Dans le contexte de la physiologie comparée de la reproduction, les amphibiens sont peu étudiés. Le travail réalisé durant cette thèse visait à analyser des marqueurs de différenciation testiculaire chez l'urodèle Pleurodeles waltl, dont le déterminisme génétique du sexe (ZZ/ZW) peut être influencé par la température. Nos études ont d'abord porté sur le gène sox9 marqueur de la différenciation testiculaire chez les vertébrés supérieurs. Le gène cloné chez le pleurodèle montre une bonne conservation par rapport aux autres vertébrés. Son expression plus élevée dans la gonade mâle n'apparaît que tardivement suggérant qu'il n'est probablement pas impliqué dans les stades précoces de la différenciation testiculaire. En outre, son expression dans le mésonéphros rend difficile son utilisation comme marqueur de différenciation testiculaire. Nous avons ensuite étudié l'Amh, hormone testiculaire impliquée dans la régression des canaux de Müller chez de nombreux vertébrés. Son expression spécifique de la gonade, précocement plus élevée chez les larves ZZ que les ZW en font un excellent marqueur de la différenciation testiculaire. Le fait que les pleurodèles mâles voient les canaux de Müller persister malgré la présence d'Amh suggère que la fonction primaire de cette hormone était en relation avec la différenciation gonadique et que la fonction de régression des canaux de Müller n'est apparue que secondairement au cours de l'évolution. Ces marqueurs ont été mis à profit pour caractériser le phénotype gonadique lors d'inversions sexuelles ou lors de développements en absence de cellules germinales. Ils ont permis de montrer que les cellules germinales ne semblent pas jouer de rôle dans la différenciation gonadique du pleurodèle / In the context of comparative physiology of reproduction, amphibians are poorly studied. This work was dedicated to the analysis of testis differentiation markers in the newt Pleurodeles waltl, which shows a ZZ/ZW genetic mode of sex determination that can be affected by temperature. First, we studied sox9, a testis differentiation marker well characterized in many higher vertebrates. The gene cloned in Pleurodeles shows a good level of identity with other vertebrates. The testis-enriched expression appears late during the testis differentiation process indicating that it is probably not involved in the early steps of testis differentiation. Its use as a marker of testicular differentiation proved difficult since it is expressed not only in the gonads but also in the mesonephros. Then, we studied amh, a testis hormone responsible for müllerian duct regression in many vertebrates. Its early expression in the gonad, significantly higher in male than in female larvae makes it an excellent marker for testis differentiation. Since in Pleurodeles waltl, Müllerian ducts persist in males, it suggests that during the course of evolution, the function of Amh on the regression of Müllerian ducts appeared secondarily after its role in gonadal differentiation. These markers have been used to characterize the gonadal phenotype during sex reversal, or in gonads developed in the absence of germ cells. They showed that these cells do not seem to play a role in gonadal differentiation of Pleurodeles waltl

Conselho Nacional de Desenvolvimento Científico e Tecnológico / Follicular development occurs in wave like patterns in monovulatory species and is regulated by a complex interaction of gonadotropins with local intrafollicular regulatory molecules. In the first study, induction of co-dominant follicles in vivo with FSH treatment was used to study morphological mechanisms of selection of the dominant follicle in cattle. We determined the functional status of the STAT3, AKT and MAPK signaling pathways in granulosa cells of dominant (DF), subordinate (SF) and co-dominant (co-DF) follicles. We observed that the relative mRNA abundance of MAPK1/3 and AKT1/2/3 was significantly higher in granulosa cells of SFs than in DFs. However, there was a tendency for lower abundance of phosphorylated MAPK3/1 and AKT proteins in SFs granulosa cells. Relative abundance of mRNA and phosphorylated isoform of STAT3 was higher in granulosa cells of SFs than DFs and co-DFs. In line with this, SF granulosa cells had higher mRNA levels of LIFR and IL6ST, the two receptors involved in STAT3 activation. In summary, in the