Expression of vascular endothelial growth factor (VEGF) and its receptors in human endometrium throughout the menstrual cycle and in early pregnancy.

Immunohistochemistry for vascular endothelial growth factor (VEGF) and its receptors, fms-like tyrosine kinase (flt-1) and kinase insert domain-containing region (KDR), was performed on human endometrium obtained from patients with normal menstrual cycles, patients given oestrogen and progesterone, and women in early pregnancy. Intense immunostaining of VEGF was observed in both glandular epithelial and stromal cells during the mid-secretory phase; the immunostaining intensity was increased by administration of oestrogen plus progesterone and strong immunostaining was observed in decidual cells of early pregnancy. In addition to the immunostaining in vascular endothelial cells, strong KDR immunostaining was observed in glandular epithelial cells and in decidualized stromal cells induced by administration of oestrogen plus progesterone, whereas flt-1 immunostaining was negligible. Strong immunostaining for flt-1 and KDR was found in both vascular endothelial cells and decidual cells in early pregnancy. Endometrial stromal cells isolated from proliferative phase endometrium were incubated with oestrogen (10(-8) mol l-1) and medroxyprogesterone acetate (MPA; 10(-6) mol l-1) for 18 days to study the regulation of VEGF, flt-1 and KDR in endometrial stromal cells by oestrogen and progesterone. Expression of VEGF and KDR mRNAs was increased significantly by oestrogen and MPA, accompanied by decidualization, whereas flt-1 mRNA expression was not affected. In conclusion, VEGF and its receptors may play important roles in implantation and maintenance of pregnancy.

Expression of vascular endothelial growth factor (VEGF) receptors in rat corpus luteum: regulation by oestradiol during mid-pregnancy.

The aim of this study was to investigate the expression of vascular endothelial growth factor (VEGF) receptors, the fms-like tyrosine kinase (flt-1) and kinase insert domain-containing region (KDR), in corpora lutea obtained at different stages of the oestrous cycle and during pregnancy in rats. Immunohistochemistry revealed that both flt-1 and KDR were localized in luteal cells in addition to vascular endothelial cells, and that the intensity of staining was stronger in pregnant rats than in cyclic rats. Rats undergoing hypophysectomy-hysterectomy on day 12 of pregnancy were treated with oestradiol until day 15 of pregnancy to determine whether oestradiol is involved in expression of flt-1 and KDR mRNA in the corpus luteum during mid-pregnancy. The flt-1 and KDR mRNA contents in the corpus luteum were decreased significantly by hypophysectomy-hysterectomy, and these decreases recovered significantly after oestradiol treatment. Changes in the mass of the corpus luteum and serum progesterone concentrations paralleled the changes in expression of flt-1 and KDR mRNA. Developmental studies indicated that flt-1 and KDR mRNA contents in the corpus luteum were constant until day 15 of pregnancy but decreased significantly on day 21 of pregnancy. In conclusion, both flt-1 and KDR were expressed in luteal cells in addition to vascular endothelial cells, and expression was upregulated by oestradiol during mid-pregnancy. flt-1 and KDR may play a role in development of the corpus luteum and in production of progesterone during mid-pregnancy in rats.

Induction of manganese superoxide dismutase by tumour necrosis factor-alpha in human endometrial stromal cells.

The present study was undertaken to investigate the effect of tumour necrosis factor-alpha (TNFalpha) on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC) and to determine whether there is a difference in responsiveness to TNFalpha between ESC and decidualized ESC. TNFalpha increased manganese-SOD (Mn-SOD) mRNA level and Mn-SOD activity in a dose-dependent manner in ESC. The concentration of TNFalpha required for an effect was lower for decidualized ESC than for non-decidualized ESC. TNFalpha had no effect on copper-zinc-SOD (Cu,Zn-SOD) expression in either type of cell. Incubation of ESC with actinomycin D, an RNA synthesis inhibitor, blocked TNFalpha-induced Mn-SOD mRNA expression, but cycloheximide, a protein synthesis inhibitor, had no effect. H7, an inhibitor of protein kinase C (PKC), also inhibited TNFalpha-stimulated Mn-SOD mRNA expression in both types of cells. These findings suggest that TNFalpha-induced Mn-SOD expression is regulated at the transcription level and mediated by PKC-dependent phosphorylation and that de-novo protein synthesis is not required for the TNFalpha effect. In summary, TNFalpha induces Mn-SOD expression in human ESC. This phenomenon may be important for protection of ESC from cytokine-mediated oxidative stress.

