Morphology and Biochemistry of Ovulation Morfologia e bioquímica da ovulação

Abstract The process of ovulation involves multiple and iterrelated genetic, biochemical, and morphological events: cessation of the proliferation of granulosa cells, resumption of oocyte meiosis, expansion of cumulus cell-oocyte complexes, digestion of the follicle wall, and extrusion of the metaphase-II oocyte. The present narrative review examines these interrelated steps in detail. The combined or isolated roles of the folliclestimulating hormone (FSH) and luteinizing hormone (LH) are highlighted. Genes indiced by the FSH genes are relevant in the cumulus expansion, and LH-induced genes are critical for the resumption ofmeiosis and digestion of the follicle wall. A nonhuman model for follicle-wall digestion and oocyte release was provided.

Resumo O processo de ovulação envolve modificações genéticas, bioquímicas e morfológicas múltiplas e interrelacionadas: suspensão da proliferação das células da granulosa, reinício da meiose do oócito, expansão das células do complexo cumulus-oócito, digestão da parede folicular, e extrusão do oócito. Esta revisão narrativa examina em detalhes cada um desses eventos e os principais genes e proteínas envolvidos. Mais importante, a ação combinada ou isolada do hormônio folículo-estimulante (HFE) e do hormônio luteinizante (HL) é destacada. Detalha-se o papel do HFE na expansão do cumulus e do HL na digestão da parede folicular, permitindo a extrusão do oócito na superfície ovariana. Proveu-se um modelo não humano para explicar a digestão da parede folicular.

Hypothalamic-pituitary-ovarian axis in thyroid dysfunction / El eje hipotalámico-pituitario-ovárico en la disfunción tiroidea

BACKGROUND: It has been established that thyroid dysfunction causes impairment of reproductive function. However, laboratory and human studies that associated this with female reproductive hormones are conflicting and data reporting the effects of thyroid dysfunction on reproductive organs are insufficient. AIM: This study investigated the effect of experimental hypothyroidism and hyperthyroidism on hypothalamic-pituitary-ovarian axis and reproductive organs morphometry and histology in female rats. METHODS: Laboratory animals were randomized into one of the three groups: control, carbimazole-induced hypothyroidism and levothyroxine-induced hyperthyroidism. RESULTS: Organ morphometry and serum follicle stimulating hormone (FSH) were statistically comparable across all groups. Serum progesterone increased in hypothyroid rats but was reduced in hyperthyroid rats when compared with the control (p < 0.05). Body weight gain, serum luteinizing hormone and oestradiol were significantly reduced in both hypothyroid and hyperthyroid states when compared to the control. Hypothyroidism and hyperthyroidism also led to alterations in organ cytoarchitecture. CONCLUSION: Findings from this study suggest that impairment ofreproductive function associated with thyroid dysfunction is attendant with derangement of hormonal milieu and alteration in reproductive organs cytoarchitecture. Luteinizing hormone and oestradiol are implicated.

ANTECEDENTES: Se ha establecido que la disfunción de la tiroides causa deterioro de la función reproductiva. Sin embargo, los estudios humanos y de laboratorio que asociaban tal disfunción a las hormonas reproductoras femeninas son contradictorios, y los datos que reportan los efectos de la disfunción tiroidea sobre los órganos reproductores son insuficientes. OBJETIVO: Este estudio investigó el efecto del hipotiroidismo y el hipertiroidismo experimentales sobre el eje hipotalámico-pituitario-ovárico, y la morfometría e histología de los órganos reproductores en ratas hembras. MÉTODOS: Los animales de laboratorio fueron asignados al azar a uno de estos tres grupos: control, hipotiroidismo inducido por carbimazol, e hipertiroidismo inducido por levotiroxina. RESULTADOS: La morfometría de los órganos y hormona folículo-estimulante (FSH) en suero, fueron estadísticamente comparables en todos los grupos. La progesterona sérica aumentó en las ratas hipotiroideas, pero se redujo en las ratas hipertiroideas en comparación con el grupo de control (p < 0.05). El aumento de peso corporal, la hormona luteinizante en suero, y el estradiol se redujeron significativamente tanto en condiciones de hipotiroidismo como en estado de hipertiroidismo, en comparación con el grupo control. El hipotiroidismo y el hipertiroidismo condujeron también a alteraciones en la citoarquitectura de los órganos. CONCLUSIÓN: Resultados de este estudio sugieren que la debilitación de la función reproductora asociada con la disfunción de la tiroides, va acompañada de trastornos del medio hormonal, e implica alteraciones de la citoarquitectura de los órganos reproductores, la hormona luteinizante, y el estradiol.

