Guideline for gynecological practice in Japan: Japan Society of Obstetrics and Gynecology and Japan Association of Obstetricians and Gynecologists 2023 edition.

Twelve years after the first edition of The Guideline for Gynecological Practice, which was jointly edited by The Japan Society of Obstetrics and Gynecology and The Japan Association of Obstetricians and Gynecologists, the 5th Revised Edition was published in 2023. The 2023 Guidelines includes 5 additional clinical questions (CQs), which brings the total to 103 CQ (12 on infectious disease, 30 on oncology and benign tumors, 29 on endocrinology and infertility and 32 on healthcare for women). Currently, a consensus has been reached on the Guidelines, and therefore, the objective of this report is to present the general policies regarding diagnostic and treatment methods used in standard gynecological outpatient care that are considered appropriate. At the end of each answer, the corresponding Recommendation Level (A, B, C) is indicated.

Effects of androgenic properties of progestin combined with ethinyl estradiol on vascular endothelial reactivity, plasma lipids and free radical production in women with endometriosis.

AIM: Endothelial reactivity is inhibited and oxidative stress is enhanced in women with endometriosis. Testosterone may adversely affect lipids and endothelium. We investigated the effects of androgenic properties of progestins combined with ethinyl estradiol (EE) on endothelial function, lipids and free radical production in such women. METHODS: Women with endometriosis were treated with 20 µg EE + 3 mg drospirenone (DRSP) or 35 µg EE + 1 mg norethisterone (NET) for 3 months. Plasma concentrations of sex hormone-binding globulin (SHBG), lipids, copper (Cu), derivatives of reactive oxygen metabolites (d-ROMs), biological antioxidant potential (BAP), nitrite/nitrate, endothelin-1 and asymmetrical dimethylarginine (ADMA) were measured before and after treatment. Flow-mediated vasodilation (FMD) of the brachial artery was measured by ultrasonography. RESULTS: DRSP group, but not NET group, significantly increased FMD and concentrations of nitrite/nitrate and small dense LDL cholesterol, while decreased endothelin-1 concentrations. In both groups, ADMA and LDL cholesterol concentrations were significantly decreased, but triglyceride, SHBG, d-ROMs, Cu and ceruloplasmin concentrations increased, and BAP concentrations did not change. DRSP group significantly increased HDL cholesterol concentrations, whereas NET group decreased its concentrations. Changes in triglyceride correlated positively either with changes in SHBG (r = 0.57, P < 0.001) or with small dense LDL cholesterol (r = 0.45, P = 0.005). Changes in Cu correlated positively with changes in d-ROMs (r = 0.87, P < 0.001). CONCLUSION: Androgenic properties of progestin may counteract EE's favorable effects on endothelial function and HDL cholesterol, while eliminating its adverse effects on increased triglyceride-induced small dense LDL cholesterol in women with endometriosis.

Trivalent Rare-Earth Metal Amide Complexes as Catalysts for the Hydrosilylation of Benzophenone Derivatives with HN(SiHMe2 )2 by Amine-Exchange Reaction.

The rare-earth metal complexes Ln(L1 )[N(SiHMe2 )2 ](thf) (Ln=La, Ce, Y; L1 =N,N''-bis(pentafluorophenyl)diethylenetriamine dianion) were synthesized by treating Ln[N(SiHMe2 )2 ]3 (thf)2 with L1 H2 . The lanthanum and cerium derivatives are active catalysts for the hydrosilylation of benzophenone derivatives with HN(SiHMe2 )2 . An amine-exchange reaction was revealed as a key step of the catalytic cycle, in which Ln-Si-H ß-agostic interactions are proposed to promote insertion of the carbonyl moiety into the Si-H bond.

Endometrial cancer arising from adenomyosis: Case report and literature review of MRI findings.

Endometrial cancer arising from adenomyosis (EC-AIA) is extremely rare, and the typical magnetic resonance imaging (MRI) findings of EC-AIA have not been established. We report a case of EC-AIA that was detected preoperatively on MRI and conduct a literature review of the MRI findings of EC-AIA.

Cerium(IV) Carboxylate Photocatalyst for Catalytic Radical Formation from Carboxylic Acids: Decarboxylative Oxygenation of Aliphatic Carboxylic Acids and Lactonization of Aromatic Carboxylic Acids.