first study, we showed that atresia of SFs is associated with increased expression of LIFR and IL6ST, and activation of STAT3 in granulosa cells. These molecular features were absent in co-DF2, suggesting that FSH rescues co-DF2s through activation of MAPK and AKT, and inhibition of STAT3 pathways. In the second study, we investigated the regulation of AMH and its receptor (AMHR2) during follicular deviation and the effect of FSH-induced codominant follicles on AMH production in two in vivo models. In this study, we observed that AMH mRNA expression was similar in F1 and F2 before deviation (Day 2). On the other hand, the AMH mRNA levels were higher in DFs than SFs at the expected time (Day 3) and after (Day 4) deviation. There was no statistical difference at AMHR2 mRNA expression during the deviation process. However, AMHR2 tended to be more expressed in DFs than SFs after deviation (day 4). In the co-dominant model, AMH mRNA levels in granulosa cells were similar among the follicles within the groups. However, FSH supplemented follicles had more AMH abundance than control follicles. These data were complemented by AMH protein which was higher in FSH-supplemented follicles (co-DFs) and DFs than SFs. On the other hand, AMHR2 mRNA was higher in DFs than in SFs and similar between co-DFs. Our results from the second study suggest that AMH expression is regulated during follicular deviation, being stimulated by FSH, whereas AMHR2 is downregulated during advanced atresia. / O desenvolvimento folicular inicial em espécies monovulatórias ocorre no padrão de ondas foliculares e é regulado por uma complexa interação entre gonadotrofinas e moléculas regulatórias intrafoliculares. No primeiro estudo, a indução de folículos codominantes in vivo através do tratamento com FSH foi utilizada para o estudo dos mecanismos de seleção do folículo dominante em bovinos. Foi determinado o status funcional dos padrões de sinalização STAT3, AKT e MAPK nas células da granulosa de folículos dominantes (DF), subordinados (SF) e codominantes (co-DF). Os resultados deste estudo demonstraram que comparados com células da granulosa de DFs, a expressão relativa de RNAm para MAPK1/3 e AKT1/2/3 foram significativamente maiores em células da granulosa de SFs. Contudo, houve uma tendência para menor abundância de proteína fosforilada de MAPK3/1 e AKT em células da granulosa de SFs. A abundância relativa de RNAm e a proteína fosforilada de STAT3 foram significativamente maiores em células da granulosa de SFs em comparação com DFs e co-DFs. Em linha com esses resultados, células da granulosa de SFs tiveram maiores níveis de RNAm para LIFR e IL6ST, dois receptores envolvidos na ativação do STAT3. Neste primeiro estudo concluímos que a atresia de SFs está associada ao aumento das expressões de LIFR e IL6ST e consequente ativação da STAT3 nas células da granulosa. Essas características moleculares estavam ausentes nos co-DF2s sugerindo que o FSH resgata co-DF2s através da ativação do MAPK e AKT, e inibição do padrão STAT3. No segundo estudo, investigamos em dois modelos bovinos in vivo a regulação do AMH e seu receptor (AMHR2) durante a divergência folicular e o efeito da indução de folículos codominantes com FSH na produção de AMH. Este estudo demonstrou que as expressões de RNAm para AMH foram similares em F1s e F2s antes da divergência folicular (Dia 2). Por outro lado, foram maiores em células da granulosa de DFs em relação a SFs no momento esperado (Dia 3) e após (Dia 4) a divergência folicular. Não houve diferença nos níveis de RNAm para AMHR2 durante o processo de divergência folicular. Contudo, após a divergência (Dia 4) houve uma tendência de aumento nos níveis de RNAm para AMHR2 em DFs em relação a SFs. No modelo de codominância, as expressões de RNAm para AMH foram similares entre os folículos dentro dos grupos. No entanto, folículos suplementados por FSH apresentaram maiores níveis de RNAm para AMH. Esses dados foram complementados pela abundância da proteína AMH nas células da granulosa, a qual foi maior em co-DFs e DFs em comparação a SFs. Por outro lado, os níveis de RNAm para AMHR2 foram maiores em DFs em relação a SFs e similares entre co-DFs. Neste segundo estudo, os resultados sugerem que o AMH é regulado na divergência folicular, sendo estimulado por FSH, enquanto que o AMHR2 é regulado na atresia folicular.

