ABSTRACT Selective progesterone receptor modulators (SPRM) represent a new class of synthetic steroids which can interact with the progesterone receptor (PR) and can exert agonist, antagonist or mixed effects on various progesterone target tissues in vivo. VA-2914 is a selective progesterone receptor modulator with potential contraceptive activity. We evaluated VA 2914 for ovulation inhibition in women, using three experimental doses ( 2,5 mg/d, 5 mg/d, 10 mg/d ) given continuously for three months. We examined the endometrial impact in each group. Anovulation (defined by absence of progesterone above 3 ng/ml ) was obtained in nearly 80% women in the 5 and 10 mg/d groups with a great rate of amenorrhea ( 81.2 and 90% cases in the 5 and 10 mg/d groups ). Estradiol levels remained in the physiological follicular phase range. Endometrial histological analysis show predominantly usual patterns of secretory phase. Some cystic glandular dilatations are observed in rare cases ; any hyperplasia was detected. VA-2914 induces amenorrhea while progestins cause endometrial spotting and bleeding. This abnormal bleeding due to progestins is a consequence of focal stromal proteolysis by increase in naked vessel size and density. We quantified the effects of VA 2914 on endometrial vascularisation, fibrillar matrix and VEGF-A expression in endometrial biopsies from 41 women before and after 12 weeks daily treatment (2,5 , 5 or 10 mg/d VA 2914 versus placebo). We did not observed changes in endometrial vessels, collagen network and VEGF-A distribution between the luteal phase at baseline and under VA 2914. From these observations, we can assess that VA 2914 does not behave like a progestin since it does not alter the endometrial matrix nor the pattern of endometrial vessels. Résumé : Les modulateurs sélectifs du récepteur de la progestérone ( SPRMs) constituent une nouvelle famille de stéroïdes présentant des propriétés mixtes agonistes ou antagonistes en fonction des gènes cibles, du contexte cellulaire, de la présence simultanée dautres ligands du récepteur de la progestérone (Spitz 2003). Le chef de file de cette famille, la mifépristone, est utilisé depuis plusieurs décennies pour ses propriétés abortives. Son intérêt dans la contraception post coïtale a été démontré. Des molécules aux propriétés abortives réduites sont à létude ou en cours de développement dans les domaines de la contraception, du cancer du sein, du traitement médical de lendométriose et des fibromes utérins (Pintiaux et al. 2009). Le VA2914 que nous étudions, fait partie de ces SPRMs en cours de développement. Nous avons démontré sa capacité à inhiber lovulation à partir de 5 mg administrés par voie orale quotidiennement. Il exerce une action endométriale participant vraisemblablement à leffet contraceptif . Il ninhibe pas le développement folliculaire et permet déviter la carence estrogénique observée sous progestatif antigonadotrope. A partir de la dose de 5 mg par jour, son utilisation saccompagne dun haut taux daménorrhée (Chabbert-Buffet et al. 2007). Lutilisation dun SPRM au long cours pose le problème dun endomètre soumis aux estrogènes endogènes sans opposition progestative. Limpact dun SPRM sur lendomètre varie en fonction de la molécule, de son dosage, de la présence concomitante dautres stéroïdes et de lespèce à laquelle ce SPRM est administré (Chwalisz et al. 2000). Des aspects histologiques particuliers sont décrits dans les endomètres soumis aux SPRMs. Il sagit de la coexistence daspects histologiques non présents de façon simultanée physiologiquement ( aspects sécrétoires et prolifératifs coexistant au sein du même endomètre, signes dapoptose et dactivité mitotique au sein dune même glande) (Mutter et al. 2008). La persistance dune activité mitotique est observée dans les glandes endométriales des patientes anovulatoires soumises au VA2914 (Chabbert-Buffet et al. 2007). Lutilisation de cette molécule quotidiennement et à long terme nest donc pas dactualité contrairement à son utilisation ponctuelle dans le cadre de la contraception postcoïtale (Creinin 2006). La place des SPRMs en contraception classique doit être définie. Différents schémas dadministration et différents dosages devront être évalués en termes defficacité et de sécurité. Lutilisation des SPRMs pourrait être utile pour contrer les saignements indésirables observés lors de la prise de progestatif seul. Contrairement aux patientes soumises aux progestatifs seuls, les patientes sous VA2914 présentent un haut taux d'aménorrhée. Lors du saignement physiologique menstruel comme lors de l'administration de progestatif seul, la dégradation locale du stroma endométrial et une lyse du réseau fibrillaire riche en collagène sont classiquement