RESUMEN
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.
Asunto(s)
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
Sexual dimorphism among mammals includes variations in the pain threshold. These differences are influenced by hormonal fluctuations in females during the estrous and menstrual cycles of rodents and humans, respectively. These physiological conditions display various phases, including proestrus and diestrus in rodents and follicular and luteal phases in humans, distinctly characterized by varying estrogen levels. In this study, we evaluated the capsaicin responses in male and female mice at different estrous cycle phases, using two murine acute pain models. Our findings indicate that the capsaicin-induced pain threshold was lower in the proestrus phase than in the other three phases in both pain assays. We also found that male mice exhibited a higher pain threshold than females in the proestrus phase, although it was similar to females in the other cycle phases. We also assessed the mRNA and protein levels of TRPV1 in the dorsal root and trigeminal ganglia of mice. Our results showed higher TRPV1 protein levels during proestrus compared to diestrus and male mice. Unexpectedly, we observed that the diestrus phase was associated with higher TRPV1 mRNA levels than those in both proestrus and male mice. These results underscore the hormonal influence on TRPV1 expression regulation and highlight the role of sex steroids in capsaicin-induced pain.
Asunto(s)
Capsaicina , Dolor , Canales Catiónicos TRPV , Animales , Canales Catiónicos TRPV/metabolismo , Canales Catiónicos TRPV/genética , Capsaicina/farmacología , Masculino , Femenino , Ratones , Dolor/metabolismo , Dolor/genética , Hormonas Esteroides Gonadales/metabolismo , Ciclo Estral/efectos de los fármacos , Umbral del Dolor/efectos de los fármacos , Ganglios Espinales/metabolismo , Ganglios Espinales/efectos de los fármacos , Ganglio del Trigémino/metabolismo , Ganglio del Trigémino/efectos de los fármacos , Regulación de la Expresión Génica/efectos de los fármacos , Caracteres Sexuales , ARN Mensajero/metabolismo , ARN Mensajero/genéticaRESUMEN
Reproduction in all mammalian species depends on the growth and maturation of ovarian follicles, that is, folliculogenesis. Follicular development can culminate with the rupture of mature follicles and the consequent expulsion of their oocytes (ovulation) or in atresia, characterized by the arrest of development and eventual degeneration. These processes are regulated by different neuroendocrine signals arising at different hypothalamic nuclei, including the suprachiasmatic nucleus (SCN). In the later, the activation of muscarinic receptors (mAChRs) and nicotinic receptors (nAChRs) by acetylcholine is essential for the regulation of the pre-ovulatory signals that stimulate the rupture of mature follicles. To evaluate the participation of the nAChRs in the SCN throughout the oestrous cycle in the regulation of the hypothalamic-pituitary-ovarian axis. For this purpose, 90-day-old adult female rats in metoestrus, dioestrus, proestrus or oestrus were microinjected into the left- or right-SCN with 0.3 µL of saline solution as vehicle or with 0.225 µg of mecamylamine (Mec), a non-selective antagonist of the nicotinic receptors, diluted in 0.3 µL of vehicle. The animals were sacrificed when they presented vaginal cornification, indicative of oestrus stage, and the effects of the unilateral pharmacological blockade of the nAChRs in the SCN on follicular development, ovulation and secretion of oestradiol and follicle-stimulating hormone (FSH) were evaluated. The microinjection of Mec decreased the serum levels of FSH, which resulted in a lower number of growing and healthy follicles and an increase in atresia. The higher percentage of atresia in pre-ovulatory follicles was related to a decrease in the number of ova shed and abnormalities in oestradiol secretion. We also detected asymmetric responses between the left and right treatments that depended on the stage of the oestrous cycle. The present results allow us to suggest that during all the stages of the oestrous cycle, cholinergic signals that act on the nAChRs in the SCN are pivotal to modulate the secretion of gonadotropins and hence the physiology of the ovaries. Further research is needed to determine if such signals are generated by the cholinergic neurons in the SCN or by cholinergic afferents to the SCN.