Reactive oxygen species stimulate prostaglandin F2 alpha production in human endometrial stromal cells in vitro.

BACKGROUND: The present study was undertaken to investigate the effect of reactive oxygen species on prostaglandin F2 alpha (PGF2 alpha) production by human endometrial stromal cells (ESC). METHODS AND RESULTS: Isolated ESC were incubated with hydrogen peroxide, which induces lipid peroxidation. Hydrogen peroxide increased both intracellular and medium concentrations of PGF2 alpha (P < 0.01). A time course study showed that hydrogen peroxide significantly increased PGF2 alpha concentrations in the medium after 6 h incubation (P < 0.01), after which no further increase was observed. To study whether the increase in PGF2 alpha production caused by hydrogen peroxide was mediated by cyclooxygenase, ESC were incubated with indomethacin (0.5 microg/ml), an inhibitor of cyclooxygenase, in the presence of hydrogen peroxide. Indomethacin significantly blocked the increases in PGF2 alpha production caused by hydrogen peroxide (P < 0.01). Hydrogen peroxide also increased PGF2 alpha production by decidualized ESC (P < 0.01), induced by the incubation with medroxyprogesterone acetate (10(-6) mol/l) and oestradiol (10(-8) mol/l). CONCLUSIONS: Reactive oxygen species stimulate PGF2 alpha production in ESC, suggesting that they might influence endometrial function by regulating PGF2 alpha production.

Changes of serum melatonin level and its relationship to feto-placental unit during pregnancy.

Serum melatonin concentrations were studied in normal pregnant women and in women with several types of pathologic pregnancies, e.g., twins, preeclampsia or intrauterine growth retardation (IUGR). Blood samples were collected from the maternal antecubital vein at 14:00 hr (daytime) and 02:00 hr (nighttime) during pregnancy, and also from the umbilical vein and artery immediately after delivery. Serum melatonin concentrations were measured by radioimmunoassay. Daytime serum melatonin levels in normal (single fetus; singleton) pregnancies were low. While the levels showed an increasing tendency toward the end of pregnancy, no statistically significant changes occurred. On the other hand, the nighttime serum melatonin levels increased after 24 weeks of gestation, with significantly (P < 0.01) high levels after 32 weeks; these values decreased to non-pregnant levels on the 2nd day of puerperium. Nighttime serum melatonin levels were significantly (P < 0.05) higher in twin pregnancies after 28 weeks of gestation than in singleton pregnancies, whereas the patients with severe preeclampsia showed significantly (P < 0.05) lower serum melatonin levels than the mild preeclampsia or the normal pregnant women after 32 weeks of gestation. Melatonin concentrations in umbilical vessels showed a higher tendency in neonates who were born during at night compared with the other neonates; moreover, those in the umbilical artery were generally higher than those in the umbilical vein. The present results indicate that in humans, the maternal serum melatonin levels show a diurnal rhythm, which increases until the end of pregnancy, reflecting some pathologic states of the feto-placental unit. Fetuses may produce melatonin with a circadian rhythm.

Regulation and role of vascular endothelial growth factor in the corpus luteum during mid-pregnancy in rats.

The present study was undertaken to investigate the role of vascular endothelial growth factor (VEGF) in luteal angiogenesis and the regulation of VEGF in the corpus luteum (CL) during mid-pregnancy in rats. Protein concentrations and mRNA levels of VEGF in the CL significantly increased from Day 9 to Day 12 and remained at the same level as Day 12 until Day 15. To study whether estradiol is involved in VEGF expression between Day 12 and Day 15, rats undergoing hypophysectomy-hysterectomy on Day 12 were treated with estradiol until Day 15. Protein concentrations and mRNA levels of VEGF in the CL were significantly decreased by hypophysectomy-hysterectomy, and this inhibitory effect was completely reversed by estradiol treatment. Changes in vascular density in the CL were parallel to those in VEGF expression. To examine whether the effect of estradiol is mediated by VEGF, anti-VEGF antibody was administered to hypophysectomized-hysterectomized rats simultaneously with estradiol. The recovery in the vascular density, CL weight, and serum progesterone concentration caused by estradiol was significantly inhibited by the anti-VEGF antibody treatment. In conclusion, the present study has demonstrated that VEGF contributes to luteal angiogenesis, CL development, and progesterone production during mid-pregnancy in rats and that luteal VEGF expression is increased by estradiol.

