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Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring.

Lim WL, Soga T, Parhar IS - Cell Tissue Res. (2013)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, Petaling Jaya, 46150, Selangor, Malaysia.

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.

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Morphological observations of GnRH neurons and fiber projections in the OVLT and ME in VEH-P0 and DEX-P0 males. Low-magnification photomontage of sagittal sections exhibited IF-GnRH neurons (red) along the caudal olfactory bulb (OB), olfactory tubercule (OT), diagonal band of Broca (DBB), MS, and OVLT/POA in VEH-P0 (a) and DEX-P0 (b) males. Few IF-GnRH neurons were observed along the forebrain distribution in DEX-P0 males. c–j GnRH fiber projections from coronal sections of OVLT and ME in VEH-P0 and DEX-P0 males. High-magnification of white insets illustrating the fiber projections in the OVLT (d, f) and ME (h, j) were shown for VEH-P0 and DEX-P0 males respectively. Thicker varicosities of IF-GnRH fibers were observed in lateral OVLT of DEX-P0 (d) compared to VEH-P0 (f) males. Bars 500 μm (a-b), 50 μm (c, e, g, i) and 20 μm (d, f, h, j)
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Fig6: Morphological observations of GnRH neurons and fiber projections in the OVLT and ME in VEH-P0 and DEX-P0 males. Low-magnification photomontage of sagittal sections exhibited IF-GnRH neurons (red) along the caudal olfactory bulb (OB), olfactory tubercule (OT), diagonal band of Broca (DBB), MS, and OVLT/POA in VEH-P0 (a) and DEX-P0 (b) males. Few IF-GnRH neurons were observed along the forebrain distribution in DEX-P0 males. c–j GnRH fiber projections from coronal sections of OVLT and ME in VEH-P0 and DEX-P0 males. High-magnification of white insets illustrating the fiber projections in the OVLT (d, f) and ME (h, j) were shown for VEH-P0 and DEX-P0 males respectively. Thicker varicosities of IF-GnRH fibers were observed in lateral OVLT of DEX-P0 (d) compared to VEH-P0 (f) males. Bars 500 μm (a-b), 50 μm (c, e, g, i) and 20 μm (d, f, h, j)

Mentions: IF-GnRH neurons were observed along the migratory route, which included the caudal olfactory bulb, DBB, MS and OVLT/POA in sagittal sections of VEH-P0 and DEX-P0 males (Fig. 6a and b). There was no difference in the distribution but fewer IF-GnRH neurons were found in the DEX-P0 compared to the VEH-P0 males. This observation is comparable with the decreased number of GnRH neurons found in the coronal sections of DEX-P0 males (Fig. 5d). The IF-GnRH fibers were observed within the lateral OVLT (Fig. 6c-f) and ME (Fig. 6g-j) on coronal sections of DEX-P0 and VEH-P0 males. Although the varicosities of IF-GnRH fibers appeared thicker in the lateral part of OVLT of DEX-P0 males (Fig. 6d) compared to VEH-P0 (Fig. 6f), we did not observe any difference in the high-density IF-GnRH fibers within the OVLT region. No differences were observed in the innervations of IF-GnRH fibers in the ME between the VEH-P0 and DEX-P0 males (Fig. 6h and j). Therefore, a quantitative study of the fiber density in the OVLT and the ME region was not carried out.Fig. 6


Maternal dexamethasone exposure during pregnancy in rats disrupts gonadotropin-releasing hormone neuronal development in the offspring.

Lim WL, Soga T, Parhar IS - Cell Tissue Res. (2013)

Morphological observations of GnRH neurons and fiber projections in the OVLT and ME in VEH-P0 and DEX-P0 males. Low-magnification photomontage of sagittal sections exhibited IF-GnRH neurons (red) along the caudal olfactory bulb (OB), olfactory tubercule (OT), diagonal band of Broca (DBB), MS, and OVLT/POA in VEH-P0 (a) and DEX-P0 (b) males. Few IF-GnRH neurons were observed along the forebrain distribution in DEX-P0 males. c–j GnRH fiber projections from coronal sections of OVLT and ME in VEH-P0 and DEX-P0 males. High-magnification of white insets illustrating the fiber projections in the OVLT (d, f) and ME (h, j) were shown for VEH-P0 and DEX-P0 males respectively. Thicker varicosities of IF-GnRH fibers were observed in lateral OVLT of DEX-P0 (d) compared to VEH-P0 (f) males. Bars 500 μm (a-b), 50 μm (c, e, g, i) and 20 μm (d, f, h, j)
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Fig6: Morphological observations of GnRH neurons and fiber projections in the OVLT and ME in VEH-P0 and DEX-P0 males. Low-magnification photomontage of sagittal sections exhibited IF-GnRH neurons (red) along the caudal olfactory bulb (OB), olfactory tubercule (OT), diagonal band of Broca (DBB), MS, and OVLT/POA in VEH-P0 (a) and DEX-P0 (b) males. Few IF-GnRH neurons were observed along the forebrain distribution in DEX-P0 males. c–j GnRH fiber projections from coronal sections of OVLT and ME in VEH-P0 and DEX-P0 males. High-magnification of white insets illustrating the fiber projections in the OVLT (d, f) and ME (h, j) were shown for VEH-P0 and DEX-P0 males respectively. Thicker varicosities of IF-GnRH fibers were observed in lateral OVLT of DEX-P0 (d) compared to VEH-P0 (f) males. Bars 500 μm (a-b), 50 μm (c, e, g, i) and 20 μm (d, f, h, j)
Mentions: IF-GnRH neurons were observed along the migratory route, which included the caudal olfactory bulb, DBB, MS and OVLT/POA in sagittal sections of VEH-P0 and DEX-P0 males (Fig. 6a and b). There was no difference in the distribution but fewer IF-GnRH neurons were found in the DEX-P0 compared to the VEH-P0 males. This observation is comparable with the decreased number of GnRH neurons found in the coronal sections of DEX-P0 males (Fig. 5d). The IF-GnRH fibers were observed within the lateral OVLT (Fig. 6c-f) and ME (Fig. 6g-j) on coronal sections of DEX-P0 and VEH-P0 males. Although the varicosities of IF-GnRH fibers appeared thicker in the lateral part of OVLT of DEX-P0 males (Fig. 6d) compared to VEH-P0 (Fig. 6f), we did not observe any difference in the high-density IF-GnRH fibers within the OVLT region. No differences were observed in the innervations of IF-GnRH fibers in the ME between the VEH-P0 and DEX-P0 males (Fig. 6h and j). Therefore, a quantitative study of the fiber density in the OVLT and the ME region was not carried out.Fig. 6

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Brain Research Institute, School of Medicine and Health Sciences, Monash University Malaysia, Petaling Jaya, 46150, Selangor, Malaysia.

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.

Show MeSH
Related in: MedlinePlus