Asunto(s)
Atresia Folicular , Antagonistas Nicotínicos , Folículo Ovárico , Receptores Nicotínicos , Núcleo Supraquiasmático , Femenino , Animales , Núcleo Supraquiasmático/metabolismo , Núcleo Supraquiasmático/efectos de los fármacos , Receptores Nicotínicos/metabolismo , Folículo Ovárico/metabolismo , Folículo Ovárico/efectos de los fármacos , Antagonistas Nicotínicos/farmacología , Ratas , Atresia Folicular/efectos de los fármacos , Atresia Folicular/metabolismo , Mecamilamina/farmacología , Ciclo Estral/efectos de los fármacos , Ratas WistarRESUMEN
Este texto discute as estratégias farmacológicas para a manipulação do ciclo estral de fêmeas taurinas de corte, com foco na inseminação artificial em tempo fixo (IATF). Os zebuínos, rebanho predominante no Brasil, apresentam características de ciclo estral diferentes das raças taurinas, o que justifica a busca por estratégias hormonais adaptadas para o controle do ciclo estral nas subespécies. O estradiol combinado com a progesterona (P4) e prostaglandina F2 alfa (PGF) é o esquema hormonal mais comumente utilizado para a manipulação do ciclo estral em protocolos de IATF. Porém, o uso de GnRH combinado ou em substituição aos ésteres de estradiol vem sendo considerado. Coletivamente, os dados do nosso grupo reforçam a necessidade de customizar as abordagens para o controle do ciclo estral de acordo com a composição genética das fêmeas bovinas.(AU)
This text discusses pharmacological strategies to manipulate the estrous cycle of taurine and synthetic females, with a focus on timed artificial insemination (TAI). Zebu cattle, the predominant herd in Brazil, have different estrous cycle characteristics than taurine breeds, requiring different synchronization hormonal strategies for each subspecies. Estradiol combined with progesterone (P4) and prostaglandin F2 alpha (PGF) is the most used hormonal scheme for estrous cycle manipulation in TAI protocols. But the use of GnRH instead of estradiol esters is being considered. Collectively, our group's data reinforce the need to customize approaches to estrous cycle control according to the genetic composition of bovine females.(AU)
Asunto(s)
Animales , Femenino , Ovulación/fisiología , Acciones Farmacológicas , Ciclo Estral/efectos de los fármacos , Progesterona , Inseminación Artificial/métodosRESUMEN
Resumen El consumo crónico de alcohol es un problema de salud mundial que afecta particularmente a la población femenina. Sin embargo, los efectos de la ingesta semicrónica en cantidades moderadas a bajas en el ovario y el oocito son poco conocidos. En un modelo murino, se administró etanol al 10% en agua de bebida (hembras tratadas) o agua (hembras control) por 15 días, y luego de la superovulación o no (ovulación espontánea), se analizó el ciclo estral y la calidad ovárico-gamética. En las hembras tratadas, la frecuencia y duración del diestro aumentó, y las frecuencias de folículos y cuerpos lúteos disminuyeron vs hembras controles, valores que se restauraron luego de la superovulación. Sin embargo, en las hembras tratadas, la tasa de proliferación celular folicular y el desbalance de la expresión ovárica de VEGF (factor de crecimiento endotelial) persistieron luego de la superovulación. El número de ovocitos ovulados con metafase II anormal, fragmentados y activados partenogenéticamente fue mayor en las hembras tratadas respecto las controles. En conclusión, el consumo semicrónico moderado de alcohol produce anestro, ciclo estral irregular, foliculogénesis deficiente y anomalías núcleo-citoplasmáticas en los oocitos ovulados. Estas alteraciones podrían constituirse en un factor etiológico de pérdida gestacional temprana y desarrollo embrionario anormal luego del consumo de alcohol.
Abstract Chronic alcohol consumption is a global health problem that particularly affects the female population. However, the ef-fects of semi-chronic ethanol intake in low-moderate amounts on the ovary and oocyte are poorly understood. In a mouse model, 10% ethanol was administered in drinking water (treated females) or water (control females) for 15 days, and after superovulation or not (spontaneous ovulation), the estrous cycle and ovarian-gametic quality were analyzed. In treated females, the frequency and duration of the diestrus increased, and the frequencies of follicles and corpus luteum decreased vs control females, values that restored after superovulation. However, in treated females, the follicular cell proliferation rate and the imbalance in ovarian expression of VEGF (endothelial growth factor) persisted after superovulation. The number of ovulated oocytes with abnormal metaphase II, fragmented and parthenogenetically activated was higher in treated females than in control ones. In conclusion, moderate semi-chronic alcohol consumption produces anestrum, irregular estrous cycle, poor folliculogenesis, and nuclear-cytoplasmic abnormalities in ovulated oocytes. These alterations could constitute an etiological factor of early gestational loss and abnormal embryonic development after alcohol consumption.