We found that in situ generated cerium(IV) carboxylate generated by mixing the precursor Ce(OtBu)4 with the corresponding carboxylic acids served as efficient photocatalysts for the direct formation of carboxyl radicals from carboxylic acids under blue light-emitting diodes (blue LEDs) irradiation and air, resulting in catalytic decarboxylative oxygenation of aliphatic carboxylic acids to give C-O bond-forming products such as aldehydes and ketones. Control experiments revealed that hexanuclear Ce(IV) carboxylate clusters initially formed in the reaction mixture and the ligand-to-metal charge transfer nature of the Ce(IV) carboxylate clusters was responsible for the high catalytic performance to transform the carboxylate ligands to the carboxyl radical. In addition, the Ce(IV) carboxylate cluster catalyzed direct lactonization of 2-isopropylbenzoic acid to produce the corresponding peroxy lactone and γ-lactone via intramolecular 1,5-hydrogen atom transfer (1,5-HAT).

Synthesis and Characterization of Alkoxide-Bridged Heterometallic Clusters of Cerium and Copper.

We prepared alkoxide-bridged heterometallic clusters of cerium and copper by the complexation of two metal alkoxides: treatment of Ce(OtBu)4 with [Cu(OtBu)]4 in a 1:1 metal ratio produced an alkoxide-bridged tetranuclear cluster, Ce2Cu2(OtBu)10 (1). Upon adding 4-substituted pyridine derivatives to complex 1, trinuclear clusters, Ce2Cu(OtBu)9(L) (2a: L = DMAP (4-dimethylaminopyridine); 2b: L = BPY (4,4'-bipyridine)), were obtained along with the release of 0.25 equiv of [Cu(OtBu)]4, in which a three-coordinated copper center was involved. In contrast, reaction of 1 with 4 equiv of 2,6-dimethylphenylisocyanide (XylNC) and 0.5 equiv of [Cu(OtBu)]4 resulted in the selective formation of CeCu2(OtBu)6(CNXyl)2 (3). In addition, Ce2K(OtBu)9 was used for complexation with CuCl2 by salt-elimination, giving Ce2CuCl(OtBu)9 (4) including a five-coordinated copper center. These complexes 1-4 were characterized by crystal structure determination as well as cyclic voltammetry of 1, 2a, and 4. The cyclic voltammogram of 4 in CH2Cl2 and THF suggested that reorganization of the coordination sphere around the copper center was observed for 4 during the Cu(I/II) redox processes assisted by the coordination of THF.

Hepatic Effects of Estrogen on Plasma Distribution of Small Dense Low-Density Lipoprotein and Free Radical Production in Postmenopausal Women.

AIM: Hepatic effects of estrogen therapy on low-density lipoprotein (LDL) subfraction or oxidative stress have not been previously evaluated. The purpose of the present study was to investigate whether the differential hepatic effects of estrogen affect plasma distribution of small dense LDL and free radical production in postmenopausal women. METHODS: In all, 45 postmenopausal women were given 0.625 mg/day of oral conjugated equine estrogen (CEE) (n=15), 1.0 mg/day of oral 17ß estradiol (E2) (n=15), or 50 µg/day of transdermal 17ßE2 (n=15) for 3 months. Subjects received either estrogen alone or with dydrogesterone at 5 mg/day. Plasma concentrations of sex hormone-binding globulin (SHBG), lipids, metallic ions, and derivatives of reactive oxygen metabolites (d-ROMs) were measured. RESULTS: CEE, but not oral 17ßE2, increased the plasma concentrations of triglyceride, copper (Cu), and d-ROMs and the ratio of small dense LDL/total LDL cholesterol, a marker for plasma distribution of small dense LDL. Transdermal 17ßE2 decreased d-ROMs concentrations but did not significantly change other parameters. Plasma concentrations of SHBG increased in the 3 groups. Estrogen-induced changes in triglyceride correlated positively either with changes in SHBG (R=0.52, P=0.0002) or the ratio of small dense LDL/total LDL cholesterol (R=0.65, P＜0.0001). Changes in Cu also correlated positively either with changes in SHBG (R=0.85, P＜0.0001) or d-ROMs (R=0.86, P＜0.0001). CONCLUSION: The hepatic effects of different routes or types of estrogen therapy may be associated with plasma distribution of small dense LDL and free radical production in postmenopausal women.

Pregnancy-induced hypertension is associated with an increase in the prevalence of cardiovascular disease risk factors in Japanese women.

