Early-Life Stress Reprograms Stress-Coping Abilities in Male and Female Juvenile Rats.

Prenatal stress (PS) is a major risk factor for the development of emotional disorders in adulthood that may be mediated by an altered hypothalamic-pituitary-adrenal axis response to stress. Although the early onset of stress-related disorders is recognized as a major public health problem, to date, there are relatively few studies that have examined the incidence of early-life stressors in younger individuals. In this study, we assessed PS impact on the stress-coping response of juvenile offspring in behavioral tests and in the induced molecular changes in the hippocampus. Furthermore, we assessed if pregnancy stress could be driving changes in patterns of maternal behavior during early lactation. We found that PS modified stress-coping abilities of both sex offspring. In the hippocampus, PS increased the expression of bdnf-IV and crfr1 and induced sex difference changes on glucocorticoids and BDNF mRNA receptor levels. PS changed the hippocampal epigenetic landscape mainly in male offspring. Stress during pregnancy enhanced pup-directed behavior of stressed dams. Our study indicates that exposure to PS, in addition to enhanced maternal behavior, induces dynamic neurobehavioral variations at juvenile ages of the offspring that should be considered adaptive or maladaptive, depending on the characteristics of the confronting environment. Our present results highlight the importance to further explore risk factors that appear early in life that will be important to allow timely prevention strategies to later vulnerability to stress-related disorders.

The epigenetics of the hypothalamic-pituitary-adrenal axis in fetal development.

The hypothalamic-pituitary-adrenal (HPA) axis is an important hormonal mechanism of the human body and is extremely programmable during embryonic and fetal development. Analyzing its development in this period is the key to understanding in fact how vulnerabilities of congenital diseases occur and any other changes in the phenotypic and histophysiological aspects of the fetus. The environment in which the mother is exposed during the gestational period can influence this axis. Knowing this, our objective was to analyze in recent research the possible impact of epigenetic programming on the HPA axis and its consequences for fetal development. This review brought together articles from two databases: ScienceDirect and PUBMED researched based on key words such as "epigenetics, HPA axis, cardiovascular disease, and circulatory problems" where it demonstrated full relevance in experimental and scientific settings. A total of 101 articles were selected following the criteria established by the researchers. Thus, it was possible to verify that the development of the HPA axis is directly related to changes that occur in the cardiovascular system, to the cerebral growth and other systems depending on the influence that it receives in the period of fetal formation.

Bisphenol a induces both transient and permanent histofunctional alterations of the hypothalamic-pituitary-gonadal axis in prenatally exposed male rats.

Exposure to bisphenol A (BPA) in utero has been shown to induce alterations in the prostate of 30-d-old Wistar rats. Herein, we examine both the time course of BPA action on the rat prostate and the effects of BPA on the male hypothalamic-pituitary-gonadal axis. This was achieved by exposing rats to BPA in utero, followed by immunohistochemistry and morphometric analysis of prostatic tissue, evaluation of estrogen receptor-alpha (ERalpha) and ERbeta mRNA expression in both the preoptic area (POA) and medial basal hypothalamus, and determination of PRL, LH, and testosterone serum levels. On d 30 (peripubertal period), the prostatic periductal stroma of BPA-exposed rats demonstrated a significantly larger layer of fibroblasts than that of controls, whereas on d 120 (adulthood) no significant differences were observed. Moreover, BPA-exposed rats on d 15 exhibited an increase in stromal cellular proliferation compared with controls. Decreased expression of both androgen receptor in prostatic stromal cells and prostatic acid phosphatase in epithelial cells was observed only on d 30 in BPA-exposed males. BPA did not alter POA ERalpha mRNA expression, whereas a 4-fold increase in POA ERbeta mRNA expression was observed on both d 30 and 120. No alterations were observed in either ERalpha or ERbeta expression in the medial basal hypothalamus. BPA-exposed males exhibited increased PRL levels only on d 30, whereas a transient increase in serum testosterone levels was observed on d 15. These results support the hypothesis that prenatal exposure to environmental doses of BPA induces both transient and permanent age-dependent alterations in the male reproductive axis at different levels.

[Participation of growth factors in human reproduction]. / Participación de los factores de crecimiento en la reproducción humana.

The Growth Factors (GFs) include a group peptidic molecules, with important trophic, mitotic and cellular differentiation effects in most human tissues. This review encompasses the different types of GFs and their biologic effects on tissues involved in the human reproductive process. The importance of the GF in the embryonic development and the implantation process is also commented. Finally, we assess the participation of the GFs in the pathophysiology of the Polycystic Ovary Syndrome and Endometriosis based on recent investigations. The review permit us appreciate the importance of the GFs as mediators of different hormones (in their secretion and biological effects) and in the regulation of some cellular events. The real value of these GFs in the daily clinical practice is as yet to be established, due to the technical laboratory limitations with respect to their identification and quantification, as well as the lack of more clinical research in humans. The GFs are promising molecules for the treatment of infertiles couples and for the application of the technics of assisted reproduction, in vivo and in vitro.

Repercussöes neurológicas do hipertiroidismo congênito / Nurological repercussion of congenital hyperthyroidism

Na literatura disponível sobre os programas de rastreamento para o hipotireoidismo congênito tem-se mencionado como objetivo principal, a prevençäo das seqüelas neurológicas decorrentes do diagnóstico e tratamento tardios desta afecçäo. No entanto, tem-se observado que, mesmo com a disseminaçäo destes programas pelo mundo e o início precoce do tratamento, algumas disfunçöes neurológicas ainda säo notadas, o que leva um contigente significativo destas crianças a necessitarem de ensino especializado em tempo integral. Neste trabalho é feita uma revisäo bibliográfica sobre a embriologia do sistema nervoso e suas inter-relaçöes com o desenvolvimento do eixo hipotálamo-hipófise-tireoidiano fetal; as alteraçöes fisiopatológicas e bioquímicas que podem ocorrer no sistema nervoso em decorrência da hipotiroxinemia, seja de início pré-natal - quando é possível haver participaçäo materna na etiopatogenia -, seja de surgimento após o parto, quando a disfunçäo tireoidiana é exclusivamente oriunda do feto; e uma abordagem sobre as repercussöes a nível comportamental e de aprendizado. Embora o rastreamento neonatal tenha a sua indiscutível importância na melhoria das condiçöes de vida da populaçäo em geral, as lesöes ocorridas na fase pré-natal que näo säo evitadas com os programas de rastreamento neonatais convencionais, nos levam a pensar que o ideal seria incluir uma forma de rastreamento para o hipotireoidismo nas rotinas de acompanhamento pré-natal para que se possa garantir o desenvolvimento neurológico pleno desta populaçäo.