact on spermatogenesis or fertility in mice, at least of a FVB/N genetic background and until 10 months of age. Mimicking a human mutation does not necessarily lead to the same human phenotype in mice, highlighting significant differences species. [ABSTRACT FROM AUTHOR]

Published
2024
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4. Ovine fetal testis stage-specific sensitivity to environmental chemical mixtures

Author

Lea, Richard G, Loup, Benoit, Poumerol, Elodie, Jouneau, Luc, Bowden, Adelle, Cotinot, Corinne, Purdie, Laura, Zhang, Zulin, Sinclair, Kevin D., Egbowon, Biola F., and Fowler, Paul A.

Subjects
Embryology, Endocrinology, Reproductive Medicine, Obstetrics and Gynecology, Cell Biology
Abstract

Exposure of the fetal testis to numerous individual environmental chemicals (ECs) is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, 'real-life' exposure involves complex mixtures of ECs. Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage). Fetal testes from continuously exposed ewes were either unaffected at day 80 or exhibited a reduced area of testis immunostained for CYP17A1 protein at day 140. Fetal testes from day 140 pregnant ewes that were exposed transiently for 80-day periods during early (0-80 days), mid (30-110 days), or late (60-140 days) pregnancy had fewer Sertoli cells and reduced testicular area stained for CYP17A1. Male fetuses from ewes exposed during late pregnancy also exhibited reduced fetal body, adrenal and testis mass, anogenital distance, and lowered testosterone; collectively indicative of an anti-androgenic effect. Exposure limited to early gestation induced more testis transcriptome changes than observed for continuously exposed day 140 fetuses. These data suggest that a short period of EC exposure does not allow sufficient time for the testis to adapt. Consequently, testicular transcriptomic changes induced during the first 80 days of gestation may equate with phenotypic effects observed at day 140. In contrast, relatively fewer changes in the testis transcriptome in fetuses exposed continuously to ECs throughout gestation are associated with less severe consequences. Unless corrected by or during puberty, these differential effects would predictably have adverse outcomes for adult testicular function and fertility.

Published
2022

5. Topaz1 suppression disrupts the expression of testicular long non-coding RNAs during murine spermatogenesis

Author

CHADOURNE, Manon, Poumerol, Elodie, Passet, Bruno, Jouneau, Luc, Pailhoux, Eric, Mandon-Pepin, Béatrice, Biologie de la Reproduction, Environnement, Epigénétique & Développement (BREED), and Université Paris-Saclay-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE)-École nationale vétérinaire d'Alfort (ENVA)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)

Subjects
Meiosis I, Topaz1, Mouse mus musculus, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, Germ cell apoptosis, Spermatogenesis, LncRNAs, ComputingMilieux_MISCELLANEOUS, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis
Abstract

International audience

Published
2021

8. Contribution à l'étude de Topaz 1, gène indispensable pour la spermatogénèse murine

Author

Poumerol, Elodie, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Ecole Pratique des Hautes Études - EPHE Paris, Béatrice Mandon-Pépin, and Flore Renaud

Subjects
[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDD.GAM]Life Sciences [q-bio]/Development Biology/Gametogenesis
Abstract

