Female Reproduction Research Articles

Reproductive toxicology of environmental endocrine-disrupting chemicals in women: a cohort study protocol.

Introduction: Epidemiological evidence over the last few decades has consistently shown that exposure to endocrine-disrupting chemicals (EDCs) is associated with adverse reproductive health outcomes, including male and female infertility, poor-pregnancy outcomes, and increased risk of diseases in childhood and beyond. To investigate the effects of EDCs and lifestyle on all aspects of reproduction (including early oocyte development, fertilization, embryo development, embryo implantation, abortion, and preterm birth). Methods: We performed this cohort study on patients receiving in vitro fertilization (IVF) treatment. Biological samples including urine, serum, follicular fluid, semen, fetal tissue, decidua, and placenta, were obtained. Results: By studying the correlations between reproductive outcomes and environmental pollutant exposure and lifestyle, we determined the toxicological mechanisms and health effects of EDCs on female reproductive health. We found that higher concentrations of per- and polyfluoroalkyl substances were correlated with polycystic ovary syndrome (PCOS). Using specific biomarkers, we also detected the concentrations of organophosphorus flame retardants (OPFRs) in urine and found that OPFRs may disrupt hormone homeostasis. Discussion: All of these results reveal EDCs may disrupt female reproduction.

Testosterone maintains male longevity and female reproduction in Chrysopa pallens

Vertebrate testosterone, an androgen present in the testes, is essential for male fertility. Vertebrate-type steroid hormones have been identified in insects, but their function remains unknown. Insect vitellogenin (Vg) is usually a female-specific protein involved in reproductive processes. However, males of some species, such as the green lacewing Chrysopa pallens, have Vg. Here, we demonstrated that the knockdown of C. pallens male Vg by RNAi significantly shortened the lifespan of males, suppressed the reproduction of post-mating females, and strikingly reduced the abundance of several immune-related compounds, including testosterone. LC-MS/MS revealed that C. pallens male testosterone had the same structure and molecular mass as vertebrate testosterone. Topical testosterone application partially restored the lifespan of Vg-deficient males and the reproduction of post-mating females. These results suggest that vertebrate-type testosterone maintains male longevity and female reproduction under the control of the male Vg in C. pallens.

Mite non-reproduction is not a consequence of the brood removal behavior of varroa sensitive hygiene honey bee colonies (Apis mellifera).

A sustainable solution to the global threat of the Varroa destructor mite is the selection of varroa-resistant honey bee (Apis mellifera) colonies. Both "mite non-reproduction" (MNR) and "varroa sensitive hygiene" (VSH) appear to be promising selection traits for achieving the goal of a resistant honey bee. MNR describes colonies that have a high number of non-reproductive mites (no offspring, no males, or delayed development of mite offspring). High numbers of non-reproductive mites have been observed in selected colonies, but the mechanism behind this trait has not yet been identified. The specialized hygienic behavior of selected honey bees, called VSH, is the removal of varroa-infested brood. These traits were thought to be linked by VSH bees preferentially removing reproductive varroa females leaving only non-reproductive mites behind in cells and thus creating colonies with high levels of MNR. To further investigate this link, we used an experimental setup and data sets from a four-year selection project designed to breed for MNR and VSH colonies. In addition, we sought to answer the question of whether non-reproductive mites are a direct consequence of worker removal behavior. To test this, we artificially induced removal behavior, and after providing the mite with enough time to re-enter another cell, we opened all capped cells, relocated the mites, and evaluated their reproduction. As shown in previous studies and in this study, VSH had no effect on MNR levels. Also, the induced removal behavior did not lead to non-reproduction in the subsequent reproductive cycle post interruption. We thus concluded that breeding for non-reproductive mites does not automatically breed for VSH behavior and worker removal behavior does not cause subsequent reproductive failure of the mites forced to flee and find a new cell for reproduction.

