Increased food intake stimulates GnRH-I, glycoprotein hormone alpha-subunit and follistatin mRNAs, and ovarian follicular numbers in laying broiler breeder hens.

The aim of this study, in 36 week-old laying broiler breeder hens, was to establish the effects on reproductive neuroendocrine gene expression of reinstating ad libitum food intake after moderate food restriction from 2 weeks of age. Seven days of ad libitum feeding increased the number of large pre-ovulatory ovarian follicles and gonadotropin releasing hormone-I (GnRH-I), glycoprotein hormone alpha-subunit and follistatin mRNAs. Plasma luteinizing hormone (LH) was also increased while plasma follicle-stimulating hormone (FSH) was reduced. There were no associated changes in gonadotropin inhibitory hormone (GnIH), LHbeta or FSHbeta mRNAs. The mechanism underlying the increased expression of alpha-subunit and follistatin mRNAs was investigated in vitro by incubating pituitary fragments with pulses of GnRH-I. This treatment increased alpha-subunit and follistatin mRNAs but did not affect gonadotropin beta-subunit mRNAs. It is concluded that lifting food restriction in laying hens increases GnRH-I gene transcription or mRNA stability which may be a consequence, or cause of increased GnRH-I release. This, in turn, increases glycoprotein hormone alpha-subunit and follistatin mRNAs, resulting in increased plasma LH and decreased plasma FSH, respectively.

Changes in reproductive neuroendocrine mRNAs with decreasing ovarian function in ageing hens.

Egg production declines with advancing age in the domestic chicken and this is particularly pronounced in breeding stocks of meat type hens (broiler breeders). The objective of this study was to establish whether declining egg production with reproductive ageing in broiler breeders is correlated with plasma LH and FSH, and with mRNAs encoding hypothalamic gonadotrophin-releasing hormone-I (GnRH-I), gonadotrophin inhibitory hormone (GnIH), and gonadotrophin subunits. Comparisons were made between hens at the peak of egg laying (young: 30 weeks) and at the end of a laying year (old: 60 weeks). Old hens were subdivided into laying and out-of-lay groups. Plasma LH and FSH were lower in old than in young laying hens. Compared with old laying hens, old out-of-lay hens had significantly increased plasma FSH but not plasma LH. There were no differences in total hypothalamic GnRH-I and GnIH mRNAs between young and old hens. In old laying hens, the decrease in plasma LH was correlated with decreased gonadotrophin alpha-subunit but not LHbeta mRNAs. The decrease in plasma FSH was not associated with a change in FSHbeta mRNA. In old out-of-lay hens, the increase in plasma FSH was correlated with increased FSHbeta mRNA, while unchanged plasma LH was associated with increased LHbeta mRNA. A regression analysis of all plasma gonadotrophin and gonadotrophin subunit mRNA data collected from the study demonstrated that plasma LH is correlated with alpha-subunit but not LHbeta mRNAs, while plasma FSH is correlated with FSHbeta but not alpha-subunit mRNAs. It is concluded that the decrease in the rate of lay in ageing broiler breeders is not correlated with decreased GnRH-I mRNA nor with increased GnIH mRNA, but it is related to a decrease in alpha-subunit mRNA which may account for the associated reduction in plasma LH but not FSH.

Gonadotrophin inhibitory hormone depresses gonadotrophin alpha and follicle-stimulating hormone beta subunit expression in the pituitary of the domestic chicken.

Studies performed in vitro suggest that a novel 12 amino acid RF amide peptide, isolated from the quail hypothalamus, is a gonadotrophin inhibitory hormone (GnIH). The aim of the present study was to investigate this hypothesis in the domestic chicken. Injections of GnIH into nest-deprived incubating hens failed to depress the concentration of plasma luteinizing hormone (LH). Addition of GnIH to short-term (120 min) cultures of diced pituitary glands from adult cockerels depressed follicle-stimulating hormone (FSH) and LH release and depressed common alpha and FSHbeta gonadotrophin subunit mRNAs, with no effect on LHbeta subunit mRNA. Hypothalamic GnIH mRNA was higher in incubating (out-of-lay) than in laying hens, but there was no significant difference in the amount of hypothalamic GnIH mRNA in out-of-lay and laying broiler breeder hens at the end of a laying year. It is concluded that avian GnIH may play a role in controlling gonadotrophin synthesis and associated constitutive release in the domestic chicken.

Incidence and significance of cryptic chromosome aberrations detected by fluorescence in situ hybridization in acute myeloid leukemia with normal karyotype.

To better define the incidence and significance of cryptic chromosome lesions in acute myeloid leukemia (AML), fluorescence in situ hybridization (FISH) studies were performed in interphase cells and, when appropriate, in metaphase cells and in morphologically intact BM smears. Fifty-five adult de novo AML (group A) and 27 elderly AML or AML after myelodysplastic syndrome (AML-MDS) (group B) were tested using probes detecting the following anomalies: -5, -7, +8, deletions of 5q31, 7q31, 12p13/ETV6, 17p13/p53, 20q11. All the patients had a normal karyotype in more than 20 cells and tested negative for the common AML-associated fusion genes. No patient in group A was found to carry occult chromosome anomalies, whereas 8/27 patients in group B (P < 0.0001) showed 5q31 or 7q31 deletion (three cases each), a 17p13/p53deletion or trisomy 8 (one case each) in 33-60% interphase cells. Metaphase cells showed only one hybridization signal at 5q31 (three cases) and 7q31 (one case), whereas two normal signals at 7q31 and chromosome 8 centromeres were seen in two patients with 7q deletion and trisomy 8 in interphase cells. The majority of blast cells (76-94%) carried the chromosome anomaly in all cases; erythroid involvement in a minority of cells was seen in three patients. In group B, the presence of occult chromosome anomalies was associated with exposure to myelotoxic agents in the workplace (5/8 cases vs 3/19, P = 0.026) and with a lower complete remission rate (0/6 patients vs 7/12, P = 0.024). We arrived at the following conclusions: (1) cryptic chromosome deletions in the order of a few hundred kb magnitude may be found in a fraction of elderly AML or MDS-related AML and not in de novo adult AML with normal karyotype; (2) these chromosome lesions are usually represented by submicroscopic rearrangements; (3) they display a specific pattern of cell-lineage involvement arguing in favor of their role in the outgrowth of the leukemic blast cells; (4) they are associated with a history of exposure to myelotoxic agents in the workplace and, possibly, with resistance to induction treatment.