observées (Galant et al. 2000). Sous VA2914, nous nobservons pas de dégradation de la matrice extracellulaire (Ravet et al. 2009). Le rôle des métalloprotéases matricielles dans les saignements normaux et pathologiques de l'endomètre humain est bien connu . Le profil d'expression des métalloprotéases matricielles dans l'endomètre des patientes traitées par VA2914 à différents dosages peut contribuer à lintégrité endométriale observée. Une angiogenèse aberrante est observée sous progestatif. Une modification de la densité vasculaire endométriale et une altération de la maturation de la paroi des vaisseaux, déficitaire en péricytes et en cellules musculaires lisses ont été décrites (Hickey et al. 1999; Hickey et al. 2000; Jondet et al. 2005; Rogers et al. 1993; Stephanie et al. 2007). L'observation de la vascularisation de lendomètre exposé au dispositif intrautérin au lévonorgestrel durant 1 à 3 mois montre une augmentation très importante (11,5 fois) des petits vaisseaux non matures constitués exclusivement d'un endothélium. Le nombre de vaisseaux partiellement matures est augmenté de 6 fois. Au plus long cours, ces vaisseaux immatures ou partiellement matures restent néanmoins 4 fois plus fréquents que dans les endomètres non soumis à cette thérapeutique. La surface vasculaire et la densité augmentent au cours du temps sous ce dispositif hormonal (Stephanie et al. 2007). De telles modifications ne sont pas observées sous VA2914 et peuvent contribuer à l'absence de saignement. Au cours du cycle témoin, nous avons observé la présence de vaisseaux matures, représentant 80 % de la surface vasculaire totale. Après 3 mois de traitement sous VA2914 aux différentes doses, aucun changement vasculaire n'est observé. Sous VA2914, nous ne constatons pas de modification de l'expression du VEGFA ni de modification de sa distribution qui apparaît prédominante au niveau de la portion apicale des cellules épithéliales de surface et glandulaires. L'absence de modification de la distribution et de l'intensité du marquage du VEGFA (Vascular endothelial growth factor) et la stabilité du rapport Ang-1/Ang-2 avant et sous traitement par VA2914 n'est pas en faveur d'un remodelage vasculaire important (Ravet et al. 2009). Au niveau du réseau vasculaire endométrial, le VA2914 ne paraît donc pas se comporter comme un agoniste du récepteur de la progestérone.

Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 5 uppsatser.

Master of Science / Department of Animal Sciences and Industry / Jeffrey S. Stevenson / Our objective was to determine the optimal time to inseminate artificially cows following the standard CO-Synch protocol that also included a progesterone-releasing intravaginal controlled internal drug release (CIDR) insert. Lactating females from 3 Kansas locations were utilized. Crossbred Angus cows (n = 212) from the Agriculture Research Center in Hays (ARCH; location 1); Angus-Hereford crossbred cows (n = 249) from the Kansas State University Cow-Calf Unit (location 2); and purebred Angus, Hereford, and Simmental cows (n = 144) from the Kansas State University Purebred Beef Unit (location 3) were used in this study. Cows within each location were blocked by parity and assigned randomly within blocks to be artificially inseminated (AI) at 4 different times after the PGF2[Alpha] injection of the protocol: 48, 56, 64, or 72 h. Pregnancy diagnosis occurred at 32 and 63 d after insemination. Blood samples were collected 9 to 10 d and just before the first GnRH injection. Radioimmunoassays were performed on the blood sera samples to determine progesterone concentrations. Progesterone concentrations determined that approximately 60% of cows were cycling at the initiation of the study. A difference in cyclicity was observed with regards to age as well as body condition score. Pregnancies per AI (P/AI) at d 32 varied according to location and cycling status. Pregnancy loss between d 32 and 63 also was greatest for cows inseminated at 48 and 72 h. As pregnancy rates at d 63 increased with the 56- and 64-h treatments, pregnancy loss decreased. A significant difference in calving interval was detected among treatments, the shortest calving interval at 56 h. Results indicated that in most situations, the 56- and 64-h treatments presented the most desirable outcomes. The 56-h treatment presented the greatest number of P/AI for younger cows (≤ 3 yr), but for older cows, inseminations anytime 56 h or later produced the most P/AI. Overall pregnancy rates at d 63 were greatest for the 56-h treatment, with the fewest pregnancy losses. Given the interactions that seem to exist among location, cycling status, and age, further work is necessary to better define these relationships with the applied protocol.

