Our studies demonstrate that administration of NR during pregnancy in mice can prevent severe developmental defects caused by genetic inhibition of NAD production. In view of the multiple clinical syndromes already linked to defective NAD production, our findings raise hope of their attenuation and perhaps prevention.

Our findings indicated that nicotinamide riboside diminished ovarian injury in sepsis via inhibiting tissue infiltration and increasing endogenous antioxidant capacity. Nicotinamide riboside administration may represent a new treatment approach for the prevention of sepsis-induced ovarian injury.

NR recovered fetal growth by increasing blood glucose levels when artificial hypoglycemia was induced during pregnancy. Our study revealed the glucose-metabolic function of NR in hypoglycemic pregnant animals, suggesting NR as a dietary supplement to improve fetal growth. Because diabetic women suffer from hypoglycemia due to insulin therapy, NR has therapeutic potential for use as a glycemic control pill.

These findings indicate that oocytes of advanced maternal age suffer from oxidative damage and mitochondrial dysfunction.

Our findings indicated that nicotinamide riboside diminished ovarian injury in sepsis via inhibition of tissue infiltration and incresing of endogenous antioxidant capacity. Nicotinamide Riboside administration may represent a new treatment approach for the prevention of sepsis induced ovarian injury.

Just one month of every-other-day fasting was sufficient to improve oocyte quality [in mice]...Positive impact of intermittent fasting on aged oocytes was mediated by restoration of the nicotinamide adenine dinucleotide (NAD+)/Sirt1-mediated antioxidant defense system, which eliminated excessive accumulated ROS to suppress DNA damage and apoptosis.

Evidence that has accumulated over the last three decades suggests that renal diseases start in utero...Low nephron number is one of the main contributors to chronic kidney disease (CKD) susceptibility in adulthood...Here, we show that a nephron number deficit and impaired renal architecture of mice born to mothers fed a low protein diet can be restored by NR supplementation during pregnancy through the induction of SIRT3 expression and activity...These findings have huge potential for clinical translation, given that inadequate nephrons at birth increase the risk in adulthood of hypertension and renal diseases. Chronic kidney disease affects over 10% of the adult population worldwide, with rising overall morbidity and mortality rates. In view of this, it is evident that prenatal kidney care is an important global health challenge.

NR treatment not only restored MII oocyte quality but also enhanced early embryonic development potential of postovulatory oocytes via alleviating mitochondrial dysfunction and maintaining normal spindle/chromosome structure. ...NR supplementation increases the oocyte quality and early embryonic development potential in post-ovulatory oocytes which could potentially increase the successful rate in assisted reproductive technology.

The rate of infertility continues to rise in the world for several reasons, including the age of conception and current lifestyle. We list in this paper potential non-invasive and invasive techniques to assess oocyte quality. We searched the database PubMed using the terms “oocytes AND quality AND evaluation”. In the first part, we study the morphological criteria, compartment by compartment, to then focus in a second part on more objective techniques such as genetics, molecular, apoptosis, or human follicular fluid that contain biologically active molecules. The main criteria used to assess oocyte quality are morphological; however, several other techniques have been studied in women to improve oocyte quality assessment, but most of them are invasive and not usable in routine.

...Here, we studied the long-term programming effects of mild NR supplementation during the suckling period on lipid and oxidative metabolism in skeletal muscle and liver tissues using an animal model. ...These pre-clinical findings suggest that mild NR supplementation in early postnatal life beneficially impacts lipid and energy metabolism in skeletal muscle and liver in adulthood, serving as a potential preventive strategy against obesity-related disorders characterized by ectopic lipid accumulation.

The level of NAM in large follicles was significantly higher than that in small follicles. In mature FF, the NAM concentration was positively correlated with the rates of oocyte maturation and fertilization. Five mM NAM treatment during IVM increased maturation rate and fertilization rate in the oxidative stress model, and significantly reduced the increase of ROS levels induced by H2O2 in mice oocytes. Higher levels of NAM in FF are associated with larger follicle development. The supplement of 5 mM NAM during IVM may improve mice oocyte quality, reducing damage caused by oxidative stress...However, we found that an excessive NAM concentration inhibited the maturation and fertilization of oocytes.

