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This study evaluated the effect of prostaglandin F2α (PGF2α) associated with gonadotropin-releasing hormone (GnRH) for ovulation induction in precocious indicus heifers submitted to a fixed-time superovulation (SOV) programme. Precocious Nellore heifers (n = 35), aged 13 months, were subjected to the SOV protocol. On day 0 (D0), all animals received intravaginal insertion of a progesterone (P4) device along with intramuscular administration of 2 mg of oestradiol benzoate, plus 200 IU of follicle-stimulating hormone in decreasing doses, with 12-h intervals between D4 and D7, in addition to 150 µg of D-cloprostenol on D6 and device removal on D7. On D8, the donors received 10.5 µg of buserelin acetate and the treatment group received 300 µg of D-cloprostenol/PGF2α. Artificial insemination was performed 12 h and 24 h after GnRH administration using frozen semen. On D15 of the protocol (i.e., D7 after insemination), the embryos were collected and evaluated. All animals passed through the control and treatment groups. Results were evaluated by analysis of variance using an adjusted mixed-effects model (p < 0.05). There was no difference in the total number of embryos between the control and treatment groups (10.40 ± 1.52 vs. 9.60 ± 1.36; p = 0.63) or viable embryos (6.30 ± 1.22 vs. 4.30 ± 0.71). For precocious indicus heifers, treatment with PGF2α in association with GnRH did not affect embryo production in the fixed-time SOV protocol.
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Dinoprost , Estradiol , Hormona Liberadora de Gonadotropina , Inseminación Artificial , Inducción de la Ovulación , Progesterona , Superovulación , Animales , Bovinos , Femenino , Dinoprost/farmacología , Dinoprost/administración & dosificación , Hormona Liberadora de Gonadotropina/farmacología , Hormona Liberadora de Gonadotropina/administración & dosificación , Superovulación/efectos de los fármacos , Inseminación Artificial/veterinaria , Inducción de la Ovulación/veterinaria , Inducción de la Ovulación/métodos , Estradiol/farmacología , Estradiol/administración & dosificación , Estradiol/análogos & derivados , Progesterona/farmacología , Progesterona/administración & dosificación , Embarazo , Cloprostenol/farmacología , Cloprostenol/administración & dosificación , Buserelina/farmacología , Buserelina/administración & dosificación , Hormona Folículo Estimulante/farmacología , Hormona Folículo Estimulante/administración & dosificaciónRESUMEN
The practice of hormone therapy is crucial in aligning secondary sex characteristics with the gender identity of transgender adults. This study examines the effects of a commonly used injectable hormone combination, specifically estradiol enanthate with dihydroxyprogesterone acetophenide (EEn/DHPA), on serum hormonal levels and self-reported satisfaction with breast development in transwomen. Our research focused on a retrospective longitudinal study involving a large cohort of transwomen evaluated between 2020 and 2022, comprising 101 participants. We assessed serum levels of estradiol (E2), testosterone (T), luteinizing hormone (LH), and follicle-stimulating hormone (FSH), comparing the EEn/DHPA hormonal regimen with other combined estrogen-progestogen (CEP) therapies. Additionally, a subset of 43 transwomen completed a 5-question survey to evaluate self-reported satisfaction with breast development using Tanner scales. Our findings indicated that participants using the EEn/DHPA regimen exhibited significantly higher serum E2 levels (mean: 186 pg/mL ± 32 pg/mL) than those using other therapies (62 ± 7 pg/mL), along with lower FSH levels, but no significant differences in T and LH levels. Concerning satisfaction with breast development, 76% reported increased fulfillment with breast augmentation while using EEn/DHPA. These results suggest that an injectable, low-cost EEn/DHPA administered every three weeks could serve as an alternative feminizing regimen, particularly considering the extensive long-term experience of the local transgender community. Further longitudinal studies on the efficacy of feminizing-body effects and endovascular risks of various parenteral CEP types are warranted to improve primary healthcare provision for transgender persons.
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Estradiol , Personas Transgénero , Humanos , Femenino , Estradiol/administración & dosificación , Estradiol/sangre , Adulto , Estudios Retrospectivos , Masculino , Estudios Longitudinales , Mama/efectos de los fármacos , Satisfacción del Paciente , Servicios de Salud Comunitaria , Testosterona/administración & dosificación , Testosterona/sangre , Hormona Luteinizante/sangre , Hormona Folículo Estimulante/administración & dosificación , Hormona Folículo Estimulante/sangre , Persona de Mediana Edad , Adulto JovenRESUMEN
The objectives of this study were (1) to investigate the effects of the preovulatory follicle (POF) size on the accuracy of Doppler-based early pregnancy detection, and (2) to determine whether the removal of PGF2α (PGF) treatment during the resynchronisation protocol would affect fertility in beef cows. In Experiment 1, Nelore suckling cows (n = 224) were enrolled in an estradiol-progesterone-based timed artificial insemination (TAI) protocol. At TAI, cows were separated based on the range of POF diameters, as follows: ≤11.0 mm (n = 50), 11.1-12.9 mm (n = 64), 13.0-14.4 mm (n = 62) and ≥14.5 mm (n = 48). On day 22 after TAI, the corpus luteum (CL) blood flow (CLBF) of all cows was examined by colour Doppler ultrasonography to diagnose nonpregnant cows. The cows with the largest POF had the greatest positive predictive value (88.6%; 31 of 35) and diagnostic accuracy (91.7%; 44 of 48). In Experiment 2, Nelore cows (n = 233) were subjected to the same TAI protocol. Fourteen days after TAI, all cows were started on a resynchronisation protocol. Cows diagnosed as nonpregnant based on CLBF, on day 22, received 0.5 mg estradiol cypionate intramuscular (im) and were assigned to receive either 150 µg of PGF (PGF; n = 50) or 2 mL of saline (control; n = 47). Cows treated with PGF had a P/AI of 30.0% compared with a 48.9% P/AI in controls (p = 0.06). Our findings demonstrate that the POF size affects the accuracy of a CLBF-based early pregnancy diagnosis and that the removal of PGF treatment from the resynchronisation protocol tended to increase P/AI of the second TAI.