Asunto(s)
Humanos , Animales , Femenino , Ratones , Oocitos/efectos de los fármacos , Consumo de Bebidas Alcohólicas/efectos adversos , Etanol/efectos adversos , Folículo Ovárico/efectos de los fármacos , Ovario/citología , Ovario/efectos de los fármacos , Oviductos/citología , Oviductos/efectos de los fármacos , Ovulación/efectos de los fármacos , Modelos Animales , Ciclo Estral/efectos de los fármacos , Proliferación Celular , Células Germinativas/citología , Células Germinativas/efectos de los fármacos , Folículo Ovárico/citologíaRESUMEN
Endometriosis is an often painful disease in reproductive-aged women, in which endometrial-like tissue grows outside the uterine cavity. Since the limited current therapeutic alternatives fail in alleviating the symptoms and based on our previous research in in vitro models using the same compounds as the ones used in the present study, we aimed to evaluate the effects of urolithins A (UA) and B (UB) on the growth and survival of endometriotic-like lesions in a murine model of endometriosis. Female BALB/C mice were surgically induced with endometriosis and treated with 2.5 mg kg-1 day-1 intraperitoneal UA or UB. The mice were monitored daily and weighed and the estrous stage was determined. After 28 days of treatment, lesions were counted, measured, excised, and fixed. Both urolithins proved not to affect the estrous cycle or body weight of the mice. UA completely prevented endometriotic-like lesions, while UB diminished the implant volume (p < 0.05). Treatment also reduced epithelial and stromal cell proliferation within the implants (p < 0.001 and p < 0.01, respectively) and apoptosis was enhanced (p < 0.05 and p < 0.01, respectively). These results are promising and reveal that urolithins A and B, separately, have a beneficial effect on the overall endometriotic growth without affecting the body weight or estrous cycle.
Asunto(s)
Cumarinas/farmacología , Endometriosis/tratamiento farmacológico , Animales , Apoptosis/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Endometriosis/metabolismo , Endometriosis/patología , Endometrio/metabolismo , Endometrio/patología , Ciclo Estral/efectos de los fármacos , Femenino , Humanos , Ratones , Ratones Endogámicos BALB CRESUMEN
Chlorpyrifos (CPF), the most used insecticide in Argentina, can act as an endocrine disruptor at low doses. We previously demonstrated that chronic exposure to CPF induces hormonal imbalance in vivo. The aim of this work was to study the effects of low concentrations of CPF (0.01 and 1 mg/kg/day) on the reproductive system of virgin adult rats. In the ovary, we studied the effects of CPF on steroidogenesis by determining steroid hormone content by RIA and CYP11 and CYP19 enzyme expression by qRT-PCR. The estrous cycle was evaluated by microscopic observation of vaginal smear, as well as by changes in uterine histology. In endometrium, we determined the fractal dimension and expression of PCNA, ERα and PR by IHC. Our results showed that chronic exposure to CPF affects ovarian steroid synthesis, causing alterations in the normal cyclicity of animals. In addition, CPF induced proliferative changes in the uterus, suggesting that it could affect reproduction or act as a risk factor in the development of uterine proliferative pathologies.
Asunto(s)
Cloropirifos/administración & dosificación , Cloropirifos/toxicidad , Ciclo Estral/efectos de los fármacos , Ovario/efectos de los fármacos , Útero/efectos de los fármacos , Animales , Relación Dosis-Respuesta a Droga , Esquema de Medicación , Femenino , Insecticidas/administración & dosificación , Insecticidas/toxicidad , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Vagina/efectos de los fármacosRESUMEN
The musculoskeletal orofacial pain is a complex symptom of Parkinson's disease (PD) resulting in stomatognathic system dysfunctions aggravated by the disease rigidity and postural instability. We tested the effect of cannabidiol (CBD), a non-psychotomimetic constituent of Cannabis sativa, in PD-related myofascial pain. Wistar adult female and male rats orofacial allodynic and hyperalgesic responses were tested by Von Frey and formalin tests, before and 21 days past 6-OHDA lesion. Algesic response was tested after masseter muscle injection of CBD (10, 50, 100 µg in 10 µL) or vehicle. Males compared to females in all estrous cycles' phases presented reduced orofacial allodynia and hyperalgesia. According to the estrous cycle's phases, females presented distinct orofacial nociceptive responses, being the estrus phase well-chosen for nociceptive analysis after 6-OHDA lesion (phase with fewer hormone alterations and adequate length). Dopaminergic neuron lesion decreased mechanical and inflammatory nociceptive thresholds in females and males in a higher proportion in females. CBD local treatment reduced the increased orofacial allodynia and hyperalgesia, in males and females. The female rats were more sensitive to CBD effect considering allodynia, responding to the lowest dose. Although females and males respond to the effect of three doses of CBD in the formalin test, males showed a superior reduction in the hyperalgesic response. These results indicate that hemiparkinsonian female in the estrus phase and male answer differently to the different doses of CBD therapy and nociceptive tests. CBD therapy is effective for parkinsonism-induced orofacial nociception.