Mecanismos neuroendócrinos envolvidos na puberdade de novilhas / Neuroendocrine mechanisms in puberty heifers / Mecanismos neuroendocrinos involucrados en la pubertad de novillas

Sob o ponto de vista fisiológico, a puberdade em novilhas Bos taurus e Bos indicus caracteriza-se por um aumento na concentração e freqüência pulsátil de LH e um decréscimo na sensibilidade do hipotálamo aos esteróides gonadais, com participação ou não de neurotransmissores com capacidade de estimular ou inibir a secreção de LH, o que resultará na primeira ovulação. Os eventos fisiológicos relacionados à primeira ovulação são similares, tanto nas novilhas Bos taurus, quanto nas novilhas Bos indicus, ocorrendo mais tardiamente nesta última. O sistema extensivo de criação do Zebu, adotado na maioria dos países sul-americanos, contribui para que a puberdade aconteça mais tardiamente, refletindo na idade ao primeiro parto. A idade à primeira ovulação é uma característica de alta herdabilidade, sendo a seleção genética, através da precocidade sexual, uma ferramenta para reduzir a idade ao primeiro parto e melhorar a eficiência reprodutiva do sistema de produção. Aliado à seleção genética, o uso de técnicas de manejo melhorando a qualidade nutricional e a oferta de alimentos, o cruzamento entre raças, a exposição das novilhas a touros e o uso de biotecnologias que permitam manipular a primeira ovulação, podem contribuir para o aumento da produtividade. Esta revisão tem como objetivo abordar aspectos fisiológicos relacionados à puberdade de novilhas Bos taurus e Bos indicus.

Under a physiological perspective, puberty in both Bos taurus and Bos indicus heifers is characterized by an increase in the LH concentration, frequency pulses, and decreasing of the hypothalamic-pituitary axis sensibility to gonadal steroid, with, or without, the participation of the neurotransmitters capable of either stimulating or to inhibiting the LH secretion, which will result in the first ovulation. The physiological events related to the first ovulation are similar for both Bos taurus and Bos indicus, occurring later for Bos indicus. The extensive Zebu management carried out in the majority of the South American countries contributes for puberty to occur later influencing the age of the first calving. Regarding the first ovulation, age is a characteristic of high heritability, as the genetic selection, through sexual precocity, is a tool for first¬calving age reduction; and the improvement of the nutritional quality and feeding supply, crossbreeding, heifer exposition to bulls and the use o biotechnologies which ensure the manipulation of the first ovulation might contribute for the productivity increasing. This review aims at approaching physiological aspects related to the puberty of both Bos taurus and Bos indicus heifers.

Phagocytic activities of neutrophilic leukocytes in women in various phases of menstrual cycle, and in pregnancy.

This study evaluated the phagocytic activities of neutrophilic leukocytes in both sexes during reproductive age and in women in different phases of the menstrual cycle and in pregnancy. In this study, 9 male and 12 female medical students, 17 to 20 years of age, 23 pregnant women and 9 women after delivery were evaluated. Heparinized blood was incubated with heat killed bacteria Staphylococcus aureus at 37 degrees C for 20 minutes. The blood films were stained with Leishman stain and the phagocytic index was found out by the number of neutrophilic leukocytes ingested with organisms in 100 cells and the total number of organisms counted therein. At the interval of 14 days, on 3 consecutive occasions, the phagocytic index was studied on the same male and female subject. The phagocytic activities of neutrophilic leukocytes were found slightly higher in females than in males; more so in pregnancy than in non-pregnant women, woman controls and after delivery. During the expected ovulation period, the phagocytic activities were observed more than during the menstrual and premenstrual phases. The phagocytic activities were found more in pregnancy and during the ovulatory period in women.

Local regulatory factors in regulation of ovarian function: role of prorenin-renin-angiotensin-system.

During reproductive life in the female, there is a continuous flow of growth, maturation and demise of ovarian follicles, unless pregnancy occurs. Although ovarian function is primarily controlled by the hypothalamus-pituitary-axis, there is no doubt that a hormonal microenvironment specific for each individual follicle is established, that finally determines whether a follicle ovulates and becomes a corpus luteum or undergoes atresia. In this respect, autocrine and paracrine factors that act alone or modulate gonadotropins action are of paramount importance. In this article, we want to introduce the ovarian prorenin-renin-angiotensin-system (PRAS) and summarize what is actually known about its involvement in ovarian physiology and pathology.

