La connaissance et la maîtrise du déterminisme du sexe et de la différenciation sont des défis majeurs pour la production de tilapia. L'élevage de populations monosexes mâles évite les effets négatifs d'une reproduction continue et profite de la meilleure croissance des mâles. Dans le contexte d'une aquaculture durable, le développement de stratégies alternatives et écologiques est nécessaire pour le contrôle du sexe du tilapia sans avoir recours aux approches hormonales. Ces alternatives reposent sur des approches génétiques ou environnementales, en utilisant l'effet masculinisant des températures élevées appliquées au cours de la différenciation sexuelle. Dans cette thèse la recherche de gènes impliqués dans la différenciation sexuelle a été réalisée dans les gonades et le cerveau en utilisant l'analyse de certains gènes candidats. L'objectif était de développer des marqueurs putatifs pour produire des populations monosexes mâles par des approches respectueuses des consommateurs et de l'environnement. Les expressions temporelles et spatiales de cyp19a1a, cyp19a1b, FOXL2, dmrt1, SOX9, DAX1 et amh ont été analysées dans plusieurs descendances de mâles ou des femelles génétiques ainsi que dans des femelles traitées à fortes températures. Leur lien avec les masculinisations par la températ ure a également été recherché sur des lignées thermosensibles de tilapia. L'un des gènes qui présente un dimorphisme sexuel important est l'amh qui est exprimé aussi bien dans les gonades que dans le cerveau pendant les premiers stades de la différenciation sexuelle. Le niveau d'expression de l'amh dans le cerveau est élevé chez les mâles quand les gonades sont toujours indifférenciées et probablement même avant la synthèse des stéroïdes gonadique. Une procédure de sexage moléculaire précoce a été développée en utilisant ce gène chez le tilapia. Cette procédure sera d'un grand intérêt pour les éleveurs et les scientifiques pour identifier rapidement des individus YY mâles avec un gain en temps et en argent, et pourra être utilisée également pour rechercher d'autres approches fiables de production de populations monosexes mâles sans l'utilisation des hormones. / Knowledge and the control of sex determination and differentiation are major challenges for tilapia production. Farming of male monosex populations avoids the negative effects of a continuous reproduction and benefits from males' fast growth. In the context of a sustainable aquaculture, alternative and ecological strategies have to be developed to control sex in tilapia without hormonal treatment. These approaches will rely on genetic and environmental treatments, such as the use of masculinising high temperatures applied during sex differentiation. The search for genes implicated in sex differentiation has been performed in both gonads and brains using the analysis of candidate genes. The objective was to develop putative markers to produce male monosex populations through consumer and environmentally friendly approaches. Temporal and organ expressions of cyp19a1a, cyp19a1b, foxl2, dmrt1, sox9, dax1 and amh were analysed in several progenies o f genetic males or females as well as in temperature-treated individuals. Their link with temperature masculinisation was also performed on the thermosensitive tilapia lines. One of the sexual dimorphic genes was amh which was found expressed in both gonads and brains during early stages of sex-differentiation. Brain amh was elevated in males when the gonads were still undifferentiated and probably before steroid synthesis took place. A precocious molecular sexing procedure was developed in tilapia using this gene. This procedure will be of great advantage for both farmers and scientists in identifying quickly male individuals and in finding reliable male monosex approaches not using hormones.

Sexually dimorphic behaviour of the house mouse (Mus musculus musculus) relies on various physical and chemical cues, however, chemical signals are the most essential cues for individual recognition and in causing various priming effects on reproductive behaviour of the receiver. House mice belong to macrosmatic mammals, and thus, their sense of smell is highly developed and is able to recognize a wide spectrum of ligands from other individuals and from their surrounding environment. Volatile signals belong to organic compounds that are produced by most tissues, and may have harmfull effects on cells, and thus they are transported out of the body with lipocalin transporters where some of them may function as signals. These volatile signals are able to stimulate chemosensory neuronal receptors, and thus, yield particular responses in neural circuits. The ligand sensing has a differential effect upon males and females, however, it has not been shown yet in wild mice whether these differences are also caused by the variation in receptors and neural processing, or rather by differential expression of signals typical for each sex. The aim of this thesis was to perform comparative analysis of orofacial mucosal tissues to determine the specificity of expression of particular lipocalins. For the first time...

