Effect of metformin on insulin resistance during catch-up growth in mice with fetal growth restriction / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the efficacy of metformin intervention on insulin resistance during catch-up growth in mice with fetal growth restriction (FGR).</p><p><b>METHODS</b>Mouse models of FGR were established by low protein diet feeding of the pregnant mice. Both the newborn female mice with FGR and normal control (NC) mice were randomized for feeding with a standard diet (SF) or a high-fat diet (HF) after weaning and treatment with gavage of either metformin or normal saline. The mice were examined for vaginal opening time and the estrous cycle at the age of 8 weeks. At the age of 12 weeks, 6 mice in anestrus from each group were fasted for 12 h for measurement of body weight, height, poundera index (PI), fasting blood glucose (FBG), fasting insulin (Fins), follicle stimulating hormone (FSH) and anti-Mullerian hormone (AMH), and the HOMA-IR was calculated. The reproductive capacity of female mice was assessed by mixing them with male mice at the ratio of 2:1. The 3 × 2 factorial analysis was conducted to determine the interactions between FGR, high-fat feeding and metformin.</p><p><b>RESULTS</b>Factorial analysis showed that FGR and high-fat feeding had significant effects on the PI index, Fins, HOMA-IR, vaginal opening time, and AMH (P<0.05). Metformin significantly affected the factors related to high-fat feeding including weight, PI, FPG, Fins, HOMA-IR and estrous cycle (P<0.05) and the factors related to FGR with the exception of height and FSH (P<0.05). FGR significantly affected the factors tested except for body weight (P<0.05); high-fat feeding affected all the factors but the FSH (P<0.05); metformin affected all the factors but the height and FSH (P<0.05). In the female mice treated with saline, the pregnancy rates differed significantly between FGR mice with high-fat feeding and control mice with standard feeding, and between FGR mice with standard feeding and high-fat feeding (P<0.05).</p><p><b>CONCLUSION</b>FGR mice can present with delayed puberty with rare ovulation and adulthood insulin resistance, and high-fat feeding after birth can promote the catch-up growth of FGR mice. Metformin intervention is effective for improving insulin resistance and reproductive-endocrine disorders in FGR mice during catch-up growth.</p>

Effect of sphingosine-1-phosphate on chemotherapy-induced ovarian damage and on the efficacy of chemotherapy in mice bearing S180 tumor / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of sphingosine-1-phosphate (S1P) on cyclophosphamid (CTX) and cisplatin (DDP)-induced ovarian damage and on the efficacy of chemotherapy in mice bearing S180 murine sarcoma.</p><p><b>METHODS</b>Fifty-two female C57BL/6 mice were randomized into normal control group (n=10), tumor-bearing model group (n=14), CTX+DDP group (n=14), and S1P+CTX+DDP group (n=14). Before medication and on day 11 of medication during diestrus stage, the mice were sacrificed to measure the ovarian weight, numbers of primordial follicles and growing follicles, tumor weight, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol ( E2).</p><p><b>RESULTS</b>At day 11 of medication, the levels of serum FSH and E2, but not LH, showed significant differences in CTX+DDP group from those in the other groups (P<0.01). FSH, E2, and LH levels were comparable between S1P+CTX+DDP group and the control group (P>0.05). The number of primodial follicles and weight of ovaries in CTX+DDP group decreased significantly compared to those in the other groups (P<0.01). The number of growing follicles in CTX+DDP group was significantly lower than that in the control and model groups(P<0.01), but similar to that in S1P group (P>0.05). The number of primodial follicles and growing follicles and ovarian weight in S1P+CTX+DDP group were close to those in the control and model groups (P>0.05). In CTX+DDP and S1P+CTX+DDP groups, the tumor weight were significantly lower than that in the other two groups (P<0.01), and the tumor inhibition rates were both higher than 60%.</p><p><b>CONCLUSION</b>S1P can ameliorate chemotherapy-induced ovarian damage in mice without affecting the efficacy of chemotherapy.</p>