Der epitheliale Natriumtransport in der postnatalen Lunge ist für einen ausgeglichenen Flüssigkeitstransport und eine gesunde Lungenfunktion unabdingbar. Eine bedeutende Rolle spielt hierbei der epitheliale Natriumkanal (ENaC). Es ist bereits bekannt, dass unter dem Einfluss von weiblichen Sexualhormonen, wie Progesteron, oder durch die Substitution von Glukokortikoiden, wie Dexamethason, die mRNA-Expression des ENaC und dessen elektrophysiologische Aktivität erhöht wird. Zur Lungenreifeinduktion werden bei Frühgeburtlichkeitsbestrebungen hohe Dosen von Glukokortikoiden verabreicht, die im fetalen Kreislauf auf hohe Progesteronkonzentrationen treffen. Die Auswirkung dieser Hormonkombination auf den epithelialen Natriumtransport ist bisher unbekannt. Um dieser Frage nachzugehen, wurden alveoläre Epithelzellen von Rattenfeten auf permeablen Membranen gezüchtet und mit unterschiedlichen Konzentrationen von Progesteron und Dexamethason inkubiert. Anschließend wurde die mRNA-Expression der drei Untereinheiten des ENaC (α, β, γ) mittels Real-Time PCR analysiert. Mit Hilfe von Ussing-Kammer Messungen wurden die Einflüsse auf den epithelialen Natriumtransport ermittelt. Durch die Experimente konnte der stimulierende Einfluss beider Hormone auf die mRNA-Expression bestätigt werden, wobei Dexamethason einen deutlich stärkeren Effekt erreichte. Durch die Kombination beider Hormone kam es zu einer signifikant geringeren mRNA-Expression und einem verminderten funktionellen Natriumtransport im Vergleich zur reinen Dexamethasoninkubation. Der Einsatz von Hormonrezeptor-Antagonisten zeigte, dass eine Blockierung des Progesteronrezeptors die mRNA-Expression erhöhte, wohingegen die Hemmung des Glukokortikoidrezeptors die mRNA-Expression der ENaCUntereinheiten verminderte. Zusammenfassend zeigen die Ergebnisse, dass Glukokortikoide und weibliche Geschlechtshormone, die einzeln zur Erhöhung der Natriumabsorption führen, durch die Kombination beider Hormone ihren Einfluss auf den Natriumtransport reduzieren.

Parkinson’s disease (PD) is a common neurodegenerative disorder that is characterised by akinesia, muscular rigidity, and postural instability, due primarily to the loss of dopaminergic neurons in the substantia nigra and depletion of upstream dopamine in the striatum. Current dopaminergic treatments reduce motor symptoms, but have diminishing benefits as the disease progresses. Treatment with the neuroactive steroid natural progesterone (PROG) improves outcomes in many experimental models of brain injury due to its pleiotropic mechanisms of neuroprotection, many of which may also benefit PD. This thesis investigated the influence of PROG on motor impairments in the unilateral intrastriatal 6-hydroxydopamine (6-OHDA) lesion model of PD in rats. We established a PD-like impairment with a d-amphetamine induced rotation test at day 7 after large lesions and then administered PROG (4 mg/kg or 8 mg/kg) once daily for 7 days starting at day 8. Both PROG doses markedly improved the primary outcome measure, forelimb akinesia on the adjusting steps test, with improvement sustained for six weeks after treatment had stopped. In a second study the beneficial influence of PROG (8 mg/kg) on akinesia was replicated for rats with large lesions and was extended to rats with small lesions so that the latter rats were now similar to sham operated controls. We also found that PROG modestly improved postural instability of the ipsilateral forelimb on the postural instability test, and sensorimotor integration on the whisker test, but did not improve skilled reaching accuracy on a single-pellet reaching task, forelimb use asymmetry on the cylinder test, sensory neglect on the corridor test, or rotation bias after apomorphine. Furthermore, PROG did not change striatal tyrosine hydroxylase density when assessed in rats with large lesions. This study has provided the most thorough examination to date regarding PROG’s influence on motor skills in an animal model of PD. Furthermore, this study has produced novel evidence of the beneficial effects of PROG treatment on forelimb akinesia. These initial promising findings suggest that PROG is an effective therapy for akinesia and thus provides an impetus to further investigate PROG’s efficacy for the treatment of PD.