OBJECTIVE: This study assessed whether pregnancy-induced hypertension (PIH) affects the prevalence of cardiovascular disease (CVD) risk factors in later life among Japanese women. METHODS: Study participants were 1,185 women (mean [SD] age, 46.5 [5.6] y; range, 38-73 y) aged 40 years or older who underwent a health checkup at a periodic health examination facility between January 2012 and December 2013 and had experienced giving birth. Questionnaires were sent to potential participants, and they were encouraged to provide their Maternal and Child Health Handbook (handbook). We recruited 101 women with a history of PIH (PIH group) and 1,084 women with uncomplicated pregnancy at delivery (control group). Groupings were based on information from the handbook. We assessed the association between PIH and CVD in later life among Japanese women by focusing on hypertension, diabetes mellitus, and dyslipidemia as risk factors for CVD. Odds ratios (ORs) for the use of antihypertensive, diabetes mellitus, and dyslipidemic medications in the PIH group were determined. RESULTS: Women with PIH had increased risk of antihypertensive medication use compared with women without PIH (2.9% vs 13.9%; OR, 4.28; 95% CI, 2.14-8.57). Triglycerides were significantly higher and high-density lipoprotein cholesterol was significantly lower in the PIH group than in the control group. The OR for dyslipidemic medication use in the PIH group relative to the control group was 3.20 (95% CI, 1.42-7.22). CONCLUSIONS: Our findings suggest that a history of PIH may be associated with an increased risk of hypertension (a risk factor for CVD) in later life among Japanese women.

Differences in vascular reactivity between pregnant women with chronic hypertension and preeclampsia.

The purpose of this study was to evaluate the distinct pathogenic mechanisms underlying chronic hypertension in pregnancy and preeclampsia in terms of oxidative stress and vascular reactivity. A total of 17 women with uncomplicated pregnancies, 30 women with preeclampsia and 17 women with chronic hypertension were evaluated. We measured serum derivatives of reactive oxygen metabolites (d-ROMs; marker of oxygen free radicals), flow-mediated vasodilation (FMD; marker of endothelial function) and intima-media thickness in the carotid artery (IMT; marker of atherogenesis) during pregnancy and 1 month after delivery. Serum d-ROM concentrations were significantly higher in women with chronic hypertension and severe preeclampsia than in the control group during pregnancy. d-ROM concentrations in all groups significantly decreased to similar levels 1 month after delivery. FMD was significantly lower during pregnancy in preeclamptic and chronic hypertension groups compared with the control group. FMD in preeclamptic groups significantly increased and normalized to control levels after delivery. Similarly, FMD in the chronic hypertension group significantly increased after delivery but was still lower. IMT in the chronic hypertension group was significantly higher than that in control and preeclamptic groups. These findings suggest that endothelial dysfunction induced by enhanced oxidative stress is reversible in women with preeclampsia, whereas impaired vascular reactivity may be associated with atherosclerotic changes in women with chronic hypertension.

Differences in levels of oxidative stress in mothers and neonate: the impact of mode of delivery.

OBJECTIVE: To determine there are differences in the production levels of oxygen free radical between mothers and neonates by the mode of delivery, we measured oxygen free radical concentrations in maternal vein and umbilical artery. METHODS: Forty-four women with singleton term pregnancies were prospectively recruited and classified into two groups: those who had a spontaneous uncomplicated vaginal delivery (VD group; n = 21), and those who had an elective cesarean delivery (CD group; n = 23). We determined maternal and fetal oxidative stress levels by measuring concentrations of derivatives of reactive oxygen metabolites (d-ROMs) in maternal vein before delivery and on postnatal day 5, and in umbilical artery at delivery. We also measured the pH, partial pressure of oxygen (PaO2), partial pressure of carbon dioxide (PaCO2) and base excess (BE) in umbilical artery blood collected at delivery. RESULTS: The concentrations of d-ROMs in maternal vein on postnatal day 5 were significantly decreased in the VD group, but were significantly increased in the CD group, compared to before delivery. The concentrations of d-ROMs in umbilical artery were significantly higher in the VD group than the CD group. Compared to the CD group, umbilical artery pH tended to be lower (p = 0.07), and BE significantly lower (p < 0.005), in the VD group. There were no significant differences in umbilical artery PaO2 and PaCO2 between the two groups. CONCLUSION: Our findings indicate that those production levels of oxygen free radical in mothers are greater by CD than by VD, while those in neonates are greater by VD than by CD.

Increased oxygen free radical production during pregnancy may impair vascular reactivity in preeclamptic women.

