Female reproductive aging refers to the process that ovarian function gradually declines with age, leading to the decline of fertility and related physiological dysfunction. In recent years, the research on anti-female reproductive aging active molecules has become a hot spot in the medical field, aiming at delaying ovarian aging and improving reproductive health. In this paper, the main sources of anti-female reproductive aging molecules are reviewed, including natural products, endogenous molecules and synthetic small molecules, with emphasis on resveratrol, curcumin, soybean isoflavones, nicotinamide adenine dinucleotide precursors (such as nicotinamide mononucleotide) and mitochondrial targeting molecules. These molecules play an important role in delaying ovarian aging and maintaining ovarian function through various mechanisms such as antioxidant stress, regulating autophagy and apoptosis, anti-inflammatory and immunomodulation, and telomere protection. However, from laboratory research to clinical application, it still faces multiple challenges such as bioavailability, long-term safety and individual differences. Future research needs to further optimize the delivery system, carry out long-term clinical trials, and explore individualized treatment strategies to promote the clinical transformation and application of anti-female reproductive aging molecules.

Female reproductive aging refers to the process that ovarian function gradually declines with age, leading to the decline of fertility and related physiological dysfunction. In recent years, the research on anti-female reproductive aging active molecules has become a hot spot in the medical field, aiming at delaying ovarian aging and improving reproductive health. In this paper, the main sources of anti-female reproductive aging molecules are reviewed, including natural products, endogenous molecules and synthetic small molecules, with emphasis on resveratrol, curcumin, soybean isoflavones, nicotinamide adenine dinucleotide precursors (such as nicotinamide mononucleotide) and mitochondrial targeting molecules. These molecules play an important role in delaying ovarian aging and maintaining ovarian function through various mechanisms such as antioxidant stress, regulating autophagy and apoptosis, anti-inflammatory and immunomodulation, and telomere protection. However, from laboratory research to clinical application, it still faces multiple challenges such as bioavailability, long-term safety and individual differences. Future research needs to further optimize the delivery system, carry out long-term clinical trials, and explore individualized treatment strategies to promote the clinical transformation and application of anti-female reproductive aging molecules.

The increased levels of intracellular reactive oxygen species (ROS) in granulosa cells (GCs) may affect the pregnancy results in women with polycystic ovary syndrome (PCOS). In this study, we compared the in vitro fertilization and embryo transfer (IVF-ET) results of 22 patients with PCOS and 25 patients with tubal factor infertility and detected the ROS levels in the GCs of these two groups. Results showed that the PCOS group had significantly larger follicles on the administration day for human chorionic gonadotropin than the tubal factor group (P < 0.05); however, the number of retrieved oocytes was not significantly different between the two groups (P > 0.05). PCOS group had slightly lower fertilization, cleavage, grade I/II embryo, clinical pregnancy, and implantation rates and higher miscarriage rate than the tubal factor group (P > 0.05). We further found a significantly higher ROS level of GCs in the PCOS group than in the tubal factor group (P < 0.05). The increased ROS levels in GCs caused GC apoptosis, whereas NADPH oxidase 2 (NOX2) specific inhibitors (diphenyleneiodonium and apocynin) significantly reduced the ROS production in the PCOS group. In conclusion, the increased ROS expression levels in PCOS GCs greatly induced cell apoptosis, which further affected the oocyte quality and reduced the positive IVF-ET pregnancy results of women with PCOS. NADPH oxidase pathway may be involved in the mechanism of ROS production in GCs of women with PCOS.
Abortion, Spontaneous ; epidemiology ; Acetophenones ; therapeutic use ; Adult ; Apoptosis ; drug effects ; Embryo Transfer ; Female ; Fertilization in Vitro ; Granulosa Cells ; metabolism ; Humans ; NADPH Oxidases ; antagonists & inhibitors ; Onium Compounds ; therapeutic use ; Oocyte Retrieval ; Oxidative Stress ; Polycystic Ovary Syndrome ; drug therapy ; Pregnancy ; Pregnancy Rate ; Reactive Oxygen Species ; metabolism

The expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) was examined in the umbilical vessels of the patients with pre-eclampsia (PE) to explore its possible role in the pathogenesis of PE.The NOSTRIN mRNA in umbilical tissues was determined by RT-PCR.The eNOS activity in umbilical vessels was spectrophotometrically detected.NO2-/NO3-,the stable metabolic end products of NO,was measured by using nitrate reductase.RT-PCR showed that the expression level of NOSTRIN was significantly higher in women with PE than in the normal group (P<0.01).The activity of eNOS was significantly decreased in PE group [(12.83±3.61) U/mg] than in normal group [(21.72±3.83) U/mg] (P<0.01).The level of NO2-/NO3- in PE patients (27.53± 7.48) μmol/mg was significantly lower than that of normal group (54.27±9.53) μmol/mg (P<0.01).The significant negative correlation existed between the expression of NOSTRIN and the activity of eNOS in umbilical vessels of women with PE (r=-0.58,P<0.01).It was concluded that the level of NOSTRIN expression was increased in umbilical vessel of women with PE,indicating that it may be involved in the pathogenesis of PE.

The expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) was examined in the umbilical vessels of the patients with pre-eclampsia (PE) to explore its possible role in the pathogenesis of PE. The NOSTRIN mRNA in umbilical tissues was determined by RT-PCR. The eNOS activity in umbilical vessels was spectrophotometrically detected. NO2-/NO3-, the stable metabolic end products of NO, was measured by using nitrate reductase. RT-PCR showed that the expression level of NOSTRIN was significantly higher in women with PE than in the normal group (P<0.01). The activity of eNOS was significantly decreased in PE group [(12.83+/-3.61) U/mg] than in normal group [(21.72+/-3.83) U/mg] (P<0.01). The level of NO2-/NO3- in PE patients (27.53+/-7.48) micromol/mg was significantly lower than that of normal group (54.27+/-9.53) micromol/mg (P<0.01). The significant negative correlation existed between the expression of NOSTRIN and the activity of eNOS in umbilical vessels of women with PE (r=-0.58, P<0.01). It was concluded that the level of NOSTRIN expression was increased in umbilical vessel of women with PE, indicating that it may be involved in the pathogenesis of PE.
Intracellular Signaling Peptides and Proteins/genetics ; Intracellular Signaling Peptides and Proteins/*metabolism ; Pre-Eclampsia/*enzymology ; Pre-Eclampsia/etiology ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Umbilical Arteries/cytology ; Umbilical Arteries/*enzymology ; Umbilical Veins/cytology ; Umbilical Veins/*enzymology

To investigate the expressions of placental growth factor (PLGF) in placenta with hypertensive disorders of pregnancy (HDP), 45 women with HDP and 20 normally pregnant women were studied. Among 45 women with HDP, there were 23 cases of severe preeclampsia and one case of eclampsia. The location and level of PLGF proteins was determined by immunohistochemistry and Western blot. The expression of PLGF mRNA in placenta was assessed by reverse transcriptionalpolymerase chain reaction (RT-PCR). The results showed that: (1) The distribution of PLGF in placenta with HDP was similar to normal one, which was mainly in the cytoplasm of villous syncytiotrophoblast and villous stroma; (2) The expression of PLGF protein was significantly decreased in placentas with mild and severe preeclampsia compared to the normal ones (0.3±0.4 vs 0.6± 0.4, 0.2±0.5 vs 0.6±0. 4, P＜0.01). There were no differences between the gestational hypertension placenta and normal one (0.5±0.6 vs 0.6±0.4, P＞0. 05); (3) The transcription levels of the PLGF mRNA in placentas with preeclampsia were significantly lower than in normal groups (3.33±0.39 vs4.87±0.60, 1.97±0.29 vs 4.87±0. 60, P＜0.01), and no differences were found between the gestational hypertension placenta and normal groups. These findings suggest that the abnormal expression of PLGF in placentas is related to the pathogenesis of HDP.

The expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) in the placenta of the patients with pregnancy induced hypertension (PIH) was detected and its role in the pathogenesis of PIH was studied. The pathological changes in placental vessels were observed by HE staining. NO2-/NO3- , the stable metabolic end products of NO, was measured with nitrate reductase. The eNOS activity in placental tissues was assayed by spectrophotometry. Western blot analysis was applied to detect NOSTRIN expression. The incidence of thickening and fibronoid necrosis of placental vessels was significantly higher in women with PIH than in the normal group (P＜0.01). The levels of placental NO2-/NO3- in PIH patients (27.53±7.48 μmol/mg) were significantly lower than in normal group (54.27±9.53 μmol/mg, P＜0.01). The activity of eNOS was significantly decreased in PIH group (12. 826±3.61 U/mg) as compared with that in normal group (21. 72±3.83 U/mg, P＜0.01). Western blot analysis revealed that both groups expressed 58 kD NOSTRIN, but the protein level was significantly higher in women with PIH than in the normal group (P＜0.01). A significant negative correlation existed between the expression of NOSTRIN protein and the activity of eNOS in placental tissue of women with PIH (r=-0. 57, P＜0. 01). It was concluded that the level of NOSTRIN expression in placenta of women with PIH was increased, which may play an important role in the pathogenesis of PIH.

