Consequences of fetal exposure to analgesics for germ cells
Hurtado Gonzalez, Pablo Ignacio
Despite the general advice of avoiding medication during pregnancy, the majority of pregnant woman use one or more ‘over the counter’ analgesics. During the last few years there has been growing evidence that analgesic exposure, such as paracetamol, ibuprofen or indomethacin, during pregnancy can have detrimental effects on rodent and human fetal gonads. The majority of previous studies have focused in alterations in testosterone production and male reproductive disorders. However, few studies have analysed the effect of these analgesics on fetal germ cells and possible consequences on fertility. During my thesis, I first focused on the effect of paracetamol and indomethacin exposure during pregnancy on rat fetal gonads. These showed that both paracetamol and indomethacin are able to alter the expression of genes important for fetal gonad and germ cell development. Previous studies on germ cells and analgesics have focused on rat models, but there is a lack of similar studies performed in human models. Therefore, I investigated the consequences of exposure of therapeutically relevant doses of paracetamol and ibuprofen on human gonads, with a special attention to the germ cells. Fetal gonads from the 1st and 2nd trimester were used in two different models: hanging drop cultures for 1st trimester testes and ovaries and a xenograft system for 2nd trimester fetal testes. Fetal gonad culture in the presence of paracetamol or ibuprofen reduced AP2γ+ (gonocyte) GC number in both 1st trimester fetal testes (22-28% reduction) and ovaries (43-49% reduction). 2nd trimester fetal testes were exposed to three different regimes, 1 or 7 days paracetamol and 7 days ibuprofen, which led to reductions of 17% and 30%, respectively in AP2γ+ GC number for paracetamol and a 53% reduction in total germ cell number for ibuprofen.