Do progesterone administration methods affect offspring development?

Progesterone (P4) is commonly used in clinical settings to support pregnancies, particularly in cases of luteal insufficiency and preterm abortion. Despite its widespread use, the long-term effects of P4 on offspring development are not well understood. Previous studies have shown conflicting results, with some suggesting benefits such as improved exercise skills, while others hint at potential risks like an increased likelihood of autistic spectrum disorder (ASD).

To fill this gap, the study, published in Reproductive and Developmental Medicine, seeks to provide clearer insights by examining the long-term impact of different P4 administration routes on offspring neurobehavior and gut microbiota. Researchers from Shanghai Institute for Biomedical and Pharmaceutical Technologies randomly classify female rats into four groups based on different administration methods: oral administration, intramuscular injection, vaginal gel application, and a control group with no treatment. P4 was administered daily for 13 consecutive days during the teratogenesis-sensitive period, a vulnerable stage for birth defects.

The results showed that offspring from the orally administered P4 group exhibited significantly prolonged swimming times compared to controls, suggesting enhanced physical stamina. In contrast, intramuscular and vaginal routes showed no such effect. Beyond endurance performance, oral administration of P4 also correlated with elevated plasma pregnenolone levels, a neurosteroid tied to exercise adaptation, and reduced non-social behaviors.

The gut microbiota analysis also showed differences across groups. Oral and intramuscular methods altered microbial composition, with oral administration uniquely reducing Oligella—a bacterium linked to poorer exercise performance in prior studies.

While P4 administration did not alter some pregnancy outcomes like pregnancy duration or birth weight, the study underscores that delivery routes may differentially impact offspring resilience. Even though this study provides valuable insights, larger-scale validation studies are needed to confirm these results and explore the underlying mechanisms.“In the future, more animal studies should be conducted to verify the relationship between motor endurance and P4 treatment routes.” the study concluded.