It is well known that female reproduction ability decreases during the forth decade of life due to age-related changes in oocyte quality and quantity; although the number of women trying to conceive has today increased remarkably between the ages of 36 to 44. The causes of reproductive aging and physiological aspects of this phenomenon are still elusive. With increase in the women’s age, during Assisted Reproductive Technologies (ART) we have perceived a significant decline in the number and quality of retrieved oocytes, as well as in ovarian follicle reserves. This is because of increased aneuploidy due to factors such as spindle apparatus disruption; oxidative stress and mitochondrial damage. The aim of this review paper is to study data on the potential role of the aging process impacting oocyte quality and female reproductive ability. We present the current evidence that show the decreased oocyte quality with age, related to reductions in female reproductive outcome...

This study not only demonstrates nicotinamide as a useful factor for cardiomyocyte production in regenerative medicine, but also implicates that nicotinamide could have a profound impact on embryogenesis if it is prescribed during pregnancy.

The NAD+ precursor nicotinamide riboside can protect against postovulatary aging in vitro…

NAD+ deficiency has recently been linked with increased occurrences of congenital abnormalities and embryonic death in human and animal subjects....Nicotinic acid supplementation increases the bioavailability of NAD+ precursors in mares, which is proposed to be beneficial during periods of peak NAD+ demand, such as during early embryo development.

There has been interest in nicotinamide as a possible therapy for preeclampsia stemming from work by Li et al., demonstrating nicotinamide ameliorated preeclampsia like features in mouse models. Utilising primary human tissues we show nicotinamide had no effect on antiangiogenic factor secretion or on key markers of endothelial dysfunction. The lack of an effect on sFlt-1 secretion from primary human tissues is in keeping with animal studies

It was recently reported in mice that miscarriage can be prevented through the administration of niacin. We conducted a prospective, exploratory pilot study involving 24 women...Neither niacin intake (P = 0.24) nor urinary vitamin B3...predicted miscarriage. However,...there may be a threshold niacin level protective in miscarriage prevention warranting further investigation.

The objective of this study was to determine the effects of in ovo injection of nicotinamide riboside (NR) on broiler embryonic myogenesis....Chicks injected with NR had greater Pectoralis major muscle weight and length...Injecting developing embryos at day 10 of incubation increased hatched chick Pectoralis major muscle morphometrics, which were partly because of the NR catalyzed increase in muscle fiber density.

Nicotinamide supplementation promotes liver fat decomposition in kids. Nicotinamide supplementation starting from the prepartum period is essential for kids.

Loss of follicles together with decreased oocyte quality and quantity contribute to age-associated ovarian senescence and infertility. Although underlying mechanisms for ovarian senescence are still unknown, mitochondrial dysfunctions have been reported. Here, we showed age-dependent decreases in ovarian Nicotinamide Adenine Dinucleotide (NAD+) levels in mice whereas supplementing aging mice with nicotinamide riboside (NR), an NAD+ precursor, increased ovarian NAD+ content. We found that increases in ovarian NAD+ levels in aging mice led to increased number of ovarian follicles and ovulatory potential as well as increased live birth rate...Our data suggested that supplementation with NAD+ precursors in vivo and in vitro could be potential therapeutic approaches for treating age-related ovarian infertility.

The objective of this study was to examine the effect of nicotinamide riboside (NR) on pectoralis major muscle (PM) development and growth...There were no treatment × location or main effects for all body morphometric measurements (P > 0.07), except chest width of chicks from eggs injected in the yolk were wider (P = 0.01) than chicks from eggs injected in the albumen... Injecting NR into the yolk sac of the developing embryo at day 10 of incubation increased pectoralis major development which was due to an increase in muscle density.