Effects of physical activity on infertility in reproductive females

ObjectivesTo explore the relationship between different types of physical activity and female infertility.MethodsThis study analyzed data from 2,796 female participants aged 18–44 years in the United States, obtained from the National Health and Nutrition Examination Survey (NHANES) database spanning the years 2013 to 2020. Multiple logistic regression analyses and generalized linear models were used to explore the relationship between different types of physical activity and infertility after adjusting for potential confounding factors.ResultsWe found a non-linear relationship between recreational activities and infertility with an inflection point of 5.83 h/week (moderate intensity), while work activities and traffic-related activities did not. On the left side of the inflection point, there was no significant association between recreational activity time and infertility (OR = 0.93, 95% CI: 0.86 to 1.02, P = 0.1146), but on the right side of the inflection point, there was a positive association between recreational activity time and the risk of infertility (OR = 1.04, 95% CI: 1.02 to 1.06, P = 0.0008).ConclusionsThe relationship between different types of physical activity and female infertility varies. We acknowledge the potential influence of confounding variables on this relationship. However, we have already adjusted for these potential variables in our analysis. Therefore, our findings suggest that appropriate recreational activity programs are essential for promoting reproductive health in women of reproductive age. Nevertheless, it is important to note that the observed association does not imply causality. Given the limitations of cross-sectional studies, further prospective cohort studies are needed to explore the causal relationship while accounting for additional confounding factors.

Molecular and Epigenetic Impacts of Pesticides on the Female Reproductive System: A Review

Pesticides, primarily originating from agricultural activities, have raised environmental and health concerns due to their suspected effects on the female reproductive system. Despite their widespread application, a significant research void exists concerning their implications for human female reproductive health. This review provides comprehensive information on the adverse effects of pesticides on female reproduction, focusing on their molecular and epigenetic mechanisms. In general, these adverse outcomes include ovarian dysfunction, hormonal irregularities, the onset of endometriosis, and an increased risk of stillbirths. From a mechanistic perspective, pesticides can interfere with the endocrine system, catalyze the formation of reactive oxygen species, and induce oxidative stress. At the molecular level, certain pesticides can act as hormone mimics, disrupting the normal hormonal balance. Moreover, they can trigger epigenetic shifts, leading to alterations in non-coding RNAs, histone configurations, and DNA methylation patterns. These epigenetic alterations not only have an immediate impact but can also be passed on to subsequent generations. Highlighting these concerns, this review underscores the urgent need for stringent regulations and aims to catalyze future in-depth studies on the relationship between pesticides and female reproductive health.

Endocrine and Transcriptome Changes Associated with Testicular Growth and Differentiation in Atlantic Salmon (Salmo salar L.).

Sexual maturation of Atlantic salmon males is marked by dramatic endocrine changes and rapid growth of the testes, resulting in an increase in the gonad somatic index (GSI). We examined the association of gonadal growth with serum sex steroids, as well as pituitary and testicular gene expression levels, which were assessed with a DNA oligonucleotide microarray. The testes transcriptome was stable in males with a GSI < 0.08% despite the large difference between the smallest and the largest gonads. Fish with a GSI ≥ 0.23% had 7-17 times higher serum levels of five male steroids and a 2-fold increase in progesterone, without a change in cortisol and related steroids. The pituitary transcriptome showed an upregulation of the hormone-coding genes that control reproduction and behavior, and structural rearrangement was indicated by the genes involved in synaptic transmission and the differentiation of neurons. The observed changes in the abundance of testicular transcripts were caused by the regulation of transcription and/or disproportional growth, with a greater increase in the germinative compartment. As these factors could not be separated, the transcriptome results are presented as higher or lower specific activities (HSA and LSA). LSA was observed in 4268 genes, including many genes involved in various immune responses and developmental processes. LSA also included genes with roles in female reproduction, germinal cell maintenance and gonad development, responses to endocrine and neural regulation, and the biosynthesis of sex steroids. Two functional groups prevailed among HSA: structure and activity of the cilia (95 genes) and meiosis (34 genes). The puberty of A. salmon testis is marked by the predominance of spermatogenesis, which displaces other processes; masculinization; and the weakening of external regulation. Results confirmed the known roles of many genes involved in reproduction and pointed to uncharacterized genes that deserve attention as possible regulators of sexual maturation.

The profile of steroid hormones in human fetal and adult ovaries.

