PMID- 19283862
OWN - NLM
STAT- MEDLINE
DCOM- 20090617
LR  - 20151119
IS  - 1542-9741 (Electronic)
IS  - 1542-9733 (Linking)
VI  - 86
IP  - 2
DP  - 2009 Apr
TI  - Effects of natalizumab, an alpha4 integrin inhibitor, on fertility in male and 
      female guinea pigs.
PG  - 108-16
LID - 10.1002/bdrb.20191 [doi]
AB  - BACKGROUND: Natalizumab is a humanized monoclonal immunoglobulin G4 antibody 
      directed against the human alpha4 integrin subunit disrupting interaction with 
      its ligands. As alpha4 integrins and/or their ligands 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 bolus 
      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 necropsy (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 reduced in females 
      treated with 30 mg/kg natalizumab, but not those treated with 3 or 10 mg/kg. 
      Pregnancy rates were 63.3, 66.7, 66.7, and 29.6% for groups treated with 0, 3, 
      10, and 30 mg/kg, respectively. 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 the high dose of 30 mg/kg.
CI  - (c) 2009 Wiley-Liss, Inc.
FAU - Wehner, Nancy G
AU  - Wehner NG
AD  - Elan Pharmaceuticals, Inc., South San Francisco, California 94080, USA. 
      nancy.wehner@elan.com
FAU - Skov, Michael
AU  - Skov M
FAU - Shopp, George
AU  - Shopp G
FAU - Rocca, Meredith S
AU  - Rocca MS
FAU - Clarke, Janet
AU  - Clarke J
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PL  - United States
TA  - Birth Defects Res B Dev Reprod Toxicol
JT  - Birth defects research. Part B, Developmental and reproductive toxicology
JID - 101155115
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Natalizumab)
RN  - 143198-26-9 (Integrin alpha4)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/blood/immunology/pharmacology/*toxicity
MH  - Antibodies, Monoclonal/blood/immunology/pharmacology/*toxicity
MH  - Antibodies, Monoclonal, Humanized
MH  - Antibody Formation
MH  - Body Weight/drug effects
MH  - Dose-Response Relationship, Drug
MH  - Drug Evaluation, Preclinical
MH  - Embryo Implantation/drug effects
MH  - Embryonic Development/*drug effects
MH  - Female
MH  - Fertility/*drug effects
MH  - Fertilization/drug effects
MH  - Fetus/drug effects
MH  - Guinea Pigs/embryology/*physiology
MH  - Infertility, Female/*chemically induced
MH  - Integrin alpha4/*immunology
MH  - Male
MH  - Natalizumab
MH  - Pregnancy
MH  - Pregnancy Rate
MH  - Random Allocation
MH  - Sperm Motility/drug effects
MH  - Spermatogenesis/drug effects
EDAT- 2009/03/14 09:00
MHDA- 2009/06/18 09:00
CRDT- 2009/03/14 09:00
PHST- 2009/03/14 09:00 [entrez]
PHST- 2009/03/14 09:00 [pubmed]
PHST- 2009/06/18 09:00 [medline]
AID - 10.1002/bdrb.20191 [doi]
PST - ppublish
SO  - Birth Defects Res B Dev Reprod Toxicol. 2009 Apr;86(2):108-16. doi: 
      10.1002/bdrb.20191.