Effects of gonadotroph-releasing hormone analogues on follicle apoptosis in rats with chemotherapy-induced ovarian damage / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effects of gonadotroph-releasing hormone (GnRH) agonist (GnRH-a) and GnRH antagonist (GnRH-ant) on cyclophosphamide (CTX)-induced follicle apoptosis in female rats.</p><p><b>METHODS</b>Thirty-six female Sprague- Dawley rats were randomized into 6 groups, namely normal saline (NS), CTX, GnRH-a+NS, GnRH-a+CTX, GnRH-ant+NS, and GnRH-ant+CTX groups. The rats were sacrificed between the first and second week after the treatments., and the follicle apoptosis was investigated using TUNEL assay and transmission electron microscopy.</p><p><b>RESULTS</b>The apoptosis rate of the granulose cells in the follicles in late development was significantly higher than that in early follicles, and the apoptosis rate of the oocytes and granulose cells in rats with CTX treatment was significantly higher than that in rats without CTX treatment (P<0.05). The apoptosis rate of the granulose cells in GnRH-a groups (ranging from 33.40 - or + 4.59 to 73.25 - or + 5.35) was significantly higher than that in GnRH-ant groups (27.46 - or + 4.52 to 49.38 - or + 5.02, P<0.05), but there was no significant difference in the oocytes of early follicles between GnRH-a groups (23.48 - or + 4.25 to 36.15 - or + 4.23) and GnRH-ant groups (21.47 - or + 3.81 to 34.04 - or + 5.54, P>0.05). Electron microscopy revealed characteristic apoptotic changes of the oocytes in early follicles and granulose cells in early and late follicles. The apoptotic changes were especially typical in the granulose cells showing the formation of the apoptotic bodies, and the oocytes only showed chromatin condensation and aggregation.</p><p><b>CONCLUSION</b>In the rat mode, GnRH-a promotes while GnRH-ant suppressed follicle apoptosis induced by CTX. GnRH analogues regulates mainly granulose cell apoptosis, but have little effect on oocyte apoptosis.</p>

Analysis of circulating DNA level in the plasma of cervical cancer patients / 南方医科大学学报

<p><b>OBJECTIVE</b>To determine the plasma DNA level and investigate its clinicopathological significance in women with cervical cancers.</p><p><b>METHODS</b>Blood samples were collected from 42 cervical cancer patients, 20 patients with cervical intraepithelial neoplasia grade III (CINIII) and 20 healthy women. The plasma DNA was extracted using a commercial kit and detected by a fluorescentmeter.</p><p><b>RESULTS</b>The mean plasma DNA level in stage I cervical cancer patients was 12.78-/+5.58 ng/ml, significantly higher than that in CINIII patients (8.10-/+3.06 ng/ml) and normal controls (7.60-/+3.87 ng/ml) (P=0.001). The mean DNA level in stage II-III patients was 17.99-/+7.81 ng/ml, significantly higher than that in stage I patients (P=0.02). No significant difference was found in plasma DNA level between CINIII patients and the normal controls (P>0.05). When the cut-off for diagnosis of cervical cancer was 15.70 ng/ml, the sensitivity, specificity, positive predictive value and negative predictive value were 38.10%, 92.50%, 84.21% and 58.73%, respectively.</p><p><b>CONCLUSION</b>Plasma DNA level is closely related with malignant transformation and development of cervical cancer, and may become a useful means for differential diagnosis of cervical cancer.</p>

Effect of GnRH analogs on the expression of Bcl-2 gene family in the ovary of rats with cyclophosphamide-induced ovarian damage / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the effect of gonadotroph-releasing hormone (GnRH) agonist (GnRH-a) and GnRH antagonist (GnRH-ant) against cyclophosphamide (CTX)-induced gonadotoxicity in female rats.</p><p><b>METHODS</b>Thirty-six female SD rats were divided randomly into 6 groups to receive treatment with normal saline (NS), CTX, GnRH-a+NS, GnRH-a+CTX, GnRH-ant+NS, GnRH-ant+CTX, respectively. The rats were sacrificed between the first and second week after termination of the medication to compare the weight of the ovaries, the number of the primordial follicles and the follicle growth. The expressions of bcl-2 and bax mRNA in the ovaries were examined using RT-PCR.</p><p><b>RESULTS</b>The number of the primordial follicles was significantly greater and that of the growing follicles significantly lower in GnRH-a+NS and GnRH-a+CTX groups than in the GnRH-ant+CTX and CTX groups (P<0.05). The rats in GnRH-a+NS and GnRH-a+CTX groups had the lowest ovarian weight among 6 the groups (P<0.05). The bcl-2 mRNA level in the GnRH-ant+NS group was significantly higher than that in the other groups (P<0.05). The Bax mRNA in the GnRH-a+NS and GnRH-a+CTX groups was significantly higher than that in the NS group (P<0.05), but close to that in the CTX group (P>0.05); bax mRNA expression in the GnRH-ant+NS group was significantly lower than that in the NS group (P<0.05), but in GnRH-ant+CTX group, its expression was close to that in the NS group (P>0.05).</p><p><b>CONCLUSIONS</b>In female rats exposed to CTX, the GnRH analogs provides ovarian protection against CTX-induced gonadotoxicity by regulating the expression of the Bax mRNA in the ovary. GnRH-a may decrease the sensitivity of the follicles to CTX-induced gonadotoxicity by promoting follicle apoptosis and inhibiting follicle proliferation, and GnRH-ant increases the sensitivity to the CTX through a reverse effect on the follicles.</p>