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Cuerpo Lúteo , Dinoprost , Estradiol , Sincronización del Estro , Inseminación Artificial , Folículo Ovárico , Progesterona , Animales , Femenino , Bovinos , Embarazo , Inseminación Artificial/veterinaria , Sincronización del Estro/métodos , Progesterona/administración & dosificación , Progesterona/sangre , Progesterona/farmacología , Estradiol/análogos & derivados , Estradiol/administración & dosificación , Estradiol/farmacología , Cuerpo Lúteo/efectos de los fármacos , Dinoprost/administración & dosificación , Dinoprost/farmacología , Dinoprost/análogos & derivados , FertilidadRESUMEN
BACKGROUND: Premenopausal, high-risk, hormone receptor-positive breast cancer patients are often treated with ovarian suppression in combination with aromatase inhibitors (AI). This combination has important adverse effects, particularly in sexual function, such as vaginal dryness and loss of libido. There is no effective therapy for reduced sexual function in this setting. Our study aimed to determine the efficacy and safety, particularly regarding sexual function, of a low-dose, topical testosterone gel administration. METHODS: This is a pilot, single-center study, designed to evaluate the efficacy of topical testosterone gel (3 mg/day) in improving sexual function in 29 premenopausal patients on ovarian suppression in combination with an AI. The primary safety endpoint was to assess serum estradiol elevation. The primary efficacy endpoint was sexual function improvement, assessed by the Female Sexual Function Index questionnaire. RESULTS: We report the results on 29 patients. Twenty-two patients (75%) completed the 3-month treatment, and seven discontinued treatment before completion, mostly due to logistical difficulties related to the COVID-19 pandemic. All patients maintained the value of baseline mass spectrometry assay for estradiol of less than 2.7 pg/mL during the undertaken measurements. We observed a significant improvement in Female Sexual Function Index measures over the visits, with an increase from a mean of 11.7 at baseline to 19.1 in the third month (p < 0.001), with the greatest improvement observed between the second and third months. CONCLUSIONS: Our findings suggest that topical testosterone seems to be safe and may be effective in improving sexual function in patients on ovarian suppression and AI. TRIAL REGISTRATION: The project was submitted and approved through the hospital's SGPP platform in 11/26/2019 (Project No. SGPP 393819) and CAAE (Research Ethics Committee) (CAAE No 25609719.5.0000.007).
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Inhibidores de la Aromatasa , Neoplasias de la Mama , Testosterona , Humanos , Femenino , Inhibidores de la Aromatasa/administración & dosificación , Inhibidores de la Aromatasa/efectos adversos , Inhibidores de la Aromatasa/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Testosterona/administración & dosificación , Testosterona/sangre , Persona de Mediana Edad , Adulto , Proyectos Piloto , Administración Tópica , Resultado del Tratamiento , Estradiol/administración & dosificación , Estradiol/efectos adversos , COVID-19 , Premenopausia , Disfunciones Sexuales Fisiológicas/etiología , Ovario/efectos de los fármacos , Ovario/metabolismo , SARS-CoV-2RESUMEN
Reproductive outcomes were evaluated in Nelore (Bos indicus) heifers submitted to one, two or no ovulation induction protocols based on progesterone (P4) and estradiol (E2) prior to a timed-artificial insemination (TAI) protocol. A total of 1,437 heifers (13.0 ± 0.8 mo old; 3.1 ± 0.1 of body condition score [BCS] and 279.9 ± 25.8 kg of body weight [BW]) were randomly assigned to 1 of 3 treatments: 0IND (n = 486): no ovulation induction protocol; 1IND (n = 481): one ovulation induction protocol; or 2IND (n = 470): two ovulation induction protocols. On Day -47, heifers from 2IND received a disinfected intravaginal P4 device (2 g, previously used for 21 d), kept until Day -40, when 0.5 mg of E2 cypionate (EC) was given. On Day -19, heifers from 2IND and 1IND underwent the same protocol. On Day 0, all heifers were submitted to the same TAI protocol, starting with a P4 device (0.5 g), 0.5 mg of cloprostenol sodium (PGF), and 1.5 mg of E2 benzoate. On Day 7, P4 device was removed, 0.5 mg of PGF, 0.5 mg of EC, and 200 IU of equine chorionic gonadotropin (eCG) were administered. The TAI was performed 2 d later (Day 9). Blood samples were collected on Days -47 and 0, to determine the presence of CL (circulating P4 concentrations ≥ 1.0 ng/mL). Ultrasound was performed on Days 40, 75 and between Day 150 and parturition to assess pregnancy per AI (P/AI) and pregnancy loss (PL). Statistical analyses were performed using SAS 9.4 (a-cP ≤ 0.05; A,B0.05 < P ≤ 0.10). The proportion of heifers with CL on Day -47 was similar among groups (3.4%). A greater proportion of heifers from 1IND had CL on Day 0, followed by 2IND, then 0IND (87.9a; 80.4b; 28.8c%). There was an effect of treatment on expression of estrus (2IND: 66.6a; 1IND: 67.2a; 0IND: 57.4b%), P/AI on Day 40 (2IND: 53.4a; 1IND: 43.9b; 0IND: 46.5b%), P/AI on Day 75 (2IND: 49.8a; 1IND: 40.5b; 0IND: 44.4ab%) and final P/AI (2IND: 45.5a; 1IND: 35.8b; 0IND: 40.5ab%). No differences were observed in PL (40-75 = 6.3%; 75-final = 9.6%; Total = 15.3%). Particularly within lighter heifers, there was an effect of treatment on P/AI on Day 40 (0IND: 39.2b; 1IND: 43.3ab; 2IND: 53.9a%) and on Day 75 (0IND: 36.6B; 1IND: 39.0AB; 2IND: 48.5A%). At the first pregnancy diagnosis, more nonpregnant heifers from 2IND had CL on Day 40 than 0IND, but 1IND did not differ from the other groups (85.4a; 74.8b; 80.8ab%). In conclusion, ovulation induction protocols performed prior to the TAI protocol increased the proportion of heifers with CL on Day 0. The use of two induction protocols resulted in greater fertility, particularly in lighter heifers, and increased cyclicity among nonpregnant heifers. These results indicate that this strategy may be an optimized method for inducing cyclicity and enhancing fertility of prepubertal Nelore heifers raised in pasture-based feeding systems.