An adequate supply of healthy oocytes is essential for female fertility. Oocytes that sustain even very low levels of DNA damage are killed, presumably because the damage is irreparable. Surprisingly, however, we show that when apoptosis is inhibited, oocytes can repair severe DNA damage via homologous recombination repair. The repair is highly efficient; it protects fertility and ensures the health and genetic integrity of offspring. These data implicate DNA repair as an additional quality control mechanism available within the female germ line.

Neonatal supplementation with resveratrol (RSV) or nicotinamide riboside (NR) programs in male mice brown adipocyte-like features in white adipose tissue (WAT browning) together with improved metabolism in adulthood...The results support epigenetic effects being involved in WAT programming by neonatal resveratrol or nicotinamide riboside supplementation in male mice.

Declining oocyte quality is considered an irreversible feature of aging and is rate limiting for human fertility. Reversing an age-dependent decline in NAD(P)H restores oocyte quality, embryo development, and functional fertility in aged mice.

Oocyte quality is one of the most important factors involving in female reproduction. The number of compromised oocytes will increase with maternal age, while mitochondrial dysfunction has implicated in age-related poor oocyte...In this review, we summarize the potential mechanism of mitochondria in oocyte and embryo development and discuss the next step for mitochondrial transfer therapy.

In this review, using the latest literature, we discuss the pathophysiology in which oocytes are more exposed and vulnerable to oxidative stress as they age, and the mechanisms by which oocyte quality is degraded.

Resveratrol and nicotinamide riboside supplementations in early postnatal life affect white adipose tissue's thermogenic/oxidative transcriptional phenotype and metabolic responses in adulthood, with upregulatory and beneficial effects evidenced in male animals.

...A new mother’s capacity for biosynthesis and functionally important nurturing is apparently limited by NAD. Here, we discuss homeorhetic flow of resources from a new mother to her offspring in the context of NAD metabolism and suggest avenues for future investigation....By boosting lactation, these mothers increased postgestational weight loss and produced pups that were larger at weaning.Unexpectedly, we found that the offspring of NR-supplemented mouse mothers are more adventurous in an open-field test, that weanling mice have better glycemic control if their mothers were NR supplemented, and that the weanling rats of supplemented mothers are learning-advantaged on a rotarod...Although the nutritional intervention only lasted for the 21 days in which new mothers nursed their pups, we discovered that the benefits of having a mother on NR last into mouse and rat adulthood. Specifically, we found that offspring of NR-supplemented mothers are less anxious, stronger, perform better on a beam walk, are more resilient to giving up in a forced swim, have better spatial memory, are advantaged in adult hippocampal neurogenesis, and have leaner body composition as adults.

Nicotinamide supplementation alleviates oxidative stress of does during the perinatal period. Perinatal Maternal nicotinamide supplementation improves the small intestinal morphology and immunity of the offspring kids. Nicotinamide supplementation starting from the prepartum period is essential for does and offspring kids.

By restoring NAD+ homeostasis, maternal nicotinamide riboside (NR) supplementation during lactation enhances postpartum weight loss, as well as juvenile development and adult neurogenesis in the offspring.

Modulation of the browning potential of adipose tissues through the intake of food bioactives in early life is a potential, yet still largely unexplored, strategy to enhance metabolic health in later life...Our studies are first to examine nutritional programming of adipose tissue metabolic features by NR and RSV supplements given directly to the lactating pups. ...The fate of preadipocytes resident in WAT of young animals toward the beige adipogenesis transcriptional program can be modulated by specific food bioactives/micronutrients [resveratrol and nicotinamide riboside] received in early postnatal life.

...NAM improved BP and kidney injury, prolonged pregnancy periods, and improved fetal growth in the pregnant MRL/lpr-LPS mice. The results suggest that SLE patients are prone to develop poor pregnancy outcome, and likely develop severe nephropathy and kidney inflammation. NAM may be a novel therapeutic option that improves kidney injury and pregnancy outcomes, thereby benefiting pregnant patients with SLE.

