Excessive exposure to progesterone in the womb may alter a gene in the frontal cortex of male sheep fetuses, which is essential for brain development and function, according to research presented at the 28th European Congress of Endocrinology in Prague. This discovery highlights the important role of hormones in fetal development and potentially adult disease susceptibility in different sexes.
Progesterone – a steroid hormone that supports and maintains pregnancy, and regulates the menstrual cycle – is commonly prescribed during early pregnancy, especially for women at increased risk of miscarriage or during assisted reproduction. While progesterone is widely used and considered safe in the short term, not much is known about its long-term effects on fetal development and function.
Researchers at Edinburgh Napier University, the University of Edinburgh and the University of Aberdeen have previously shown that increased prenatal exposure to progesterone can increase progesterone levels in male sheep fetuses and alter their pituitary and testicular function, as well as their steroid profiles. Now, in this study, researchers injected pregnant sheep with 200 mg of progesterone twice a week, from days 20 to 75 (equivalent to 15 weeks of pregnancy in humans) and found that, in male fetuses, exposure to progesterone was associated with increased accumulation of a gene called SRD5A1 in the frontal cortex – a gene whose encoded product is involved in the processing of sex hormones that are important for brain development and function. Are. While no changes were found in major hormone receptors or related enzymes in either sex, changes in several important biological pathways such as calcium signaling were observed in male fetuses.
Our findings suggest that male and female sheep fetuses may respond differently to maternal progesterone treatment, with some effects observed only in males. “As we look at effects at the gene level, however, we do not know whether these have any consequences – either positive or negative – on normal development, health and behavior after birth and as the offspring age.”
Dr Katarzyna Siemienowicz, lead author, Edinburgh Napier University, UK
He added: “Although sheep are highly valued animal models in research due to their human-like size, organ dimensions and long lifespan, this is still an early stage study in an animal model and further research is needed to understand whether these findings are relevant to humans.”
Researchers now plan to investigate the exact mechanisms by which progesterone may alter brain development and whether these changes have any lasting effects later in life. “Given that the developing brain is responsive to progesterone, this exposure may affect neural development but again the fetal brain is highly plastic and changes observed during fetal life may not continue postnatally. Thus, our goal is to better understand how progesterone and related hormones affect the developing brain, including by measuring hormone levels directly in brain tissue,” Dr. Siemienowicz said.
