Prenatal Progesterone Treatment Induces Sex-dependent Anxiety and Depressive-like Behaviour in Adult Offspring

Abstract

Exogenous treatment during pregnancy with steroid hormones (estrogens, androgens, or glucocorticoids) affects the development of the fetus and the sexually mature generation. In clinical practice, the hormone progesterone is used therapeutically in programmes for assisted reproduction, infertility treatment, threatened abortion and premature birth. The hormone has a key role in establishing and maintaining pregnancy through its endocrine and immunological effects. Despite the fact that progesterone is widely used during pregnancy, the long-term effects of fetal exposure to exogenous progesterone on child development have barely been investigated. The aim of the present study is to investigate sex-dependent changes in the emotional status of a generation of prenatally treated with progesterone offspring. Female pregnant rats were treated subcutaneously with progesterone (50 mg/kg) from gestational (G) period G0 to G10. Anxiety and depressive-like behaviour of male and female adult offspring were evaluated with an open field (OF) test, elevated plus maze test (EPM), light dark test (LDT), sucrose preference test (SPT) and forced swimming test (FST). Prenatal treated with progesterone male and female offspring exhibited lower horizontal and vertical activity compared to the male and female control rats in the open field test and decreased distance and time spent in the open arms compared to the matched controls in the EPM test. They demonstrated depressive-like responses with anhedonia in the SPT and increased immobility time in the FST compared to the matched controls. Prenatal treatment with progesterone significantly affected emergence latency, time spent and crossing to the lit compartment in LDT. In conclusion, our results suggest that prenatal treatment with 50 mg/kg progesterone exerts a detrimental effect on emotional behaviour in male and female offspring. Future studies are needed to ascertain the underlying mechanism associated with these sustained behavioural abnormalities due to prenatal hormonal treatment.