Prenatal Progestin Exposure Induces Neurodevelopmental Alterations in Offspring Rats

Progestin, a synthetic progesterone analog, is widely used during pregnancy to prevent complications. Considering the cerebellum’s critical role in coordinating motor and higher cognitive functions implicated in autism spectrum disorder (ASD), this study examined the consequences of prenatal progestin exposure on cerebellar development and autism-related behaviors in offspring.

Twenty-four pregnant rats were randomly assigned to treatment (progestin 10 mg/kg BW) or control groups (n=12 each), with injections administered on gestational days 1, 7 and 14. Male offspring (n=10/group, randomly selected from different litters) were evaluated at 10 weeks using validated behavioral assays, including marble burying and nestlet shredding, to assess repetitive traits. Cerebellar tissue was processed for histological examination, oxidative stress profiling and immunohistochemical detection of estrogen receptor β (ERβ).

Progestin-exposed offspring exhibited significantly heightened repetitive behaviors. Histological analysis showed marked cerebellar alterations, particularly Purkinje cell degeneration and loss of Nissl bodies. Oxidative stress markers revealed disrupted redox balance, with elevated NADPH oxidase activity and decreased antioxidant enzyme levels. ERβ expression was significantly reduced across the cerebellar cortex, especially in Purkinje cells.