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Inseminación Artificial , Inducción de la Ovulación , Progesterona , Animales , Bovinos/fisiología , Femenino , Inseminación Artificial/veterinaria , Inseminación Artificial/métodos , Embarazo , Progesterona/sangre , Progesterona/farmacología , Progesterona/administración & dosificación , Inducción de la Ovulación/veterinaria , Inducción de la Ovulación/métodos , Estradiol/farmacología , Estradiol/sangre , Estradiol/administración & dosificación , Maduración Sexual/efectos de los fármacos , Alimentación Animal/análisisRESUMEN
This study aimed to evaluate the localised effects of intrauterine ozone therapy on endometrial recovery in mares with endometritis. Our investigation assessed changes in gene expression profiles of anti-inflammatory (IL-1RA and IL-10), proinflammatory (IL-R1B3i and TNFα) and pleiotropic (IL-6) cytokines, along with detailed histological measurements of epithelial and endometrial thickness and the glandular area ratio. Twenty mares were assigned to a 2 × 2 factorial design based on endometritis diagnosis and treatment (control or 42 µg/mL ozone insufflation), resulting in four groups: NC (negative for endometritis/control), NO (negative/ozone), PC (positive/control) and PO (positive/ozone). Oestrus was induced with 2 mg of oestradiol benzoate on Days -1, 1 and 3, plus 1 mg on Day 5. Day 0 marked the initial uterine treatment, followed by insufflations on Days 1 and 2 with O3 (ozone) or O2 (control). Uterine biopsies were taken before treatment on Day 0 and Day 6 for histological analysis and gene expression assessment. Data were analysed using a statistical model that included endometritis status, treatment type, biopsy times (D0 and D6) and their interactions, analysed with Proc Glimmix. Regardless of treatment or endometritis status, significant biopsy effects (p < 0.01) indicated increased epithelial height and endometrial thickness in Day 6 samples. Analysis of IL-1 and TNFα revealed a significant interaction (p < 0.05) among endometritis, treatment and biopsy, with higher IL-1B3i expression on Day 6 in the PC group. The treatment effect (p < 0.04) showed a higher frequency (p < 0.01) of animals with positive modulation in the PC group (66.7%) versus the PO group (0.0%). An interaction effect (p = 0.08) between endometritis and treatment resulted from higher IL-1RA expression on Day 6 in the PC group compared to the PO group. Biopsy effect was significant for IL-10 (p < 0.01), indicating higher values in the second sample associated with tissue repair. In the short-term evaluation, ozone therapy did not influence endometrial morphology and may modulate cytokine expression, specifically the reduction in IL-1 and TNFα levels. Therefore, this therapy appears to be a safe and potentially effective treatment for modulating the inflammatory response in mares with endometritis.
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Citocinas , Endometritis , Enfermedades de los Caballos , Ozono , Útero , Animales , Femenino , Ozono/farmacología , Endometritis/veterinaria , Endometritis/tratamiento farmacológico , Caballos , Enfermedades de los Caballos/tratamiento farmacológico , Útero/patología , Citocinas/genética , Citocinas/metabolismo , Endometrio/efectos de los fármacos , Endometrio/metabolismo , Endometrio/patología , Estradiol/farmacología , Estradiol/análogos & derivados , TranscriptomaRESUMEN
There is a growing regulatory and scientific interest in the studies of environmental substances that are capable of interfering with the reproductive system. Among them, parabens stand out due to their widespread use and frequent detection as contaminants in human tissues and biological fluids. Therefore, we evaluated the toxic effects of butylparaben on the viability and follicular staging of bovine ovarian follicles in vitro. Fragments of ovaries from five cyclic bovine females were cultured for 44 h in a minimal essential medium (MEM; control) or MEM supplemented with 50 µg/mL and 100 µg/mL of butylparaben (BP 50 and BP 100 groups, respectively). The ovarian fragments were subjected to follicular staging, morphological analysis, morphometric analysis, estradiol analysis and oxidative profiling. No significant changes were observed between the experimental groups in follicular staging, estradiol analysis and oxidative profile analysis. However, the BP 50 group showed a significant decrease in the number of intact ovarian follicles. Moreover, a decrease in the follicular and oocyte diameters was observed in the groups that were exposed to butylparaben. In conclusion, butylparaben impairs the integrity and size of ovarian follicles in an in vitro bovine model, but does not affect the oxidative profile and steroidogenesis.
