According to a new study, published in the April edition of the journal Environmental Health Perspectives, taking painkillers such as paracetamol (acetaminophen) and ibuprofen during pregnancy could affect the fertility of the child in later life; these drugs may also affect the fertility of future generations, by leaving epigenetic marks on DNA.
Current guidelines say that, if necessary, paracetamol should be used at the lowest possible dose for the shortest possible time; ibuprofen should be avoided during pregnancy. Image credit: Steve Buissinne.
“We would encourage women to think carefully before taking painkillers in pregnancy and to follow existing guidelines — taking the lowest possible dose for the shortest time possible,” said study senior author Dr. Rod Mitchell, from MRC Centre for Reproductive Health at the University of Edinburgh, UK.
Dr. Mitchell and his colleagues the University of Edinburgh and Copenhagen University Hospital, Denmark, looked at the effects of paracetamol and ibuprofen on samples of human fetal testes and ovaries.
They found similar effects using several different experimental approaches, including lab tests on human tissue samples and animal studies.
Human tissues exposed to either drug for one week in a dish had reduced numbers of cells that give rise to sperm and eggs, called germ cells, the study found.
Ovaries exposed to paracetamol for one week had more than 40% fewer egg-producing cells. After ibuprofen exposure, the number of cells was almost halved.
“This is important because girls produce all of their eggs in the womb, so if they are born with a reduced number it could lead to an early menopause,” Dr. Mitchell and co-authors said.
Painkiller exposure during development could have effects on unborn boys too, the study found.
Testicular tissue exposed to painkillers in a culture dish had around a quarter fewer sperm-producing cells after exposure to paracetamol or ibuprofen.
The researchers also tested the effects of painkiller treatment on mice that carried grafts of human fetal testicular tissue.
These grafts have been shown to mimic how the testes grow and function during development in the womb.
After just one day of treatment with a human-equivalent dose of paracetamol, the number of sperm-producing cells in the graft tissue had dropped by 17%. After a week of drug treatment, there were almost one third fewer cells.
Dr. Mitchell’s team found that exposure to paracetamol or ibuprofen triggers mechanisms in the cell that make changes in the structure of DNA, called epigenetic marks.
These marks can be inherited, helping to explain how the effects of painkillers on fertility may be passed on to future generations.
Painkillers’ effects on germ cells are likely caused by their actions on molecules called prostaglandins, which have key functions in the ovaries and testes, the study authors found.
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Pablo Hurtado-Gonzalez et al. 2018. Effects of Exposure to Acetaminophen and Ibuprofen on Fetal Germ Cell Development in Both Sexes in Rodent and Human Using Multiple Experimental Systems. Environ Health Perspect 126 (4); doi: 10.1289/EHP2307