Hipersecreçäo do hormônio luteinizante / Hypersecretion of luteinizing hormone

O hormônio luteinizante (LH), glicoproteína estruturada em duas subunidades com 121 aminoácidos e 4 sítios de glicosilaçäo, é sintetizado pelos gonadotropos hipofisários de modo pulsátil, em resposta aos pulsos de GnRH. Na foliculogênese o LH estimula a síntese basal de progesterona pelos folículos antrais menores que 7mm e de androstenediona e testosterona, de modo crescente, nos folículos maiores. No folículo dominante, que contém agora receptores para o LH nas células da granulosa, esta gonadotrofina induz a luteinizaçäo, atenuaçäo da enzima P450 17 e a síntese de progesterona. O pico de LH no meio do ciclo reinicia e completa a primeira divisäo meiótica, inibe o inibidor da maturaçäo do oocisto e estimula a síntese de prostaglandinas e proteínas líticas responsáveis pela extrusäo física do oocisto. A hipersecreçäo do LH na fase folicular inicial afeta a maturaçäo do oocisto, acelera o consumo dos oocistos e está relacionada com baixas taxas de fertilizaçäo, esterilidade e a altas taxas de abortamentos espontâneos. Os mecanismos responsáveis pela hipersecreçäo incluem as alteraçöes na pulsatilidade, a elevaçäo precoce do inibidor da maturaçäo do oocisto, deficiência do fator atenuador do pico de LH e alteraçöes nos moduladores intragonadais da açäo do LH

Post-Transcription Regulation of mRNA and Hormone Synthesis and Release at the Anterior Pituitary Gland: Information derived from the recovery of pituitary gonadotrope cell function after with a GnRH agonist

This review presents a summary of post-transcription regulation of mRNAs with a focus on the anterior pituitary gland. The control of gene transcription and production of mRNAs is the predominant form of regulation of hormone synthesis. However, post-transcription regulation of mRNAs provides another level of control of hormone synthesis. Examples of how hormone synthesis can be controlled at the level of mRNA include mRNA nuclear export and subcellular localization, mRNA stability and turnover, and regulation of mRNA translation. The gonadotrope cells of the anterior pituitary have multiple internal effector systems and provide an ideal model cell to study post-transcription regulation of mRNAs. Gonadotrope cells are stimulated to release LH and FSH by hypothalamic GnRH that binds to GnRH receptors. GnRH receptors are coupled to G-proteins and second messenger signaling pathways that involve cAMP and IP3. These signaling pathways are associated with the release of LH and FSH and transcription of mRNAs for LH and FSH. The stability of these mRNAs can be influenced by androgens, estrogens and progestagens. Therapy with a GnRH agonist leads to desensitization of gonadotrope cells to GnRH and a depletion of cellular stores of LH and FSH mRNAs, and content of LH and FSH. After discontinuation of therapy with GnRH agonist, levels of LH and FSH mRNAs return to normal some time before LH and FSH content and secretion are restored. This is indicative of post-transcription regulation of LH and FSH mRNAs. Future studies on post-transcription regulation of mRHAs will provide new molecular insights into how gonadotrope cells balance and integrate stimulation by GnRH with feedback modulation by the gonads.

Testicular changes due to graded doses of nicotine in albino mice.

Administration of graded doses of nicotine (0.2 mg, 0.4 mg and 0.6 mg/100 g body weight) for 15 days to the adult mice reduced the weight of testis, number of spermatocytes and spermatids, but increased the number of spermatogonia which may be due to reduced conversion to subsequent stages. There is a high cholesterol content and Sudanophilic lipid accumulation in the treated testis. The weight of accessory sex organs which is dependent on androgens produced by the testis is also reduced. These changes are brought because of the non-availability of pituitary gonadotrophins essential for initiation and completion of spermatogenesis and steroidogenesis in the testis due to the administration of nicotine, which being CNS depressor might have caused inhibition in the neural stimulus essential for release of pituitary gonadotrophins.

Response of the adult female rats to ovariectomy as determined by luteinsing hormone radioimmunoassay

This study was carried out to see the response of ovariectomy in adult female rats as determined by rat Luteinising Hormone [rLH] Radioimrnunoassy [RIA]. Animals were divided in two groups. Group I [control, n=6] were sham ovariectomised and group II [experimental, n=4] were ovariectomised. Next day at 1400 hours rats were sacrificed and their plasma was collected for rLH, RIA. It was observed that there was highly significant increase in plasma rLH [P<0.001] in experimental group as compared to controls. Also the increase in the weights of hypothalamus and anterior pituitary of experimental group was highly significant [P<0.001] as compared to controls. This shows that this rise in plasma rLH and weights of hypothalamus and anterior pituitary was due to loss of negative feed back effect of ovarian steroids