Orientador: Rafael Henrique Nóbrega / Resumo: A decisão se a gônada indiferenciada irá se desenvolver em um testículo ou um ovário é uma etapa crítica na diferenciação sexual dos vertebrados. Este processo consiste em uma complexa cascata gênica que culmina na diferenciação das células somáticas presente na gônada indiferenciada. Neste sentido, o hormônio anti-Mülleriano é um importante efetor nesta decisão. Estudos com o peixe medaka mutante hotei, no qual o receptor do Amh tipo 2 (amhrII) é mutado, mostram elevado índice gonadossomático, e reversão sexual de macho para fêmea. Com base nestas informações, acredita-se que o Amh possa regular o número de células germinativas e diretamente ou indiretamente este fato pode influenciar na decisão da gônada bipotencial em se tornar um testículo ou ovário. Sendo assim, o objetivo do presente trabalho foi de se avaliar a sinalização do Amh durante a diferenciação sexual no medaka. Para tanto, estudos de perda de função gênica foram empregados, no qual o gene amh foi deletado através do sistema CRISPR/Cas9. Também foi avaliada a expressão dos genes que atuam na janela de diferenciação sexual por RT-qPCR. Inicialmente, identificamos dois tipos de mutação nos animais heterozigotos (amh (-/+) da F1. A mutação mais interessante foi a deleção de 759 pares de base entre os exons 6 e 7 que compreende parte dos domínios Amh_N e TGF-β. Na geração F2, os mutantes homozigotos amh (-/-) machos XY apresentaram 100% de reversão sexual para fêmeas fenotípicas. Além disso os animais amh (-/-) ap... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The decision whether the undifferentiated gonad will develop in a testicle or an ovary is a critical step in the sexual differentiation of vertebrates. This process consists of a complex genetic cascade that culminates in the differentiation of the somatic cells present in the undifferentiated gonad. In this context, the anti-Müllerian hormone is an important effector in this decision. Studies with the medaka hotei fish, in which the Amh type 2 receptor (amhrII) is mutated, show high gonadosomatic index, and sexual reversion from male to female. Based on this information, it is postulated that the Amh regulates the number of germ cells, and directly or indirectly this fact may influence the decision of the bipotential gonad to become a testicle or ovary. Therefore, the objective of the present study was to evaluate the signaling of Amh during sexual differentiation in medaka. For that, studies of loss of gene function were employed, in which the amh gene was deleted through the CRISPR / Cas9 system. We also evaluated the expression of genes that act in the window of sexual differentiation by RT-qPCR. We initially identified two types of mutation in F1 heterozygous (amh -/+) animals. The most interesting mutation was the deletion of 759 base pairs between exons 6 and 7 which comprises part of the Amh_N and TGF-β domains. In the F2 generation, the homozygous amh (-/-) mutants XY males presented 100% of sexual reversion. In addition, the amh (-/-) animals presented gonadal hyper... (Complete abstract click electronic access below) / Doutor

Background: The aim of this thesis was to study the relationship of pre-diagnostic circulating concentrations of sex steroid hormones (androgens, estradiol, 17-hydroxyprogesterone, and progesterone), growth factors (insulin-like growth factor-I (IGF-I), placental growth hormone (GH)), sex hormone binding globulin (SHBG), and anti-Müllerian hormone (AMH) with risk of epithelial ovarian cancer (EOC) overall, and by tumor invasiveness and histology. A longitudinal study was used to assess patterns of hormonal changes during a single pregnancy, and in two consecutive pregnancies. Materials & Methods: A case-control study was nested within the Finnish Maternity Cohort and the Northern Sweden Maternity Cohort. A total of 1 052 EOC cases were identified through linkages with the cancer registries in both countries. For each case, 2-3 controls were selected. Cases and controls were matched on cohort, age and date at blood draw, as well as for parity at blood draw and at diagnosis (n=2 695). Odds ratios (OR) and corresponding 95% confidence intervals [CI] were estimated using conditional logistic regression. The longitudinal study was based on 71 pregnant Finnish women, who donated blood samples in each trimester of pregnancy. Results: Higher androgen concentrations were associated with an increased risk of overall EOC (e.g., testosterone ORT3 vs. T1: 1.56 [1.30-1.87], ptrend<0.0001), while the risk of endometrioid tumors increased with higher estradiol concentrations (ORT3 vs. T1: 2.76 [1.04-7.33], ptrend=0.03). Higher IGF-I was associated with a non-significant decrease in risk for invasive (ORT3 vs. T1: 0.79 [0.62-1.02], ptrend=0.07) and endometrioid tumors (ORT3 vs. T1: 0.55 [0.28-1.07], ptrend=0.07). The inverse association between IGF-I levels and risk of invasive EOC was stronger in analyses limited to women aged <55 years at diagnosis (ORT3 vs. T1: 0.74 [0.57-0.96], ptrend=0.03). No associations were observed between pre-diagnostic progesterone, SHBG, placental GH, and AMH with EOC risk overall, or by tumor invasiveness and histology. The longitudinal study showed that hormone concentrations were more strongly correlated between consecutive trimesters of a pregnancy than between the 1st and 3rd trimesters. Further, 3rd trimester hormone concentrations can be estimated from 1st or 2nd trimester measurements. Conclusion: Higher pre-diagnostic androgens, estradiol, and IGF-I are associated with EOC risk, and associations differ by tumor invasiveness and histology.