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Estradiol , Folículo Ovárico , Parabenos , Animales , Femenino , Parabenos/toxicidad , Bovinos , Folículo Ovárico/efectos de los fármacosRESUMEN
In brief: The hypoglycemic drug metformin has shown reproductive effects in women, although its mechanism of action is not fully understood. In this study, we demonstrate the direct effects of metformin on the ovary of healthy mice, with no alterations in fertility. Abstract: Metformin is a hypoglycemic drug widely used in type-2 diabetes (T2D) patients. In recent years, this drug has been suggested as a treatment for gestational diabetes and recommended to women with ovarian hyperstimulation syndrome (PCOS) to increase the chances of pregnancy or avoid early miscarriages. However, the exact effects of metformin on the female reproductive tract in general, and on the ovary in particular, are still not completely understood. In this study, we analyzed the effect of metformin on fertility and ovarian physiology in healthy female mice. We found that this drug altered the estrous cycle, early follicular development, serum estradiol and progesterone levels, and ovarian steroidogenic enzyme expression. Moreover, ovarian angiogenesis was lower in metformin-treated animals compared with untreated ones, whereas natural or gonadotropin-induced fertilization rates remained unchanged. However, offspring of metformin-treated animals displayed decreased body weight at birth. In this work, we unraveled the main effects of metformin on the ovary, isolated from other conditions such as hyperglycemia and hyperandrogenism, which is essential for a better understanding of metformin's mechanisms of action on reproduction and fertility.
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Ciclo Estral , Fertilidad , Hipoglucemiantes , Metformina , Ovario , Animales , Femenino , Metformina/farmacología , Ratones , Ovario/efectos de los fármacos , Ovario/metabolismo , Fertilidad/efectos de los fármacos , Hipoglucemiantes/farmacología , Ciclo Estral/efectos de los fármacos , Embarazo , Estradiol/sangre , Progesterona/sangreRESUMEN
Knowledge on hormonal regulation of reproductive cycles in viperid snakes is still incipient, especially when it comes to females and tropical species. There is an urgent need to understand the reproduction of venomous snakes to improve assisted reproduction techniques and optimize the maintenance of these animals in captivity. With this in mind, we monitored Northern pit viper females year-round throughout different seasons via serum levels of progesterone (P4) and estradiol (E2) in conjunction with ultrasound examinations. Ovarian follicles were classified according to their size and stage of vitellogenesis in F-I and F-II (non-vitellogenic phase) or in F-III and F-IV (vitellogenic phase). During autumn and winter, five adult males were rotated among these females for reproductive pairing, which resulted in 17 copulations and 2 pregnancies in the first year and 12 copulations and 5 pregnancies in the second year. Then, we assessed changes in P4 and E2 levels according to seasons, predominant ovarian structures and the presence of embryos or eggs in the oviduct. Our findings showed high levels of E2 when a greater number of vitellogenic follicles were detected, indicating a possible influence of E2 on vitellogenesis and higher levels of P4 whenever eggs and embryos were visualized in the oviduct, implying its role in maintaining pregnancy. Descriptive analysis of the vipers' ovarian cycles revealed a greater number of vitellogenic follicles during winter, probably as a result of increases in E2; whereas pregnancies occurred predominantly in spring, under the influence of P4. The use of ultrasound images, as a minimally invasive methodology, associated with serum steroid levels has proven to be an efficient approach in the reproductive monitoring of Northern pit vipers in vivo. In addition, these data suggest that female pit vipers under human care display a seasonal reproductive cycle, despite earlier studies involving captive males of the species indicating a lack of seasonality in sperm production and quality.
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Estradiol , Progesterona , Ultrasonografía , Animales , Femenino , Progesterona/sangre , Estradiol/sangre , Estaciones del Año , Masculino , Bothrops , Ovario/diagnóstico por imagen , Ovario/metabolismo , Folículo Ovárico/diagnóstico por imagen , Folículo Ovárico/metabolismo , Genitales Femeninos/diagnóstico por imagen , Bothrops atroxRESUMEN
BACKGROUND: Burning mouth syndrome (BMS) is a chronic pain condition affecting the oral cavity. This condition mostly affects peri- or postmenopausal women; for this reason, sexual hormonal changes have been implicated in BMS pathogenesis. METHODS: A systematic review was performed in MEDLINE/PubMed, Scopus, Web of Science, Cochrane Library and EMBASE without restriction for language or year. Eligibility criteria were controlled studies addressing the PICO question: (P) patients with BMS; (I) detection of the sex hormones; (C) patients without BMS; (O) changes on sexual hormones as a risk factor for BMS severity. Risk of bias was performed with Newcastle-Ottawa Quality Assessment Scale. RESULTS: Four studies were included. Salivary levels were evaluated in three studies and serum blood was used in one. Three studies analysed oestradiol and/or dehydroepiandrosterone (DHEA), two assessed progesterone and one evaluated follicle-stimulating hormone (FSH). Oestradiol results were contradictory, with two studies reporting lower levels in BMS patients compared to controls and one finding the opposite. DHEA was statistically lower in the BMS group in one study. Progesterone showed opposite results in two studies, although none with statistical significance. FSH was statistically higher in the BMS group compared to controls. Correlation of hormones with quality of life was performed in three studies and there was no significant correlation with self-perceived symptoms severity. CONCLUSION: Sexual hormones can be altered in BMS, especially oestradiol. Despite these changes, we did not find correlation between hormone fluctuation and BMS symptoms intensity affecting quality of life. These findings suggested the need for further investigation on hormonal alterations, which may be a promising target on BMS management.