Doctoral; Ce diplôme EPHE décrit le rôle indispensable du gène Topaz1 dans la spermatogenèse murine. Ce gène, hautement conservé chez les vertébrés, est spécifique des cellules germinales et possède deux domaines conservés: le motif en doigt de zinc et PAZ. Le domaine PAZ est retrouvé dans les protéines PIWI impliquées dans la voie des piRNAs. Afin d'étudier le rôle de Topaz1, nous avons généré un modèle murin dépourvu de ce gène. L'absence de la protéine TOPAZ1 ne perturbe ni le développement, ni la fertilité des souris hétérozygotes et des femelles homozygotes. Par contre, les mâles Topaz1-/- sont stériles dû à un arrêt de la spermatogenèse lors de la première division méiotique. Ce blocage méiotique n’est ni dû à un défaut de formation du complexe synaptonémal, ni à une dérégulation de l’inactivation transcriptionnelle des chromosomes sexuels, ou à une régulation de l'expression des rétrotransposons. D'un point de vue histologique, les différences observées entre les testicules de souris Topaz1-/- et Topaz+/+ apparaissent entre 15 et 20 jours après la naissance. Une absence de cellules germinales haploïdes et une augmentation de l’apoptose sont détectées dans les testicules de souris Topaz1-/-. C’est au stade métaphase I que ces différences phénotypiques deviennent visibles. En effet, les spermatocytes I des testicules de souris Topaz1-/- sont bloqués en prométaphase I, et ne rentrent jamais en métaphase I. Ce blocage est corrélé à un défaut de formation du réseau de microtubules et à une perturbation de la triméthylation de la lysine 20 de l’histone H4 des centromères des chromosomes en pro-métaphase. Les testicules de ces souris Topaz1-/-, comparés à ceux d'animaux normaux, montrent des transcriptomes différents avec notamment une dérégulation de l'expression de nombreux ARNs non codants longs. L’invalidation, par CripsR/Cas9, d’un de ces longs ARNs non codants ne perturbe cependant pas la spermatogénèse des souris Topaz1-/-. Cette étude a permis de démontrer que TOPAZ1 est indispensable à la spermatogenèse de souris. Une mutation dans le gène Topaz1 pourrait être impliquée dans des cas d’infertilités azoospermiques non obstructives chez l’Homme. La poursuite de l'étude de Topaz1 pourrait permettre de caractériser de nouveaux acteurs de la spermatogenèse, notamment, des ARN non codants longs et/ou des protéines nécessaires à la formation du fuseau de microtubules lors de la première étape de la méiose.

Published
2019

9. Long non-coding RNA function during meiotic divisions of spermatogenesis in mammals : link with Topaz1

Author

CHADOURNE, Manon, Poumerol, Elodie, Passet, Bruno, Jouneau, Luc, Pailhoux, Eric, Mandon-Pepin, Béatrice, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Université Paris Saclay (COmUE), Génétique Animale et Biologie Intégrative (GABI), AgroParisTech-Institut National de la Recherche Agronomique (INRA), and GdR 3606 REPRO (Groupe de Recherche Reproduction). FRA.

Subjects
meiotic arrest, [SDV.GEN]Life Sciences [q-bio]/Genetics, [SDV.GEN.GA]Life Sciences [q-bio]/Genetics/Animal genetics, [SDV]Life Sciences [q-bio], topaz1, [INFO]Computer Science [cs], testis, ComputingMilieux_MISCELLANEOUS, LncRNA, mouse
Abstract

National audience

Published
2019

10. Long non-coding RNA function during meiotic divisions of spermatogenesis in mammals

Author

CHADOURNE, Manon, Poumerol, Elodie, Mandon-Pepin, Béatrice, Biologie du Développement et Reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Institut National de la Santé et de la Recherche Médicale (INSERM). FRA.

Subjects
[SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2018

11. Identification of transcripts involved in meiosis and follicle formation during ovine ovary development

Author

Poumerol Elodie, Cabau Cédric, Mandon-Pépin Béatrice, Baillet Adrienne, Pailhoux Eric, and Cotinot Corinne

