Maternal hyperthermia disrupts developmental competence of follicle-enclosed oocytes: In vivo and ex vivo studies in mice

Mammalian oocytes are susceptible to thermal stress at various stages of follicular development. We examined whether the ovarian pool of oocytes is susceptible to maternal hyperthermia and if so, whether hyperthermia at the germinal vesicle (GV) stage further affects the developmental competence of preimplantation embryos and offspring quality. Synchronized female mice were exposed to thermal stress (40 degrees C, 65% RH) for 1.5-2 h or maintained under normothermal conditions (25 degrees C, 45% RH). Thereafter, mice were paired with stud males. In the first experiment, mated mice were sacrificed 20 h post hCG administration, and in vivo-derived zygotes were recovered and cultured in vitro. Maternal hyperthermia decreased the percentage of putative zygotes of apparent normal morphology in the heat-stressed group (81 +/- 1.3%) as compared to the control group (86 +/- 1.2%). Developmental competence was also compromised as expressed by the disruption in cleavage timing pattern, resulting in a reduced developmental rate to the blastocyst stage (57 +/- 2.6% versus 84 +/- 1.9%). In the second experiment, both groups were left with stud males until litter delivery. Litter size in the first delivery cycle was lower for the heat-stressed group (7.7 +/- 1.1 pups), followed by a slight increase throughout consecutive cycles as compared to the control group (11.3 +/- 1.0 pups). Behavioral examinations of 8-week-old pups revealed similar locomotor activity and learning potential between the groups. In summary, the findings indicate that a subpopulation of the ovarian pool of follicles is highly sensitive to thermal stress and that maternal hyperthermia disrupts developmental competence of GV-stage oocytes. Pups that developed from oocytes that survived thermal stress exhibited a developmental potential similar to that of the of control pups. (c) 2006 Elsevier Inc. All rights reserved.