Premature ovarian Insufficiency (POI) is the cessation of the ovarian function before the age of 40, defined by high serum gonadotrophins, low estradiol and amenorrhea for at least 4 months. The etiology may be iatrogenic after a surgery, chemotherapy or radiotherapy treatment, environmental, autoimmune or genetic. However, in most of the cases the cause remains unknown. Clinical and family studies suggest a strong heritability of age at menopause and POI, but the number of genetic causes and genes identified to be involved in human POI remains very small. In POI patients, the two crucial functions of the ovary, hormonal secretion and reproduction, are absent. In the last decades, however, new advances in assisted reproduction techniques have allowed the possibility of carrying pregnancies to POI women, thanks to oocyte donation. The aim of this study was to identify new genetic factors implicated in the development of POI women and to analyse the reproductive possibilities and outcome of women with a genetic cause of POI. For the first part of the study, the DNA of a cohort of POI women recruited in the Fertility Clinic of the Hôpital Erasme of the Université Libre de Bruxelles was used to sequence five candidate genes (FSHR, GDF9, BMP15, AMH and AMHR2) known to be implicated in the ovarian folliculogenesis. The most important findings were two very rare variants and one unknown variant in the AMH gene. The functional study performed with these variants suggested a diminished function of the mutant protein. Furthermore, one of the variants was found in the mother of one of the patients, who was also diagnosed of POI at 32 years old. These arguments strongly suggest that a defective AMH could play a role in the development of POI. This is supported by previous studies with knock out mice models, which show an earlier depletion of the ovarian follicle pool due to a faster recruitment of the primordial follicles that constitute the ovarian reserve. The sequencing of the BMP15 gene led to the identification of two new variants not identified among controls but not predicted to be deleterious. Interestingly, one variant previously reported in POI women and predicted to be deleterious for the protein function, was found in a Sub-Saharan African POI patient as well as in our control cohort. This variant was already studied functionally and shown to have a reduced biological activity. However, we identified this variant in 6% of the Sub-Saharan African control population, which suggests that this is a more prevalent variant in the African genotype and raises up the importance of the ethnicity when studying genetic variants.The sequencing of the other genes (FSHR, GDF9 and AMHR2) did not lead to any association with POI.In the second part of the study, 24 women with Turner syndrome and POI were analysed in terms of reproductive, obstetrical and perinatal outcome after oocyte donation. This specific group of patients was chosen because of their specific systemic anomalies that could interfere with pregnancy outcome and because very few reports have been published on this subject. In the 23 patients finally transferred, the pregnancy rate was similar to that obtained after oocyte donation in other cohorts. There was a miscarriage rate of 23% and a rate of complications of pregnancy as high as 50%, mainly caused by pregnancy-induced hypertensive diseases. Four women at risk of genetic POI were included in the fertility preservation program in order to vitrify their oocytes. Three of them have already vitrified successfully their oocytes but none of them has yet used them.Oocyte vitrification represents a new hope for those women with genetic risk of POI to be able to carry a pregnancy with their own oocytes.In conclusion, three variants of the AMH gene could be implicated in the development of POI as demonstrated by the reduced in vitro bioactivity of the variants and the familial segregation of the cases. Since then, it sounds plausible to propose AMH sequencing in the case of familial POI and secondary amenorrhea.In the BMP15 gene, 2 new variants were predicted to be tolerated. A potentially deleterious variant of the BMP15 gene (L148P) previously associated to POI, was also found in 6% of the Sub-Saharan African controls which suggests that it is a common variant in the African ethnic. No clear association was found between the other tested candidate genes and our POI cohort.Regarding Turner’s Syndrome pregnancies, we can conclude that they are high-risk pregnancies that need of a multidisciplinary follow-up before and during pregnancy.Oocyte cryopreservation represents a new tool to be offered to women at risk of genetic POI to preserve their fertility, but not without previous genetic counselling. / Doctorat en Sciences médicales (Médecine) / info:eu-repo/semantics/nonPublished

