Effects of feed restriction on fertility in female rats.
BACKGROUND
Feed restriction with its resultant body weight loss impacts the rodent estrous cycle; however, the manifestation of these changes in a regulatory study design has not been documented. This study reports the effects of feed restriction in the context of an FDA regulatory submission.


METHODS
Adult female rats (n = 20/group; weighing approximately 200 g each) were provided rodent chow ad lib (control) or at 20, 15, 10, or 7.5 g/rat/day (g/day) during a 2-week pre-mating phase, throughout the mating phase, and up to gestation day (GD) 7. On GD 8, all animals were provided ad lib feed until necropsy on GD 14. Estrous cyclicity, mating, and fertility parameters were evaluated.


RESULTS
Ad lib rats consumed approximately 20 and 28 g/day during the pre-mating and gestation phases, respectively. All measured fertility parameters in the 20 g/day group were similar to control values. In the 15 g/day group, body weight was reduced by 16% at 2 weeks, prolonged diestrus occurred, and fertility was compromised due to reductions in corpora lutea. Within 2 weeks, mean body weight in groups receiving < or = 10 g/day was reduced by > or = 29% compared to ad lib values, and overt changes in estrous cyclicity, mating, and fertility occurred. The 7.5 g/day group was not sustainable beyond the pre-mating phase.


CONCLUSIONS
For this study type, feed intake at < or = 50% ad lib values (< or = 10 g/day) was inadequate due to the magnitude and rapidity of body weight effects. Estrous parameters appeared slightly more sensitive than functional measures, as body weight changes of approximately 16% appeared near the threshold of changing routinely calculated estrous cycle parameters and were later associated with reduced fertility. In general, body weight differences of 10-15% by themselves were not adverse to normal reproduction (20 g/day).
Terry
K K
KK
Pfizer Global Research and Development, Groton, Connecticut 06340, USA. ketti.k.terry@pfizer.com
Chatman
L A
LA
Foley
G L
GL
Kadyszewski
E
E
Fleeman
T L
TL
Hurtt
M E
ME
Chapin
R E
RE
D000818:Animals; D001835:Body Weight; D030762:Estrous Cycle / Q000502:physiology*; D005260:Female; D005298:Fertility / Q000502:physiology*; D005508:Food Deprivation / Q000502:physiology*; D008297:Male; D009929:Organ Size; D011247:Pregnancy; D051381:Rats; D012726:Sexual Behavior, Animal