Embryonic and postnatal development in experimental tryptophan deprived rats. A preliminary study

Abstract

An ontogenetic and endocrinological study has been designed on developing rats in uterus of mothers tryptophan deprived at day 1 (exp. 1) and day 14.5 (exp. 2) of conception to verify the supposed determining role of the serotoninergic system (SS) in sexual differentiation in mammals. Tryptophan-free feeding has been pursued uninterruptedly in the litter after birth, during lactation and postnatal development. Tryptophan-free pregnant rats were obtained by exclusion of tryptophan sources from chow. In both exp. 1 and exp. 2 the litter showed at birth a significant physical under evolution, that worsened, during post-natal development, to a much more marked dwarfism in exp. 1 pups. At 30 days postnatal age, whereas the female exp. 1 rats showed a right-timed onset of puberty, neither descensus of the testes nor spermatogenesis could be observed in the male rats of the same experiment. Endocrinologically the males showed a significant reduction of plasma FSH levels, but also a slight increase of those of LH. Moreover, a marked hypoandrogenism and a severe hypoprolactinemia characterized the males of this group. Hypoprolactinemia was the major endocrinological finding also in the female litter, which, however, at 30 days p.n. age showed the typical histological patterns of a cycling ovary, i.e. growing secondary follicles with scattered antral spaces, and thus a right-timed pubertal maturation, in spite of the significant lower plasma levels of pituitary gonadotropins and sex steroids. When mothers were tryptophan deprived at 14.5 of pregnancy (exp. 2), the litters showed a less marked dwarfism, persistent, severe hypoprolactinemia as in exp. 1 rats, but a normal right-timed onset of puberty in both male and female rats. Taken together these findings confirm on the one hand the close relationship between SS and PRL. On the other hand, they suggest a major, crucial role of PRL played in the male rat before day 14.5 of intrauterine development, presumably intervening in the synthesis of LH receptors sites by the maturing Leydig cells in the male gonads. Growth hormone concentrations in both sexes dwarf rats were lower than in control rats.

Pregnancy, embryo-fetal development and nutrition: physiology around fetal programming

“…In mice, the nutritional stress, during the pre-implantation phase, is often responsible of blastocyst death and pregnancy block [4]. Reduction, deprivation or imbalance of nutrients in the very early stages of pregnancy, before implantation, results not only in an obvious impaired somatic development at birth [5,6], but also in the profound alterations of endocrine and metabolic functions [7] and, often, in the impaired maturation of reproductive system in postnatal life [8]. In addition, observations from clinical, epidemiological and experimental studies in vivo and in vitro, showed that different nutrients seem to be able to influence both the normal course of pregnancy and the embryo-fetal development in different animal species, including humans ( Figure 1) [1][2][3].…”

“…In addition, observations from clinical, epidemiological and experimental studies in vivo and in vitro, showed that different nutrients seem to be able to influence both the normal course of pregnancy and the embryo-fetal development in different animal species, including humans ( Figure 1) [1][2][3]. Experimental results showed that undernutrition during pregnancy significantly reduces the number of infants in mice, by increasing the phenomenon of fetal resorption and neonatal mortality [9]; in sheep, it defers intrauterine development of the fetus [10] and in rats, it reduces the weight of pups at birth [8] (Table 1). In case of a severe maternal undernutrition, due to reduced caloric intake, there is a proportional increase in catabolic activity of maternal tissues that results in the release into the maternal-fetal circulation of many amino acids, vitamins and minerals, which are able to balance the insufficient "diet" of the fetus.…”

Serotonin/growth hormone/insulin-like growth factors axis on pre- and post-natal development: A contemporary review

“…In previous studies we investigated the lack of l-Trp, precursor of 5HT, in the diet of pregnant rats to analyse the effects on offspring. We showed impaired growth and development in pups of experimental rats and also alterations in sexual development in growing rats 33 . The most recent literature 31,34 shows the possible negative influence of the excess of 5HT on differentiation of serotonergic neurons of the raphe nuclei in the brainstem; consequently the reduction of pituitary GH production has a direct effect on hepatic production of IGF-I.…”

The Role of Malnutrition during Pregnancy and Its Effects on Brain and Skeletal Muscle Postnatal Development

“…Scientific data clearly indicates that the pre-implantation phase is the period of the greatest vulnerability for the future embryo in relation to several endogenous and/or exogenous factors, including nutritional ones [1]. Nutrient reduction, deprivation or imbalance before implantation, could result in somatic hypoevolutism at birth [2], alterations in endocrine and metabolic functions during postnatal life [3] and, often, impaired maturation of the reproductive system [4]. From clinical, epidemiological, and experimental studies, several nutrients seem to influence the regular course of pregnancy and the embryo-foetal development in different animal species, including humans.…”

“…From clinical, epidemiological, and experimental studies, several nutrients seem to influence the regular course of pregnancy and the embryo-foetal development in different animal species, including humans. Experimental results in mice have shown that undernutrition in pregnancy significantly reduces the number of puppies, increases the resorption of foetuses and increases neonatal mortality [5]; in sheep, it retards intrauterine development of the foetus [6]; in rats, it reduces the weight of pups at birth [4]. In relation to humans, to evaluate the specific influence of different nutrients on prenatal development is difficult, since a severe maternal undernutrition, with a reduction in caloric intake, will trigger a proportional increase in catabolic activity of the maternal tissues that cause the release in blood, and then in maternal-foetal circulation, of many amino acids, vitamins and minerals that will balance the deficit "diet" of the foetus.…”