To determine whether enhanced oxidative stress during pregnancy impairs vascular endothelial function and improves after delivery in preeclamptic women, we measured serum parameters of oxidative stress and endothelial function during pregnancy and 1 month after delivery in women with or without preeclampsia. We evaluated 18 participants with uncomplicated pregnancies, 11 with mild preeclampsia and 13 with severe preeclampsia. The plasma concentrations of reactive oxygen metabolite derivatives (d-ROMs) were measured, and the biological antioxidant potential (BAP) was determined to evaluate the oxygen free radicals and antioxidants, respectively. Flow-mediated vasodilation (FMD) was also assessed as a marker of endothelial function. FMD was decreased significantly in both preeclamptic groups compared with control during pregnancy. FMD did not change after delivery in the control group, but it significantly increased after delivery in both the mildly and severely preeclamptic groups, nearing control levels 1 month after delivery (mild, 6.5±3.6-9.0±3.5%; severe, 4.3±3.3-9.7±2.6%). No changes in d-ROM concentrations were observed in the control group; however, the concentrations in both the mildly and severely preeclamptic groups significantly decreased to normal levels 1 month after delivery (mild, 562.0±106.5-430.5±90.5 CARR U (Carratelli units); severe, 681.0±239.0-411.8±69.7 CARR U). The plasma BAP levels did not change significantly in all three groups. A negative correlation between FMD and d-ROM concentrations was observed in the preeclamptic group, but not in the control group (r=-0.497; P<0.05). Our findings indicated that enhanced oxidative stress during pregnancy may impair endothelial function and improve after delivery in preeclamptic women.

The severity of hypoxic changes and oxidative DNA damage in the placenta of early-onset preeclamptic women and fetal growth restriction.

OBJECTIVE: To investigate the relation between the severity of hypoxic changes and oxidative DNA damage in the placenta of early and late-onset preeclampic women and fetal growth restriction (FGR), serum parameters of oxidative stress, placental hypoxic change, and oxidative DNA damage were determined. METHODS: We examined 10 participants with uncomplicated pregnancies, 13 with early-onset and 12 with late-onset preeclampsia. Maternal and umbilical plasma derivatives of reactive oxygen metabolites (d-ROMs) were measured as markers of oxygen free radicals. Immunohistochemical analysis was performed to measure the proportion of placental trophoblast cell nuclei staining positive for 8-hydroxy-2'-deoxyguanosine (8-OHdG), redox factor-1 (ref-1), and hypoxia-induced factor-1α (HIF-1α), which are markers of oxidative DNA damage, repair functions, and hypoxia status, respectively. RESULTS: 8-OHdG was higher in both preeclamptic groups, but significantly higher in the early-onset preeclamptic group. Ref-1 was higher in the late-onset preeclamptic group. HIF-1α was higher in both preeclamptic groups, with a tendency towards a higher in the early-onset preeclamptic group. CONCLUSIONS: Our findings indicate that the severity of hypoxic changes and oxidative DNA damage are greater in the placenta of women with early-onset preeclampsia, and that the prolonged preeclamptic conditions may reduce placental blood flow, ultimately leading to FGR.

PP043. Oxidative stress in the maternal body also affects the fetus in preeclamptic women with fetal growth restriction.

The purpose of the present study was to determine whether oxidative stress occurring in the maternal body also affects the fetus in preeclamptic women with FGR. We ∥@consecutively recruited 17 preeclamptic women with FGR, 16 preeclamptic women without FGR, and 16 healthy pregnant women with uncomplicated pregnancy. We measured concentrations of derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxygen free radicals in a maternal vein, umbilical artery, and umbilical vein. ∥@Maternal d-ROM levels were higher in preeclamptic groups compared to the control group. Umbilical artery and vein d-ROM levels were elevated in preeclamptic women with FGR compared to the control group. Umbilical artery d-ROM levels were significantly higher than in the vein in preeclamptic women with FGR, but not in those without FGR. Umbilical arterial blood pH was significantly lower in preeclamptic women with FGR. The partial pressure of oxygen (PaO2) in umbilical arterial blood tended to be lower in preeclamptic women with FGR (p=0.08). The partial pressure of carbon dioxide (PaCO2) in umbilical arterial blood was significantly higher in preeclamptic women with FGR. These results indicate that oxidative stress occurring in the maternal body also affects the fetus in preeclamptic women with FGR.

Increased oxidant generation in the metabolism of hypoxanthine to uric acid and endothelial dysfunction in early-onset and late-onset preeclamptic women.