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Síndrome de Boca Ardiente , Femenino , Humanos , Síndrome de Boca Ardiente/sangre , Síndrome de Boca Ardiente/metabolismo , Síndrome de Boca Ardiente/psicología , Deshidroepiandrosterona/sangre , Deshidroepiandrosterona/metabolismo , Estradiol/sangre , Estradiol/metabolismo , Hormona Folículo Estimulante/sangre , Hormona Folículo Estimulante/metabolismo , Hormonas Esteroides Gonadales/sangre , Hormonas Esteroides Gonadales/metabolismo , Progesterona/sangre , Progesterona/metabolismo , Calidad de Vida , Saliva/química , Saliva/metabolismoRESUMEN
This study assessed morphometric traits of the ampulla of the oviducts in prepubertal gilts treated with chorionic gonadotropins. With the day of slaughter as D0, gilts were assigned to four treatments (n = 8 each): control (untreated), eCG (200 IU eCG on D3), eCG+hCG (1200 IU eCG on D6 plus 500 IU hCG on D3), and eCG+hCG+AI (the previous treatment plus artificial insemination on D1). Blood and ampullae samples were collected at slaughter. Serum progesterone concentrations were higher for gilts treated with hCG than for those in the eCG and control treatments (p < 0.001), but estradiol concentrations did not differ (p > 0.05). The epithelium, muscle and lumen areas and the inner and larger ampullae diameters did not differ across treatments (p > 0.05). Therefore, treatment with chorionic gonadotropins did not alter the ampullae morphometry of prepubertal gilts.
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Gonadotropina Coriónica , Estradiol , Inseminación Artificial , Progesterona , Maduración Sexual , Animales , Femenino , Gonadotropina Coriónica/farmacología , Gonadotropina Coriónica/administración & dosificación , Progesterona/sangre , Progesterona/farmacología , Estradiol/sangre , Estradiol/farmacología , Maduración Sexual/efectos de los fármacos , Inseminación Artificial/veterinaria , Porcinos , Sus scrofaRESUMEN
The G-protein-coupled estrogen receptor (GPER) has been described to exert several cardioprotective effects. However, the exact mechanism involved in cardiac protection remains unclear. The aim of this study is to investigate the role of GPER activation on excitation-contraction coupling (ECC) and the possibility that such effect participates in cardioprotection. The cardiac myocytes of male Wistar rats were isolated with a digestive buffer and loaded with Fura-2-AM for the measurement of intracellular calcium transient (CaT). Sarcomere shortening (SS) and L-type calcium current (ICaL) were also registered. The confocal technique was used to measure nitric oxide (NO) production in cells loaded with DAF-FM-diacetate. Cardiac myocytes exposed to 17-ß-estradiol (E2, 10 nM) or G-1 (1 µM) for fifteen minutes decreased CaT, SS, and ICaL. These effects were prevented using G-36 (antagonist of GPER, 1 µM), L-Name (NO synthase -NOS- inhibitor, 100 nM), or wortmannin (phosphoinositide-3-kinase -PI3K- inhibitor, 100 nM). Moreover, G1 increased NO production, and this effect was abolished in the presence of wortmannin. We concluded that the selective activation of GPER with E2 or G1 in the isolated cardiac myocytes of male rats induced a negative inotropic effect due to the reduction in ICaL and the decrease in CaT. Finally, the pathway that we proposed to be implicated in these effects is PI3K-NOS-NO.
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Acoplamiento Excitación-Contracción , Miocitos Cardíacos , Óxido Nítrico , Fosfatidilinositol 3-Quinasas , Receptores Acoplados a Proteínas G , Animales , Masculino , Ratas , Estradiol/farmacología , Estradiol/metabolismo , Acoplamiento Excitación-Contracción/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/efectos de los fármacos , Óxido Nítrico/metabolismo , Óxido Nítrico Sintasa/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Ratas Wistar , Receptores de Estrógenos/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal/efectos de los fármacosRESUMEN
Batch spawner fishes develop successive clutches of oocytes which allows them to participate in many reproductive cycles during their adult life (iteroparous) and spawn in multiple events within each breeding cycle. Here, ovarian follicular development was morpho-functionally analyzed in females of the iteroparous batch spawner fish Gymnocorymbus ternetzi. To obtain better insights into the reproductive morpho-physiology in batch spawners, the objective of this research was to analyze the dynamics of the follicular development, with its hormonal regulation between two active reproduction events. We found that over 16 days, follicles progressed asynchronously to chromatin nucleolus, Primary and Secondary growth stages of oogenesis with progressive secretion of 17ß-estradiol (E2). During the end of secondary growth, the increase in 17α,20ß-dihydroxy-4-pregnen-3-one (17,20ß-p) was measured relative to the maturation process of the ovarian follicles (e.g., nuclear migration and its rupture during the resumption of meiosis). Interestingly, an additional increase in E2 was observed after fish reproduction, probably related to the recruitment of new batch follicles for secondary growth. We also measured the high values of multiple condition factor post-reproduction measurements, reflecting more energy invested during the pre-reproductive process. We also quantified high concentrations of 17,20ß-p, probably related to the recruitment of a new batch of oogonia to meiosis, presumably secreted by post-ovulatory follicles, after fish reproduction. We finally found that fish without exposure to reproductive stimulus developed a regression phase at day 24, characterized by massive follicle atresia, that allow them to recycle energy and constitutive materials of the follicles invested during oogenesis for another reproductive cycle.