Processes of biological changes of organism over time distinctly manifest themselves in a face morphology. The present study age changes are observed as shape and size changes of transversal dates of surface 3D virtual models of faces of 443 women and men (22-88 years old) devided into six age groups in decade. Differences in faces among each age group with respect to the sex were investigated and a sexual dimorphism and its gradual progress with the age using methods of geometric morphometrics (coherent point drift - dense correspondence algorithm, principal component analysis, per vertex t-test, shell-to-shell deviation). A significant difference among age categories was observedd both in shape as well as in form of the face. The faces of women and men were becoming wider with age and convexity was decreasing at the same time. A decline of the whole forehead and of the profile of the men's nose was observed, whereas the women's foreheadwas getting bevel due to the decline of the top part and a profile of the nose wasn't changed with the age. On contrary, the men's chin was unvarying with the age, while the women's chin was sliding out foward. There was observed a distinct decline in the front part of a upper jaw with the both sex. It was found out that after the seventh life decade the face gets...

While the role of cholesterol in liver carcinogenesis remains controversial, hepatocellular carcinoma generally prevails in males. Herein, we uncover pathways of female-prevalent progression to hepatocellular carcinoma due to chronic repression of cholesterogenic lanosterol 14α-demethylase (CYP51) in hepatocytes. Tumors develop in knock-out mice after year one, with 2:1 prevalence in females. Metabolic and transcription factor networks were deduced from the liver transcriptome data, combined by sterol metabolite and blood parameter analyses, and interpreted with relevance to humans. Female knock-outs show increased plasma cholesterol and HDL, dampened lipid-related transcription factors FXR, LXRα:RXRα, and importantly, crosstalk between reduced LXRα and activated TGF-β signalling, indicating a higher susceptibility to HCC in aging females. PI3K/Akt signalling and ECM-receptor interaction are common pathways that are disturbed by sex-specific altered genes. Additionally, transcription factors (SOX9)2 and PPARα were recognized as important for female hepatocarcinogenesis, while overexpressed Cd36, a target of nuclear receptor RORC, is a new male-related regulator of ECM-receptor signalling in hepatocarcinogenesis. In conclusion, we uncover the sex-dependent metabolic reprogramming of cholesterol-related pathways that predispose for hepatocarcinogenesis in aging females. This is important in light of increased incidence of liver cancers in post-menopausal women.

Anti-müllerian hormone (AMH) is expressed in male embryos and represses development of müllerian ducts during testis differentiation in mammals, birds and reptiles. Amh orthologues have been identified in teleosts despite them lacking müllerian ducts. Previously we found sexually dimorphic aromatase activity in tilapia brains before ovarian differentiation. This prompted us to search for further dimorphisms in tilapia brains during sex differentiation and see whether amh is expressed. We cloned the tilapia amh gene and found that it contains 7 exons but no spliced forms. The putative protein presents highest homologies with Amh proteins of pejerrey and medaka as compared to other Perciformes. We analysed amh expression in adult tissues and found elevated levels in testes, ovary and brain. Amh expression was dimorphic with higher levels in XY male brains at 10–15 dpf, when the gonads were still undifferentiated and gonadal amh was not dimorphic. Male brains had 2.7-fold higher amh expression than gonads. Thereafter, amh levels decreased in the brain while they were up-regulated in differentiating testes. Our study indicates that amh is transcribed in male brains already at 10 dpf, suggesting that sexual differentiation may be occurring earlier in tilapia brain than in gonads. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

Anti-müllerian hormone (AMH) is expressed in male embryos and represses development of müllerian ducts during testis differentiation in mammals, birds and reptiles. Amh orthologues have been identified in teleosts despite them lacking müllerian ducts. Previously we found sexually dimorphic aromatase activity in tilapia brains before ovarian differentiation. This prompted us to search for further dimorphisms in tilapia brains during sex differentiation and see whether amh is expressed. We cloned the tilapia amh gene and found that it contains 7 exons but no spliced forms. The putative protein presents highest homologies with Amh proteins of pejerrey and medaka as compared to other Perciformes. We analysed amh expression in adult tissues and found elevated levels in testes, ovary and brain. Amh expression was dimorphic with higher levels in XY male brains at 10–15 dpf, when the gonads were still undifferentiated and gonadal amh was not dimorphic. Male brains had 2.7-fold higher amh expression than gonads. Thereafter, amh levels decreased in the brain while they were up-regulated in differentiating testes. Our study indicates that amh is transcribed in male brains already at 10 dpf, suggesting that sexual differentiation may be occurring earlier in tilapia brain than in gonads. / Dieser Beitrag ist mit Zustimmung des Rechteinhabers aufgrund einer (DFG-geförderten) Allianz- bzw. Nationallizenz frei zugänglich.