OBJECTIVE: The purpose of this study was to evaluate the association of vascular endothelial dysfunction with increased oxidant generation in the metabolism of hypoxanthine to uric acid in early-onset compared to late-onset preeclampsia. METHODS: We investigated 12 women with early-onset preeclampsia, 14 women with late-onset preeclampsia, and 20 women with uncomplicated pregnancies. We measured serum derivatives of reactive oxygen metabolites (d-ROMs) as a marker of oxygen free radicals, serum biological antioxidant potential (BAP), hypoxanthine, uric acid, uric acid clearance (CUA), and flow-mediated vasodilation (FMD) as a marker of endothelial function in preeclamptic women. RESULTS: Concentration of d-ROMs was significantly higher in both preeclamptic groups compared to the control group. Plasma levels of uric acid were significantly elevated in both preeclamptic groups compared to the control group. Plasma levels of hypoxanthine were significantly higher in early-onset preeclamptic women compared to controls, but not in late-onset preeclamptic women. CUA was significantly lower in late-onset preeclamptic women compared to controls, but not in early-onset preeclamptic women. The concentrations of hypoxanthine and uric acid correlated positively with the concentration of d-ROMs in all pregnant women. FMD was significantly lower in both preeclamptic groups compared with controls, but FMD in the early-onset preeclamptic group was significantly lower than in the late-onset preeclamptic group. CONCLUSIONS: We found that increased oxidant generation during metabolism of hypoxanthine to uric acid may impair endothelial function in early-onset preeclampsia.

Prophylactic administration of melatonin to the mother throughout pregnancy can protect against oxidative cerebral damage in neonatal rats.

OBJECTIVE: The purpose of this study was to investigate whether prophylactic administration of melatonin to the mother throughout pregnancy could protect against ischemia/reperfusion (I/R)-induced oxidative brain damage in neonatal rats. METHODS: The utero-ovarian arteries were occluded bilaterally for 30 min in female Wistar rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation. A sham operation was performed in control rats. Melatonin solution or vehicle alone was administrated orally throughout pregnancy. We collected brain mitochondria from neonatal rats, evaluated mitochondrial structure by electron microscopy, and measured the respiratory control index (RCI) as an indicator of mitochondrial respiratory activity as well as the concentration of thiobarbituric acid-reactive substances (TBARS), a marker of oxidative stress. Histological analysis was performed at the Cornu Ammonis 1 (CA1) and Cornu Ammonis 3 (CA3) regions of the hippocampus. RESULTS: I/R significantly reduced the RCI and significantly elevated the concentration of TBARS. Melatonin treatment reversed these effects, resulting in values similar to that in untreated, sham-ischemic animals. Electron microscopic evaluation showed that the number of intact mitochondria decreased in the I/R group, while melatonin treatment preserved them. Histological analysis revealed a decrease in the ratio of normal to whole pyramidal cell number in the CA1 and CA3 regions in the I/R group. While melatonin administration protected against degeneration. CONCLUSIONS: These results indicate that prophylactic administration of melatonin to the mother throughout pregnancy may prevent I/R-induced oxidative brain damage in neonatal rats.

Increased asymmetric dimethylarginine and enhanced inflammation are associated with impaired vascular reactivity in women with endometriosis.

OBJECTIVE: Enhanced inflammatory responses which may inhibit vascular reactivity, are associated with endometriosis development. Asymmetric dimethylarginine (ADMA), an inhibitor of endogenous nitric oxide synthase, is also implicated in endothelial dysfunction. We aimed to determine whether plasma ADMA and systemic inflammation are associated with endothelial function in women with endometriosis. METHODS: We evaluated 41 women with and 28 women without endometriosis. Plasma levels of lipids and inflammatory markers such as high sensitive-C reactive protein (hs-CRP), serum amyloid protein A (SAA), and interleukin-6 (IL-6) were measured in the two groups. We also measured levels of ADMA and symmetric dimethylarginine (SDMA). High-resolution ultrasonography measured flow-mediated vasodilation (FMD) to assess vasodilatory responses. RESULTS: FMD was significantly lower in women with endometriosis compared to those without endometriosis (8.39 ± 0.43% vs 10.79 ± 0.54%, P = 0.001). While plasma lipid levels did not differ significantly between groups, levels of AMDA, but not SDMA, were significantly higher in women with endometriosis (409.7 ± 10.1 pmol/L vs 383.0 ± 48.3 pmol/L, P = 0.04). Inflammatory markers were also significantly higher in these women (hs-CRP: 1053.3 ± 252.0 ng/mL vs 272.0 ± 83.3 ng/mL, P = 0.02; SAA: 8.00 ± 1.53 µg/mL vs 3.82 ± 0.42 µg/mL, P = 0.04; IL-6: 2.73 ± 0.75 pg/mL vs 1.05 ± 0.60 pg/mL, P = 0.04). FMD was negatively correlated with plasma levels of ADMA (r = -0.37, P=0.01) and log hs-CRP (r = -0.34, P = 0.01). CONCLUSION: Increased plasma ADMA levels and enhanced inflammation are associated with inhibited endothelial function in women with endometriosis.