Reproduction in women is at risk due to exposure to chemicals that can disrupt the endocrine system during different windows of sensitivity throughout life. Steroid hormone levels are fundamental for the normal development and function of the human reproductive system, including the ovary. This study aims to elucidate steroidogenesis at different life-stages in human ovaries. We have developed a sensitive and specific LC-MS/MS method for 21 important steroid hormones and measured them at different life stages: in media from cultures of human fetal ovaries collected from elective terminations of normally progressing pregnancy and in media from adult ovaries from Caesarean section patients, and follicular fluid from women undergoing infertility treatment. Statistically significant differences in steroid hormone levels and their ratios were calculated with parametric tests. Principal component analysis (PCA) was applied to explore clustering of the ovarian-derived steroidogenic profiles. Comparison of the 21 steroid hormones revealed clear differences between the various ovarian-derived steroid profiles. Interestingly, we found biosynthesis of both canonical and "backdoor" pathway steroid hormones and corticosteroids in first and second trimester fetal and adult ovarian tissue cultures. 17α-estradiol, a less potent naturally occurring isomer of 17β-estradiol, was detected only in follicular fluid. PCA of the ovarian-derived profiles revealed clusters from: adult ovarian tissue cultures with relatively high levels of androgens; first trimester and second trimester fetal ovarian tissue cultures with relatively low estrogen levels; follicular fluid with the lowest androgens, but highest corticosteroid, progestogen and estradiol levels. Furthermore, ratios of specific steroid hormones showed higher estradiol/ testosterone and estrone/androstenedione (indicating higher CYP19A1 activity, p < 0.01) and higher 17-hydroxyprogesterone/progesterone and dehydroepiandrosterone /androstenedione (indicating higher CYP17A1 activity, p < 0.01) in fetal compared to adult ovarian tissue cultures. Human ovaries demonstrate de novo synthesis of non-canonical and "backdoor" pathway steroid hormones and corticosteroids. Elucidating the steroid profiles in human ovaries improves our understanding of physiological, life-stage dependent, steroidogenic capacity of ovaries and will inform mechanistic studies to identify endocrine disrupting chemicals that affect female reproduction.

Experimental queen removal stimulates caste flexibility of females in Neotropical social wasps (Vespidae Polistinae Epiponini)

Caste plasticity is an essential trait in social insects, and it facilitates the allocation of individuals in different tasks according to population demands in the colony (e.g. workers can become queens upon loss or death of their “original queen”). The process of caste determination can take place in immature stages (preimaginal) or through adult stages (imaginal). Neotropical social wasp tribe Epiponini has both types of caste determination process and is thus a fascinating group to study caste plasticity. We performed queen removal tests in five Epiponini species with preimaginal and imaginal caste determination to better understand caste plasticity and queen selection processes. Queen absence stimulates the establishment of new reproductive females in Chartergellus and Metapolybia (imaginal), while females in Protopolybia (preimaginal) attempt to lay eggs even in the presence of their “original queen”. Contrary to what has been hypothesized, we found that age is not a predictive factor in the female’s potential to become a queen. Caste flexibility seems to be a crucial trait which aids Epiponini tropical colonies to survive, as it allows the colony to replace lost workers and queens promptly until a new generation of wasps can emerge.

Influence of Ascorbic Acid on Di-(2-Ethylhexyl) Phthalate-induced Ovarian Gene Alterations in Pubertal Female Wistar Rats

Background Di-(2-ethylhexyl) phthalate (DEHP), a plasticizer compound affecting female reproduction, leads to scenarios, such as polycystic ovarian syndrome (PCOS) and infertility through oxidative stress (OS) mechanisms. Ascorbic acid (AA) is one of the antioxidants in infertility issues. Objectives The present study investigates the ameliorative effect of AA on DEHP-induced ovarian toxicity in pubertal female Wistar rats. Materials and Methods Thirty female Wistar rats of four weeks of age were stratified into five groups. Group I was treated with corn oil (Vehicle), groups II and III with low and high dose DEHP, and groups IV and V with low and high dose DEHP+AA were administered for 30 days. Results Increased body weight gain was noted in DEHP groups. Estradiol hormone was considerably reduced, whereas progesterone levels were increased in both low- and high-dose DEHP-treated groups. DEHP+AA groups have shown significant ( p &lt; 0.005) protection of these hormone levels as equal to the control group. The high-dose DEHP group shows an increased, ovarian estrogen receptor (ER) alpha, ER-beta, and progesterone receptor gene expression, and DEHP+AA groups have significantly ( p &lt; 0.005) showed expression similar to the control. OS was noted with decreased superoxide dismutase and increased malondialdehyde expression in Group III (GR III) compared to control, whereas the DEHP+AA treated group significantly protected OS by restoring the expression levels. DEHP-treated groups show elevated levels of both Bcl-2 and BAX which is specific to apoptotic expression and restored by AA treatment ( p &lt; 0.005). Conclusion Evidence suggests that AA may protect against DEHP-induced ovarian toxicity by decreasing OS levels, improving folliculogenesis, and restoring the hormonal with receptor level alterations.

