Niacin Inhibits Apoptosis and Rescues Premature Ovarian Failure

Abstract

Background/Aims: Over 99% of mouse and human ovarian follicles will undergo specialized cell death including atresia and apoptosis. Reduction of apoptosis may help reduce infertility and maintain the reproductive ability in women. Methods: 3-day B6D2F1 mice were used to culture small follicle and ovary tissue with niacin and 18-day mice were intraperitoneal injected with niacin to determine its effect on follicle development. Then establish 8-weeks POF animal model with cytoxan (CTX) or radiation. Treatment group was given 0.1 mL of 100 mM niacin by an intraperitoneal injection twice before ovulation. The ovaries were collected and the follicles were counted and categorized, and ovarian histologic sections were stained for TUNEL. Ovarian function was then evaluated by monitoring ovulation. Microarray analyses, Western blot, immunofluorescence and real-time quantitative PCR were used to assess the mechanism of ovarian injury and repair. Results: We found that niacin promotes follicle growth in the immature oocyte and it increased the levels of a germ-line cell marker DDX4, and a cell proliferation marker PCNA in the ovary. Addition of niacin to the cell culture reduced oocyte apoptosis in vitro. Administration of niacin to treat premature ovarian failure (POF) in mouse models showed inhibition of follicular apoptosis under harmful conditions, such as radiation and chemotherapy damage, by markedly reducing cumulus cell apoptosis. Additionally, the number of developing follicles increased after administration of niacin. Conclusion: Niacin may have an important function in treating POF by reducing apoptosis in clinical applications.

Consumption of red maple in anticipation of beech mast‐seeding drives reproduction in eastern chipmunks

“…4-19 times more than other deciduous trees and conifers; Burkholder & McVeigh, 1944). Dietary content in niacin is crucial for mammal reproduction (Mishra, Aderao, Chaudhary, & Raje, 2018;Tissier, Handrich, Dallongeville, Robin, & Habold, 2017;Wang et al, 2018). Deficiencies in this vitamin lead to reproductive failure in another food-hoarding rodent, whereas dietary supplementation in this vitamin led to above-average reproductive rates (Tissier et al, 2017).…”

Fetal liver mesenchymal stem cells restore ovarian function in premature ovarian insufficiency by targeting MT1

“…Together, these data highlight that MT1, JNK1, PCNA, and AMPK may participate in cellular proliferation, apoptosis, migration, and ovary damage. Although stem cell therapy restores ovarian function in POI by directly mediating MT1, JNK1, PCNA, and AMPK, which has not been previously reported, a supporting study revealed that melatonin effectively elevated the percentage of PCNA-positive granulosa and theca cells [29] and that the radiation-POF mouse model treated with niacin highly expressed PCNA in the GCs [55]. In a recent study, human ovaries and hGCs were exposed to cisplatin in vitro, which elevated the levels of the phosphorylated forms of SAPK/JNK and triggered apoptosis [56].…”

Niacin Stimulates Mammary Gland Development in Pubertal Mice through Activation of the AKT/mTOR and ERK1/2 Signaling Pathways

“…To our knowledge, this is the first study to assess the effect of niacin on mammary gland development in pubertal mice. It has also been reported that niacin can promote the proliferation of breast cancer cells and cancer stem cells and promote the development of immature oocytes[19-21]. Compared with other vitamins, vitamin A and vitamin D currently inhibit puberty mammary gland development[10, 11].…”

“…Niacin promotes the synthesis of growth hormone[17, 18]. In addition, previous studies have shown that niacin can promote the development of immature follicular cells and the proliferation of cancer cells[19-21].…”