There is accumulating evidence from many directions indicating that gender plays a critical role in drug abuse. Biological factors, including gonadal sex hormones, contribute in a significant although incompletely understood manner, to gender differences in drug abuse. Female sex hormones have been shown to affect central nervous system function and modulate the effects of drugs of abuse. For example, GABAA receptor function is positively modulated by progesterone. There is evidence from preclinical in vitro and in vivo studies as well as some clinical research suggesting that progesterone and its metabolites may enhance the behavioral effects of benzodiazepines, which also serve as positive modulators of GABAA receptors. The three studies presented here utilize within subject designs to assess the role of progesterone on the discriminative stimulus, subjective, performance and cardiovascular effects of triazolam, a short-acting benzodiazepine, in healthy, premenopausal women. The first study examined the effect of menstrual cycle phase on the discriminative stimulus effects of triazolam (0.00, 0.06, 0.12 and 0.25 mg/70 kg). The results of this study indicated that when progesterone levels peak (mid luteal phase), the discriminative stimulus effects of triazolam (0.12 mg/70 kg) are enhanced. The second study examined the separate and combined effects of a range of acute doses of oral micronized progesterone (0, 100 and 200 mg) and oral triazolam (0.00, 0.12 and 0.25 mg/70 kg) on the subjective, psychomotor and physiological effects of these medications, tested under conditions of low circulating sex hormones. The results of this study indicated that progesterone alone has some short-acting, sedative-like effects and enhances the subjective and performance effects of triazolam. The final study examined the effects of progesterone (0 and 100 mg) on the discriminative stimulus effects of triazolam (0.00, 0.06, 0.12 and 0.25 mg/70 kg), also under conditions of low circulating sex hormones. The results of this study indicated that the parent hormone progesterone does not appear to alter sensitivity to the discriminative stimulus effects of triazolam. Increases in sensitivity to triazolam in studies 1 and 2 may have been the result of neuroactive progesterone metabolites (e.g., allopregnanolone, TH-DOC), although future studies will be required to further examine this possibility. Taken together, these studies help clarify the manner in which the ovarian hormone progesterone and its metabolites modulate the behavioral effects of the benzodiazepines.