Subjects
Biotechnology, TP248.13-248.65, Genetics, QH426-470
Abstract

Abstract Background The key steps in germ cell survival during ovarian development are the entry into meiosis of oogonies and the formation of primordial follicles, which then determine the reproductive lifespan of the ovary. In sheep, these steps occur during fetal life, between 55 and 80 days of gestation, respectively. The aim of this study was to identify differentially expressed ovarian genes during prophase I meiosis and early folliculogenesis in sheep. Results In order to elucidate the molecular events associated with early ovarian differentiation, we generated two ovary stage-specific subtracted cDNA libraries using SSH. Large-scale sequencing of these SSH libraries identified 6,080 ESTs representing 2,535 contigs. Clustering and assembly of these ESTs resulted in a total of 2,101 unique sequences depicted in 1,305 singleton (62.11%) and 796 contigs (37.9%) ESTs (clusters). BLASTX evaluation indicated that 99% of the ESTs were homologous to various known genes/proteins in a broad range of organisms, especially ovine, bovine and human species. The remaining 1% which exhibited any homology to known gene sequences was considered as novel. Detailed study of the expression patterns of some of these genes using RT-PCR revealed new promising candidates for ovary differentiation genes in sheep. Conclusion We showed that the SSH approach was relevant to determining new mammalian genes which might be involved in oogenesis and early follicle development, and enabled the discovery of new potential oocyte and granulosa cell markers for future studies. These genes may have significant implications regarding our understanding of ovarian function in molecular terms, and for the development of innovative strategies to both promote and control fertility.

Published
2008
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12. The Topaz1 gene is necessary for spermatogenesis

Author

Luangpraseuth, Alix, Poumerol, Elodie, Baillet, Adrienne, Cotinot, Corinne, Mandon-Pepin, Béatrice, Biologie du développement et reproduction (BDR), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, topaz1, testis, sterility, meiosis
Abstract

International audience; Background: Previously, we identified genes preferentially expressed during prophase I of meiosis and early folliculogenesis in the sheep ovary (1). We isolated a novel gene, named TOPAZ1 (Testis and Ovary-specific PAZ domain gene 1) present in male and female gonads. This gene is germ cell-specific and strongly expressed during male meiosis (2). Its nucleotide sequence is highly conserved in vertebrates and contained one PAZ and one CCH domains. Thus, Topaz1 could have an important role during germ cells development and gametogenesis. Aim: What is the consequence of Topaz1 gene deletion in mice? Material & Methods: We generated knock-in mouse and compared it to their wild-type counterpart.

Published
2014

13. Topaz1, un gène indispensable à la spermatogénèse et la fertilité mâle

Author

Luangpraseuth, Alix, Poumerol, Elodie, Baillet, Adrienne, Cotinot, Corinne, Mandon-Pepin, Béatrice, Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), Biologie du développement et reproduction (BDR), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)

Subjects
méiose, spermatogenèse, testicule, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract

absent

Published
2013

14. Topaz1 is essential for spermatogenesis and male fertility

Author

Luangpraseuth, Alix, Baillet, Adrienne, Poumerol, Elodie, Cotinot, Corinne, Mandon-Pepin, Beatrice, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), European Society for Sexual Medicine (ESSM). ITA., Institut Curie. FRA., Biologie du Développement et Reproduction (BDR), and Institut National de la Recherche Agronomique (INRA)

Subjects
endocrine system, urogenital system, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract

Knockout of Topaz1 in mice results in male sterility with no post-meiotic spermatids or spermatozoa. Expression of most of genes involved in the PIWI pathway, DNA methylation and retrotransposons silencing will be investigated. The high degree of TOPAZ1 conservation in vertebrates and the presence of its protein in germline stimulate our interest to determine the essential role of Topaz1 in mouse.

Published
2012

15. Caractérisation d'un nouveau gène, Topaz1, spécifique des cellules germinales et conservé au cours de l'évolution des Vertébrés

Author

Mandon-Pepin, Béatrice, Baillet, Adrienne, Luangpraseuth, Alix, Poumerol, Elodie, Cotinot, Corinne, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Institut National de Recherche Agronomique (INRA). UAR Département Physiologie Animale et Systèmes d'Elevage (0558).