Status of visfatin in female reproductive function under normal and pathological conditions: a mini review.

Adipokines are now well-known to regulate reproduction. Visfatin is an adipokine expressed in the hypothalamus, pituitary, ovary, uterus, and placenta of different species, and since it has been found to modulate the endocrine secretion of the hypothalamus, pituitary gland and ovary, it may be considered a novel regulator of female reproduction. Although the majority of the literature explored its role in ovarian regulation, visfatin has also been shown to regulate uterine remodeling, endometrial receptivity and embryo development, and its expression in the uterus is steroid dependent. Like other adipokines, visfatin expression and levels are deregulated in pathological conditions including polycystic ovary syndrome. Thus, the present mini-review focuses on the role of visfatin in female reproduction under both physiological and pathological conditions.

Long-chain acyl-CoA synthetase-4 regulates endometrial decidualization through a fatty acid β-oxidation pathway rather than lipid droplet accumulation

ObjectiveLipid metabolism plays an important role in early pregnancy, but its effects on decidualization are poorly understood. Fatty acids (FAs) must be esterified by fatty acyl-CoA synthetases to form biologically active acyl-CoA in order to enter the anabolic and/or catabolic pathway. Long-chain acyl-CoA synthetase 4 (ACSL4) is associated with female reproduction. However, whether it is involved in decidualization is unknown. MethodsThe expression of ACSL4 in human and mouse endometrium was detected by immunohistochemistry. ACSL4 levels were regulated by the overexpression of ACSL4 plasmid or ACSL4 siRNA, and the effects of ACSL4 on decidualization markers and morphology of endometrial stromal cells (ESCs) were clarified. A pregnant mouse model was established to determine the effect of ACSL4 on the implantation efficiency of mouse embryos. Modulation of ACSL4 detects lipid anabolism and catabolism. ResultsThrough examining the expression level of ACSL4 in human endometrial tissues during proliferative and secretory phases, we found that ACSL4 was highly expressed during the secretory phase. Knockdown of ACSL4 suppressed decidualization and inhibited the mesenchymal-to-epithelial transition induced by MPA and db-cAMP in ESCs. Further, the knockdown of ACSL4 reduced the efficiency of embryo implantation in pregnant mice. Downregulation of ACSL4 inhibited FA β-oxidation and lipid droplet accumulation during decidualization. Interestingly, pharmacological and genetic inhibition of lipid droplet synthesis did not affect FA β-oxidation and decidualization, while the pharmacological and genetic inhibition of FA β-oxidation increased lipid droplet accumulation and inhibited decidualization. In addition, inhibition of β-oxidation was found to attenuate the promotion of decidualization by the upregulation of ACSL4. The decidualization damage caused by ACSL4 knockdown could be reversed by activating β-oxidation. ConclusionsOur findings suggest that ACSL4 promotes endometrial decidualization by activating the β-oxidation pathway. This study provides interesting insights into our understanding of the mechanisms regulating lipid metabolism during decidualization.

Hydroelectric dam impacts shorten and delay the reproductive periods of female leaf-nosed bats in Western Amazonia

Abstract The life cycles of bats are constrained by availability of resources such as food and shelter. Disruptions limiting otherwise naturally regulated access to these resources ultimately affect the fitness of bat populations and may eventually lead to local extinctions. We sampled bats before and after an Amazonian mega-dam water filling and retrieved data on their reproductive phenology, testing if and how sex ratio, seasonal abundance, and reproductive patterns respond to impacts of the newly operating hydroelectric dam. We analyzed data from 3,298 bat captures of 49 species. Females outnumbered males, previously and after the dam implementation, and we observed seasonal variations in the abundance of bats, which was lower after the implementation of the dam for most species. All species had at least 1 reproductive peak of pregnancy and/or lactation beginning at a variable time across seasons. Most species and functional ensembles were reproductively bimodal, with exceptions being the polymodal Artibeus obscurus and unimodal Phylostomus elongatus. Operations of the hydroelectric dam affected the abundance of both sexes equally, and effects were stronger in the rainy season, altering the timing of reproduction for females, delaying and shortening pregnancy and lactation. These changes expressed in female reproductive activity may be related to the shortfall of resources because of loss of irreplaceable vegetation caused by the dam filling. As we cannot predict the roles of variation of reproductive patterns observed after the filling in the long run we reinforce the importance of long-term, continuous monitoring and management to safeguard the reestablishment of reproductive patterns of females in order to repopulate and keep bat populations healthy in remaining areas along following dam construction.