To investigate the expressions of placental growth factor (PLGF) in placenta with hypertensive disorders of pregnancy (HDP), 45 women with HDP and 20 normally pregnant women were studied. Among 45 women with HDP, there were 23 cases of severe preeclampsia and one case of eclampsia. The location and level of PLGF proteins was determined by immunohistochemistry and Western blot. The expression of PLGF mRNA in placenta was assessed by reverse transcriptional-polymerase chain reaction (RT-PCR). The results showed that: (1) The distribution of PLGF in placenta with HDP was similar to normal one, which was mainly in the cytoplasm of villous syncytiotrophoblast and villous stroma; (2) The expression of PLGF protein was significantly decreased in placentas with mild and severe preeclampsia compared to the normal ones (0.3 +/- 0.4 vs 0.6 +/- 0.4, 0.2 +/- 0.5 vs 0.6 +/- 0.4, P < 0.01). There were no differences between the gestational hypertension placenta and normal one (0.5 +/- 0.6 vs 0.6 +/- 0.4, P > 0.05); (3) The transcription levels of the PLGF mRNA in placentas with preeclampsia were significantly lower than in normal groups (3.33 +/- 0.39 vs 4.87 +/- 0.60, 1.97 +/- 0.29 vs 4.87 +/- 0.60, P < 0.01), and no differences were found between the gestational hypertension placenta and normal groups. These findings suggest that the abnormal expression of PLGF in placentas is related to the pathogenesis of HDP.
Placenta/*metabolism ; Pre-Eclampsia/*metabolism ; Pregnancy/*metabolism ; Pregnancy Proteins/*biosynthesis ; Pregnancy Proteins/genetics

The expression of endothelial nitric oxide synthase traffic inducer (NOSTRIN) in the placenta of the patients with pregnancy induced hypertension (PIH) was detected and its role in the pathogenesis of PIH was studied. The pathological changes in placental vessels were observed by HE staining. NO2-/NO3-, the stable metabolic end products of NO, was measured with nitrate reductase. The eNOS activity in placental tissues was assayed by spectrophotometry. Western blot analysis was applied to detect NOSTRIN expression. The incidence of thickening and fibronoid necrosis of placental vessels was significantly higher in women with PIH than in the normal group (P < 0.01). The levels of placental NO2-/NO3- in PIH patients (27.53 +/- 7.48 micromol/mg) were significantly lower than in normal group (54.27 +/- 9.53 micromol/mg, P < 0.01). The activity of eNOS was significantly decreased in PIH group (12.826 +/- 3.61 U/mg) as compared with that in normal group (21.72 +/- 3.83 U/mg, P < 0.01). Western blot analysis revealed that both groups expressed 58 kD NOSTRIN, but the protein level was significantly higher in women with PIH than in the normal group (P < 0.01). A significant negative correlation existed between the expression of NOSTRIN protein and the activity of eNOS in placental tissue of women with PIH (r = -0.57, P < 0.01). It was concluded that the level of NOSTRIN expression in placenta of women with PIH was increased, which may play an important role in the pathogenesis of PIH.

The expression of transforming growth factor-β1 (TGF-β1) in placental tissue of pregnancy-induced hypertension (PIH) and the relationship between the level of expression of TGF-β1 and the amount of vascular cell adhesion molecule-1 (VCAM-1) in serum was studied. Immunohistochemistry ABC was used to detect the expression and distribution of TGF-β1 in placental tissues in 40 PIH women and 20 normal pregnancy women. High resolution pathological image analysis system was used to determine the quality of TGF-β1. The VCAM-1 in serum was examined by enzyme linked immunoabsorbent assay (ELISA). The results showed that TGF-β1 could be express in syncytiotrophoblast. The levels of TGF-β1 expression in placental tissues of the patients with moderate and severe PIH were significantly higher (P＜0.05), while the serum VCAM-1 was significantly lower than in normal group (P＜0.01). There was a significant positive correlation between the expression of TGF-β1 in placental tissues and the serum VCAM-1 (r=0. 969, P＜0.01). It was concluded that the level of TGF-β1 expression in PIH was increased and was positively correlated with the amount of serum VCAM-1, indicating that they might be involved in the pathogenesis of PIH.