Expression of Bcl-2 and Bax in the human corpus luteum during the menstrual cycle and in early pregnancy: regulation by human chorionic gonadotropin.

To investigate the relationship between apoptosis and the Bcl-2/ Bax system in the human corpus luteum (CL), the frequency of apoptosis and expression of Bcl-2 and Bax were examined in the CL during the menstrual cycle and in early pregnancy. In situ analysis of DNA fragmentation showed that the number of apoptotic cells was much greater in the regressing CL than that in the midluteal phase CL, whereas there were almost no apoptotic cells in the CL of early pregnancy. Immunohistochemistry revealed that Bcl-2 expression was observed in the luteal cells in the midluteal phase and early pregnancy, but not in the regressing CL. In contrast, Bax immunostaining was observed in the regressing CL, but not in the midluteal phase and early pregnancy. bcl-2 messenger ribonucleic acid (mRNA) levels in the CL during the menstrual cycle were highest in the midluteal phase and lowest in the regressing CL. In the CL of early pregnancy, bcl-2 mRNA levels were significantly higher than those in the midluteal phase. In contrast, bax mRNA levels were highest in the regressing CL and remarkably low in the CL of early pregnancy. Western blot analyses revealed that Bcl-2 expression was significantly lower in the regressing CL than in the midluteal phase and early pregnancy, and that Bax expression was, in contrast, significantly higher in the regressing CL than in the midluteal phase and was remarkably low in the CL of early pregnancy. When corpora lutea of the midluteal phase were incubated with hCG, hCG significantly increased the mRNA and protein levels of Bcl-2 and significantly decreased those of Bax. In conclusion, Bcl-2 and Bax may play important roles in the regulation of the life span of the human CL by controlling the rate of apoptosis. hCG may act to prolong the life span of the CL by increasing Bcl-2 expression and decreasing Bax expression when pregnancy occurs.

Expression of vascular endothelial growth factor and its receptors in the human corpus luteum during the menstrual cycle and in early pregnancy.

To investigate the possible role of vascular endothelial growth factor (VEGF) and its receptors in the human corpus luteum (CL), expression of VEGF and its receptors, the fms-like tyrosine kinase and the kinase insert domain-containing region (KDR), was analyzed in the CL during the menstrual cycle and in early pregnancy. Immunohistochemistry revealed that VEGF was localized in luteal cells and both flt-1 and KDR were also localized in luteal cells, in addition to vascular endothelial cells. Messenger RNA (mRNA) expression of VEGF, flt-1, and KDR remained constant in the CL during the luteal phase and was lower in the regression phase. In the pregnant CL, VEGF mRNA expression was higher compared with that in the midluteal phase, and mRNA expression of both flt-1 and KDR was the same as that in the midluteal phase. Western blot analyses revealed that the change in protein expression of VEGF, flt-1, and KDR was similar to that in their mRNA expression. To study the effect of human CG (hCG) on VEGF expression in the CL, corpora lutea obtained from the midluteal phase were incubated with hCG (1 IU/ml) for 6 h. hCG increased the expression of mRNA and protein of VEGF. In conclusion, VEGF and its receptors may play important roles in development and function of the CL, and VEGF may exert a paracrine-autocrine role in regulating luteal function. hCG may act to prolong the life span of the CL by stimulating VEGF expression when pregnancy occurs.

Decreased superoxide dismutase expression and increased concentrations of lipid peroxide and prostaglandin F(2alpha) in the decidua of failed pregnancy.

To study the possible role of the superoxide radical and its scavenging system in the decidua of early pregnancy, superoxide dismutase (SOD) values and concentrations of lipid peroxide and prostaglandin F(2alpha) (PGF(2alpha)) were analysed in the decidua obtained from normal pregnancy and failed pregnancy. Failed pregnancy was divided into two groups; spontaneous abortion with or without vaginal bleeding. In the spontaneous abortion with vaginal bleeding, total SOD activities, Cu,Zn-SOD activities and Cu,Zn-SOD mRNA values in the decidua were significantly lower, and concentrations of lipid peroxide and PGF(2alpha) were significantly higher, than those in the normal pregnancy and the spontaneous abortion without vaginal bleeding. In contrast, activities and mRNA values of Mn-SOD were significantly higher in the spontaneous abortion with vaginal bleeding than the other two groups. There was no significant difference in all of these parameters between the normal pregnancy and the spontaneous abortion without vaginal bleeding. In conclusion, the decrease in Cu,Zn-SOD expression and the increase in lipid peroxide in the decidua could be involved in the termination of spontaneous abortion, mediated through the increase in PGF(2alpha) synthesis. In other words, Cu,Zn-SOD may contribute to the maintenance of pregnancy by preventing the accumulation of superoxide radicals that cause PGF(2alpha) synthesis.