Adipocytokines and endothelial function in preeclamptic women.

Visceral fat accumulation stimulates the production of adipocytokines in patients with metabolic syndrome. Excess body weight gain during pregnancy is a risk factor for preeclampsia. To evaluate whether the pathogenesis of preeclampsia is similar to that of metabolic syndrome, we measured plasma adipocytokine concentrations and investigated the association between plasma adiponectin concentrations and body weight gain or endothelial function in preeclamptic women. We investigated 15 preeclamptic and 17 women with uncomplicated pregnancies. Women with preeclampsia had significantly lower plasma concentrations of adiponectin (10.2+/-2.0 vs. 7.3+/-2.2 microg ml(-1), P<0.01), but higher concentrations of leptin, plasminogen activator inhibitor-1, interleukin-6, vascular cell adhesion molecule-1, E-selectin and C-reactive protein. Plasma triglyceride levels were significantly higher in preeclamptic patients, but the levels of other lipids did not differ significantly between the two groups. We found that flow-mediated vasodilation was significantly decreased in preeclamptic women compared with controls (10.6+/-6.4 vs. 3.8+/-2.0%, P<0.001). Plasma adiponectin concentrations correlated negatively with body mass index (r=-0.50, P<0.05) and body weight gain during pregnancy (r=-0.63, P<0.01), and positively with flow-mediated vasodilation (r=0.50, P<0.05) in preeclamptic women, but not in women with uncomplicated pregnancies. Similar to the patients with metabolic syndrome, we found that dysregulation of adipocytokines, such as low adiponectin levels and high levels of other adipocytokines, and excess body weight gain during pregnancy, may decrease plasma adiponectin concentrations that are associated with endothelial dysfunction in preeclamptic women.

Therapeutic effects of maternal melatonin administration on ischemia/reperfusion-induced oxidative cerebral damage in neonatal rats.

BACKGROUND: We have previously demonstrated that prophylactic administration of melatonin to pregnant rats can protect against ischemia/reperfusion (I/R)-induced oxidative cerebral damage in fetal rats. However, the effects of maternal administration of melatonin after an ischemic episode on the brains of neonatal rats exposed to oxidative stress in utero have not been evaluated. OBJECTIVES: The purpose of the present study was to investigate whether maternal administration of melatonin after an ischemic episode can prevent oxidative cerebral damage in neonatal rats. METHODS: The utero-ovarian arteries were occluded bilaterally for 30 min in female Wistar rats on day 16 of pregnancy to induce fetal ischemia. Reperfusion was achieved by releasing the occlusion and restoring circulation. Melatonin solution (10 mg/kg) or vehicle was injected intraperitoneally at 0, 1, 3, 6, and 12 h after reperfusion. After surgery, melatonin solution (20 microg/ml) or vehicle was administered freely via drinking water up to vaginal delivery. Control rats underwent a sham operation. We collected brain tissue from neonatal rats that were delivered naturally and measured the respiratory control index (RCI) as indicators of mitochondrial respiratory activity. Histological evaluation was performed on the cornu ammonis (CA1) and CA3 regions of the hippocampus. RESULTS: I/R significantly reduced the RCI, but melatonin administration at postreperfusion hour 0 or 1 reversed I/R-induced reductions in the RCI. In contrast, melatonin administration at postreperfusion hours 3-12 had no protective effect. Histological analysis revealed a decrease in the ratio of normal to whole pyramidal cell number in the CA1 and CA3 regions in the I/R group. While melatonin administration within 3 h protected against degeneration, administration 6 h after reperfusion failed to protect. CONCLUSIONS: These results suggest that maternal administration of melatonin within 1 h after an ischemic/oxidative episode can prevent I/R-induced oxidative cerebral damage in neonatal rats.