Role of estrogen and progesterone receptors in neonatal uterine cell proliferation in the mouse

The major endocrine regulators of the female reproductive tract are 17β-estradiol (E2) and progesterone (P4). This review discusses our recent work related to the roles of E2 and P4 and their receptors, estrogen receptor 1 (ESR1) and progesterone receptor (PR), respectively, in the neonatal uterus. Neonatal uterine cells in mice are mitogenically responsive to estrogens, but neonatal ovariectomy does not inhibit pre-weaning uterine cell proliferation, indicating that this process does not require endogenous estrogens. Neonatal terine cell proliferation could result from ligand-independent growth factor activation of ESR1, or be independent of ESR1 neonatally despite its obligatory role in adult uterine epithelial proliferation. To determine the role of ESR1 in uterine development, we analyzed cell proliferation and uterine gland development (adenogenesis) in wild-type (WT) and Esr1 knockout (Esr1KO) mice postnatally. Our results indicate that pre-weaning uterine cell proliferation and adenogenesis are independent of ESR1, but these processes become dependent on E2/ESR1 signaling for maintenance and further proliferation and uterine growth during puberty. How pre-weaning uterine cell proliferation and adenogenesis occur independently of E2/ESR1 signaling remains unknown, but ligand-independent activation of ESR1 is not involved in this process. The synthetic glucocorticoid dexamethasone (Dex) inhibits luminal epithelial (LE) proliferation in neonatal mouse uteri, but it has been unclear whether Dex effects were mediated by glucocorticoid receptor (GR) and/or PR. We have used PR knockout (PRKO) mice to test whether PR is required for Dex inhibition of LE proliferation. Our results indicate that maximal inhibitory Dex effects on uterine LE proliferation require PR, possibly reflecting Dex crosstalk with PR. (AU)

Role of estrogen and progesterone receptors in neonatal uterine cell proliferation in the mouse

The major endocrine regulators of the female reproductive tract are 17β-estradiol (E2) and progesterone (P4). This review discusses our recent work related to the roles of E2 and P4 and their receptors, estrogen receptor 1 (ESR1) and progesterone receptor (PR), respectively, in the neonatal uterus. Neonatal uterine cells in mice are mitogenically responsive to estrogens, but neonatal ovariectomy does not inhibit pre-weaning uterine cell proliferation, indicating that this process does not require endogenous estrogens. Neonatal terine cell proliferation could result from ligand-independent growth factor activation of ESR1, or be independent of ESR1 neonatally despite its obligatory role in adult uterine epithelial proliferation. To determine the role of ESR1 in uterine development, we analyzed cell proliferation and uterine gland development (adenogenesis) in wild-type (WT) and Esr1 knockout (Esr1KO) mice postnatally. Our results indicate that pre-weaning uterine cell proliferation and adenogenesis are independent of ESR1, but these processes become dependent on E2/ESR1 signaling for maintenance and further proliferation and uterine growth during puberty. How pre-weaning uterine cell proliferation and adenogenesis occur independently of E2/ESR1 signaling remains unknown, but ligand-independent activation of ESR1 is not involved in this process. The synthetic glucocorticoid dexamethasone (Dex) inhibits luminal epithelial (LE) proliferation in neonatal mouse uteri, but it has been unclear whether Dex effects were mediated by glucocorticoid receptor (GR) and/or PR. We have used PR knockout (PRKO) mice to test whether PR is required for Dex inhibition of LE proliferation. Our results indicate that maximal inhibitory Dex effects on uterine LE proliferation require PR, possibly reflecting Dex crosstalk with PR.

Colonization of cashew plants by Lasiodiplodia theobromae: microscopical features.

Lasiodiplodia theobromae is a phytopathogenic fungus causing gummosis, a threatening disease for cashew plants in Brazil. In an attempt to investigate the ultrastructural features of the pathogen colonization and its response to immunofluorescence labeling, light, confocal and electron microscope studies were conducted on different severity scale patterns of diseased plants. Lasiodiplodia-antisera was checked for cross reactivity against common cashew plants fungi. Optical microscopy analysis revealed a longitudinally sectioned hyphae located within the xylem vessels, showing an extensive hyphal development in the secondary xylem tissue. SEM images demonstrated that the fungus was found in some asymptomatic samples, particularly within the xylem vessels as confirmed by the optical images. Symptomatic sample images showed an extensive distribution of the fungus along the secondary xylem, within the vessels, infecting xylem parenchyma. A closer look in the secondary xylem parenchyma reveals a heavy and profuse invasion of the cells with a distinguishable cell wall disintegration and fully hyphae dispersal. There was no reactivity of Lasiodiplodia-antisera against mycelial extracts of Colletotrichum gloeosporioides, Phomopsis anardii and Pestalotiopsis guepinii. Following incubation of sections with the polyclonal antisera, the hyphae were intensely and regularly labeled. Rays, vessels and parenchyma cells were the preferred pathway for L. theobromae colonization. Artificial infection provides the information that the vascular cylinder is undoubtedly employed and used by the fungus for hyphae distribution. Immunofluorescence assay employed in situ was applied and the polyclonal antisera produced was able to recognize the fungus and proved to be a sensitive technique to detect it.