Induction of superoxide dismutase by decidualization in human endometrial stromal cells.

The present study was undertaken to investigate the effect of decidualization on superoxide dismutase (SOD) expression in human endometrial stromal cells (ESC). To induce decidualization, isolated ESC were incubated with medroxyprogesterone acetate (MPA, 10(-6) mol/l) and oestradiol (10(-8) mol/l) for 23 days. Insulin-like growth factor-binding protein-1 (IGFBP-1) was used as a marker of decidualization. SOD mRNA in ESC was significantly increased on day 12 of the hormone treatment (P < 0.01), which was concomitant with the onset of IGFBP-1 mRNA expression, and further increased until day 23 of the treatment in a manner similar to the change in IGFBP-1 expression. To examine the synergistic effect of human chorionic gonadotrophin (HCG) with MPA and oestradiol on SOD and IGFBP-1 expression, ESC were incubated with HCG in the presence or absence of MPA and oestradiol. HCG had no synergistic effect on SOD and IGFBP-1 expression. SOD activities in the decidualized endometrial tissue obtained from patients given oestradiol and progesterone for 7-10 days were significantly higher than those in the non-decidualized endometrial tissue from patients without the hormone treatment (P < 0.01). In conclusion, SOD expression in ESC was induced by MPA and oestradiol accompanied by decidualization, suggesting that SOD may play important roles in decidualization of ESC.

Rescue of the corpus luteum and an increase in luteal superoxide dismutase expression induced by placental luteotropins in the rat: action of testosterone without conversion to estrogen.

The superoxide radical and its scavenger, superoxide dismutase (SOD), play important roles in the regulation of corpus luteum function. The present study was undertaken to investigate whether SOD is related to pregnancy-induced maintenance of corpus luteum function. Placentae obtained from rats on Day 12 of pregnancy were incubated for 24 h, and the supernatant was used as placental luteotropins. Pseudopregnant rats were given the placental incubation medium from Day 9 to Day 12 of pseudopregnancy. The treatment significantly increased serum progesterone concentrations on Day 12 of pseudopregnancy. Both activities and mRNA levels of copper-zinc SOD (Cu,Zn-SOD) and manganese SOD (Mn-SOD) in the corpus luteum were also increased on Day 12 of pseudopregnancy. Treating the placental incubation medium with charcoal significantly eliminated the stimulatory effects of placental incubation medium on serum progesterone concentrations and luteal Mn-SOD expression, but not on Cu,Zn-SOD expression. The inhibitory effect of the charcoal treatment on luteal Mn-SOD expression was reversed by supplementation with testosterone or dihydrotestosterone (DHT), but serum progesterone concentrations were recovered only by DHT. Testosterone or DHT alone had no effect on serum progesterone concentrations and luteal SOD expression. In conclusion, placental luteotropins increased SOD expression in the corpus luteum and stimulated progesterone production, suggesting that SOD is involved in the maintenance of the corpus luteum function by placental luteotropins. In addition, androgen, with other placental luteotropins, acted to stimulate progesterone production and Mn-SOD expression in pseudopregnant rats.

Superoxide dismutase expression in the human corpus luteum during the menstrual cycle and in early pregnancy.

To investigate the possible role of the superoxide radical and its scavenging system in the human corpus luteum, superoxide dismutase (SOD) values and lipid peroxide concentrations were analysed in the corpora lutea during the menstrual cycle and in early pregnancy. Copper-zinc SOD (Cu,Zn-SOD) activities increased from the early to mid-luteal phase, and gradually decreased thereafter and were the lowest in the regression phase. In pregnant corpus luteum, Cu,Zn-SOD activities were significantly higher than those in the mid-luteal phase. In contrast, manganese SOD (Mn-SOD) activities were low in the mid-luteal phase and increased toward the regression phase. Changes in mRNA expression of both types of SOD were similar to changes in their activities. Lipid peroxide concentrations were the highest in the regression phase whereas they were remarkably low in pregnant corpus luteum. The effects of human chorionic gonadotrophin (HCG) on luteal SOD were studied in vitro. HCG significantly increased Cu,Zn-SOD expression in mid-luteal phase corpora lutea, but not in late luteal phase corpora lutea. In conclusion, the present study suggests that the superoxide radical and its scavenging system, especially Cu,Zn-SOD, play important roles in the regulation of human luteal function. The stimulation of luteal Cu, Zn-SOD expression by HCG may be important in maintaining luteal cell integrity when pregnancy occurs.