Asunto(s)
Anticonvulsivantes/farmacología , Cannabidiol/farmacología , Dolor Facial/fisiopatología , Hiperalgesia/fisiopatología , Nocicepción/efectos de los fármacos , Trastornos Parkinsonianos/fisiopatología , Analgésicos/farmacología , Animales , Ciclo Estral/efectos de los fármacos , Ciclo Estral/fisiología , Femenino , Masculino , Oxidopamina/toxicidad , Ratas , Ratas WistarRESUMEN
Caffeine is a commonly used stimulant of the central nervous system that reduces fatigue, increases alertness, and exerts positive effects on emotion through actions on various brain structures. High doses of caffeine can cause headaches, heart palpitations, hyperactivity, and anxiety symptoms. Consequently, reducing the consumption of stimulant substances, such as sugar and caffeine, is proposed to ameliorate symptoms of premenstrual syndrome in women. The administration of steroid hormones has been suggested to modulate the effects of caffeine, but unknown is whether endogenous hormone variations during the estrous cycle modulate the pharmacological effects of caffeine. The present study evaluated the effects of caffeine (10, 20, and 40 mg/kg) during metestrus-diestrus and proestrus-estrus of the ovarian cycle in rats on anxiety-like behavior using the elevated plus maze and light/dark box. During metestrus-diestrus, all doses of caffeine increased anxiety-like behavior, indicated by the main variables in both behavioral tests (i.e., higher Anxiety Index and lower percent time spent on the open arms in the elevated plus maze and less time spent in the light compartment in the light/dark box). During proestrus-estrus, only 20 and 40 mg/kg caffeine increased these parameters of anxiety-like behavior, albeit only slightly. In conclusion, caffeine increased anxiety-like behaviors in metestrus-diestrus, with an attenuation of these effects of lower doses of caffeine in proestrus-estrus. These effects that were observed in metestrus-diestrus and proestrus-estrus may be associated with low and high concentrations of steroid hormones, respectively, that naturally occur during these phases of the ovarian cycle.
Asunto(s)
Ansiedad , Conducta Animal , Cafeína/farmacología , Estimulantes del Sistema Nervioso Central/farmacología , Ciclo Estral , Aprendizaje por Laberinto , Animales , Ansiedad/inducido químicamente , Ansiedad/metabolismo , Conducta Animal/efectos de los fármacos , Conducta Animal/fisiología , Cafeína/administración & dosificación , Estimulantes del Sistema Nervioso Central/administración & dosificación , Prueba de Laberinto Elevado , Ciclo Estral/efectos de los fármacos , Ciclo Estral/metabolismo , Femenino , Aprendizaje por Laberinto/efectos de los fármacos , Aprendizaje por Laberinto/fisiología , RatasRESUMEN
The present study investigated hyperalgesia during sickness syndrome in female rats. Hyperalgesia was induced by an intraperitoneal injection of lipopolysaccharide (LPS) or an intracerebroventricular injection of prostaglandin E2 (PGE2). No differences were found in basal mechanical and thermal thresholds or in LPS-induced hyperalgesia in sham-operated animals in the diestrus or proestrus phase or in ovariectomized (OVX) animals. However, higher levels of PGE2 where found in the cerebrospinal fluid of OVX animals compared to sham-operated females. Intracerebroventricular injection of PGE2 produced rapid mechanical hyperalgesia in sham-operated rats while these responses were observed at later times in OVX animals. The protein kinase A (PKA) inhibitor H-89 reduced mechanical PGE2-induced hyperalgesia in OVX female rats, whereas no effect was observed in sham-operated animals. In contrast, the exchange protein activated by cyclic adenosine monophosphate (cAMP; Epac) inhibitor ESI-09 reduced mechanical PGE2-induced hyperalgesia, whereas no effect was observed in OVX animals. PGE2 also induced thermal hyperalgesia in sham-operated and OVX female rats and a similar effect of ESI-09 was observed. These results suggest that PGE2-induced hyperalgesia that is observed during sickness syndrome has different signaling mechanisms in cycling and OVX female rats involving the activation of the cAMP-Epac or cAMP-PKA pathways, respectively.
