Knockdown of regulatory associated protein of TOR (raptor) in hypothalamus-stimulated folliculogenesis and induced ovarian cysts.

CONTEXT: Mammalian target of rapamycin complex 1 (mTORC1) is an essential sensor that regulates fundamental biological processes like cell growth, proliferation and energy metabolism. The treatment of disease by sirolimus, a mTORC1 inhibitor, causes adverse effects, such as female fertility disorders. AIMS: The objective of the study was to decipher the reproductive consequences of a downregulation of mTORC1 in the hypothalamus. METHODS: The reduced expression of mTORC1 was induced after intracerebroventricular injection of lentivirus expressing a short hairpin RNA (shRNA) against regulatory associated protein of TOR (raptor) in adult female mice (ShRaptor mice). KEY RESULTS: The ShRaptor mice were fertile and exhibited a 15% increase in the litter size compared with control mice. The histological analysis showed an increase in antral, preovulatory follicles and ovarian cysts. In the hypothalamus, the GnRH mRNA and FSH levels in ShRaptor mice were significantly elevated. CONCLUSIONS: These results support the hypothesis that mTORC1 in the central nervous system participates in the regulation of female fertility and ovarian function by influencing the GnRH neuronal activity. IMPLICATIONS: These results suggest that a lower mTORC1 activity directly the central nervous system leads to a deregulation in the oestrous cycle and an induction of ovarian cyst development.

Maternal dietary supplementation with grape seed extract in reproductive hens increases fertility in females but decreases semen quality in males of the F1 generation.

Genetic selection in parental broiler breeders has increased their susceptibility to metabolic disorders and reproductive dysfunction. We have recently shown that maternal dietary grape seed extract (GSE) supplementation in hens improves fertility parameters, egg quality, oxidative stress in different tissues and the quality of F1 chicks. Here, we analysed the growth and fertility (both female and male) of the F1 generation animals and the quality of their offspring (F2 generation). Eggs issued from hens supplemented with GSE presented lower ROS production than control hens, suggesting a change in the embryonic environment. However, this did not affect the growth nor the body composition of male and female F1s from hatching to adulthood (37 weeks of age). At 37 weeks of age, the biochemistry analysis of the GSE-F1 muscle has revealed an increase in sensitivity to oxidative stress and a slight change in lipid composition. Both male and female F1-GSE groups presented a delay in puberty with a lower testis volume at 30 weeks of age and lower ovary development at 26 weeks of age. Adult GSE-F1 males did not present histological alterations of seminiferous tubules or semen production, but the semen quality was degraded due to higher oxidative stress and DNA-damaged spermatozoa compared with control F1 animals. In adult GSE-F1 females, despite the delay in puberty, the females laid more eggs of better quality (fewer broken eggs and a higher hatching rate). At hatching, the weight of the chicks from GSE-F1 females was reduced, and this effect was stronger in F2 male chicks (F2) compared with F2 control chicks (F2), because of the lower muscle volume. In conclusion, we can raise the hypothesis that maternal dietary GSE supplementation produces eggs with change in embryonic metabolism, which may affect in adulthood the fertility. The data obtained from the F1-GSE group pointed to a sex-specific modification with higher egg quality in females but semen sensitive to stress in males. Finally, male F2 chicks were leaner than control chicks. Thus, maternal dietary grape seed extract (GSE) supplementation in hens may impact on the fertility of the offspring in a sex-specific manner in subsequent generations.