Changes in nitric oxide synthase activity in the ovary of gonadotropin treated rats: the role of nitric oxide during ovulation.

Immature rats receiving equine chorionic gonadotropin (eCG) and human CG (hCG) were used to study the time course changes in nitric oxide synthase (NOS) activity in the ovary during ovulation. To study the role of NO in ovulation, the effects of intrabursal injection of L-N(G)-monomethylarginine (L-NMMA, 125 microg/20 microl/bursa), a NOS inhibitor, on the number of ova shed were also examined. Rats were sacrificed at -48, 0, 3, 6, 9, 12, and 24 h after hCG injection, and the ovaries were collected for the NOS activity assay, Western blotting, NADPH-diaphorase histochemistry and immunohistochemistry. Total NOS and constitutive NOS activities in the ovary increased significantly at 9 h after hCG injection and the values remained high thereafter. Inducible NOS (iNOS) activity was detectable as a small peak at 3 and 6 h after hCG injection. Endothelial NOS (eNOS) protein production increased after hCG injection with a peak at 12 h, whereas iNOS protein production decreased at 12 and 24 h after hCG injection. NADPH-diaphorase positive cells increased at the thecae of growing follicles after hCG injection, appeared at mural granulosa cells before ovulation, and were detected in newly formed corpora lutea, which coincided with the results in eNOS positive cells by immunohistochemistry. L-NMMA given to rats at 5 or 7 h after hCG was most effective in reducing the number of ova shed. These results indicate that the NOS activity and NOS positive cells increased after hCG injection, and that eNOS was likely the main NOS increasing in the ovary during ovulation. It is concluded that NO produced between 5 and 9 h after hCG might play a supportive role in ovulation.

Suppression of intracellular superoxide dismutase activity by antisense oligonucleotides causes inhibition of progesterone production by rat luteal cells.

Superoxide radicals are known to inhibit progesterone production by luteal cells and have also been reported to cause apoptosis in various cells. The corpus luteum has an antioxidant enzyme to scavenge superoxide radicals: copper-zinc superoxide dismutase (Cu, Zn-SOD). However, it remains unknown how the decrease in intracellular Cu,Zn-SOD activity influences luteal function. This study was therefore undertaken to investigate whether suppression of intracellular Cu,Zn-SOD activity inhibits progesterone production by rat luteal cells and causes apoptosis. To suppress intracellular Cu, Zn-SOD activity, dispersed rat luteal cells were incubated with Cu, Zn-SOD antisense oligonucleotides. The 48-h treatment with antisense oligonucleotides (10 microM) inhibited Cu,Zn-SOD activity by 50% and Cu,Zn-SOD mRNA level by 30%, whereas sense oligonucleotides used as the control had no effect. Progesterone concentration in the medium was significantly decreased by the 48-h treatment with antisense oligonucleotides in the presence of hCG, and this inhibitory effect was completely blocked by the simultaneous addition of N-acetyl-L-cysteine, an antioxidant. Treatment with antisense oligonucleotides caused no significant change in the percentage of apoptotic cells as morphologically evaluated by the nuclear staining with Hoechst dye. In conclusion, the decrease in intracellular Cu, Zn-SOD activities inhibits progesterone production by rat luteal cells, which may be mediated by superoxide radicals, suggesting that intracellular Cu,Zn-SOD plays important roles in the regulation of luteal function.

Changes in interleukin-1beta mRNA expression in the rat ovary during the estrous cycle in response to lipopolysaccharide.

