Cyclosporine A exposure during pregnancy in mice: effects on reproductive performance in mothers and offspring.
BACKGROUND
Pregnancies after organ transplantation and under immunosuppressive treatment are associated with slightly elevated risks for obstetric and post-natal complications but can usually be managed well. However, little is known about the effects of intrauterine exposure (IUE) to immunosuppressants in the growing and adult offspring. One major issue is the potentially negative effects of immunosuppressive medication on reproduction. This study investigates the effect of exposure during pregnancy to the most commonly used immunosuppressant in organ transplantation, cyclosporine A (CsA), on the reproductive outcome in mothers and offspring.


METHODS
Female C57CBA-F1 mice received 0, 10, 20 or 30 mg/kg bodyweight of CsA daily by subcutaneous mini-osmotic pumps during mating and pregnancy. Blood concentrations of CsA, implantation rates, resorption rates and fetal weights were analysed. In addition, female and male mice exposed to CsA in utero were mated to unexposed partners and pregnancy outcomes were analysed.


RESULTS
Direct maternal exposure to CsA at high doses reduced implantation rates and fetal survival. IUE to CsA reduced adolescent growth but did not affect fertility, although a reduction in birthweight was seen in offspring of females exposed to CsA in utero.


CONCLUSIONS
CsA exposure during pregnancy correlates with impaired reproductive outcome, but offspring fertility is not affected. The cause of reduction in adolescent weight gain and low birthweight in offspring of females exposed to CsA in utero need further investigation.
Groth
K
K
Department of Obstetrics and Gynecology, Institute for Clinical Science, Sahlgrenska Academy at the University of Gothenburg, Sahlgrenska University Hospital, S-413 45 Göteborg, Sweden.
Brännström
M
M
Mölne
J
J
Wranning
C A
CA
D000818:Animals; D001724:Birth Weight / Q000187:drug effects; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000097:blood / Q000494:pharmacology*; D010064:Embryo Implantation / Q000187:drug effects; D005260:Female; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008297:Male; D051379:Mice; D018812:Paternal Exposure; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000187:drug effects*; D011297:Prenatal Exposure Delayed Effects; D012098:Reproduction / Q000187:drug effects*
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003404:Creatinine