The effects of intra-uterine growth retardation and postnatal undernutrition on onset of puberty in male and female rats.

The nutritional status, prenatally and early postnatally, plays a critical role in postnatal growth and development. Early malnutrition may change the original programming of organs, especially those in developmental phases, which can result in long-term changes in metabolism. The association between a low birth weight and the increased risk on type 2 diabetes, hypertension and cardiovascular disease is well known. In the present study we investigated whether intrauterine malnutrition or direct postnatal food restriction affects the onset of puberty in male and female rats. Intrauterine growth retardation (IUGR) was induced by uterine artery ligation on day 17 of gestation and postnatal food restriction (FR) by litter-enlargement to 20 pups per mother from day 2 after birth until weaning (24 d). Both models of malnutrition resulted in a persistent growth failure postnatally. The parameter of the onset of puberty was balano-preputial-separation (BPS) in the male rat and vaginal opening (VO) in the female rat. In both male IUGR (n = 26) and FR (n = 20) rats, the age at BPS was significantly delayed, with 48.1 +/- 1.9 d (p < 0.0001) and 50.4 +/- 2.9 d (p < 0. 0001), respectively, compared with controls (n = 30) with 45.8 +/- 1.4 d. In female IUGR rats (n = 37) the age at VO was significantly delayed, with 37.4 +/- 2.7 d (p < 0.04) compared with 36.1 +/- 1.5 d in controls (n = 23), but not in female FR rats (n = 18) with 36.5 +/- 2.2 d. Weight at onset of puberty did not differ between male IUGR and control rats, 194.5 +/- 20.0 g and 201.7 +/- 16.8 g, respectively, but was significantly lower in male FR rats with a weight of 175.6 +/- 17.5 g (p < 0.0001). In female IUGR as well as in female FR rats, weight at onset of puberty was significantly lower compared with controls: weight in IUGR 106.1 +/- 13.1 g (p < 0.001), weight in FR 85.3 +/- 7.6 g (p < 0.0001) and weight in controls 116.9 +/- 9.3 g. We conclude that early malnutrition, during late gestation or direct postnatally, results in a delayed onset of puberty in IUGR and FR male rats and in IUGR female rats, but not in FR female rats. The onset of puberty in these growth retarded rats as well as in controls does not depend on the achievement of a certain, crucial weight. The perinatal period appears to be a "critical time period" for the maturational process of pubertal development.