Consequences of fetal exposure to analgesics for germ cells
View/ Open
Date
30/06/2018Author
Hurtado Gonzalez, Pablo Ignacio
Metadata
Abstract
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.