Momento de ovulación y efecto del intervalo entre el inicio del estro y la inseminación artificial sobre el porcentaje de concepción de vaquillas Holstein / Timing of ovulation and the effect of the interval between the onset of estrus and artificial insemination on the conception rate in Holstein heifers

El objetivo del presente estudio fue establecer la relación temporal entre el estro, el pico preovulatorio de LH y la ovulación en vaquillas Holstein, y evaluar la fertilidad obtenida al inseminar en diferentes momentos en relación al inicio del estro en este tipo de animales. En la primera parte del trabajo se utilizaron 25 vaquillas vírgenes, a las cuales se les tomaron muestras de sangre cada 3 h desde 48 h antes del inicio esperado del estro y hasta confirmarse la ocurrencia de la ovulación mediante palpación rectal. El inicio y final del estro se determinaron observando el comportamiento homosexual las 24 h del día. El pico preovulatorio de LH y la ovulación ocurrieron respectivamante 4.7 ñ 1.3 y 29.9 ñ 0.1 h después del inicio del estro. Entre el pico preovulatorio de LH y la ovulación transcurrieron 25 ñ 3.5 h y entre el final del estro y la ovulación 12.5 ñ 6.2 h. La duración total de la elevación preovulatoria de LH fue de 13.7 ñ 3.6. En la segunda parte del trabajo se detectaron estros en forma continua durante las 24 h del día hasta acumular 1548 observaciones de estro. En cada caso se registró la fecha y hora del inicio del estro, la hora de la inseminación y el mes del año en que se inseminó. El intervalo entre el inicio del estro no tuvo efecto significativo (P> 0.05) sobre el porcentaje de concepción, aunque dicho porcentaje tendió a ser menor en las vaquillas inseminadas cuando habían transcurrido menos de 8 o más de 20 h desde el inicio del estro. La fertilidad se redujo entre más inseminaciones previas hubiese tenido el animal (P< 0.05). Se concluye que en vaquillas Holstein el inicio del estro y el pico preovulatorio de LH son predictores confiables del momento de ovulación. Por otra parte, el momento de inseminación relativo al inicio del estro no afecta el porcentaje de concepción, lo cual permite seguir que bajo un régimen de observación continua de calores se puede programar la inseminación una vez al día sin reducir la fertilidad

Relación de la tasa de litio con los cambios hormonales del ciclo menstrual / Relation between the lithium ratio and hormonal changes during the menstrual cycle

Se evaluó los cambios en la tasa de litio (TL), paralelamente a los cambios hormonales (LH, FSH, progesterona, estradiol y testosterona) durante un ciclo mestrual completo, en 6 voluntarias sin antecedentes de desorden afectivo bipolar ni de alteraciones endocrinológicas. Los valores de la TL oscilaron a lo largo del ciclo menstrual, observándose los valores más bajos en los días cercanos a la ovulación. No se encontraron asociaciones significativas entre TL y la concentración de hormonas o las relaciones estradiol/progesterona y estradiol/testosterona. Debido a que se cuantificó la fracción total de hormonas esteroideas y no la fracción libre (biológicamente activa), aún no es posible descartar una relación entre TL y estas hormonas. Se observó además que tres de las voluntarias, quienes mostraban valores de TL elevados con respecto al resto en la fase folicular temprana(p<0.05) y la fase luteal tardía (p<0.01), sufrían de sindrome premenstrual. Sin embargo, no se encontraron diferencias significativas en los niveles hormonales entre ambos grupos.

Prediction of ovulation through urinary LH

Luteinising Hormone [LH] levels were screened in the urine samples taken from normal menstruating women, in order to establish the phase of their menstrual cycle on the basis of their urinary LH concentrations. Urinary LH was quantified using WHO RIA Reagents for serum LH. All the results agreed in the determination of the early follicular ovulation, Peak and Luteal Phases, as indicated by the day of sampling during the menstrual cycle. This suggests that urinary LH, instead of serum LH, can be used for predicting ovulation reliably

Hormonas tímicas como mediadoras de la integración inmunogonadotropa / Thymic hormones as mediators of the inmunogonadotroph integration