Menopause is a natural transition heralded by the cessation of menstrual cycles and ovulation, and it occurs in all women at an average of about 50 years of age. While not a disease, menopause is often accompanied by symptoms that interfere with the quality of life and these symptoms are due to the relatively abrupt deprivation of E2 and P4 experienced during reproductive aging. Reproductive aging consists of changes in the synthesis and release of hormones from the hypothalamus, pituitary and gonad, which make up the HPG axis. Because gonadal hormones play critical roles in many systems throughout the body and brain, not just reproduction, treatment of menopausal symptoms to date largely involves hormone replacement therapy (HRT) with E2, P4 or their combination. While not intended to treat other neurobiological symptoms beyond hot flushes, HRT has the potential to exert widespread actions due to the abundance of hormone receptors throughout the nervous system. Thus, a fuller understanding of the neurobiology of menopause is badly needed. Although much of the research into the mechanisms that underlie reproductive aging focuses on ovarian failure and follicular atresia (cell death), there is evidence that there are significant alterations in the function of the neuroendocrine levels - the hypothalamus and pituitary - that also contribute to this process. As the mean age of the population increases, the number of post-menopausal women continues to grow with broad economic, healthcare and social costs. It is increasingly important to understand the complex mechanisms underlying reproductive aging and the effects of HRT. In this dissertation, I focus on the question of how the female non-human primate hypothalamus changes both with aging and in response to steroid hormone treatments. / text

Doxorubicin is one of the most potent anticancer drugs used in the treatment of wide spectrum of neoplastic diseases including breast, thyroid, colon and liver cancer. However, doxorubicin use is associated with undesirable side effects including cardiomyopathy and congestive heart failure. In the present study we have established that treatment of rat cardiac myoblasts (H9c2 cells) with doxorubicin resulted in H9c2 cell injury in a dose and time dependent manner with almost 50% cell death obtained at 5 μM of doxorubicin treatment for 24 hours. We have selected about 50% cell injury as optimum doxorubicin-induced cell injury because once this threshold is reached, cells became irreversibly injured and could not respond to protective treatment. Another potent antineoplastic drug cyclophosphamide had no cardiotoxic effects on H9c2 cells even at 35 μM concentration and up to 72 hours of treatment. Pretreatment of H9c2 cells for 24 hours with dexamethasone, cortisol, corticosterone or progesterone, significantly protect H9c2 myoblasts against subsequent 5 μM doxorubicin treatment for 24 hours in a concentration dependent manner with maximum protection obtained at 100 nM dexamethasone, 100 nM progesterone, 500 nM cortisol and 500 nM corticosterone. However, testosterone or dehydroepiandrosterone had no protective effects even at 10 μM concentration. It is concluded that both glucocorticoids and progesterone protect H9c2 cells against doxorubicin-induced cell injury.

Orientador: José Luiz Moraes Vasconcelos / Banca: Pietro Sampaio Baruselli / Banca: Ciro Moraes Barros / Resumo: O objetivo desses experimentos foi avaliar os efeitos da concentração de progesterona pré e pós-ovulação em fêmeas Nelore submetidas ao protocolo: D0-benzoato de estradiol (2,0mg, Estrogin®) + CIDR®; D9-retirada do dispositivo + cipionato de estradiol (0,5mg, ECP®) + dinoprost trometamina (PGF2α, 12,5mg, Lutalyse®); D11- IATF. No Exp.1, 1.153 novilhas Nelore cíclicas foram divididas aleatoriamente para receber CIDR® sem utilização prévia ou utilizados previamente por 18 dias e 0, 200 ou 300UI de eCG (Folligon®) no D9. No Exp.2, 702 vacas Nelore solteiras foram divididas para receber aplicação de PGF2α no D7 ou D9 e 0 ou 300 UI de eCG no D9. Nestes experimentos o diâmetro do maior folículo (ØFD) foi avaliado no D11. Amostras de sangue para dosagem de P4 foram colhidas no D9 e D18 (7d pós-IATF). No Exp.3, 1.332 vacas paridas foram avaliadas no D7 quanto à presença de CL, sendo divididas para receber PGF2α no D7 ou D9. Amostras de sangue foram colhidas no D9. O diagnóstico de gestação foi realizado no D41. Variáveis contínuas foram avaliadas pelo PROC GLM e binomiais