Environmental Impact on the Hypothalamus-Pituitary-Ovary Axis

Abstract

Dysfunction of hypothalamic-pituitary-gonadal (HPG) axis can be caused by complex and multilevel interactions between altered sleep quality, behavioral disturbances,and chemicals that interfere with normal functioning of the endocrine system, known as endocrine disruptors (EDs). Sleep deprivation disrupts circadian rhythm and via modulation of melatonin secretion and hypothalamic neural outputs inhibits gonadotropin-releasing hormone (GnRH) secretion and reduces the levels of gonadotropins and androgens. Although many evidence suggest that EDs may affect the function of HPG axis, the precise actions on EDs on reproductive health are still controversial. More studies have been performed in female than in male animals. Major mechanisms of deleterious action of EDs on HPG axis include stimulation or inhibition of nuclear hormone receptors via direct binding, alter actions of steroid biosynthesis and degradation, and changes in neurotransmitter release and effects. Some EDs may also cause the apoptosis of GnRH neurons or induce epigenetic changes that can be transmitted to the offspring. In ovaries, EDs may inhibit key steroidogenic enzymes and estrogen synthesis or directly injure granulosa or theca cells. They can also have high affinity for estrogen, androgen, progesterone, or glucocorticoid receptors, and to stimulate or inhibit different signaling pathways in the cell. All of these changes may impair oocyte maturation , increase the frequency of anovulatory cycles, and ultimately lead to disturbed puberty onset, reduced female fecundity, and premature ovarian failure. This chapter summarizes the current knowledge on the effects of sleep disturbances and major EDs on reproductive function from prenatal to adult period.