Asunto(s)
Proteínas Quinasas Dependientes de AMP Cíclico/antagonistas & inhibidores , Dinoprostona/farmacología , Ciclo Estral/efectos de los fármacos , Factores de Intercambio de Guanina Nucleótido/antagonistas & inhibidores , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Conducta de Enfermedad/efectos de los fármacos , Animales , AMP Cíclico/antagonistas & inhibidores , Dinoprostona/administración & dosificación , Modelos Animales de Enfermedad , Femenino , Hidrazonas/farmacología , Isoquinolinas/farmacología , Isoxazoles/farmacología , Lipopolisacáridos/farmacología , Ovariectomía , Ratas , Ratas Wistar , Transducción de Señal/efectos de los fármacos , Sulfonamidas/farmacologíaRESUMEN
BACKGROUND: Polycystic ovary syndrome (PCOS) is the most common complex endocrine disorder affecting approximately 2-20% of reproductive aged females. Tumour Treating Fields (100-300 kHz) is a recent innovative, non-invasive therapeutic approach to cancer therapy. This frequency as an alternative therapy for the management of polycystic ovaries has not yet been explored. OBJECTIVES: To explore the effect of full-body exposure of 150 kHz Electromagnetic Radiation (EMR), on the development of polycystic ovaries in an estradiol valerate-induced PCO rat model. METHOD: Twenty-one female adult rats were divided into three groups (n = 7 each): control, Estradiol Valerate (EV) and EV + EMR groups. The EV + EMR group was subjected to full body exposure at 150 kHz EMR continuously for eight consecutive weeks. Estradiol valerate was administered orally to induce polycystic ovaries in EV and EV + EMR groups. Body and ovarian weights were recorded and analysed. The regularity of the estrous cycle was assessed in all three groups. The histological study of ovarian tissue was carried out by haematoxylin and eosin staining. The serum concentration levels of Luteinizing Hormone (LH), Follicle-Stimulating Hormone (FSH) and testosterone were measured using the ELISA method. RESULTS: The body and ovary weights did not differ significantly between the EV and EV + EMR groups. The estrous cycle was found to be irregular in both the EV and EV + EMR groups. Ovarian histology revealed near normal morphology with little or no degenerative and morphological changes in developing follicles in the exposed group. Histometrical analysis showed an increased number of developing follicles and a significant reduction in the number and size of follicular cysts (p < 0.05) in the EV + EMR group. Hormonal analysis revealed no significant difference in the testosterone and FSH levels between the EV + EMR and EV groups. However, the LH, LH/FSH ratio decreased significantly in the EV + EMR group compares to the EV group. CONCLUSION: The 150 kHz EMR appear to have little or no degenerative and morphological changes in the developing follicles, an increased number of typical developing follicles and a significant reduction in the number and size of the follicular cysts (p < 0.05).
Asunto(s)
Radiación Electromagnética , Ciclo Estral/efectos de la radiación , Folículo Ovárico/efectos de la radiación , Ovario/efectos de la radiación , Síndrome del Ovario Poliquístico/patología , Animales , Peso Corporal , Modelos Animales de Enfermedad , Estradiol/toxicidad , Estrógenos/toxicidad , Ciclo Estral/efectos de los fármacos , Femenino , Hormona Folículo Estimulante/sangre , Hormona Luteinizante/sangre , Tamaño de los Órganos , Folículo Ovárico/efectos de los fármacos , Ovario/efectos de los fármacos , Ovario/patología , Síndrome del Ovario Poliquístico/sangre , Síndrome del Ovario Poliquístico/inducido químicamente , Síndrome del Ovario Poliquístico/radioterapia , Ratas , Ratas Sprague-Dawley , Testosterona/sangreRESUMEN
Benzo(a)pyrene (BaP) is an ubiquitous environmental pollutant which can lead to adverse effects on male reproduction. However, the persistence of these changes on a multigenerational scale has not been sufficiently explored. This study evaluated if peripubertal exposure to BaP in male rats can induce reproductive impairment in offspring. Male rats received BaP at environmentally relevant doses (0, 0.1, 1, or 10⯵g/kg/day) orally from post-natal (PND) 23-53. On PND 90, treated males were mated with non-treated females for obtaining the next generation (F1). The paternal exposure to BaP decreased the body weight of offspring on PND 1, 13 and 22, as well as it provoked a reduction in the relative anogenital distance of the males. This exposure also brought forward the onset of puberty, evidenced by an earlier vaginal opening and first estrous in females of the lowest dose group and by a delay in the testicular descent and preputial separation ages in males. The males presented a decrease in the daily sperm production and a disrupted sperm morphology. Furthermore, the testicular histology was altered, evidenced by a reduction in the Leydig cell numbers and in the seminiferous tubules diameter, as well as a disrupted seminiferous tubules staging. The estrous cyclicity and some fertility parameters were changed in the females, as well as alterations in the ovary and uterus histology were observed. BaP compromised several reproductive parameters of the F1 generation, suggesting that peripubertal exposure to this compound provokes permanent modifications in male germ line of F0 generation.