pelo PROC LOGISTIC. Considerou-se efeito significativo quando P<0,05 e tendência quando P<0,1. No Exp.1, as novilhas tratadas com CIDR® sem utilização prévia apresentaram maior [P4D9] (3,06±0,09 vs. 2,53±0,09 ng/ml). A [P4D9] afetou negativamente o ØFD. Novilhas que não receberam eCG apresentaram menor ØFD (0UI: 11,5±0,1a; 200UI: 11,9±0,1b; 300UI: 12,0±0,1bmm). O ØFD afetou positivamente a [P4D18]. Houve efeito de dose de eCG na [P4D18] (0UI: 2,77±0,11a; 200UI: 3,18±0,11b; 300UI: 4,87±0,11cng/ml) e na taxa de sincronização [TS; 0UI: 83,8%(337/402)a; 200UI:88,5%(339/383)ab; 300UI: 94,3%(347/368)b]. A [P4D9] tendeu a afetar negativamente e o ØFD influenciou positivamente a TS. Houve interação entre eCG e [P4D9] na taxa de... / Abstract: The aim of this trial was to evaluate the effect of pre- and post-ovulatory progesterone concentration in Nellore cattle treated with the protocol: D0-estradiol benzoate (2.0mg, Estrogin®) + CIDR®; D9-CIDR® withdrawal + of estradiol cypionate (0.5mg, ECP®) + dinoprost trometamine (12.5mg, Lutalyse®); D11-TAI. In Exp.1, 1,153 cycling Nellore heifers were randomly assigned to receive on D0 either a non-previously used or a 18d-previously CIDR® and 0, 200UI or 300UI of eCG (Folligon®) on D9. In Exp.2, 702 non-lactating Nellore cows were assigned to receive PGF2α treatment either on D7 or D9 and 0 or 300 IU of eCG on D9. On these experiments, the diameter of the largest follicle (ØFD) was measured on D11. Blood samples were collected on D9 and D18 (seven days after TAI) to evaluate serum progesterone concentrations. In Exp.3, 1,332 suckled Nellore cows were evaluated on D7 for luteal tissue presence. Cows were assigned to receive PGF2α either on D7 or D9. Blood samples were collected on D9. Pregnancy diagnosis was performed on D41. Continuous variables were evaluated by PROC GLM and binary by PROC LOGISTIC. Significant differences were considered when P<0.05 and tendencies when P<0.1. In Exp.1, heifers treated with non-previously used CIDR® had greater [P4D9] (3.06±0.09 vs. 2.53±0.09 ng/ml). The [P4D9] negatively affected the ØFD. There was effect of eCG dosage on ØFD (0IU: 11.5±0.1a; 200IU: 11.9±0.1b; 300IU: 12.0±0.1bmm). The ØFD positively affected the [P4D18]. The eCG dosage influenced the [P4D18] (0UI: 2.77±0.11a; 200UI: 3.18±0.11b; 300UI: 4.87±0.11cng/ml). Treatment with eCG affected synchronization rate [SR; 0IU: 83.8% (337/402)a; 200IU: 88.5% (339/383)ab; 300IU: 94.3% (347/368)b]. The [P4D9] tended to negatively affect, and the ØFD positively affected the SR. There was interaction between eCG and [P4D9] on conception... / Mestre

A progesterona desempenha uma função de extrema importância para o desenvolvimento embrionário inicial, por meio da regulação do ambiente uterino no período prévio à adesão dos embriões ao endométrio. Nesse contexto o objetivo do presente estudo foi avaliar os efeitos da suplementação com progesterona ou progestágeno durante a fase inicial da gestação sobre o ambiente uterino e desenvolvimento embrionário de suínos, bem como seus efeitos no desempenho da leitegada nascida. Foram realizados dois experimentos. No experimento 1 utilizou-se 40 porcas e 28 marrãs que no 6&ordm; dia de gestação foram distribuídas em um dos três grupos experimentais: fêmeas suplementadas com 20 mg de altrenogest (Regumate&reg;) do 6&ordm; ao 12&ordm; dia de gestação (RU; n = 23); fêmeas suplementadas com 2,15 mg/kg de progesterona de longa ação (Sincrogest&reg;), injeção única no 6&ordm; dia de gestação (PG; n = 24); fêmeas não suplementadas (CON; n = 21). Esse experimento foi delineado de maneira inteiramente casualizada em um arranjo fatorial, sendo que a categoria (marrã ou porca) foi considerada fator 1 e os grupos (CON, RU e PG) fator 2. 18 fêmeas foram eutanasiadas no 13&ordm; dia de gestação, e 50 fêmeas no 28&ordm; dia de gestação. Foram analisados: taxa de prenhez, taxa de ovulação, sobrevivência embrionária, tamanho e peso de embriões e útero, volume e peso de corpos lúteos, volume das vesículas embrionárias, dosagem sérica de progesterona e 17&#946;- estradiol, morfometrias glandular e de epitélio luminal do uterino. No experimento 2 foram utilizadas 75 matrizes, que no 6&ordm; dia de gestação foram alocadas de maneira interiramente casualisada em um dois grupos: fêmeas suplementadas com 20 mg de altrenogest (Matrix&reg;) do 6&ordm; ao 12&ordm; dia de gestação (ALT; n = 36); fêmeas não suplementadas (CTR; n = 36). Analisadas: taxa de prenhez, período gestacional, peso