Environmental BaP/BPDE suppressed trophoblast cell invasion/migration and induced miscarriage by down-regulating lnc-HZ01/MEST/VIM axis

Environmental benzo(a)pyrene (BaP) and itsmetabolite benzo(a)pyrene-7, 8-dihydrodiol-9, 10-epoxide (BPDE), classic endocrine disrupting chemical and persistent organic pollutant, could cause miscarriage. However, the detailed mechanisms are still largely unclear and should be further explored. In this study, we discovered that exposure of trophoblast cells with BPDE could suppressed cell invasion/migration by inhibiting MEST/VIM (Vimentin) pathway. Moreover, BPDE exposure also increased lnc-HZ01 expression level, which further inhibited MEST/VIM pathway and then suppressed invasion/migration. Knockdown of lnc-HZ01 or overexpression of MEST could efficiently rescue invasion/migration of BPDE-exposed Swan 71 cells. Furthermore, lnc-HZ01 was highly expressed and MEST/VIM were lowly expressed in recurrent miscarriage (RM) villous tissues compared with healthy control (HC) group. Finally, we also found that BaP exposure inhibited murine Mest/Vim pathway in placental tissues and induced miscarriage in BaP-exposed mice. Therefore, the regulatory mechanisms were similar in BPDE-exposed human trophoblast cells, RM villous tissues, and placental tissues of BaP-exposed mice with miscarriage, building a bridge to connect BaP/BPDE exposure, invasion/migration, and miscarriage. This study provided novel insights in the toxicological effects and molecular mechanisms of BaP/BPDE-induced miscarriage, which is helpful for better elucidating the toxicological risks of BaP/BPDE on female reproduction.

New insight about the role of microbiome and probiotics in female reproduction: A review 6

New insight about the role of microbiome and probiotics in female reproduction: A review 6

The role of kisspeptin in female and male reproduction

Kisspeptin is a neuropeptide responsible for controlling the synthesis of gonadotropin-releasing hormone (GnRH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH). The G-protein-coupled receptor 54/kisspeptin 1 receptor (GPR54/KISS1R) is involved in its action. The comprehension of kisspeptin and its actions represents a significant breakthrough in the field of reproductive biology. Kisspeptins play a crucial role in the development and optimal functioning of the reproductive system in both female and male. Additionally, it contributes to the onset of puberty, regulating feedback processes, and influencing sexual desire and arousal. It regulates a number of reproductive functions in women, including ovulation, lactation, ovarian development, follicle development, oocyte maturation, and pregnancy via the hypothalamic-pituitary-gonadal (HPG) axis. Spermatogenesis, sperm function, Leydig cells, and reproductive behaviour are all impacted by it in men. Infertility and polycystic ovarian syndrome (PCOS) are among the diseases linked to kisspeptin dysregulation, according to the research. For potential future use in diagnosing and treating problems, it may be helpful to understand the mechanisms behind kisspeptin's effects on the reproductive system. This review focuses on the regulatory function of kisspeptin on the HPG axis and the impact of kisspeptin on reproductive processes in both female and male.

Cyanidin-3-O-glucoside protects Zearalenone-induced in vitro maturation disorders of porcine oocytes by alleviating NOX4-dependent oxidative stress and endoplasmic reticulum stress in cumulus cells