Asunto(s)
Benzo(a)pireno/toxicidad , Contaminantes Ambientales/toxicidad , Exposición Paterna/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Reproducción/efectos de los fármacos , Maduración Sexual/efectos de los fármacos , Animales , Benzo(a)pireno/administración & dosificación , Peso Corporal/efectos de los fármacos , Ciclo Estral/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Genitales/efectos de los fármacos , Genitales/crecimiento & desarrollo , Masculino , Tamaño de los Órganos , Embarazo , Ratas , Ratas Wistar , Espermatozoides/efectos de los fármacosRESUMEN
Paracetamol (PAR) is one of the most commonly used drugs by pregnant women because it is considered safe for the mother and fetus. However, PAR is transferred into breast milk and crosses the blood-placental barrier, being present in the progeny during important stages of development. Intrauterine exposure to PAR may decrease the anogenital distance and follicle reserve in female rodent offspring. Therefore, the aim of the present study was to evaluate whether maternal PAR treatment altered the reproductive behaviour of dams and the sexual development of female rat offspring. Pregnant Wistar rats were gavaged daily with 350mg kg-1 day-1 PAR or water during gestation (from Gestation Day (GD) 6 until delivery) or during gestation and lactation (from GD6 until weaning). Maternal PAR treatment had maternal effects (increased grooming behaviour), and resulted in impaired sexual behaviour, decreased follicle reserve and increased plasma oestradiol concentrations in female offspring.
Asunto(s)
Acetaminofén/farmacología , Hormonas Esteroides Gonadales/metabolismo , Conducta Materna/efectos de los fármacos , Efectos Tardíos de la Exposición Prenatal/metabolismo , Animales , Animales Recién Nacidos , Ciclo Estral/sangre , Ciclo Estral/efectos de los fármacos , Femenino , Hormonas Esteroides Gonadales/sangre , Masculino , Exposición Materna/efectos adversos , Embarazo , Efectos Tardíos de la Exposición Prenatal/sangre , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Ratas , Ratas Wistar , Reproducción/efectos de los fármacos , Maduración Sexual/efectos de los fármacosRESUMEN
This study was conducted to assess effects of different doses of pFSH on follicular recruitment, superovulatory response, ova/embryo recovery, and embryo yield in lactating ewes. Ewes (nâ¯=â¯24) had a superovulation treatment regimen imposed. All ewes were implanted with a progesterone intravaginal device for 9 d, and administered either 100 (G-100) or 200 (G-200) mg pFSH, proportioned into six doses administered at 12-h intervals, starting 60â¯h before device removal. At 7 days subsequent to progesterone device removal, there were non-surgical embryo recoveries (NSER) from ewes having three or more corpora lutea. At the time of the first pFSH injection, number of antral follicles were similar (Pâ¯<â¯0.05) between ewes in the G-100 and G-200 group, however, there were more 3.1-4.0â¯mm follicles in ewes of the G-200 than G-100 group at the time of the second pFSH administration. Estrous response and CL number were less (Pâ¯<â¯0.05) in ewes of the G-100 (66.7 % and 2.6⯱â¯0.7) than G-200 (91.7 % and 11.6⯱â¯1.2) group. There were embryo collections from 100 % and 90.9 % of ewes in the G-100 and G-200 groups, respectively (Pâ¯>â¯0.05). Viable embryo numbers and ova/embryo recovery rate were greater (Pâ¯<â¯0.05) in ewes of the G-200 (6.9⯱â¯1.1 and 67.8 %) than G-100 (1.0⯱â¯0.5 and 27.6 %) group. A dose of 200 mg pFSH was more effective in inducing a superovulatory response and embryo yield after NSER in ewes, however, the 100 mg dose was insufficient for these purposes.
