Wehner et al. Effects of natalizumab, an alpha4 integrin inhibitor, on fertility in male and female guinea pigs. Birth Defects Res B Dev Reprod Toxicol. 2009 Apr;86(2):108-16.
Background: Natalizumab is a humanized monoclonal immunoglobulin IgG4 antibody directed against the human adhesion molecule subunit, alpha4 integrin, disrupting interaction with its binding partners. As alpha4 integrins and/or their binding partners appear to be involved in reproductive function, the effects of natalizumab on fertility in male and female guinea pigs were investigated.
Methods: Natalizumab was administered by intravenous injection every other day at doses of 0, 3, 10, and 30 mg/kg. Males began treatment at least 28 days prior to mating until they were sacrificed for the study (approximately 3 to 5 days after mating). Dosing in females was done from gestational day (GD) of an existing pregnancy to GD 30 of a second pregnancy.
Results: In male guinea pigs, natalizumab treatment had no effect on sperm parameters, reproductive organ weights, organ-weight ratios, or histology of the testis or epididymis. Natalizumab did not affect the ability of treated males to produce pregnancies in untreated females. In female guinea pigs, no treatment-related changes were seen in uterine weights or ovary weights. Pregnancy rates were, however, reduced in females treated with 30 mg/kg natalizumab, but not those treated with 3 or 10 mg/kg. Pregnancy rates were 63, 67, 67, and 30% for groups treated with 0, 3, 10, and 30 mg/kg, respectively. The effects observed at 30 mg/kg were at exposures 36-fold those observed in humans.
Conclusions: Natalizumab had no effects on male fertility, but did result in a reduction in pregnancy rates in females treated with very high doses of natalizumab.