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Estradiol , Folículo Ovárico , Ovulación , Animales , Femenino , Folículo Ovárico/fisiología , Estradiol/metabolismo , Ovulación/fisiología , Oogénesis/fisiología , Reproducción , HidroxiprogesteronasRESUMEN
Two experiments evaluated the effect of different hormonal treatments to synchronize follicle wave emergence on follicle dynamics and pregnancies per AI (P/AI) in estradiol (E2)/progesterone (P4) timed-AI (TAI) protocols in lactating dairy cows. In Experiment 1, lactating, primiparous Holstein cows (n = 36) received a P4 releasing device (Day 0) and were allocated at random to one of the following three treatment groups: Group EB received 2 mg E2 benzoate (EB) intramuscularly (i.m.), Group EB + GnRH received 2 mg EB+20 µg buserelin (GnRH) i.m., or Group EB + P4 received 2 mg EB + 100 mg of injectable P4 (iP4) in oil i.m. All cows received 0.150 mg D-Cloprostenol on Days 7 and 8 followed by P4 device removal, 400 IU eCG and 1 mg ECP on Day 8. Daily ultrasound examinations revealed that although the interval from P4 device removal to ovulation was not affected by treatment, cows that received EB + GnRH had an earlier (P < 0.05) emergence of the new follicular wave (Day 2.6 ± 0.2) than the other two treatment groups (Days 3.5 ± 0.3 and 6.1 ± 0.3, for EB and EB + P4, respectively). In Experiment 2, 808 lactating cows were assigned randomly to the three treatments evaluated in Experiment 1, and all the cows were TAI to determine P/AI. Cows in the EB + GnRH group had greater P/AI (57.4 %, P < 0.01) than those in the EB (44.6 %) or EB + P4 (45.7 %) groups. In conclusion, the administration of GnRH, but not iP4, on the day of insertion of a P4 device improves P/AI in lactating dairy cows synchronized for TAI with an estradiol/P4-based protocol.
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Estradiol , Sincronización del Estro , Hormona Liberadora de Gonadotropina , Inseminación Artificial , Lactancia , Folículo Ovárico , Progesterona , Animales , Bovinos/fisiología , Femenino , Inseminación Artificial/veterinaria , Inseminación Artificial/métodos , Lactancia/efectos de los fármacos , Folículo Ovárico/efectos de los fármacos , Folículo Ovárico/fisiología , Progesterona/administración & dosificación , Progesterona/farmacología , Estradiol/farmacología , Estradiol/administración & dosificación , Estradiol/análogos & derivados , Sincronización del Estro/métodos , Embarazo , Hormona Liberadora de Gonadotropina/farmacología , Hormona Liberadora de Gonadotropina/administración & dosificación , Buserelina/farmacología , Buserelina/administración & dosificaciónRESUMEN
The study evaluated the effects of Arthrospira maxima phycobiliproteins (PBPs), rosiglitazone (RSG), and 17ß-estradiol (E) on the differentiation process of 3T3-L1 cells and on their regulation of lipogenic and inflammatory gene expression at different stages of the process. The results showed that phycobiliproteins promoted cell proliferation after 24 h of treatment. Furthermore, for all three treatments, the regulation of the highest number of markers occurred on days 6 and 12 of differentiation, regardless of when the treatment was applied. Phycobiliproteins reduced lipid droplet accumulation on days 3, 6, 10, and 13 of the adipogenic process, while rosiglitazone showed no differences compared to the control. On day 6, both phycobiliproteins and rosiglitazone positively regulated Acc1 mRNA. Meanwhile, all three treatments negatively regulated Pparγ and C/ebpα. Phycobiliproteins and estradiol also negatively regulated Ucp1 and Glut4 mRNAs. Rosiglitazone and estradiol, on the other hand, negatively regulated Ppara and Il-6 mRNAs. By day 12, phycobiliproteins and rosiglitazone upregulated Pparγ mRNA and negatively regulated Tnfα and Il-1ß. Additionally, phycobiliproteins and estradiol positively regulated Il-6 and negatively regulated Ppara, Ucp2, Acc1, and Glut4. Rosiglitazone and estradiol upregulate C/ebpα and Ucp1 mRNAs. The regulation exerted by phycobiliproteins on the mRNA expression of the studied markers was dependent on the phase of cell differentiation. The results of this study highlight that phycobiliproteins have an anti-adipogenic and anti-inflammatory effect by reducing the expression of adipogenic, lipogenic, and inflammatory genes in 3T3-L1 cells at different stages of the differentiation process.
