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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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Distribution of the GnRH neurons in P0 (n = 5/sex), P5 (n = 6/sex) and young adult (P47 female, n = 3; P52 male, n = 3) transgenic rats. a Total TG-GnRH neuronal number was decreased in P0 and P5 stages compared to P47-P52 stage. b Number of IF-GnRH neurons did not differ across age and gender. c GnRH promoter activity expressed as Tg-GnRH/IF-GnRH neuron ratios was increased in the P42-P52 stage compared to the early P0 and P5 stages. Rostral to caudal distribution of TG-GnRH and IF-GnRH neurons in P0 (d–e) and P5 (f–g) male and female, plotted as the number of GnRH neurons in series of 180 μm thickness aligned by organum vasculosom of the lamina terminalis (OVLT). Increased TG-GnRH neuronal number was observed in the rostral region (−540 μm from the OVLT) and IF-GnRH neurons (−1800 μm from the OVLT) in P0 females. h–i Rostral to caudal distribution of TG-GnRH and IF-GnRH neurons in P47-52 stages, plotted as GnRH neuronal number in series of 250 μm thickness aligned by the OVLT. Gender difference was not observed in the distribution of TG-GnRH and IF-GnRH neurons in P47-P52 stages. Data are represented by the mean ± SEM for each group. *, P < 0.05; ***, P < 0.001
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Fig3: Distribution of the GnRH neurons in P0 (n = 5/sex), P5 (n = 6/sex) and young adult (P47 female, n = 3; P52 male, n = 3) transgenic rats. a Total TG-GnRH neuronal number was decreased in P0 and P5 stages compared to P47-P52 stage. b Number of IF-GnRH neurons did not differ across age and gender. c GnRH promoter activity expressed as Tg-GnRH/IF-GnRH neuron ratios was increased in the P42-P52 stage compared to the early P0 and P5 stages. Rostral to caudal distribution of TG-GnRH and IF-GnRH neurons in P0 (d–e) and P5 (f–g) male and female, plotted as the number of GnRH neurons in series of 180 μm thickness aligned by organum vasculosom of the lamina terminalis (OVLT). Increased TG-GnRH neuronal number was observed in the rostral region (−540 μm from the OVLT) and IF-GnRH neurons (−1800 μm from the OVLT) in P0 females. h–i Rostral to caudal distribution of TG-GnRH and IF-GnRH neurons in P47-52 stages, plotted as GnRH neuronal number in series of 250 μm thickness aligned by the OVLT. Gender difference was not observed in the distribution of TG-GnRH and IF-GnRH neurons in P47-P52 stages. Data are represented by the mean ± SEM for each group. *, P < 0.05; ***, P < 0.001

Mentions: The total numbers of IF-GnRH and TG-GnRH neurons in the forebrain region of the transgenic rats across the postnatal developmental stages were counted in serial sections collected from the caudal olfactory bulb to the ME. The original raw count of IF-GnRH and TG-GnRH neurons showed similar results to the corrected GnRH cell count across postnatal development in the intact transgenic rat brains. The total number of TG-GnRH neurons varied significantly across postnatal developmental stages [F (2, 22) = 229.61, P < 0.001] (Fig. 3a) but no gender difference or gender–age interaction was detected. Tukey post-hoc comparisons revealed significant decrease (P < 0.001) in the number of TG-GnRH neurons in the P0 stages (female: 158.9 ± 11.0; male: 115.5 ± 16.7) and P5 (female: 88.8 ± 12.9; male: 67.5 ± 8.2) compared to the young adult stages (P47 female: 710.3 ± 38.6; P52 male: 667.3 ± 94.8). However, there was no difference in the total number of IF-GnRH neurons taken from the same serial sections of transgenic rats across the age group and gender (Fig. 3b). Promoter activity of GnRH neurons across the postnatal developmental stages was expressed as TG-GnRH/IF-GnRH cell ratio (Fig. 3c). The TG-GnRH/IF-GnRH cell ratio varied across postnatal developmental stages [F (2, 22) = 638.30, P < 0.001] and gender [F (1, 22) = 8.28, P < 0.01] but no gender-age interaction was detected. Tukey post-hoc comparisons revealed a significant decrease (P < 0.001) in the TG-GnRH/IF-GnRH cell ratio in the P0 (female: 0.17 ± 0.01; male: 0.14 ± 0.02) and P5 (female: 0.10 ± 0.01; male: 0.08 ± 0.01) compared to the young adult stages (P47 female: 0.91 ± 0.01; P52 male: 0.81 ± 0.06). The TG-GnRH/IF-GnRH cell ratio in the P5 stages was also decreased (P < 0.05) compared to the P0 stages.Fig. 3


