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MJ Engelbregt, MM van Weissenbruch, C Popp-Snijders, and HA Delemarre-van de Waal

In the present study we examined the consequences of intrauterine growth retardation and postnatal food restriction on the maturational process of sexual development by studying onset of first cycle. In addition, we investigated the effect of pregnant mare serum gonadotropin (PMSG) on ovarian growth and ovulation in intrauterine growth-retarded (IUGR) and postnatally food-restricted (PFR) rats. Intrauterine growth retardation was induced by uterine artery ligation on day 17 of gestation and food restriction was achieved by enlarging the litter to 20 pups per mother from day 2 after birth until weaning (day 24). In control rats, vaginal opening and the first cycle took place on the same day. In IUGR rats, uncoupling occurred between vaginal opening and the first cycle. Vaginal opening was delayed (P<0.05) and the first cycle was even further delayed (P<0.01) compared with controls. Body weight in IUGR rats was lower (P<0.05) at vaginal opening, but at first cycle and after stimulation with 50 IU PMSG in the first cycle it was similar to that in controls. In the ovaries of IUGR rats, the numbers of primordial (P<0.05), growing (P<0.01) and antral follicles (P<0.01), and the total number of follicles (P<0.01) were lower than in controls after stimulation with 50 IU PMSG at first cycle. The number of corpora lutea in the ovaries of the IUGR rats and the controls was similar and reflected superovulation. In the PFR rats, vaginal opening occurred at the same time as in control rats, but at a lower body weight (P<0.01). First cycle was much delayed (P<0.01), by which time body weight was greater (P<0.01) than that of controls at first cycle. On the basis of the differences in weight and age between PFR rats and controls at first cycle, we performed two studies. In study A, ovaries were analysed histologically 42 h after stimulation with PMSG at first cycle of control rats and age-matched PFR rats. In study B, the ovaries of PFR rats at first cycle and age-matched control rats were examined 42 h after PMSG stimulation. In the ovaries of the PFR rats in study A, a greater total number of follicles (P<0.05) was observed, represented by a greater number of primordial follicles (P<0.01) and a lower number of antral follicles (P<0.05), including corpora lutea. The number of corpora lutea in the ovaries of the PFR rats was significantly lower than that in controls (P<0.01). The total number of follicles in the ovaries of the PFR rats of study B did not differ from the age-matched controls after PMSG stimulation at first cycle, and neither did the number of the follicles in the different classes. We conclude that, in IUGR rats at first cycle, PMSG can induce multiple follicular growth and development followed by superovulation comparable to that in controls, despite a decreased total number of follicles in the ovaries. However, in PFR rats of the same age, the ovary is not capable of responding adequately to PMSG, despite a greater total number of follicles. Stimulation with PMSG at first cycle resulted in follicular growth and superovulation comparable to those in age-matched controls. Undernutrition in different critical time periods around birth in the rat leads to ovarian development in such a way that, in both groups, an increased risk of reduced reproductive capacity can be expected.