Abstract

The migration of gonadotropin-releasing hormone (GnRH) neurons from the olfactory placode to the preoptic area (POA) from embryonic day 13 is important for successful reproduction during adulthood. Whether maternal glucocorticoid exposure alters GnRH neuronal morphology and number in the offspring is unknown. This study determines the effect of maternal dexamethasone (DEX) exposure on enhanced green fluorescent protein (EGFP) driven by GnRH promoter neurons (TG-GnRH) in transgenic rats dual-labelled with GnRH immunofluorescence (IF-GnRH). The TG-GnRH neurons were examined in intact male and female rats at different postnatal ages, as a marker for GnRH promoter activity. Pregnant females were subcutaneously injected with DEX (0.1 mg/kg) or vehicle daily during gestation days 13–20 to examine the number of GnRH neurons in P0 male offspring. The total number of TG-GnRH neurons and TG-GnRH/IF-GnRH neuronal ratio increased from P0 and P5 stages to P47–52 stages, suggesting temporal regulation of GnRH promoter activity during postnatal development in intact rats. In DEX-treated P0 males, the number of IF-GnRH neurons decreased within the medial septum, organum vasculosom of the lamina terminalis (OVLT) and anterior hypothalamus. The percentage of TG-GnRH neurons with branched dendritic structures decreased in the OVLT of DEX-P0 males. These results suggest that maternal DEX exposure affects the number and dendritic development of early postnatal GnRH neurons in the OVLT/POA, which may lead to altered reproductive functions in adults.

Highlights

  • The gonadotropin-releasing hormone (GnRH) neurons located in the preoptic area (POA) are important for the central regulation of fertility in mammals

  • Few TG-GnRH neurons were observed in the OVLT of postnatal day 0 (P0) (Fig. 1a) and P5 (Fig. 1b) males compared to the P52 males (Fig. 1c)

  • It is well-documented that the number of GnRH neurons in the brain is established during birth and maintained throughout adult stages (Wray and Hoffman 1986; Jennes 1989)

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Summary

Introduction

The gonadotropin-releasing hormone (GnRH) neurons located in the preoptic area (POA) are important for the central regulation of fertility in mammals. GnRH neurons originate from progenitor cells in the olfactory placode during embryonic day 10.5 (E10.5) in mice (Schwanzel-Fukuda and Pfaff 1989; Wray et al 1989) and E13.5 in rats (Daikoku and Koide 1998). This unique characteristic of embryonic GnRH neuronal migration into the brain is conserved across vertebrates (Parhar 2002). Disrupted embryonic migration and abnormal number or distribution of GnRH neurons in the brain are linked to hypogonadism and reproductive dysfunction (Schwanzel-Fukuda et al 1989; Wierman et al 2011)

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