The effects of small litter rearing on ovarian function at puberty and adulthood in the rat

Rearing rats in small litters lead to obesity and reproductive dysfunction. We investigated the effects of rearing female rats in small litters on various reproductive parameters during puberty and into adulthood, and examined the possible involvement of local ovarian sympathetic nerve activity. The litter size was adjusted on postnatal day one to four pups per dam for the small litters and 12 pups per dam for the normal litters. Vaginal opening was recorded, and estrous cyclicity was monitored daily immediately post puberty for 14 days and again at 8–9 weeks of age. At the time of puberty and 10 weeks of age, the ovaries were collected. The number of different types of follicles was counted and the thickness of the theca interna of the largest antral follicles was measured. Ovarian sympathetic nerve activity was assessed immunohistochemically by measuring levels of ovarian nerve growth factor receptor (p75NGFR) and tyrosine hydroxylase (TH). In rats reared in small litters, there was a significant advancement of puberty and disruption of estrous cyclicity immediately post puberty. The number of antral follicles increased in the small litter reared rats at puberty compared with their controls. The thickness of the theca interna increased and the expression profiles of ovarian p75NGFR and TH increased in small litter reared rats at puberty, but this did not persist into adulthood. These data suggest that rearing rats in small litters lead to irregular reproductive cycles, which might involve increased local ovarian sympathetic nerve activity.