Abstract
Maternal dexamethasone [(DEX); a glucocorticoid receptor agonist] exposure delays pubertal onset and alters reproductive behavior in the adult offspring. However, little is known whether maternal DEX exposure affects the offspring’s reproductive function by disrupting the gonadotropin-releasing hormone (GnRH) neuronal function in the brain. Therefore, this study determined the exposure of maternal DEX on the GnRH neuronal spine development and synaptic cluster inputs to GnRH neurons using transgenic rats expressing enhanced green fluorescent protein (EGFP) under the control of GnRH promoter. Pregnant females were administered with DEX (0.1 mg/kg) or vehicle (VEH, water) daily during gestation day 13–20. Confocal imaging was used to examine the spine density of EGFP–GnRH neurons by three-dimensional rendering and synaptic cluster inputs to EGFP–GnRH neurons by synapsin I immunohistochemistry on postnatal day 0 (P0) males. The spine morphology and number on GnRH neurons did not change between the P0 males following maternal DEX and VEH treatment. The number of synaptic clusters within the organum vasculosum of the lamina terminalis (OVLT) was decreased by maternal DEX exposure in P0 males. Furthermore, the number and levels of synaptic cluster inputs in close apposition with GnRH neurons was decreased following maternal DEX exposure in the OVLT region of P0 males. In addition, the postsynaptic marker molecule, postsynaptic density 95, was observed in GnRH neurons following both DEX and VEH treatment. These results suggest that maternal DEX exposure alters neural afferent inputs to GnRH neurons during early postnatal stage, which could lead to reproductive dysfunction during adulthood.
Highlights
Gonadotropin-releasing hormone (GnRH) neurons regulate fertility in the vertebrates by stimulating the secretion of pituitary gonadotropins, thereby promoting gonadal hormone secretion and function
The number of filopodia emerging from the soma and primary dendrite of gonadotropin-releasing hormone (GnRH) neurons in the OVLT (H) and anterior hypothalamic area (AHA) (J) region did not differ between VEH-postnatal day 0 (P0) and DEX-P0 males
This study examines the effect of maternal DEX exposure on the GnRH neuronal spine number and alterations of synaptic inputs to the GnRH neurons in P0 male offspring
Summary
Gonadotropin-releasing hormone (GnRH) neurons regulate fertility in the vertebrates by stimulating the secretion of pituitary gonadotropins, thereby promoting gonadal hormone secretion and function. Morphological plasticity of GnRH neurons and synaptic inputs from various neuropeptides and neurotransmitters to GnRH neurons are modulated by the developmental stage, gender, hormonal, and environmental cues [10, 11]. Immunohistochemical studies have identified morphologically smooth and spiny subtypes of GnRH neurons in the brain, and number of spiny GnRH neurons increase with pubertal maturation in male and female rats [12]. Biocytin-filled GnRH neurons expressing GFP in mice show increased spine density on GnRH soma and dendrite in adult stages, indicating increased afferent inputs to GnRH neurons during pubertal maturation [13]. Increase in somatic and dendritic spine density in subpopulation of GFP–GnRH neurons expressing cFos protein during preovulatory luteinizing hormone (LH) surge further implicates the role of gonadal steroids in modulating spine plasticity of GnRH neurons [14]. Changes in γ-amino butyric acid (GABA)-ergic and glutamatergic synaptic terminal appositions contacting GnRH neurons in rats are demonstrated during estradiol-induced LH surge and reproductive aging [15, 16]
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