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Comment |
Piontkewitz Y et al collected ovaries from immature rats before and
at different time points after PMSG (0, 6, 24, and 48 h) and hCG (0.25, 1, 3, 10, and 24 h) treatment for
analyses of the contents of C/EBP alpha mRNA and protein and the cell-specific immunohistochemical
localization of the protein. C/EBP alpha mRNA increased to maximal levels 24 h after PMSG treatment.
C/EBP alpha
mRNA decreased 10 h after hCG treatment and increased again in newly formed corpora lutea.
Immunohistochemistry and immunoblotting demonstrated a similar increase in C/EBP alpha during
follicular development. To examine the involvement of specific hormones in the regulation of C/EBP
alpha, hypophysectomized immature rats were injected sequentially with estradiol and FSH. This
treatment resulted in a substantial increase in C/EBP alpha mRNA and protein. These results demonstrate
that C/EBP alpha is hormonally regulated in the ovary and suggest a role for C/EBP alpha during
differentiation of ovarian cells and follicular development.
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Mutations |
2 mutations
Species: mouse
Mutation name: None
type: null mutation
fertility: infertile - ovarian defect
Comment: Flodby et al. (1996) made transgenic knockout mice in which the CEBPA gene was selectively disrupted. The
homozygous mutant Cebpa -/- mice died, usually within the first 20 hours after birth and had defects in the control of
hepatic growth and lung development.
Piontkewitz Y et al explored the function of C/EBPalpha in the rat ovary. To
achieve this, the expression of C/EBPalpha in follicular cells was attenuated in vivo by the local
administration of antisense oligonucleotides (AS) into the ovarian bursa, i.e., the sac-like structure
surrounding the ovary of immature rats. This administration resulted in an impaired response to
subsequent injections of exogenous gonadotropins (PMSG, hCG) with an attenuated expression of
C/EBPalpha protein and finally a decreased ovulation rate. Thus, C/EBPalpha seems to be a necessary factor for follicular development in the rat ovary.
Species: mouse
Mutation name: None
type: null mutation
fertility: subfertile
Comment: CCAAT/Enhancer-Binding Proteins (C/EBP)-{alpha} and -{beta} Are Essential for Ovulation, Luteinization, and the Expression of Key Target Genes. Fan HY et al. LH activation of the epidermal growth factor receptor/RAS/ERK1/2 pathway is essential for ovulation and luteinization because granulosa cell (GC) depletion of Erk1/2 (Erk1/2(gc-/-) mice) renders mice infertile. As mediators of ERK1/2-dependent GC differentiation, the CCAAT/enhancer-binding proteins, (C/EBP)a and C/EBP? were also disrupted. Female Cebpb(gc-/-) mutant mice, but not Cebpa(gc-/-) mice, were subfertile whereas Cebpa/b(gc-/-) double-mutant females were sterile. Follicles failed to ovulate, ovaries were devoid of corpora lutea, luteal cell marker genes (Lhcgr, Prlr, Ptgfr, Cyp11a1, and Star) were absent, and serum progesterone levels were low. Microarray analyses identified numerous C/EBPa/?target genes in equine chorionic gonadotropin (eCG)-human (h)CG-treated mice. At 4 h post-hCG, a subset (19%) of genes altered in the Cebpa/b-depleted cells was also altered in Erk1/2-depleted cells; hence they are common effectors of ERK1/2. Additional genes down-regulated in the Cebpa/b-depleted cells at 8 and 24 h post-hCG include known (Akr1b7, Runx2, Star, Saa3) and novel (Abcb1b, Apln, Igfbp4, Prlr, Ptgfr Timp4) C/EBP targets and effectors of luteal and vascular cell development. Bhmt, a gene controlling methionine metabolism and thought to be expressed exclusively in liver and kidney, was high in wild-type luteal cells but totally absent in Cebpa/b mutant cells. Because numerous genes potentially associated with vascular development were suppressed in the mutant cells, C/EBPa/?appear to dictate the luteinization process by also controlling genes that regulate the formation of the extensive vascular network required to sustain luteal cells. Thus, C/EBPa/?mediate the terminal differentiation of GCs during the complex process of luteinization.
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