Female mice haploinsufficient for an inactivated androgen receptor (AR) exhibit age-dependent defects that resemble the AR null phenotype of dysfunctional late follicle development, ovulation, and fertility

Abstract

The role of classical genomic androgen receptor (AR) mediated actions in female reproductive physiology remains unclear. Female mice homozygous for an in-frame deletion of exon 3 of the Ar (AR-/-) were subfertile, exhibiting delayed production of their first litter (AR+/+ = 22 d vs. AR-/- = 61 d, P < 0.05) and producing 60% fewer pups/litter (AR+/+: 8.1 ± 0.4 vs. AR-/-: 3.2 ± 0.9, P < 0.01). Heterozygous females (AR+/-) exhibited an age-dependent 55% reduction (P < 0.01) in pups per litter, evident from 6 months of age (P < 0.05), compared with AR+/+, indicating a significant gene dosage effect on female fertility. Ovulation was defective with a significant reduction in corpora lutea numbers..