Neuroendocrine regulation and effects of stress on female reproduction

Abstract

The knowledge of the control mechanisms of fertility has several sorts of implications: social (e.g., in the human species, the option of conception or anti-conception, populational control, the therapeutical development for several pathologies), economic (e.g., improvement of the fertility of domestic or captive wild species to provide food and clothing) and environmental (e.g., maintenance or reestablishment of ecosystems equilibrium, environment repopulation). On the other hand, fertility in humans and other species can be markedly influenced by stress. However, the neuroendocrine mechanisms that have been altered by the environmental stimulation are still not entirely understood. Natural reproduction depends on complex interactions of the nervous system and hormones produced in the brain, pituitary, gonads and other organs in order to prepare the gametes and induct sexual behavior to ensure fertilization. Due to the difficulties inherent to the complexity of the cyclic hormonal variations in females, there are much more studies regarding to physiological mechanisms in males than in females. In Brazil, there are very few researches working in this field, among them, the ones who got together in the thematic project which ends this year (2000-2004) and now, in this new project that includes two foreign researchers. The objective of this project is to study: a) neural circuits and central neuromediators (norepinephrine, angiotensin II, neuropeptide Y, nitric oxide, leptin, serotonin, oxytocin) involved in tonic and cyclic control of gonadotropins and prolactin secretion as well as its modulation by ovarian steroids; b) the interaction between the neuroendocrine control and ovarian innervation on the secretion of steroidal hormones and c) the effects of stressor stimuli in the neonatal period or in adulthood on the control of reproductive functions. It will be employed techniques like: vaginal smearing, to follow the estrus cycle; egg counting; ovariectomy associated or not with hormonal replacement to compare the action of ovarian steroids and correlate them to the estrus cycle; adrenalectomy. to evaluate the action of adrenal-originated progesterone; electrolytic or chemical lesions and chemical stimulation, to study the function of brain structures in the control of the hypothalamus pituitary-ovary axis; jugular vein cannulation for serial blood sampling; radioimmunoassay for hormonal and neuromediators measurement in plasma and tissues; cerebral structures microdialysis and microdissection to collect material for hormones and neuromediators measurement; HPLC/ED for measurement of cathecolamines in brain structures; NO synthase activity measurement, to evaluate nitric oxide formation; immunohistochemistry to evaluate neuronal activity, localization and co-localization of neuromediators and hormones receptors; stressful stimuli (neonatal manipulation, restraint, immobilization, cold, ether or predator exposure); morphometry (total number of neurons in brain structures or the number of neurons expressing selected neuromodulators or receptors); RT-PCR, western-blotting, immunobloting e in situ hybridization, to evaluate the neuronal expression of neuromediators, receptors and intracellular messengers; computerized behavioral registers to evaluate the effects of hormones and stressful stimuli on behavioral;.electrophvsiologic registers to evaluate the effect of ovarian steroids on neuronal electrical activity in brain structures. (AU)