Morphometric Analysis of Foilicular Development in the Rat

Hirshfield, Anne N.; Midgley, A. Rees

doi:10.1095/biolreprod19.3.597

Cited by 244 publications

(179 citation statements)

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“…The ovarian weights at 5 mo of age of the control (n ϭ 12) and cycling GPR-4 transgenic females (n ϭ 6) were not different; however, the ovarian weight of the noncycling females (n ϭ 6) was significantly decreased (31.7 Ϯ 4, 31.4 Ϯ 6, 20.7 Ϯ 6 mg͞100 g body weight, respectively). By histological evaluation of hematoxylin͞eosin-stained sections, the ovaries from controls contained large numbers of corpora lutea and developing follicles, as seen in normal rats (29) (Fig. 5).…”

Section: Resultsmentioning

confidence: 68%

Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats

Paruthiyil

Majdoubi

Conti

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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Experiments in the GT1 gonadotropin-releasing hormone (GnRH) cell line have shown that the cAMP signaling pathway plays a central role in regulating the excitability of the cells. Lowering cAMP levels by expressing the constitutively active cAMP-specific phosphodiesterase PDE4D1 in GT1 cells inhibited spontaneous Ca 2؉ oscillations and intrinsic pulsatile GnRH secretion. To address the role of cAMP levels in endogenous GnRH neurons, we genetically targeted expression of PDE4D1 (P) to GnRH neurons in transgenic rats (R) by using the GnRH gene promoter͞enhancer regions (G). Three lines of transgenic rats, GPR-2, -4, and -5, were established. In situ hybridization and RT-PCR studies demonstrated that transgene expression was specifically targeted to GnRH neurons. Decreased fertility was observed in female but not in male rats from all three lines. The mean luteinizing hormone (LH) levels in ovariectomized rats were significantly reduced in the GPR-4 and -5 lines but not in the GPR-2 line. In castrated male and female GPR-4 rats, the LH pulse frequency was dramatically reduced. Six of twelve GPR-4 females studied did not ovulate and had polycystic ovaries. The remaining six females ovulated, but the magnitude of the preovulatory LH surge was inhibited by 63%. These findings support the hypothesis that cAMP signaling may play a central role in regulating excitability of GnRH neurons in vivo. The GPR-4 line of transgenic rats provides a genetic model for the understanding of the role of pulsatile gonadotropin release in follicular development.T he pulsatile release of gonadotropin-releasing hormone (GnRH) underlies reproductive function in male and female mammals. Understanding the molecular mechanisms regulating pulsatile GnRH secretion has been hampered by the low number of GnRH neurons and their scattered localization throughout the preoptic area in rodents. Further complicating the understanding of these questions is the complexity of the neural connectivity of GnRH neurons. The development of the highly differentiated GT1 GnRH neuronal cell lines (1) and the demonstration that pulsatile release was an intrinsic property of the cells provided a model to study molecular events underlying pulsatile GnRH release (2-4). However, one is always faced with the problem of translating findings from an immortalized cell line to the physiological setting. We have attempted to bridge observations made in GT1 cells regarding signaling events regulating GnRH pulsatility to the physiological setting by developing a transgenic rat model. We used an established genetic approach to alter the activity of a signaling pathway that could be used in parallel experiments in GT1 cells and transgenic rats. Transgenic rats, unlike transgenic mice, permit the reliable analysis of pulsatile luteinizing hormone (LH) release that closely mimics pulsatile GnRH release in castrated animals (5).The secretion of GnRH in GT1 neurons is stimulated by elevations in cAMP levels (6-8). The stimulation of GnRH secretion by elevated cAMP levels appears to...

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Section: Resultsmentioning

confidence: 68%

Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats

Paruthiyil

Majdoubi

Conti

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

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“…According to Hirshfield & Midgley (1978) it takes a small antral follicle in the rat 3^1 days to grow to ovulatory size. Our study therefore indicates that normal numbers of follicles grew through from the small antral stage in the absence of any adrenergic innervation.…”

Section: Discussionmentioning

confidence: 99%

Ovulation after sympathetic denervation of the rat ovary produced by freezing its nerve supply

Wylie¹,

Roche²,

Gibson³

1985

Reproduction

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Summary. The ovaries of cyclic female rats were unilaterally or bilaterally denervated or sham-operated. Denervation was achieved by freezing the ovarian vascular pedicle and suspensory ligament about 1 cm from the ovary; this technique renders the ovary devoid of innervation for up to 10 days. Denervated ovaries from 6 unilaterally and 7 bilaterally operated animals exhibited normal ovulation rates (5\m=.\8\ m=+-\1\m=.\0and 5\m=.\2\ m=+-\1\ m=. \ 2 respectively, mean \m=+-\ s.e.m.) compared with intact (5\m=.\6 \m=+-\ 0\m=.\4) and sham-operated controls (4\m=.\4 \m=+-\ 0\m=.\6unilaterally sham-operated; 4\m=.\1\ m=+-\ 0\m=.\8 bilaterally sham-operated). It is concluded that the mechanism of follicular rupture is unaffected by the absence of ovarian sympathetic innervation.

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“…Preantral follicles (PAF) present an oocyte surrounded by two to four layers of GC and are 120-200 mm in diameter, whereas a small antral cavity and a thin theca layer can be distinguished in early antral follicles (EAF), which are about 300-400 mm in diameter. The oocyte becomes acentrically displaced by the developing antrum in preovulatory follicles (PF), which present a well-defined and thick granulosa layer and are more than 450 mm in diameter (Hirshfield & Midgley 1978).…”

Section: Follicular Granulosa and Theca Cells Express Fmrp At All Stamentioning

confidence: 99%

Expression of fragile X mental retardation protein and Fmr1 mRNA during folliculogenesis in the rat

et al. 2013

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Fragile X mental retardation protein (FMRP) belongs to a small family of RNA-binding proteins. Its absence or inactivity is responsible for fragile X syndrome, the most common cause of inherited mental retardation. Despite its ubiquitous expression, FMRP function and expression remain almost understudied in non-neuronal tissues, though previous studies on germline development during oogenesis may suggest a special function of this protein also in ovarian tissue. In addition, the well-documented association of FMR1 premutation state with fragile X-related premature ovarian insufficiency adds interest to the role of FMRP in ovarian physiology. The aim of the present work was to investigate the expression of Fmr1 mRNA and its protein, FMRP, at different stages of rat follicular development. By immunohistochemical studies we demonstrated FMRP expression in granulosa, theca and germ cells in all stages of follicular development. In addition, changes in Fmr1 expression, both at the protein and mRNA levels, were observed. FMRP levels increased upon follicular development while preantral and early antral follicles presented similar levels of Fmr1 transcripts with decreased expression in preovulatory follicles. These observations suggest that Fmr1 expression in the ovary is regulated at different and perhaps independent levels. In addition, our results show expression of at least four different isoforms of FMRP during all stages of follicular growth with expression patterns that differ from those observed in brain and testis. Our study shows a regulated expression of Fmr1, both at mRNA and protein levels, during rat follicular development.

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Morphometric Analysis of Foilicular Development in the Rat

Cited by 244 publications

References 10 publications

Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats

Phosphodiesterase expression targeted to gonadotropin-releasing hormone neurons inhibits luteinizing hormone pulses in transgenic rats

Ovulation after sympathetic denervation of the rat ovary produced by freezing its nerve supply

Expression of fragile X mental retardation protein and Fmr1 mRNA during folliculogenesis in the rat

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