médio e homogeneidade da leitegada, número de leitões mumificados, natimortos e nascidos vivos, quantidade de leitões nascidos com menos de 800 gramas. Não houve influência dos tratamentos sobre a taxa de prenhez e a sobrevivência embrionária foi prejudicada apenas para marrãs do grupo RU. Para o desenvolvimento embrionário os resultados divergiram entre as categorias, as marrãs do grupo CON apresentaram embriões maiores e mais pesados quando comparados aos grupos suplementados, bem como vesículas embrionárias maiores. Para as porcas o grupo RU apresentou embriões maiores e mais pesados. De maneira geral as suplementações com progesterona ou progestágeno estimularam o crescimento do epitélio glandular aos 13 dias de gestação, mas não tiveram efeito sobre epitélio luminal. Já aos 28 dias de gestação o efeito da estimulação foi apenas observado para marrãs do grupo PG. Os tratamentos estimularam também o crescimento dos corpos lúteos que foram maiores e mais pesados para os grupos suplementados. Em relação ao desempenho da leitegada, analisado no experimento 2, não houve efeito de tratamento para nenhuma das variáveis analisadas. A suplementação de progesterona/progestágeno a partir do 6&ordm; dia de gestação estimulou o crescimento do epitélio glandular uterino e afetou o desenvolvimento embrionário inicial, mas não exerceu efeito significativo sobre o desempenho da leitegada. / Progesterone plays a role of extreme importance for early embryonic development by regulating the uterine environment in the period prior to the adhesion of the embryos to the endometrium. In this context, the objective of the present study was to evaluate the effects of progesterone or progestogen supplementation during early gestation on the uterine environment and embryo development of pigs, as well as their effects on litter performance. Two experiments were carried out. In the experiment 1, 40 sows and 28 gilts were used, which were distributed in one of the three experimental groups: females supplemented with 20 mg altrenogest (Regumate&reg;) from the 6th to the 12thh day of gestation (RU; n = 23); females supplemented with 2.15 mg / kg long acting progesterone (Sincrogest&reg;), single injection at 6th day of gestation (PG; n = 24); females not supplemented (CON; n = 21). This experiment was completely randomized in a factorial arrangement, with the category (gilt or sow) being considered as factor 1 and the groups (CON, RU and PG) factor 2. 18 females were euthanized on the 13th day of gestation, and 50 females on the 28th day of gestation. Pregnancy rate, ovulation rate, embryo survival, embryo and uterus size and weight, volume and weight of corpora lutea, volume of embryonic vesicles, serum progesterone and 17&#946;-estradiol concentrations, morphometric of uterine glandular epithelium and uterine luminal epithelium. In the experiment 2, 75 sows were used, which at the 6th day of gestation were allocated in a randomized manner in one of two groups: females supplemented with 20 mg of altrenogest (Matrix&reg;) from 6 to 12 days of gestation (ALT; = 36); females not supplemented (CTR; n = 36). The variables analyzed were: pregnancy rate, gestation length, average of litter weight, within-litter variation, number of mummified, stillborn and live born piglets, number of piglets born with less than 800 grams. There was no influence of treatments on the pregnancy rate and embryo survival was impaired only for gilts in the RU group. For embryonic development the results differed among the categories, the gilts of the CON group had larger and heavier embryos when compared to the supplemented groups, as well as larger embryonic vesicles. For the sows the RU group presented larger and heavier embryos. In general, progesterone or progestogen supplementation stimulated the growth of the glandular epithelium at 13 days of gestation, but had no effect on luminal epithelium. However, on day 28 of gestation the stimulatory effect was only observed for gilts of the PG group. Treatments also stimulated the growth of corpora lutea that were larger and heavier for the supplemented groups (RU and PG). Regarding the performance of the litter, analyzed in experiment 2, there was no treatment effect for any of the variables analyzed. In conclusion, Progesterone / progestogen supplementation from day 6 of gestation affected the uterine glandular epithelium area, and early embryonic development, but did not have a significant effect on the litter performance.