Avoidance by host tissues of attack by autologous complement proteins is dependent in part on the activities of
membrane regulatory factors. One molecule involved in this control is a 70-kD glycoprotein termed decay-accelerating
factor (DAF). Interruption by DAF of the complement sequence at an early step in activation effectively halts
progression of the cascade and prevents consequent cell injury. In man, DAF is expressed on the plasma membrane of
all cell types that are in intimate contact with plasma complement proteins.
General function
Ligand
Comment
Cellular localization
Plasma membrane
Comment
Ovarian function
Ovulation, Oogenesis
Comment
Decay-accelerating factor in the periovulatory rat ovary Gieske MC, et al .
One of the most prominent inflammatory reactions is the activation of the complement system. The activated complement system does not distinguish between pathogens and the host cell. In order to prevent autologous complement-mediated attack, host cells express a variety of both membrane-bound and fluid-phase complement regulatory proteins which control activity of the complement cascade by acting on convertase enzymes or the membrane-attack complex. Although the process of ovulation is facilitated by the inflammatory reaction, this reaction has the potential to cause serious damage to growing follicles, ovulated follicles, and other important ovarian tissues. This study was undertaken to characterize the expression and regulation of decay-accelerating factor (DAF), a complement regulator, as a potential mediator of ovarian tissue protection from ovulatory inflammation. DNA microarray and Northern blot analyses showed that an ovulatory gonadotropin stimulus dramatically yet transiently induced DAF mRNA expression in the immature rat ovary. Northern blot and PCR analyses revealed that of the three known DAF isoforms, glycosylphosphatidylinositol (GPI)-, soluble-, and transmembrane-(TM) DAF, GPI-DAF was the predominant form. In situ hybridization localized GPI-DAF mRNA expression in the theca-interstitial cells of the periovulatory ovary. Neither the anti-progestin RU486 nor the cyclooxygenase inhibitor indomethacin significantly inhibited human chorionic gonadotropin (hCG)-induced GPI-DAF mRNA expression in vivo. In vitro theca cell culture studies indicated that hCG induces GPI-DAF mRNA expression through the protein kinase A pathway. This study suggests that gonadotropin-induced GPI-DAF may be involved in the protection of ovarian tissues from the potential attack by the complement system activated by the inflammatory response associated with ovulation.
Expression regulated by
LH
Comment
[P2-252] Involvement of Complement System in the Ovulation.
Giyoun Na, Mary C Gieske, CheMyong Ko, Yongbum Koo. Sch of Biotechnology and Biomed Sci, Inje Univ, Gimhae, Republic of Korea; Clin Scis, Univ of Kentucky, Lexington, KY
It is well known that the ovulation is an inflammatory-like process, which may involve the activation of complement system. Complement system is composed of various proteins that are sequentially activated by inflammatory signal resulting in the formation of membrane attack complex (MAC), which disrupts various types of cell membranes. At the site of inflammatory reaction, on the other hand, host cells produce regulators of complement systems which inhibit the MAC formation. In order to see whether complement system is involved in the ovulatory process, expression patterns of the membrane bound forms of regulators of complement activation (RCA) were examined in the periovulatory stage ovaries. For this purpose, a rat ovarian gene expression database (rOGED) was used. rOGED provides quantitative temporal mRNA expression profiles of 31,000 genes at ovarian (OVA), granulosa cell (GC), and non-granulosa/oocyte ovarian tissue (NGO) levels at various stages of follicular development (Abstract #852214). Of the three main types of RCAs, rOGED detected the expressions of mRNAs for membrane inhibitor of reactive lysis (CD59) and decay accelerating factor (DAF; CD55), but not membrane co-factor protein (MCP). CD59 mRNA was expressed both in GC and NGO all over the time points examined, with the peak expression at 12 h post treatment hCG. Expression of DAF mRNA was dramatically, yet transiently increased at 6 h post hCG treatment. Ten fold higher expression of DAF mRNA was detected in NGO than in GC at all time points examined. Northern blot analyses have confirmed the tissue- and time-dependent expression patterns of the rOGED data. We further examined the expression patterns of the various components of complement system. Surprisingly, within 6 hours of hCG treatment, two fold increase in mRNA expression was observed in the mRNAs for C1q , C3 and C4 proteins. Interestingly, those components were detected only in the NGO, except C1 that is expressed both in GC and NGO. The ovulatory inflammatory reaction is known to facilitate the process of follicle rupture. The inflammatory reaction, however, may give serious damages to the growing follicles, ovulated follicles and other important ovarian tissues. Present study strongly indicates that complement system may be involved in the ovulatory inflammation and the RCAs are expressed to protect ruptured follicles as well as other parts of the ovarian tissues from the potential attack by the complement system.
Ovarian localization
Oocyte, Granulosa, Theca
Comment
Sasson R, et al 2003 reported novel genes modulated by FSH in normal and immortalized FSH-responsive
cells and new insights into the mechanism of FSH action.
Follicle-stimulating hormone (FSH) controls the development of follicle-enclosed oocytes in the
mammalian ovary by interacting with specific receptors located exclusively on granulosa cells. Its
biological activity involves stimulation of intercellular communication, intracellular signaling, and
up-regulation of steroidogenesis; the entire spectrum of genes regulated by FSH is not yet fully
characterized. The authors have established monoclonal rat FSH-responsive granulosa cell lines that
express FSH receptors at 20-fold higher rates than with primary cells, and thus increased the
probability of yielding a distinct spectrum of genes modulated by FSH. Using Affymetrix DNA
microarrays, they discovered 11 genes not reported earlier to be up-regulated by FSH and 9 genes
not reported earlier to be down-regulated by FSH. Modulation of signal transduction associated
with G-protein signaling, phosphorylation of proteins, and intracellular-extracellular ion balance
was suggested by up-regulation of decay accelerating factor GPI-form precursor (DAF), membrane
interacting protein RGS16, protein tyrosine phosphatase (PTPase), oxidative stress-inducible protein tyrosine phosphatase (OSIPTPase), and down-regulation of rat prostatic acid phosphatase
(rPAP), Na+, K+-ATPase, and protein phosphatase 1beta. Elevation in granzyme-like proteins 1
and 3, and natural killer (NK) cell protease 1 (NKP-1) along with reduction in carboxypeptidase E
indicates possible FSH-mediated preparation of the cells for apoptosis.
Follicle stages
Secondary, Antral, Preovulatory
Comment
Decay accelerating factor (DAF, CD55) expressed in human reproductive organs
and gametes is thought to play a pivotal role in protection against autologous
complement activation in the genital tract. To investigate the role of
DAF in reproduction, He C, et al 2000 studied decay accelerating factor in guinea-pig reproductive organs and analysed DAF distribution in reproductive organs using
guinea-pigs that express multiple DAF isoforms. In females,
DAF was detected on the plasma membranes of oocytes through follicle
development and on the apical region of uterine epithelium.