Short term intrauterine exposure of glucocorticoids does affect lipid metabolism and reproduction of common marmoset monkey

Program: Abstracts - Orals, Featured Poster Presentations, and Posters
Session: MON 498-514-Female Reproductive Endocrinology
Monday, June 17, 2013: 1:45 PM-3:45 PM
Expo Halls ABC (Moscone Center)

Poster Board MON-514
Almuth Einspanier*1, Ulrike Buchwald2, Nancy Schmieder2 and Richard Utsch2
1Inst of Physiological Chemistry, Leipzig, Germany, 2Institute of Physiological Chemistry, Leipzig, Germany
Application of synthetic glucocorticoids is commonly used during human fetal development (e.g. for reduction of morbidity and mortality in preterm infants). There is rising evidence that intrauterine exposure of glucocorticoids may compromise health and development in the offspring. The aim of the study was to investigate effects of short term dexamethasone (DEX) application during pregnancy on the lipid metabolism and reproduction of the filial generations in common marmosets. Blood parameters of lipid metabolism from filial generations (F1: n=6, F2: n=6, F3: n=5) of DEX treated monkeys were compared to control animals (n=12). Furthermore, reproduction capability of female (n= 12) and male offspring (n=12) was analyzed.

Peripheral sex steroid levels ranged similar in the intrauterine DEX treated female and male offspring versus control at adult stage. DEX treated females showed significantly earlier signs of sexual cycle activity than control (~ 16 versus ~ 20 months) at similar breeding success. For the male situation, enhanced testicular gene and protein expression were apparent in the DEX group for the following parameters: androgen receptor, aromatase, estrogen receptor 1, 17β-hydroxysteroid dehydrogenase type 7, relaxin receptor 2, Ki 67 and ras.

Analyzing the blood parameters of lipid metabolism, the F1 generation showed no significant differences, whereas in the F2 and F3 generation higher cholesterol and lower triglyceride levels were observed. Moreover, F2 generation exhibited significantly more low density lipoprotein cholesterol (median 1.8mmol/l compared to 1.0mmol/l, p=0.01) and significantly less high density lipoprotein triglycerides (median 21.0mg/dl versus 34.7mg/dl, p=0.01). F3 generation exhibited significantly higher levels of LDL cholesterol (median 2.2mmol/l compared to 1.0mmol/l, p=0.03) and significantly lower levels of HDL triglycerides (median 25.3mg/dl versus 34.7mg/dl, p=0.03), too. There was a significantly lower percentage of blood n3 fatty acids in F1, F2 and F3 offspring of DEX treated dams compared to controls.

In summary, prenatal environment has profound effects on adult life as well as on following generations, showing gender depending effects. It needs further analysis if the enhanced local testicular factors lead to a highly effective steroid biosynthesis or would possibly create tumors. Finally, short term prenatal DEX application led to higher amounts of cardiovascular risk factors like LDL cholesterol and less protective n3 fatty acids in F2 and F3 generation, but not in the direct effected F1 generation. The intergenerational consequences suggest prenatal programming through epigenetic effects.

Nothing to Disclose: AE, UB, NS, RU

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