Existe significativa evidencia sobre la existencia de un eje timo-hipofiso-gonadal. En razón de que estudios previos de los autores habían demostrado que la Hormona Homeostática Tímica, un dímero de histonas H2A y H2B, posee múltiples efectos in vivo sobre la secreción de hormonas hipofisarias, resultó de interés evaluar el efecto in vitro de distintas preparaciones tímicas y proteínas nucleares relacionadas, sobre la liberación de prolactina (Prl), hormona foliculoestimulante (FSH) y hormona luteinizante (LH). Células hipofisarias frescas de ratas hembras se dispersaron con colagenasa y se empaquetaron en una columna de Biogel P-2 mantenida a 37oC. Las células se perifundieron continuamente con medios EBSS, o,5 por ciento de BSA, 1 por ciento de ácido ascórbico y 50 IU de aprotinina/ml (medio de perifusión, MP). Las sustancias a ser testeadas (estímulos) se disolvieron en MP, perifundiéndose en un volumen de 1,5 ml por estímulo a través del circuito de perifusión, al final del cual se recogieron fracciones de 1 ml. Las hormonas liberadas se dosaron por radioinmunoensayo. La viabilidad de las células dispersas osciló entre 84 y 96 porciento. Distintas diluciones de extractos de eminencia media de rata generaron, para cada hormona, una respuesta estimulatoria dosis-dependiente. En general, tanto las preparaciones de histona H2A como las de nucleohistona (ambas a una concentración de 500 µg/ml) indujeron picos secretorios significativos de LH, FSH y Prl, siendo los más elevados los correspondientes a Prl. Asimismo, la hormona tímica timulina y sobrenadantes provenientes de cultivo de células epiteliales tímicas de rata y ratón, pero no la timosina fracción ÷ o el péptido tímico MB-35, resultaron estimulatorios. Los resultados del presente trabajo sugieren que ciertos productos tímicos podrían participar en la integración inmuno-gonadotropa, actuando como señales hipofisotropas

Percepcao de mudancas fisicas e psiquicas durante o ciclo menstrual em relacao ao dia ovulatorio / Perception of physical and psychological changes during the menstrual cycle in relation to the ovulatory day

Ha uma importante parcela da populacao que opta pela abstinencia periodica para evitar a gravidez. Muitos outros casais gostariam de usar este metodo se pudessem identificar com maior certeza o periodo infertil. Com o objetivo de pesquisar que sinais e sintomas poderiam estar influenciados pelas mudancas fisiologicas que acometem durante o ciclo menstrual, foram estudadas 35 mulheres durante tres ciclos consecutivos, tentando relacionar as mudancas fisicas ou psicologicas que experimentaram durante esse periodo com pico de LH...

Effect of unilateral ovariectomy and subsequent ovum implantation in mice.

Unilateral ovariectomy (ULO) was done on any stage of the cycle and the animals were mated within day 1 to day 21 to observe the acute and long term effect of ULO on ovum implantation. Implantation reduced in proportion to single ovary if the animals were mated within 24 hr of ULO. Increase in ovarian weight along with an increase in implantation number continued in mated mice and reached at peak on day 19-21 of ULO (sacrificed after 6 days i.e., 25-27 days of ULO). After ULO the remaining ovary compensated within day 5-6 of ULO even during pregnancy. Ovarian histology showed stimulation of small antral follicles in mice mated on day 3 of ULO (sacrificed after 6 days i.e., day 9 of ULO) along with a decrease of large antral follicles and pre-antral follicles. Preantral follicles were at peak on day 12-14. Large antral follicles attained a peak on day 4 which slowly decreased. The occurrence of implantation in such ULO conditions are discussed.

El efecto del estradiol y la progesterona sobre los mecanismos de control de la secreción de la hormona luteinizante en la oveja / The effect of estradiol and progesterone onthe contro mechanisms that regulate luteinizing hormone secretion in the ewe

La secreción de LH en los animales castrados es mayor que en los animales enteros. Esto sugiere la existencia de un mecanismo de control por retroalimentación negativa proveniente del ovario, que ejerce su efecto sobre el eje hipotalámico-pituitario, de tal manera que la secreción de LH se inhibe cuando hay secreción de estrógenos ováricos. En función de este postulado, se administraron cantidades fisiológicas de esteroides ováricos a animales ovariectomizados, con el fin de determinar cuál componente de la secreción ovárica es más eficaz para inhibir la secreción de LH pituitaria. Los resultados de este estudio fueron: La infusión intravenosa de 0.015 - 0.3 Mg por hora de estradiol durante 36 horas y la infusión intravenosa de 250 mg por hora de progesterona con 0.1 mg por hora de estradiol durante 24 horas de 0.1 mg/hora de estradiol con 0.05 mg/hora de estrona durante 36 horas. Todas fallaron para producir un decremento en la secreción pulsátil de LH a niveles similares a los observados en ovejas normales. Se concluyó que la duración de la infusión y la dosis de esteroides ováricos deben aumentarse buscando imitar una liberación pulsátil, con altas y bajas de concentración similares a las observadas en condiciones naturales.