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Progesterone in Early Pregnancy Tied to Male Fetal Brain Gene Changes in Sheep

The team cautions these animal results are preliminary.

Overview

  • Researchers presenting at a major endocrinology meeting reported that giving pregnant ewes progesterone early in gestation changed gene activity in the frontal cortex of male fetuses.
  • Male fetuses showed higher expression of SRD5A1, a gene that helps turn progesterone and testosterone into brain‑active metabolites linked to neural development.
  • RNA sequencing found 437 nominal gene-expression changes with pathway shifts that included reduced CREB and reelin signaling and altered calcium signaling, which help guide neuron growth and communication.
  • The effects appeared sex specific and did not include changes to key steroid hormone receptors, with females showing no comparable shifts under the same dosing plan.
  • Progesterone is widely used in early pregnancy to lower miscarriage risk and is considered safe short term, and the researchers said more mechanistic and follow‑up studies are planned to test if these fetal changes last and matter for humans.