Asunto(s)
Hormona Folículo Estimulante/farmacología , Ovinos/embriología , Superovulación/efectos de los fármacos , Animales , Cuerpo Lúteo/efectos de los fármacos , Estudios Cruzados , Relación Dosis-Respuesta a Droga , Ciclo Estral/efectos de los fármacos , Femenino , Hormona Folículo Estimulante/administración & dosificación , EmbarazoRESUMEN
PROBLEM: Gut dysbiosis is caused by several factors, including the use of antibiotics. Since intestinal dysbiosis is associated with a wide range of immunopathological and reproductive conditions, the main goal of this study was to evaluate amoxicillin-induced gut dysbiosis and its influence on the oestrous cycle in mice. METHOD OF STUDY: Mice were treated with amoxicillin or PBS, and faecal microbiota was evaluated by 16S rDNA metagenomic sequencing. The oestrous cycle was evaluated by vaginal cytology, vaginal opening and flow cytometry. After the induction of gut dysbiosis, the ovaries and the caecum were analysed to differential expression of IL-1ß and IL-10 genes and histological analysis. RESULTS: Amoxicillin-treated mice presented differing bacterial groups in the faecal microbiota when compared to the PBS-treated group indicating that amoxicillin treatment-induced gut dysbiosis and they gained weight. The vaginal cytology analysis showed that amoxicillin-induced gut dysbiosis decreased the number of cells but increased the relative number of leucocytes and altered the oestrous cycle. IL-1ß was shown to be upregulated in the caecum and in the ovary of the dysbiotic mice. On the other hand, IL-10 expression was shown to be diminished in both organs of the dysbiotic mice. The oocyte area from dysbiotic group presented lower than non-dysbiotic mice with increasing thickness of the pellucid zone. The follicular teak from dysbiotic mice showed lower thickness than non-dysbiotic mice. CONCLUSION: The results indicate that amoxicillin induces gut dysbiosis and influences the oestrous cycle and the inflammatory status of the ovary and the caecum.
Asunto(s)
Amoxicilina/efectos adversos , Antibacterianos/efectos adversos , Ciego/fisiología , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/inmunología , Disbiosis/inmunología , Ciclo Estral/efectos de los fármacos , Ovario/fisiología , Animales , Citocinas/metabolismo , Disbiosis/etiología , Femenino , Microbioma Gastrointestinal/efectos de los fármacos , Regulación de la Expresión Génica , Humanos , Interleucina-10/genética , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Ratones , Ratones de la Cepa 129RESUMEN
This study aimed to analyse the effects of clotrimazole (CTZ) on estrogen production pathway in endometriosis progression. Experimental endometriosis was induced by autologous transplantation in female Wistar rats, and then the rats were treated with clotrimazole (200 mg/kg) or vehicle, both orally and intraperitoneally, for 15 consecutive days. Serum estrogen levels and vaginal smear analyses were performed and ERα (estrogen receptor alpha) and CYP19 (cytochrome P450 aromatase) levels in the endometriotic lesions were analysed morphologically and immunohistochemically. The clotrimazole group presented a reduction in serum estrogen levels, which were not influenced by the estrous cycle of the animals. The expression of ERα and CYP19 in endometriotic lesions was also reduced in the clotrimazole group compared to the control group. Moreover, clotrimazole treatment decreased the size of the lesions, as confirmed by histological examination, which showed glandular atrophy for both routes of administration. These results suggest that clotrimazole interferes with the estrogen production pathway by downregulating CYP19 and, therefore, reducing serum estrogen levels. Thus, the drug decreases endometriotic lesion size and consequently disease progression.
Asunto(s)
Aromatasa/metabolismo , Clotrimazol/uso terapéutico , Regulación hacia Abajo/efectos de los fármacos , Endometriosis/tratamiento farmacológico , Endometrio/efectos de los fármacos , Estrógenos/sangre , Animales , Clotrimazol/farmacología , Modelos Animales de Enfermedad , Endometriosis/metabolismo , Endometrio/metabolismo , Receptor alfa de Estrógeno/metabolismo , Ciclo Estral/efectos de los fármacos , Femenino , Ratas , Ratas WistarRESUMEN
Heat stress (HS) has deleterious effects on bovine reproduction, including prolongation of the luteal phase in Holstein cows, perhaps due to compromised luteolysis. The objective was to characterize effects of HS on luteolytic responses of nonlactating Holstein cows given 25 or 12.5 mg of PGF2α on d 7 of the estrous cycle. Cows were randomly distributed into 2 environments: thermoneutral (n = 12; 25°C) or HS (n = 12; 36°C). In each environment, cows were treated with 2 mL of saline, 25 or 12.5 mg of PGF2α (n = 4 cows per group). The HS environment induced a significant increase in rectal temperature and respiratory rate compared with the thermoneutral environment. Heat stress did not have significant effects on luteolytic responses or circulating progesterone concentrations. Rapid and complete luteolysis occurred in all cows given 25 mg of PGF2α and in 4 of 8 cows given 12.5 mg; the other 4 cows given 12.5 mg had partial luteolysis, with circulating progesterone concentrations initially suppressed, but subsequently rebounding. Therefore, we conclude that HS does not change corpus luteum sensitivity to PGF2α.