Subjects
topaz1, vertebré, gonade, ovaires, brebis, [SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology, ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2012

16. Maternal exposure to a complex mixture of environmentally-relevant chemicals during critical developmental windows differentially affects fetal ovarian follicles and ovarian transcriptome

Author

Loup, Benoît, Mandon-Pepin, Beatrice, Amezaga, Maria R, Poumerol, Elodie, Kyle, Carol E, Lea, Richard G, Sinclair, Kevin D, Rhind, Stewart M, Fowler, Paul A, Cotinot, Corinne, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), ANR REEF, Biologie du Développement et Reproduction (BDR), and Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract

This work was supported by the EC7th Framwork Programme (FP7/2007-2013) grant agrement n° 212885; absent

Published
2011

17. Exposure of fetal germ cells (F2) to a complex mixture of environmentally-relevant chemicals via grand-maternal (F0) ingestion subtly affects the fetal ovarian proteome

Author

Amezaga, Maria R, Skiba, JA, Fraser, M, Loup, Benoît, Mandon-Pepin, Beatrice, Poumerol, Elodie, Kyle, CE, Lea, RG, Sinclair, KD, Rhind, SM, Cotinot, Corinne, Fowler, PA, Biologie du Développement et Reproduction (BDR), Institut National de la Recherche Agronomique (INRA), ANR REEF, Biologie du développement et reproduction (BDR), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV.BDLR]Life Sciences [q-bio]/Reproductive Biology, [SDV.BDD]Life Sciences [q-bio]/Development Biology
Abstract

This work was supported by the European Community 'S Seveneth Framework Programme (FP/2007-2013) agreement n° 212885; absent

Published
2011

18. Impact des polluants environnementaux sur le développement de l'ovaire chez le mouton

Author

Mandon-Pepin, Béatrice, Loup, Benoît, Poumerol, Elodie, Cotinot, Corinne, Biologie du développement et reproduction (BDR), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)

Subjects
POLLUANTS ENVIRONNEMENTAUX, [SDV]Life Sciences [q-bio], BIOLOGIE DU DEVELOPPEMENT, [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2009

19. REFOLLIS , Restitution des résultats scientifiques dans les projets financés par l'ANR

Author

Bonnet, Agnès, Benne, Francis, Bodin, Loys, Sarry, Julien, Liaubet, Laurence, San Cristobal, Magali, Tosser-Klopp, Gwenola, Cotinot, Corinne, Mandon-Pepin, Béatrice, Poumerol, Elodie, ProdInra, Migration, Laboratoire de Génétique Cellulaire (LGC), Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National Polytechnique (Toulouse) (Toulouse INP), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Station d'Amélioration Génétique des Animaux (SAGA), Institut National de la Recherche Agronomique (INRA), Génétique Physiologie et Systèmes d'Elevage (GenPhySE ), École nationale supérieure agronomique de Toulouse [ENSAT]-Institut National de la Recherche Agronomique (INRA)-Ecole Nationale Vétérinaire de Toulouse (ENVT), Biologie du développement et reproduction (BDR), École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)-Centre National de la Recherche Scientifique (CNRS), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract

National audience

Published
2009

20. Identification of genes expressed during sheep ovarian development

Author

Baillet, Adrienne, Mandon-Pepin, Béatrice, Cabau, Cédric, Poumerol, Elodie, Pailhoux, Eric, Cotinot, Corinne, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Hungarian Society for Animal Reproduction. HUN.

Subjects
[SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2008
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21. Expression and the regulation of SOCS3 in ovine uterine cells

Author

Rodde, Nathalie, Reinaud, Pierrette, Poumerol, Elodie, Leroux-Coyau, Mathieu, Poehlmann, T.G., Markert, U.R., Houdebine, Louis, Sandra, Olivier, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), and Friedrich-Schiller-Universität = Friedrich Schiller University Jena [Jena, Germany]

Subjects
[SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], SUPPRESSOR OF CYTOKINE SIGNALLING, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

22. Ovine progesterone-induced blocking factor at the feto-maternal interface during implantation

Author

Fovet, Claire Maëlle, Camous, Sylvaine, Poumerol, Elodie, Aubrière, Marie-Christine, Giraud-Delville, Corinne, Dahirel, Michèle, Nolent, F., Dubanchet, S., Szekeres-Bartho, J., Lea, R.G., Sandra, Olivier, ProdInra, Migration, Biologie du développement et reproduction (BDR), Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA), Unité 782, Institut National de la Santé et de la Recherche Médicale (INSERM), Pecs University Medical School, and University of Nottingham, UK (UON)