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)

Distribution of the GnRH neurons in P0 (n = 5/sex), P5 (n = 6/sex) and young adult (P47 female, n = 3; P52 male, n = 3) transgenic rats. a Total TG-GnRH neuronal number was decreased in P0 and P5 stages compared to P47-P52 stage. b Number of IF-GnRH neurons did not differ across age and gender. c GnRH promoter activity expressed as Tg-GnRH/IF-GnRH neuron ratios was increased in the P42-P52 stage compared to the early P0 and P5 stages. Rostral to caudal distribution of TG-GnRH and IF-GnRH neurons in P0 (d–e) and P5 (f–g) male and female, plotted as the number of GnRH neurons in series of 180 μm thickness aligned by organum vasculosom of the lamina terminalis (OVLT). Increased TG-GnRH neuronal number was observed in the rostral region (−540 μm from the OVLT) and IF-GnRH neurons (−1800 μm from the OVLT) in P0 females. h–i Rostral to caudal distribution of TG-GnRH and IF-GnRH neurons in P47-52 stages, plotted as GnRH neuronal number in series of 250 μm thickness aligned by the OVLT. Gender difference was not observed in the distribution of TG-GnRH and IF-GnRH neurons in P47-P52 stages. Data are represented by the mean ± SEM for each group. *, P < 0.05; ***, P < 0.001
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Fig3: Distribution of the GnRH neurons in P0 (n = 5/sex), P5 (n = 6/sex) and young adult (P47 female, n = 3; P52 male, n = 3) transgenic rats. a Total TG-GnRH neuronal number was decreased in P0 and P5 stages compared to P47-P52 stage. b Number of IF-GnRH neurons did not differ across age and gender. c GnRH promoter activity expressed as Tg-GnRH/IF-GnRH neuron ratios was increased in the P42-P52 stage compared to the early P0 and P5 stages. Rostral to caudal distribution of TG-GnRH and IF-GnRH neurons in P0 (d–e) and P5 (f–g) male and female, plotted as the number of GnRH neurons in series of 180 μm thickness aligned by organum vasculosom of the lamina terminalis (OVLT). Increased TG-GnRH neuronal number was observed in the rostral region (−540 μm from the OVLT) and IF-GnRH neurons (−1800 μm from the OVLT) in P0 females. h–i Rostral to caudal distribution of TG-GnRH and IF-GnRH neurons in P47-52 stages, plotted as GnRH neuronal number in series of 250 μm thickness aligned by the OVLT. Gender difference was not observed in the distribution of TG-GnRH and IF-GnRH neurons in P47-P52 stages. Data are represented by the mean ± SEM for each group. *, P < 0.05; ***, P < 0.001
Mentions: The total numbers of IF-GnRH and TG-GnRH neurons in the forebrain region of the transgenic rats across the postnatal developmental stages were counted in serial sections collected from the caudal olfactory bulb to the ME. The original raw count of IF-GnRH and TG-GnRH neurons showed similar results to the corrected GnRH cell count across postnatal development in the intact transgenic rat brains. The total number of TG-GnRH neurons varied significantly across postnatal developmental stages [F (2, 22) = 229.61, P < 0.001] (Fig. 3a) but no gender difference or gender–age interaction was detected. Tukey post-hoc comparisons revealed significant decrease (P < 0.001) in the number of TG-GnRH neurons in the P0 stages (female: 158.9 ± 11.0; male: 115.5 ± 16.7) and P5 (female: 88.8 ± 12.9; male: 67.5 ± 8.2) compared to the young adult stages (P47 female: 710.3 ± 38.6; P52 male: 667.3 ± 94.8). However, there was no difference in the total number of IF-GnRH neurons taken from the same serial sections of transgenic rats across the age group and gender (Fig. 3b). Promoter activity of GnRH neurons across the postnatal developmental stages was expressed as TG-GnRH/IF-GnRH cell ratio (Fig. 3c). The TG-GnRH/IF-GnRH cell ratio varied across postnatal developmental stages [F (2, 22) = 638.30, P < 0.001] and gender [F (1, 22) = 8.28, P < 0.01] but no gender-age interaction was detected. Tukey post-hoc comparisons revealed a significant decrease (P < 0.001) in the TG-GnRH/IF-GnRH cell ratio in the P0 (female: 0.17 ± 0.01; male: 0.14 ± 0.02) and P5 (female: 0.10 ± 0.01; male: 0.08 ± 0.01) compared to the young adult stages (P47 female: 0.91 ± 0.01; P52 male: 0.81 ± 0.06). The TG-GnRH/IF-GnRH cell ratio in the P5 stages was also decreased (P < 0.05) compared to the P0 stages.Fig. 3

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