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Impaired fertility in T-stock female mice after superovulation

¹ Biology and Biotechnology Research Program, L-448, Lawrence Livermore National Laboratory, 7000 East Avenue, Livermore, CA 94550, USA and ² Developmental Genetic Toxicology, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA

Correspondence should be addressed to Francesco Marchetti; Email: marchetti2{at}llnl.gov

Superovulation of female mice with exogenous gonadotrophins is routinely used for increasing the number of eggs ovulated by each female in reproductive and developmental studies. We report an unusual effect of superovulation on fertilization in mice. In vivo matings of superovulated T-stock females with B6C3F1 males resulted in a two-fold reduction (P < 0.001) in the frequencies of fertilized eggs compared with control B6C3F1 matings. In addition, approximately 22 h after mating, only 15% of fertilized eggs recovered in T-stock females had reached the metaphase stage of the first cleavage division versus 87% in B6C3F1 females (P < 0.0001). Matings with T-stock males did not improve the reproductive performance of T-stock females. To investigate the possible cause(s) for the impaired fertilization and zygotic development, the experiments were repeated using in vitro fertilization. Under these conditions, the frequencies of fertilized eggs were not different in superovulated T-stock and B6C3F1 females (51.7 ± 6.0 and 64.5 ± 3.8%, P = 0.10). There was a seven-fold increase in the frequencies of fertilized eggs that completed the first cell cycle of development after in vitro versus in vivo fertilization in T-stock females. These results rule out an intrinsic deficiency of the T-stock oocyte as the main reason for the impaired fertility after in vivo matings, and suggest that superovulation of T-stock females may induce a hostile oviductal and uterine environment with dramatic effects on fertilization and zygotic development.

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