Anti-Müllerian hormone appears to play central role in regulation of oocyte recruitment and folliculogenesis. Serum AMH concentration was found to be one of the best predictors of ovarian performance in IVF treatment. Consequently many fertility centres have introduced AMH for the assessment of ovarian reserve and as a tool for formulation of ovarian stimulation strategies in IVF. However published evidence on reliability of AMH assay methods and the role of AMH-tailored individualisation of ovarian stimulation in IVF appear to be weak. Consequently, I decided to conduct a series of studies that directed towards an improvement of the scientific evidence in these areas of research. The studies on performance of Gen II AMH assay revealed the assay suffers from significant instability and provides erroneous results. Consequently, the manufacturer introduced a modification on assay method. In view of the observed issues with Gen II assay, I conducted a critical appraisal of all published research on the previous and current assay methods that reported AMH variability, assay method comparison and sample stability. The literature indicated clinically important variability between AMH measurements in repeated samples, which was reported to be more significant with Gen II assay. The studies on between-assay conversion factors derived conflicting conclusions. Correspondingly, the review of studies on sample stability revealed conflicting reports on the stability of AMH under normal storage and processing conditions, which was reported to be more significant issue in Gen II assay. In view of above findings, we concluded that AMH in serum may exhibit pre-analytical instability, which may vary with assay method. Therefore robust, international standards for the development and validation of AMH assays are required. In the analysis of determinants of ovarian reserve, I evaluated the effect of ethnicity, BMI, endometriosis, causes of infertility and reproductive surgery on AMH, AFC and FSH measurements using data on a large cohort of infertile patients. Using robust multivariable regression analysis in a large cohort of IVF cycles, I established the effect of age, AMH, AFC, diagnosis, attempt, COS protocol changes, gonadotrophin type, USOR operator, regime and initial dose of gonadotrophins on oocyte yield. Then, I examined effect of gonadotrophin dose and regime on total and mature oocyte numbers. The study found that, after adjustment for all above variables, there was no increase in oocyte yield with increasing gonadotrophin dose categories beyond the very lowest doses. This suggests that there may not be significant direct dose-response effect and consequently strict protocols for tailoring the initial dose of gonadotrophins may not necessarily optimize ovarian performance in IVF treatment. In summary, studies described in this thesis have revealed instability of Gen II assay samples and raised awareness of the pitfalls of AMH measurements. These studies have also demonstrated the effect of clinically measurable factors on ovarian reserve and provided data on the effect of AMH, other patient characteristics and treatment interventions on oocyte yield in cycles of IVF. Furthermore, a robust database and statistical models have been developed, which can be used in future studies on ovarian reserve and IVF treatment interventions.

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Abstract  Master thesis in Business Administration, School of Business and Economics Linnaeus University 4FE17E VT2022  Authors: Eric Månsson & Marcus Nykvist  Supervisor: Magnus Willesson  Examiner: Christopher von Koch  Title: Identifying Reflexivity  Keywords: Reflexivity, EMH, AMH, fundamental value, market value, feedback loop, cognitive function, manipulative function.  Background: Current economic theory describes the risks the financial markets face as exogenous in nature. Several studies suggest the presence of an unaccounted-for risk which is not exogenous in nature but endogenous. Seemingly, the initial risk is exogenous but through the interaction between the market and its participants this risk can be either amplified or dulled. As such, current economic theory illustrates only partially the risks of financial markets as they do not account for endogenous risk. A theory is necessary which not only acknowledges the influence of exogenous risk but also considers the impact of endogenous risk after the fact. The theory of reflexivity offers a solution to this problem as it considers the interactions between the market and its participants and how these two affect each other, through the so-called cognitive- and manipulative function.  