Niveles séricos de inmunoglobulina G, A y M en individuos con infección VIH/SIDA tratados con terapia antirretroviral de alta eficiencia / Serum levels of G, A and M immunoglobulin in individuals with HIV/AIDS infection treated with highly active antiretroviral therapy

Antecedentes. El tratamiento de la infección por VIH-1 con terapia antirretroviral de alta eficiencia (TAAE) promueve la supervisión viral, el incremento de las cifras de las células T CD4+ y el mejoramiento de numerosas funciones inmunes. Objetivos. Comparar los niveles séricos de IgG, IgA e IgM en individuos con infección VIH/SIDA tratados con TAAE en relación con los niveles detectados en individuos sin TAAE y establecer relaciones entre niveles de inmunoglobulinas (Ig) y el estado inmunológico y virológico. Población. En este estudio transversal participaron 69 individuos, que fueron clasificados en 2 grupos según recibieran o no TAAE y subclasificados según el nivel de linfocitos T CD4+ (<200 CD4/mL o ò500 CD4/mL). El grupo de control estuvo integrado por 20 sujetos que concurrieron para análisis prenupciales. Resultados. En pacientes sin TAAE hubo aumento de IgG, IgA eIgM respecto de los controles, correlación negativa entre niveles de Ig y cifras de linfocitos T CD4+ y correlación positiva entre carga viral y niveles séricos de IgA, mientras que en pacientes con tratamiento solo hubo incremento de IgG e IgM. En pacientes sin TAAE con <200 CD4/mL hubo un aumento de IgA e IgM respecto de los pacientes con TAAE y similares niveles de linfocitos T CD4+. En pacientes sin tratamiento con ò500 CD4/mL hubo aumento de IgG e IgM respecto de los pacientes con tratamiento y ò500 CD4/mL. Conclusión. Estos hallazgos sugieren una modulación de la activación policlonal de las células B por la TAAE en el contexto de la recuperación inmunológica y la reducción de la replicación viral (AU)

Niveles séricos de inmunoglobulina G, A y M en individuos con infección VIH/SIDA tratados con terapia antirretroviral de alta eficiencia / Serum levels of G, A and M immunoglobulin in individuals with HIV/AIDS infection treated with highly active antiretroviral therapy

Antecedentes. El tratamiento de la infección por VIH-1 con terapia antirretroviral de alta eficiencia (TAAE) promueve la supervisión viral, el incremento de las cifras de las células T CD4+ y el mejoramiento de numerosas funciones inmunes. Objetivos. Comparar los niveles séricos de IgG, IgA e IgM en individuos con infección VIH/SIDA tratados con TAAE en relación con los niveles detectados en individuos sin TAAE y establecer relaciones entre niveles de inmunoglobulinas (Ig) y el estado inmunológico y virológico. Población. En este estudio transversal participaron 69 individuos, que fueron clasificados en 2 grupos según recibieran o no TAAE y subclasificados según el nivel de linfocitos T CD4+ (<200 CD4/mL o ò500 CD4/mL). El grupo de control estuvo integrado por 20 sujetos que concurrieron para análisis prenupciales. Resultados. En pacientes sin TAAE hubo aumento de IgG, IgA eIgM respecto de los controles, correlación negativa entre niveles de Ig y cifras de linfocitos T CD4+ y correlación positiva entre carga viral y niveles séricos de IgA, mientras que en pacientes con tratamiento solo hubo incremento de IgG e IgM. En pacientes sin TAAE con <200 CD4/mL hubo un aumento de IgA e IgM respecto de los pacientes con TAAE y similares niveles de linfocitos T CD4+. En pacientes sin tratamiento con ò500 CD4/mL hubo aumento de IgG e IgM respecto de los pacientes con tratamiento y ò500 CD4/mL. Conclusión. Estos hallazgos sugieren una modulación de la activación policlonal de las células B por la TAAE en el contexto de la recuperación inmunológica y la reducción de la replicación viral

Neonatal hypothyroidism causes delayed Sertoli cell maturation in rats treated with propylthiouracil: evidence that the Sertoli cell controls testis growth.

BACKGROUND: The testes of rats treated neonatally with propylthiouracil (PTU) grow to almost twice their normal size. The cause of testicular enlargement has been suggested to be the result of delayed maturation of Sertoli cells, allowing Sertoli cell division to occur beyond the 15th postnatal day, the commonly recognized cutoff date for Sertoli cell divisions. It has been shown that an increased population of Sertoli cells in postnatal development supports increased numbers of germ cells in adult animals. After examining developing rats treated neonatally with PTU, we hypothesized that an approximate 10-day delay in maturation was occurring and proceeded to test this hypothesis experimentally. Thus the purpose of this report was to determine if a 10-day delay in maturation could explain the increased numbers of Sertoli cells and increased testis size in PTU-treated animals. METHODS: Both control animals and animals treated neonatally with PTU N = 5/group were sacrificed at 15 and 25 days of age and prepared for electron microscopy. RESULTS: Micrographs show and morphometric ultrastructural analysis of numerous parameters demonstrated at the 95% probability level that Sertoli cells from 25-day-old PTU animals are not different in size and most constituents (volume and surface area) from 15-day-old control animals and are less mature than 25-day-old control animals. Mitosis of Sertoli cells was observed in PTU-treated animals in 25-day-old animals but not in age-matched controls. The number of Sertoli cells in 25-day-old PTU-treated animals is significantly increased over age-matched controls. Micrographs show the presence of immature Sertoli cell nuclei in 25-day-old animals receiving PTU as well as increased germ cell degeneration in this group. Sertoli cell tight junction formation is also delayed in PTU-treated animals as compared with controls. CONCLUSIONS: Together, the data show that delayed maturation of Sertoli cells occurs in treated animals that corresponds to a minimum of 10 developmental days. In the immature state, Sertoli cells continue to divide. Data presented herein and published data related to PTU treatment indicate that delayed maturation of the Sertoli cell results in delayed maturation and proliferation of other testicular cell types. From this and from published data, the hypothesis is presented that the Sertoli cell is responsible for the overall control of testis development.