Effect of intrauterine hyperandrogen exposure in late-gestation on chronic low-grade inflammation and insulin sensitivity in female SD offspring of rats
10.3760/cma.j.cn101441-20210312-00126
- VernacularTitle:孕晚期宫内高雄激素环境对SD子代雌鼠持续性低度炎症状态及胰岛素敏感性的影响
- Author:
Yuan HUANG
1
;
Min CHEN
;
Wen XU
;
Qi CAO
;
Chunlin SU
;
Xiaoxi SUN
Author Information
1. 复旦大学附属妇产科医院，上海 200032
- Publication Type:Journal Article
- Keywords:
Intrauterine hyperandrogen exposure;
Offspring;
Chronic low-grade inflammation;
Insulin sensitivity
- From:
Chinese Journal of Reproduction and Contraception
2021;41(8):747-753
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To observe the weight,fat distribution,pesistent low-grade inflammation and insulin sensitivity of SD female rats in neonatal,adolescent and adult periods,which were exposed with intrauterine high androgen.Methods:Fifteen offspring female rats which were exposed to high level of intrauterine testosterone in late pregnancy were obtained by subcutaneous injection of 2 mg testosterone into pregnant SD rats at 18-20 d of gestation. They were ascribed to the intrauterine testosterone group. At the same time, fifteen female offspring obtained from the pregnant SD rats injected with the same volume saline were as control group. The weight and body fat content were observed in neonatal stage (4 d), adolescent stage (15 d) and adult stage (35 d) of offspring female rats. Tumor necrosis factor (TNF)-α and monocyte chemotactic factor (MCP)-1 were tested by enzyme-linked immunosorbent assay (ELISA). The expression of CD16 in peritoneal adipose tissue was detected by immune fluorescence staining. Intraperitoneal glucose tolerance test (IGTT) was performed in adolescent and adult female rats.Results:1) The weight of neonatal and adolescent female offspring in intrauterine testosterone group were significantly increased compared with control group [(101.17±9.19) g vs. (71.59±7.56) g, P<0.001; (211.61±11.94) g vs. (189.85±6.97) g, P=0.003]. Similarly, there was a significant difference in the ratio of fat and weight between the two groups (0.16±0.18 vs. 0.11±0.17, P=0.002; 0.27±0.18 vs. 0.21±0.18, P=0.006), while there were no obvious significance in adult offspring between the two groups ( P>0.05). 2) The body fat and muscle ratio of female offspring in intrauterine testosterone group were higher than those in control group during neonatal, adolescent and adult periods (0.05±0.04 vs. 0.08±0.05, P=0.031; 0.08±0.05 vs. 0.13±0.07, P=0.007; 0.12±0.04 vs. 0.18±0.06, P=0.005). 3) The serum TNF-α and MCP-1 levels in intrauterine testosterone group were higher than those in control group ( P<0.001, P=0.004),and the expression of CD16 in peritoneal adipose tissue was significantly increased ( P=0.018, P=0.031, P=0.004). 4) Following IGTT, compared with control group, the intrauterine testosterone group in puberty showed significantly higher 120 min glucose level [(165.00±58.68) mg/dL vs. (123.90±65.16) mg/dL, P=0.028] and the adulthood showed higher 60 min [(189.73±69.87) mg/dL vs. (136.67±37.14) mg/dL, P=0.035] and 120 min [(170.18±32.66) mg/dL vs. (102.56±12.27) mg/dL, P=0.008] glucose level. Conclusion:The hyperandrogen exposure at late-geastation can lead to the excessive androgen and centripetal obesity of female offspring from newborn to adolescence, but the adverse effect on muscle formation can extent to adulthood. The intrauterine high testosterone environment facilitated to promote macro-phage to M1-subtype and maintain chronic low-degree inflammation. In addition, the insulin sensitivity decreased from puberty to adulthood, which was even worsen in adulthood.