Asunto(s)
Bovinos/fisiología , Cuerpo Lúteo/efectos de los fármacos , Dinoprost/farmacología , Respuesta al Choque Térmico , Luteólisis/efectos de los fármacos , Animales , Ciclo Estral/efectos de los fármacos , Femenino , Calor , Oxitócicos/farmacología , Progesterona/farmacologíaRESUMEN
Arsenic is a metalloid widely found in the environment in organic and inorganic forms. Exposure to inorganic arsenic forms via drinking water has been associated with an increased incidence of negative health effects, including reproductive disorders and dysfunction of the endocrine system. However, the impact of arsenic exposure on female reproductive development is still unclear. Therefore, in the present study, we evaluated the effects of prenatal exposure to arsenic on the initial sexual development and puberty onset, and in the morphology of the female reproductive organs, estrous cycle regularity and fertility parameters during adulthood. To do that, pregnant female Wistar rats were exposed to 10 mg/L sodium arsenite via drinking water from gestational day (GD) 1 until GD 21 and the female offspring was evaluated in different postnatal days. Our results showed that prenatal arsenic exposure induced a decrease of litter weight and morphological masculinization in females at postnatal day 1. Moreover, these females had a delay in the age of puberty onset and alteration in estrous cycle number and length. During adulthood, females from the sodium arsenite group showed an increase in endometrium, myometrium and perimetrium areas, and an imbalance in uterine antioxidant enzyme activity. These animals also presented an increase in post-implantation loss and reabsorption number, leading to reduced viable fetus number. In conclusion, prenatal arsenic exposure in rats was able to promote female masculinization, alter sexual development and impair reproductive performance.
Asunto(s)
Arsenitos/toxicidad , Ciclo Estral/efectos de los fármacos , Exposición Materna/efectos adversos , Efectos Tardíos de la Exposición Prenatal , Pubertad/efectos de los fármacos , Reproducción/efectos de los fármacos , Compuestos de Sodio/toxicidad , Animales , Peso Corporal/efectos de los fármacos , Femenino , Fertilidad/efectos de los fármacos , Modelos Animales , Embarazo , Ratas , Ratas WistarRESUMEN
Vanadium is a metal present in particulate matter and its reprotoxic effects have been demonstrated in males and pregnant females in animal models. However, the effects of this metal on the reproductive organs of nonpregnant females have not been sufficiently studied. In a vanadium inhalation model in nonpregnant female mice, we found anestrous and estrous cycle irregularity, as well as low serum concentrations of 17ß-estradiol and progesterone. A decrease in the diameter of secondary and preovulatory follicles, as well as a thickening of the myometrium and endometrial stroma, was observed in the vanadium-treated mice. There was no difference against the control group with respect to the presence of the estrogen receptor α in the uterus of the animals during the estrous stage. Our results indicate that when vanadium is administered by inhalation, effects are observed on the female reproductive organs and the production of female sex hormones.
Asunto(s)
Ciclo Estral/efectos de los fármacos , Ovario/efectos de los fármacos , Útero/efectos de los fármacos , Vanadio/toxicidad , Administración por Inhalación , Animales , Estradiol/sangre , Receptor alfa de Estrógeno/metabolismo , Femenino , Ratones , Ovario/patología , Progesterona/sangre , Útero/metabolismo , Útero/patologíaRESUMEN
Although combining of eCG and hCG administrations is known to enhance LH-like actions, there have been few studies where there was comparison of the effects of treatment of anestrous ewes with eCG and hCG and eCG alone. In Experiment 1, 18 ewes in seasonal anestrus were administered an intravaginal device (IVD) containing medroxyprogesterone acetate for 12 days, and at the time of IVD removal (D0), were allocated into the following groups (n = 6/group): no further treatment (control); 400 IU eCG (eCG); or 400 IU eCG and 200 IU hCG (eCG + hCG). There was greater ovarian follicular growth in the groups treated with gonadotropins, compared to the control, and there were greater progesterone concentrations in the eCG + hCG group on D9 (P < 0.05). In Experiment 2, 66 ewe lambs were assigned to the same treatment groups described for Experiment 1, and subsequently there was natural mating with rams. There was a greater rate of behavioral estrous manifestation in the eCG (88.5 %; 23/26) and eCG+hCG (85.2 %; 23/27), than control (30.8 %; 4/13; P < 0.05) group. Pregnancy rate was also greater in the eCG (34.6 %; 9/26) and eCG+hCG (18.6 %; 5/27) than control (0 %; 0/13; P < 0.05) group, whereas conception rate, considering only ewe lambs that were mated, was only greater in the eCG group. Although there were greater progesterone concentrations 9 days after treatment in the eCG+hCG group, there was no difference in follicular growth in anestrous ewes, nor was there an effect on estrous behavior manifestation and pregnancy rates in ewe lambs, compared to treatment with only eCG.