The Hedgehog signaling pathway regulates many processes during embryogenesis and the homeostasis of adult organs. Recent data suggest that central metabolic processes and signaling cascades in the liver are controlled by the Hedgehog pathway and that changes in hepatic Hedgehog activity also affect peripheral tissues, such as the reproductive organs in females. Here, we show that hepatocyte-specific deletion of the Hedgehog pathway is associated with the dramatic expansion of adipose tissue in mice, the overall phenotype of which does not correspond to the classical outcome of insulin resistance-associated diabetes type 2 obesity. Rather, we show that alterations in the Hedgehog signaling pathway in the liver lead to a metabolic phenotype that is resembling metabolically healthy obesity. Mechanistically, we identified an indirect influence on the hepatic secretion of the fibroblast growth factor 21, which is regulated by a series of signaling cascades that are directly transcriptionally linked to the activity of the Hedgehog transcription factor GLI1. The results of this study impressively show that the metabolic balance of the entire organism is maintained via the activity of morphogenic signaling pathways, such as the Hedgehog cascade. Obviously, several pathways are orchestrated to facilitate liver metabolic status to peripheral organs, such as adipose tissue.

<p dir="ltr">People suffering from COPD are also known to suffer from other musculoskeletal issues like fracture risk, back pain, etc. Intervertebral disc degeneration (IVD) is a prominent cause of back pain and inflammation, influenced by factors such as aging, sudden loading, and genetics. <i>SERPINA1</i>, a common genetic variant in individuals with chronic obstructive pulmonary disease (COPD), encodes the alpha-antitrypsin protein (AAT). AAT deficiency is also associated with IVD degeneration, bone loss, and gait impairment. Currently, AAT-deficient individuals receive costly and short-lived weekly AAT injections, with no established guidelines for managing IVD degeneration and osteoporosis. Our primary research objective was to examine the effects of <i>serpinA1a/c</i> using a mouse model with global knockout (KO) of <i>serpinA1a/c</i>, generated through CRISPR technology, on intervertebral discs (IVD) and bone. We found that global deletion of <i>serpinA1a/c</i> was found to cause IVD elastin degradation, leading to a loss of mechanical properties. Moreover, <i>serpinA1</i> was associated with increased bone-resorbing cells (osteoclasts) and a reduction in bone-forming cells (osteoblasts). Notably, sexual dimorphism was observed, with female IVDs exhibiting less degeneration than male counterparts, and <i>serpinA1a/c</i> KO mice were protected from mechanically-induced tail compression. Even in human IVDs, males expressed more AAT-1 compared to female IVDs. There are no FDA-approved drugs currently existing for IVD degeneration. Since IVD degeneration frequently occurs in individuals with osteoporosis, it shows a probable cross-talk happening between IVD and bone. In our study, we found the association of <i>serpinA1 </i>with estrogen receptor alpha and osteoclasts. Hence, we investigated the potential of raloxifene, an FDA-approved selective estrogen receptor modulator (SERM) typically prescribed to post-menopausal women for osteoporosis treatment, in averting IVD degeneration and improving mechanical characteristics in IVD. Our findings suggest that raloxifene injection may retard IVD degeneration induced by AAT deficiency, particularly in male mice. Furthermore, the latter study touched upon a conditional <i>serpinA1a</i> mouse model crossed with aggrecan-cre, specifically targeting <i>serpinA1a</i>-expressing cells in the IVD while sparing bone. Conditional <i>serpinA1a</i> deletion induced mild IVD degeneration without affecting bone loss. In summary, this study serves as a foundation for testing potential treatments for AAT patients with IVD degeneration and osteoporosis. It also provides compelling evidence for considering raloxifene as a treatment option for IVD degeneration in AAT-deficient patients experiencing IVD-related pain.</p>