Purpose: As reflexivity entails a more complete description of the behavior of financial markets than current economic theory, the purpose of this study is to identify its occurrence.  Method: This study uses a deductive research approach along with a quantitative strategy to test its purpose. The utilized model is constructed through the theory of reflexivity and the implications this theory poses toward statistical testing. The study conducts its testing on a random sample of firms from the S&P 500 between 1992-2021 using annual data.  Results: The results of the study are invalidated due to the use of weak instruments in the market model, and due to a lack of endogeneity in the fundamental model. As such, the occurrence of reflexivity cannot be confirmed through this study. An interesting ancillary finding however is a methodological implication which suggests that different proxies for fundamental value as well as different instrumental variables may be necessary given a certain context to identify endogeneity and instrumental relevance respectively. / Sammanfattning  Examensarbete, Ekonomihögskolan vid Linnéuniversitetet, Företagsekonomi 4FE17E VT2022  Författare: Eric Månsson & Marcus Nykvist  Handledare: Magnus Willesson  Examinator: Christopher von Koch  Titel: Identifying Reflexivity  Sökord: Reflexivity, EMH, AMH, fundamental value, market value, feedback loop, cognitive function, manipulative function.  Bakgrund: Nuvarande ekonomiska teorier behandlar de risker som finns på de finansiella marknader som exogena. Hursomhelst, flertalet studier indikerar att det även finns risker som inte har tagits i beaktning och som eventuellt kan anses vara endogena. Det verkar därmed som att den ursprungliga risken är endogen, men genom samspelet mellan marknad och dess deltagare kan denna stärkas eller dämpas. Till följd av detta verkar det som att de nuvarande ekonomiska teorierna bara tar hänsyn till en del av alla de risker som existerar på de finansiella marknaderna. Med andra ord, det behövs en teori som inte bara tar hänsyn till de exogena riskerna, men som också uppmärksammar de endogena riskerna. Reflexivity erbjuder en sådan lösning i och med dess hänseende till interaktionen mellan marknad och marknadsdeltagare och dessas påverkan på varandra genom de så kallade kognitiva och manipulativa funktioner.  Syfte: Syftet med detta arbete är att identifiera reflexivity på marknaderna, eftersom att denna teori erbjuder en mer heltäckande beskrivning av marknadsbeteendet.  Metod: Tillvägagångssättet i denna studie är i form av en deduktiv forskning med en kvantitativ strategi för att testa syftet. Modellen som används är uppbyggd genom reflexivity-teorin och dess innebörd som denna teori har för statistisk testning. Testningen utgår från ett slumpmässigt urval av företag från S&P 500 mellan 1992 och 2021 på en årlig basis.  Resultat: Resultaten från denna studie ogiltigförklarades på grund av svaga instrumentala variabler i testningen och till följd av bristande endogenitet i den fundamentala modellen. Det gick därmed inte att bekräfta förekomsten av reflexivity genom denna studie.

Dans le contexte de la physiologie comparée de la reproduction, les amphibiens sont peu étudiés. Le travail réalisé durant cette thèse visait à analyser des marqueurs de différenciation testiculaire chez l'urodèle Pleurodeles waltl, dont le déterminisme génétique du sexe (ZZ/ZW) peut être influencé par la température. Nos études ont d'abord porté sur le gène sox9 marqueur de la différenciation testiculaire chez les vertébrés supérieurs. Le gène cloné chez le pleurodèle montre une bonne conservation par rapport aux autres vertébrés. Son expression plus élevée dans la gonade mâle n'apparaît que tardivement suggérant qu'il n'est probablement pas impliqué dans les stades précoces de la différenciation testiculaire. En outre, son expression dans le mésonéphros rend difficile son utilisation comme marqueur de différenciation testiculaire. Nous avons ensuite étudié l'Amh, hormone testiculaire impliquée dans la régression des canaux de Müller chez de nombreux vertébrés. Son expression spécifique de la gonade, précocement plus élevée chez les larves ZZ que les ZW, en fait un excellent marqueur de la différenciation testiculaire. Le fait que les pleurodèles mâles voient les canaux de Müller persister malgré la présence d'Amh suggère que la fonction primaire de cette hormone était en relation avec la différenciation gonadique et que la fonction de régression des canaux de Müller n'est apparue que secondairement au cours de l'évolution. Ces marqueurs ont été mis à profit pour caractériser le phénotype gonadique lors d'inversions sexuelles ou lors de développements en absence de cellules germinales. Ils ont permis de montrer que les cellules germinales ne semblent pas jouer de rôle dans la différenciation gonadique du pleurodèle.