Asunto(s)
Células 3T3-L1 , Adipocitos , Adipogénesis , Diferenciación Celular , Estradiol , Ficobiliproteínas , Rosiglitazona , Animales , Ratones , Estradiol/farmacología , Rosiglitazona/farmacología , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Adipocitos/citología , Diferenciación Celular/efectos de los fármacos , Adipogénesis/efectos de los fármacos , Adipogénesis/genética , Ficobiliproteínas/farmacología , Ficobiliproteínas/metabolismo , Ficobiliproteínas/genética , Regulación de la Expresión Génica/efectos de los fármacos , Lipogénesis/efectos de los fármacos , Lipogénesis/genética , PPAR gamma/metabolismo , PPAR gamma/genética , Proliferación Celular/efectos de los fármacos , Inflamación/metabolismo , Inflamación/genética , SpirulinaRESUMEN
The aim of this study was to examine the impact of maternal obesity on the reproductive capacity of the female offspring (F1) and on the early development of the second generation (F2). To this end, rats were fed either standard (SD) or cafeteria (CD) diet. CD rats and their offspring were divided into 2 groups: rats with 18% and ≥25% overweight (CD18 and CD25, respectively) and offspring from CD18 and CD25 rats (OCD18 and OCD25, respectively). Both OCD groups achieved greater weight gain than controls, without changes in the serum levels of glucose, cholesterol or triglycerides. However, they showed increased gonadal cholesterol concentration and fat content compared to controls. Female OCD groups showed a slight prolongation of the estrous cycle and different pattern of changes in the weight gain during pregnancy. The OCD25 group displayed an increased fertility index and preimplantation losses, and changes in some fetal measurements. Some OCD25 dams gave birth to a larger litter of pups and displayed a lower viability index and lactation rate than controls. OCD25 dams also showed an increase in estradiol and a decrease in testosterone and anti-Müllerian hormone. OCD25 rats showed increased mRNA levels of steroidogenenic enzymes. The offspring from OCD25 females (F2OCD25 offspring) showed early vaginal opening and higher ovulation rate in females, and lower ano-genital distances in males, compared to controls. In conclusion, these results reflect that maternal obesity impacts on the reproductive health of successive generations, probably as a result of epigenetic changes in different systems, including germ cells.
Asunto(s)
Obesidad Materna , Efectos Tardíos de la Exposición Prenatal , Reproducción , Animales , Femenino , Embarazo , Obesidad Materna/metabolismo , Ratas , Masculino , Dieta Alta en Grasa/efectos adversos , Testosterona/sangre , Ciclo Estral , Dieta/efectos adversos , Estradiol/sangre , Obesidad/metabolismo , Obesidad/etiologíaRESUMEN
Despite significant advances in the study of fear and fear memory formation, little is known about fear learning and expression in females. This omission has been proven surprising, as normal and pathological behaviors are highly influenced by ovarian hormones, particularly estradiol and progesterone. In the current study, we investigated the joint influence of serotonin (5-HT) neurotransmission and estrous cycle phases (low or high levels of estradiol and progesterone) on the expression of conditioned fear in a group of female rats that were previously divided according to their response to stressful stimuli into low or high anxiety-like subjects. The baseline amplitude of the unconditioned acoustic startle responses was high in high-anxiety female rats, with no effect on the estrous cycle observed. Data collected during the proestrus-estrus phase revealed that low-anxiety rats had startle amplitudes similar to those of high-anxiety rats. It is supposed that high-anxiety female rats benefit from increased estradiol and progesterone levels to achieve comparable potentiated startle amplitudes. In contrast, female rats experienced a significant decrease in hormone levels during the Diestrus phase. This decrease is believed to play a role in preventing them from displaying a heightened startle response when faced with strongly aversive stimuli. Data collected after 5-HT and 8-OH-DPAT were administered into the basolateral nuclei and dorsal periaqueductal gray suggest that 5-HT neurotransmission works with progesterone and estrogen to reduce startle potentiation, most likely by activating the serotonin-1A receptor subtype.
Asunto(s)
Complejo Nuclear Basolateral , Estradiol , Miedo , Sustancia Gris Periacueductal , Progesterona , Receptor de Serotonina 5-HT1A , Reflejo de Sobresalto , Animales , Femenino , Ratas , Ansiedad/metabolismo , Ansiedad/fisiopatología , Complejo Nuclear Basolateral/metabolismo , Complejo Nuclear Basolateral/efectos de los fármacos , Condicionamiento Clásico/fisiología , Condicionamiento Clásico/efectos de los fármacos , Estradiol/farmacología , Estradiol/metabolismo , Ciclo Estral/fisiología , Miedo/fisiología , Miedo/efectos de los fármacos , Sustancia Gris Periacueductal/metabolismo , Sustancia Gris Periacueductal/efectos de los fármacos , Progesterona/farmacología , Progesterona/metabolismo , Ratas Wistar , Receptor de Serotonina 5-HT1A/metabolismo , Reflejo de Sobresalto/fisiología , Reflejo de Sobresalto/efectos de los fármacos , Serotonina/metabolismoRESUMEN
This study evaluated the effect of bovine somatotropin (bST) on pregnancy rate (PR) and size of the dominant follicle (DF) on the day of intravaginal progesterone (P4) removal in protocols for fixed-time artificial insemination (FTAI). Bos indicus (Nellore) females (n = 392) were distributed into three groups. The control group (CG; n = 92) received an intravaginal P4 device + estradiol benzoate on day (d)0; prostaglandin F2α on d7 (first application); removal of P4 + estradiol cypionate (EC) + PGF2α (second application) + ultrasound (US) of the DF on d9; the FTAI was performed on d11; and pregnancy diagnosis (PD) was performed on d45. The bST group (bSTG; n = 142) underwent the same protocol as the CG, except that the animals received 125 mg of bST on d7. The equine chorionic gonadotropin (eCG) group (eCGG; n = 158) underwent the same protocol as the CG, except that the animals received 300 IU of eCG on d9. The PRs of the bSTG, eCGG, and CG were 48%, 48%, and 35%, respectively (p < .05); the bSTG and eCGG showed greater PRs, with follicles 6-7.9 mm (p < .05) and 8-8.9 mm in diameter, respectively. The bSTG exhibited a greater dimension of the DF on d9 of the protocol (p < .05). The eCGG had higher PRs with a body condition score (BCS) of 2.5, and the bSTG had a BCS of 3.0 (p < .05). It was concluded that bST increased PR, bST showed better performance in smaller DF and larger follicular diameter on d9 of the protocol, eCG acted better on animals with lower BCSs, and bST can be used in FTAI.
