Caloric restriction (CR), an energy-restricted intervention with undernutrition instead of malnutrition, is widely known to prolong lifespan and protect against the age-related deteriorations. Recently it is found that CR significantly affects female reproduction via hypothalamic (corticotropin releasing hormone, neuropeptide Y, agouti-related peptide) and peripheral (leptin, ghrelin, insulin, insulin-like growth factor) mediators, which can regulate the energy homeostasis. Although CR reduces the fertility in female mammals, it exerts positive effects like preserving reproductive capacity. In this review, we aim to discuss the comprehensive effects of CR on the central hypothalamus-pituitary-gonad axis and peripheral ovary and uterus. In addition, we emphasize the influence of CR during pregnancy and highlight the relationship between CR and reproductive-associated diseases. Fully understanding and analyzing the effects of CR on the female reproduction could provide better strategies for the management and prevention of female reproductive dysfunctions.

Kisspeptin and its G protein-coupled receptor KISS1R play key roles in mammalian reproduction due to their involvement in the onset of puberty and control of the hypothalamic-pituitary-gonadal axis. However, recent studies have indicated a potential role of extra-hypothalamic kisspeptin in reproductive function. Here, we summarize recent advances in our understanding of the physiological significance of kisspeptin/KISS1R in the peripheral reproductive system (including the ovary, testis, uterus, and placenta) and the potential role of kisspeptin/KISS1R in reproductive diseases. A comprehensive understanding of the expression, function, and potential molecular mechanisms of kisspeptin/KISS1R in the peripheral reproductive system will contribute to the diagnosis, treatment and prevention of reproductive diseases.

Background: Titanium dioxide nanoparticles (TiO₂ NPs) have recently found applications in a wide variety of consumer goods. TiO₂ NPs exposure significantly increases fetal deformities and mortality. However, the potential toxicity of TiO₂ NPs on the growth and development of placenta has been rarely studied during mice pregnancy. Purpose: The objective of this study was to investigate the effects of maternal exposure of TiO₂ NPs on the placentation. Methods: Mice were administered TiO₂ NPs by gavage at 0, 1 and 10 mg/kg/day from gestational day (GD) 1 to GD 13. Uteri and placentas from these mice were collected and counted the numbers of implanted and resorbed embryo and measured the placental weight on GD 13. Placental morphometry was observed by hematoxylin and eosin staining. The levels of Hand1, Esx1, Eomes, Hand2, Ascl2 and Fra1 mRNA were assessed by qRT-PCR. Uterine NK (uNK) cells were detected by using DBA lectin. Laminin immunohistochemical staining was to identify fetal vessels. Western blotting and transmission electron micrograph (TEM) were used to assess the apoptosis of placenta. Results: No treatment-related difference was observed in the numbers of implanted and resorbed embryos and weight of placenta between the groups. However, 1 mg/kg/day TiO₂ NPs treatment significantly reduced the ratio of placenta/body weight on GD 13. The proportion of spongiotrophoblast in the 10 mg/kg/day dose group became higher than that in the control group, yet that of labyrinth was significantly lower in 10 mg/kg/day mice. The expression levels of Hand1, Esx1, Eomes, Hand2, Ascl2 and Fra1 mRNA markedly decreased in TiO₂ NP treated placentas. Furthermore, TiO₂ NPs treatment impaired the formation of intricate networks of fetal vessels and reduced the number of uNK cells, and inhibited proliferation and induced apoptosis of placenta by nuclear pyknosis, the activation of caspase-3 and upregulation of Bax protein and downregulation of Bcl-2 protein on GD 13. Conclusion: Gestational exposure to TiO₂ NPs significantly impairs the growth and development of placenta in mice, with a mechanism that seems to be involved in the dysregulation of vascularization, proliferation and apoptosis. Therefore, our results suggested the need for great caution while handling of the nanomaterials by workers and specially pregnant consumers.