...We tested the hypotheses that postpartum might dysregulate maternal NAD and that increasing systemic NAD with NR might benefit mothers and offspring...NR supplementation of new mothers increases lactation and nursing behaviors and stimulates maternal transmission of macronutrients, micronutrients, and BDNF into milk. Pups of NR-supplemented mothers are advantaged in glycemic control, size at weaning, and synaptic pruning. Adult offspring of mothers supplemented during nursing retain advantages in physical performance, anti-anxiety, spatial memory, delayed onset of behavioral immobility, and promotion of adult hippocampal neurogenesis. Thus, postgestational maternal micronutrition confers lasting advantages to offspring.

All NR treatments had longer pectoralis major muscles than the saline treatment (PP0.41). Embryos treated with 10.0 and 2.5 mM NR had thicker pectoralis major muscles than saline injected embryos (PP=0.58).

...The studies in rodent models thus clearly demonstrate that nicotinamide has the potential to reverse serious maternal sequelae of Preeclampsia to allow prolongation of pregnancy and improve infant outcomes, regardless of the cause that leads to PE. While translation of the findings made in mice to humans is not a simple issue, it is important to test the effects of this vitamin in humans because there is no real treatment available, and because even a few more days of intra-uterine life for the babies of human patients with early-onset PE would have real benefits.

In this review, we provide a summary of the main putative causes for the age-related decrease in oocyte/embryo competence, along with the mechanisms underlying aging and the main clinical strategies proposed to prevent/limit the impact of advanced maternal age upon in vitro fertilization (IVF) success.

Up to 8% of pregnant women suffer from preeclampsia (PE), a deadly disease characterized by high blood pressure (BP), blood vessel damage, called endotheliosis (vascular endothelial swelling with narrowing of capillary lumen), and high levels of protein in the urine. PE is often associated with premature delivery, which is a risk factor of cardiovascular and metabolic diseases among the offspring. Accordingly, establishing drug treatments of PE is in immediate needs...We have found that vitamin B3 nicotinamide (Nam) is the first safe drug that alleviates PE, and that Nam also alleviates or prevents miscarriage, prolongs pregnancy period, and improves the growth of the fetuses in mice with PE. Importantly, Nam has been used for pregnant and nursing women who have difficulty in taking sufficient meal. Nam could help treat or prevent PE and FGR associated with PE, if the treatment works in humans.

Disruption of NAD synthesis caused a deficiency of NAD and congenital malformations in humans and mice. Niacin supplementation during gestation prevented the malformations in mice.

Disruption of NAD synthesis caused a deficiency of NAD and congenital malformations in humans and mice. Niacin supplementation during gestation prevented the malformations in mice.

Preeclampsia (PE), high blood pressure and protein in the urine in the last third of pregnancy, complicates about 1 in 20 human pregnancies, and it is one of the leading causes of pregnancy-related maternal deaths. The only definitive treatment, induced delivery, invariably results in premature babies. Blood pressure-lowering drugs help, but results in preventing preterm delivery and correcting the fetal growth restriction (FGR) that also occurs in PE have been disappointing. Here we show that feeding high doses of nicotinamide, a vitamin, improves the maternal condition, prolongs pregnancies, and prevents FGR in mice having PE-like conditions due to two contrasting causes. Because nicotinamide benefits both mothers and pups, it merits evaluation for preventing or treating PE in humans.

The present study found that maternal nicotinamide supplementation increased fetal body weight at the dose of 1 g/kg diet, but decreased fetal body weight at the dose of 4 g/kg diet...The human equivalent doses are about 13 and 52 mg/kg, respectively, which equals to approximately 780 and 3000 mg niacin for a 60 kg person, respectively.

The control group had elevated glucose and reduced insulin while nicotinamide (100 & 200 mg/kg) supplementation reversed these changes...These findings provide evidence for utilizing nicotinamide as supplement or adjunct to support existing therapeutic agents for gestational diabetes and in pregnant individuals with weakened immune systems.