Asunto(s)
Hormona del Crecimiento , Inseminación Artificial , Índice de Embarazo , Progesterona , Animales , Femenino , Inseminación Artificial/veterinaria , Inseminación Artificial/métodos , Embarazo , Bovinos , Hormona del Crecimiento/farmacología , Hormona del Crecimiento/administración & dosificación , Progesterona/administración & dosificación , Progesterona/farmacología , Estradiol/administración & dosificación , Estradiol/farmacología , Estradiol/análogos & derivados , Folículo Ovárico/efectos de los fármacos , Dinoprost/administración & dosificación , Dinoprost/farmacología , Sincronización del Estro/métodos , Administración IntravaginalRESUMEN
AIMS: Estradiol 17ß-d-glucuronide (E217G) induces cholestasis by triggering endocytosis and further intracellular retention of the canalicular transporters Bsep and Mrp2, in a cPKC- and PI3K-dependent manner, respectively. Pregnancy-induced cholestasis has been associated with E217G cholestatic effect, and is routinely treated with ursodeoxycholic acid (UDCA). Since protective mechanisms of UDCA in E217G-induced cholestasis are still unknown, we ascertained here whether its main metabolite, tauroursodeoxycholate (TUDC), can prevent endocytosis of canalicular transporters by counteracting cPKC and PI3K/Akt activation. MAIN METHODS: Activation of cPKC and PI3K/Akt was evaluated in isolated rat hepatocytes by immunoblotting (assessment of membrane-bound and phosphorylated forms, respectively). Bsep/Mrp2 function was quantified in isolated rat hepatocyte couplets (IRHCs) by assessing the apical accumulation of their fluorescent substrates, CLF and GS-MF, respectively. We also studied, in isolated, perfused rat livers (IPRLs), the status of Bsep and Mrp2 transport function, assessed by the biliary excretion of TC and DNP-SG, respectively, and Bsep/Mrp2 localization by immunofluorescence. KEY FINDINGS: E217G activated both cPKC- and PI3K/Akt-dependent signaling, and pretreatment with TUDC significantly attenuated these activations. In IRHCs, TUDC prevented the E217G-induced decrease in apical accumulation of CLF and GS-MF, and inhibitors of protein phosphatases failed to counteract this protection. In IPRLs, E217G induced an acute decrease in bile flow and in the biliary excretion of TC and DNP-SG, and this was prevented by TUDC. Immunofluorescence studies revealed that TUDC prevented E217G-induced Bsep/Mrp2 endocytosis. SIGNIFICANCE: TUDC restores function and localization of Bsep/Mrp2 impaired by E217G, by preventing both cPKC and PI3K/Akt activation in a protein-phosphatase-independent manner.
Asunto(s)
Colestasis , Endocitosis , Estradiol , Hepatocitos , Fosfatidilinositol 3-Quinasas , Transducción de Señal , Ácido Tauroquenodesoxicólico , Animales , Colestasis/metabolismo , Colestasis/inducido químicamente , Colestasis/prevención & control , Ratas , Transducción de Señal/efectos de los fármacos , Estradiol/metabolismo , Estradiol/farmacología , Estradiol/análogos & derivados , Hepatocitos/metabolismo , Hepatocitos/efectos de los fármacos , Endocitosis/efectos de los fármacos , Ácido Tauroquenodesoxicólico/farmacología , Ácido Tauroquenodesoxicólico/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Miembro 11 de la Subfamilia B de Transportador de Casetes de Unión al ATP/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas Wistar , Femenino , Masculino , Proteína Quinasa C/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismoRESUMEN
Understanding the normal physiology of the canine mammary gland (CMG) is crucial, as it provides a foundational reference for understanding canine mammary neoplasms. The relation between the Proliferation Index (PI) indicated by Ki-67 expression, along with the Apoptotic Index (AI) determined through Caspase-3 expression during the oestrous cycle, is inadequately documented in existing literature. This study seeks to offer insights into the interplay between PI and AI in the CMG across oestrous cycle phases. An extensive investigation was conducted on a diverse case series of bitches (n = 18). Oestrous cycle stages were determined through vaginal cytology, histological examination of the reproductive tract and serum progesterone and oestradiol concentrations. The entire mammary chain was histologically examined, and proliferation and apoptosis were assessed via double immunohistochemistry employing anti-Ki-67 and Caspase-3 antibodies. PI and AI were evaluated through a systematic random sampling approach, counting a minimum of 200 cells for each cell type. There was a significantly higher PI during early dioestrus in all mammary gland components, with a greater proportion of positive cells observed in epithelial cells compared to stromal cells. The highest PI was detected in epithelial cells within the end buds. Significant differences were found in Ki-67 labelling across the cranial mammary glands. A positive and strong correlation was noted between progesterone concentration and PI in epithelial cells. The AI remained consistently low throughout the oestrous cycle, with few differences observed across histological components. Caspase-3 labelling displayed the highest positivity in caudal mammary pairs. A negative and moderate correlation was identified between progesterone concentration and AI in interlobular mesenchymal cells. This study highlights the influence of endocrine regulation on cell proliferation indices in mammary tissue, emphasizing the need to consider these hormonal variations in toxicopathological studies involving canine mammary gland.