Failure to Demonstrate Effects in the Progeny of Rats Treated with Gonadotropin Prior to Mating

Abstract

Gonadotropins are commonly used for superovulation in animals and humans, as for instance, prior to in vitro fertilization. In humans, superovulation, in vitro fertilization and subsequent embryo transfer with successful pregnancy are known to have a high incidence of low birth-weight babies (Doyle et ul. 1992). In animals, small-sized offspring following maternal superovulation has been attributed to overcrowded uteri (Evans et ul. 1981). However, foetal growth retardation was also found in animals treated with ovulation-inducing human chorionic gonadotropin hormone alone (Ertzeid et al. 1992). Previous studies showed that mice treated with pregnant mare serum gonadotropin and human chorionic gonadotropin or with human chorionic gonadotropin alone prior to mating exhibited delayed implantation and produced premature-like progeny with dekayed maturation of skeletal structures (Ertzeid & Storeng 1992; Ertzeid et ul. 1993). Because delayed physical development might be expected to influence behavioural performance, we designed a preliminary study to investigate a possible association between hormone treatment and postnatal development in rats. Animals and treatment.Sixteen virus-free DNOLNHSD female rats, 12 weeks old, (Shaws Farm, Oxfordshire, England) were kept for acclimatisation and examination of vaginal smears for the determination of the oestrus cycles for 4 weeks. The animals were housed two to each cage in Macrolone cages type 111. The room temperature was kept at 20" with a relative humidity of 40-60 %. The light cycle was from 8.00 a.m. to 8.00 p.m. of light/darkness. They were fed a commercial pelleted diet for rats (Ewos, Siidertiilje, Sweden) ad libitum with free access to drinking water. Following the examination of vaginal Author for correspondence: lnger Nafstad, Norwegian College of Veterinary Medicines, Pb. 8146 Dep, N-0033, Oslo, Norway (fax +472565704).smears to determine the stages in the hormonal cycle, the rats were divided in two groups. Each animal in the test group was treated with a subcutaneous injection of 5 1U pregnant mare serum gonadotropin (Antex, LEO, Copenhagen, Denmark) in 0.2 ml sterile saline, followed by a subcutaneous injection of 5 IU human chronionic gonadotropin (Physex, LEO) in 0.2 ml sterile saline after 48 hours. The animals in the control group were treated at an identical scheme with 0.2 ml sterile saline as subcutaneous injections. Immediately after the last injection, each animal of both groups was mated with a male rat of the same strain obtained from the same supplier.Examination of physicul development and learning performance. The dams that littered were allowed to keep their offspring for a period of 4 weeks during which the pups were subjected to examinations of their physical development according to the methods described by Alder (1983). After weaning, 8 pups selected from 3 litters in the test group and 8 pups selected from 4 litters in the control group were subjected to behavioural testing. Due to uneven sex distribution, the test group consisted of 3 m...