Introdução. A Síndrome Pré-menstrual (SPM) é caracterizada por sintomas de estresse somáticos e comportamentais que se desenrolam logo após a ovulação, atingindo um pico máximo próximo à data da menstruação e desaparecendo em média em até quatro dias após o início do sangramento. A presença da formação do corpo lúteo seria necessária para a presença dos sintomas, contudo essa dinâmica dos hormônios da fase lútea associados à SPM é pouco conhecida. O hormônio antimülleriano (HAM) é um dos melhores marcadores de declínio da capacidade reprodutiva das mulheres. Até o momento o mesmo não foi correlacionado a sintomas da SPM. A percepção de piora dos sintomas da SPM na perimenopausa é sugerida, existindo a possibilidade de que com a menor função ovariana (redução do HAM) exista uma exacerbação da SPM durante essa fase da vida reprodutiva da mulher. Objetivo: avaliar o padrão de SPM em mulheres com idade superior a 35 anos e correlacionar seus sintomas com a redução de HAM. Métodos: Estudo observacional, transversal, com uma amostra de conveniência composta por mulheres recrutadas através da mídia local. O questionário Registro Diário da Intensidade de Problemas (DRSP) de 2 meses foi utilizado para o diagnóstico de SPM. As participantes (N = 101) foram avaliadas em seus perfis antropométricos (peso, altura, índice de massa corporal) e social (paridade, nível educacional, uso de contracepção oral). Depois de completar o questionário DRSP por 2 meses, as mulheres retornaram no período prémenstrual para a coleta do sangue. Entre as participantes que utilizaram contracepção hormonal, foi solicitado um período de wash out de um mês para a coleta de sangue e dosagem de HAM no soro. O HAM foi analisado usando um kit comercial ELISA, de acordo com as instruções do fabricante. A análise estatística foi realizada na versão SPSS 18.0. O nível de significância adotado para todas as análises foi estabelecido em 5%. Resultados: A análise de HAM mostrou uma redução significativa após a idade de 35 anos, e não foi relacionada à severidade dos sintomas de SPM. Os sintomas físicos na fase lútea, mas não os emocionais, foram maiores em mulheres com mais de 35 anos de idade. A análise de Spearman mostrou uma correlação positiva entre um grupo de ≥35 anos e uma correlação negativa entre o uso de contracepção oral com piora dos sintomas físicos da SPM. Conclusão: este estudo mostrou que não houve piora dos sintomas emocionais entre as mulheres com SPM após os 35 anos de idade, apenas piora dos sintomas físicos, que necessitam uma investigação mais aprofundada. Não há relação entre os sintomas físicos e emocionais com níveis de HAM nas mulheres com SPM. / Background. Premenstrual Syndrome (PMS) is characterized by somatic and behavioral stress symptoms that take place soon after ovulation, reaching a peak near the time of menstruation and disappears on average within 4 days after the start of the bleeding. The presence of the corpus luteum formation would be needed for the presence of symptoms, however, these dynamics luteal phase of hormones associated with PMS is not well known. The anti-müllerian hormone (AMH) is one of the best markers of decline in women's reproductive capacity, and AMH has not been correlated with PMS symptoms. The perception of worsening of PMS symptoms in perimenopause is suggested, with the possibility that with less ovarian reserve (reduction of AMH) there is an exacerbation of PMS during this phase of the woman's reproductive life. Objective: To evaluate the pattern of PMS in women aged over 35 years, and correlate its symptoms to the reduction of AMH. Methods: It was an observational, cross-sectional study with a convenience sample composed of women recruited through local media. The 2-months DRSP questionnaire was used for PMS diagnosis. The participants (N=101) were evaluated in their anthropometric (weight, height, body mass index) and social (parity, educational level, use of oral contraception) profiles. After completing the DRSP questionnaire for 2 months, women returned in the pre-menstrual period for serum collection. Among participants using hormonal contraception, a one-month washout period was requested for serum collection and AMH dosage. AMH was analyzed using an ELISA commercial kit, according the manufacturer’s instructions. Statistical analysis was carried out in SPSS version 18.0. Significance level adopted for all analyzes was set at 5%. Results: AMH analysis showed a significant reduction after the age of 35 years, and it was not related to PMS symptoms severity. Physical symptoms in luteal stage were greater in women aged over 35 years, emotional symptoms were equal in both ages. Spearman’s analysis showed a positive correlation between ≥ 35years group and a negative correlation between the use of oral contraception with PMS physical symptoms worsening. Conclusion: this study showed that there is no worsening of emotional symptoms among women with PMS after 35 years of age, with a greater physical complaint, that needs further investigation. There is no relation between the physical and emotional symptoms with AMH levels in PMS women.