The changes in interleukin-1 (IL-1) beta mRNA expression and the number of macrophages were studied in the ovary during the estrous cycle in rats and after intraperitoneal injection of lipopolysaccharide (LPS, 2 mg/body) 2 hours before autopsy. IL-1beta mRNA expression was very low in the ovary, and there was no statistically significant change during the estrous cycle. Hybridization signals of IL-1beta mRNA were localized intensely in the thecal layer, moderately in the corpora lutea, and slightly in granulosa cells of the ovary during the cycle. The number of macrophages seen mainly in the hilum and interstitium significantly increased on proestrus compared with other estrous days. LPS significantly increased IL-1beta mRNA expression on each day with the highest response to LPS at 1500 h on proestrus, and caused an increase in the number of macrophages in the ovary within 2 hours. These results indicate that IL-1beta mRNA expressions are low during the estrous cycle in rats, and proestrus is the day of maximal IL-1beta synthesis in response to LPS. The increase in IL-1beta synthesis caused by LPS might be due to at least the influx of macrophages into the ovary.

Pinealectomy of melatonin implantation does not affect prolactin surge or luteal function in pseudopregnant rats.

The effects of melatonin on twice daily surges in PRL and luteal function were studied in pseudopregnant (PSP) rats. Cyclic rats received pinealectomy or sham operation under pentobarbital anesthesia on diestrus 1. Pinealectomized rats immediately received a melatonin capsule (the PINX+Mel group) or a blank capsule (the PINX group), and sham group of rats received a blank capsule (the control group). After operation, all rats were maintained under the same photoperiod conditions (14L: 10D), and estrous cyclicity was examined. At the 8th estrous cycle after operation, PSP was induced by mechanical stimulation of the uterine cervix. The last day on which the rat exhibited the estrous smear was designated as day 1 of PSP. Blood samples were obtained by jugular venipuncture under light ether anesthesia between 1200 and 1300 h on days 1, 3, 5, 7, 9 and 11, and between 0000 and 0100 h on day 13 of PSP. All rats were decapitated between 1200 and 1300 h on day 13 of PSP, and trunk blood was collected. A silicon catheter was inserted into the right jugular vein under ether anesthesia on day 4 of PSP. Blood samplings were performed every 2 h between 1000 h on day 5 and 1000 h on day 6 of PSP. Serum concentrations of melatonin, PRL and progesterone were measured by radioimmunoassay. Pinealectomy or melatonin installation did not disturb the estrous cyclicity or the induction of PSP. There were no differences among the three groups of rats during PSP in the pattern or serum PRL concentrations, and there were no significant differences among these three groups in the serum progesterone concentration or weight of the corpus luteum. The present results indicated that the continuously high or low melatonin in the physiological range did not affect the rhythm or strength of PRL surges or luteal function in PSP rats.

Melatonin directly suppresses steroid production by preovulatory follicles in the cyclic hamster.

The purpose of these studies was to investigate the effects of melatonin on the production of steroids (progesterone, testosterone, and estradiol) and cAMP by preovulatory follicles and to examine changes in melatonin concentrations in the ovary during the estrous cycle. Adult cyclic hamsters were used in this study. Melatonin concentrations in the ovary, pineal gland, and serum were measured at mid-light and mid-dark during the estrous cycle. Effects of melatonin on steroidogenesis by preovulatory follicles, thecae, and granulosa cells were examined, and its effect on cAMP production by preovulatory follicles was also investigated. Melatonin (0.1-10 ng/ml) had no effect on steroid production in the absence of hCG, but melatonin decreased progesterone and estradiol production by preovulatory follicles in a dose-dependent and time-dependent manner in the presence of hCG (100 mIU/ml). The target of melatonin was thecae but not granulosa cells, and melatonin significantly reduced cAMP production by preovulatory follicles. Melatonin concentrations in the ovary showed a similar phasic variation with high levels during mid-dark and low during mid-light, as in the pineal gland and serum. These results show that the ovarian melatonin levels also exhibit a circadian rhythm and suggest that the high melatonin milieu in the ovary may induce gonadal regression in the cyclic hamster.

Roles of reactive oxygen species in the regulation of luteal function.

Ephemerality and prolongation of luteal function have been matters of great concern in reproduction for many years. However, their control mechanisms are very complex and differ among mammals. Recently, evidence has indicated that reactive oxygen species may play important roles in the regulation of luteal function. Reactive oxygen species are present in most somatic cells and are involved in apoptosis, or 'physiological cell death'. In the corpus luteum, reactive oxygen species also exert luteolytic effects as well as some paradoxical luteotrophic effects. This paper discusses the possible roles of reactive oxygen species in the control of luteal function.