Subjects
[SDV] Life Sciences [q-bio], [SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], PROGESTERONE, [INFO] Computer Science [cs], ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2007

23. Identification of genes expressed during sheep ovarian development by SSH

Author

Mandon-Pepin, Béatrice, Baillet, Adrienne, Poumerol, Elodie, Cotinot, Corinne, Biologie du développement et reproduction (BDR), and Centre National de la Recherche Scientifique (CNRS)-École nationale vétérinaire d'Alfort (ENVA)-Institut National de la Recherche Agronomique (INRA)

Subjects
[SDV]Life Sciences [q-bio], [INFO]Computer Science [cs], GENETIQUE, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2006

24. Maternal high-fat diet induces follicular atresia but does not affect fertility in adult rabbit offspring

Author

Léveillé, Pauline, primary, Tarrade, Anne, additional, Dupont, Charlotte, additional, Larcher, Thibaut, additional, Dahirel, Michèle, additional, Poumerol, Elodie, additional, Cordier, Ann-Gaël, additional, Picone, Olivier, additional, Mandon-Pepin, Béatrice, additional, Jolivet, Geneviève, additional, Lévy, Rachel, additional, and Chavatte-Palmer, Pascale, additional

Published
2014
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25. Dietary Lipid and Cholesterol Induce Ovarian Dysfunction and Abnormal LH Response to Stimulation in Rabbits

Author

Cordier, Anne-Gaël, primary, Léveillé, Pauline, additional, Dupont, Charlotte, additional, Tarrade, Anne, additional, Picone, Olivier, additional, Larcher, Thibaut, additional, Dahirel, Michèle, additional, Poumerol, Elodie, additional, Mandon-Pepin, Béatrice, additional, Lévy, Rachel, additional, and Chavatte-Palmer, Pascale, additional

Published
2013
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28. Ovine fetal testis stage-specific sensitivity to environmental chemical mixtures.

Author

Lea RG, Mandon-Pépin B, Loup B, Poumerol E, Jouneau L, Egbowon BF, Bowden A, Cotinot C, Purdie L, Zhang Z, Fowler PA, and Sinclair KD

Subjects
Animals, Female, Fetus, Humans, Male, Pregnancy, Sewage adverse effects, Sheep, Testosterone metabolism, Sheep, Domestic, Testis metabolism
Abstract

Exposure of the fetal testis to numerous individual environmental chemicals (ECs) is frequently associated with dysregulated development, leading to impaired adult reproductive competence. However, 'real-life' exposure involves complex mixtures of ECs. Here we test the consequences, for the male fetus, of exposing pregnant ewes to EC mixtures derived from pastures treated with biosolids fertiliser (processed human sewage). Fetal testes from continuously exposed ewes were either unaffected at day 80 or exhibited a reduced area of testis immunostained for CYP17A1 protein at day 140. Fetal testes from day 140 pregnant ewes that were exposed transiently for 80-day periods during early (0-80 days), mid (30-110 days), or late (60-140 days) pregnancy had fewer Sertoli cells and reduced testicular area stained for CYP17A1. Male fetuses from ewes exposed during late pregnancy also exhibited reduced fetal body, adrenal and testis mass, anogenital distance, and lowered testosterone; collectively indicative of an anti-androgenic effect. Exposure limited to early gestation induced more testis transcriptome changes than observed for continuously exposed day 140 fetuses. These data suggest that a short period of EC exposure does not allow sufficient time for the testis to adapt. Consequently, testicular transcriptomic changes induced during the first 80 days of gestation may equate with phenotypic effects observed at day 140. In contrast, relatively fewer changes in the testis transcriptome in fetuses exposed continuously to ECs throughout gestation are associated with less severe consequences. Unless corrected by or during puberty, these differential effects would predictably have adverse outcomes for adult testicular function and fertility.

Published
2022
Full Text
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