Zearalenone (ZEN) is widely found in foodstuffs and has serious harmful effects on female fertility, especially in pigs. Cyanidin-3-O-glucoside (C3G), a type of anthocyanin, exists in most dark fruits and vegetables; it has many positive dietary effects including as an antioxidant, anti-inflammatory, or anti-apoptotic agent. However, the beneficial effects of C3G alongside ZEN-induced damage in porcine oocytes and the underlying molecular mechanism have not been investigated. In this work, porcine cumulus-oocyte complexes (COCs) were divided into Control (Ctrl), ZEN, ZEN + C3G (Z + C), and C3G, and treated for 44–46 h in vitro. The results showed that C3G could alleviate ZEN-induced disorders of first polar body (PBI) extrusion, abnormalities of spindle assembly, cortical granule distribution, and mitochondrial distribution; these results were produced via restoring transzonal projections (TZPs), and inhibiting nicotinamide adenine dinucleotide phosphate oxidase (NOX4)-dependent oxidative stress and ‘glucose regulatory protein 78/protein kinase-like endoplasmic reticulum kinase/α subunit of eukaryotic initiation factor 2α/activating transcription factor 4/C/EBP-homologous protein’ (GRP78/PERK/eIF2α/ATF4/CHOP)-mediated endoplasmic reticulum stress (ERS) during oocyte maturation. Moreover, the over-expression of NOX4 in cumulus cells could result in a significant increase in ROS levels and ER fluorescence intensity in oocytes. In conclusion, C3G promoted in vitro maturation of porcine oocytes exposed to ZEN via mitigating NOX4-dependent oxidative stress and ERS in cumulus cells. These results contribute to our comprehension of the molecular mechanisms underlying the protective effects of C3G against ZEN toxicity in porcine oocytes, and they provide a novel theoretical foundation and strategy for future applications of C3G in the improvement of female reproduction.

Genetic parameters for cloacal gland, sexual maturity, reproductive organs weight, and body weight in meat-type quail

Selection to increase body weight in poultry can hamper reproduction traits and compromise production efficiency. Thus, attention to reproduction traits is essential to improving the sustainability of breeding programs. Data from a domestic quail breeding program for meat production were used to estimate genetic parameters. We analyzed five traits: 4-week body weight, age at sexual maturity for males and females, cloacal gland area, female, and male reproductive organs weights. A multi-trait mixed model analysis with fixed effects of generation/hatch was performed, assuming environmental covariance equals zero for sex-limited traits. Heritability estimates range from low to moderate for male sexual maturity and cloacal gland area, and high for other traits. Intersexual genetic correlation for age at sexual maturity is positive, which can lead to correlated responses in the other sex. Reproductive organs weights are genetically correlated with body weight, but not significantly between sexes and nor with sexual maturity. Genetic correlations for the cloacal gland area were positive with body weight and negative with age at sexual maturity of males and females, demonstrating a potential use of this trait for selection with favorable outcomes in reproduction. The use of the cloacal gland area can be used in the same way as the scrotal circumference in mammals, improving female reproduction traits by selecting a trait recorded in males.

White-nose syndrome, winter duration, and pre-hibernation climate impact abundance of reproductive female bats.

White-nose syndrome (WNS) is an infectious disease that disrupts hibernation in bats, leading to premature exhaustion of fat stores. Though we know WNS does impact reproduction in hibernating female bats, we are unsure how these impacts are exacerbated by local climate factors. We compiled data from four southeastern U.S. states and used generalized linear mixed effects models to compare effects of WNS, pre-hibernation climate variables, and winter duration on the number of reproductive females in species across the range of WNS susceptibility. We predicted we would see a decline in the number of reproductive females in WNS-susceptible species, with the effect exaggerated by longer winter durations and pre-hibernation climate variables that lead to reductions in foraging. We found that the number of reproductive females in WNS-susceptible species was positively correlated with pre-hibernation local climate conditions conducive to foraging; however, WNS-susceptible species experienced an overall decline with the presence of WNS and as winter duration increased. Our long-term dataset provides evidence that pre-hibernation climate, specifically favorable summer weather conditions for foraging, greatly influences the reproduction, regardless of WNS status.

A Molecular Perspective and Role of NAD+ in Ovarian Aging.

The decline in female fecundity is linked to advancing chronological age. The ovarian reserve diminishes in quantity and quality as women age, impacting reproductive efficiency and the aging process in the rest of the body. NAD+ is an essential coenzyme in cellular energy production, metabolism, cell signaling, and survival. It is involved in aging and is linked to various age-related conditions. Hallmarks associated with aging, diseases, and metabolic dysfunctions can significantly affect fertility by disturbing the delicate relationship between energy metabolism and female reproduction. Enzymes such as sirtuins, PARPs, and CD38 play essential roles in NAD+ biology, which actively consume NAD+ in their enzymatic activities. In recent years, NAD+ has gained much attention for its role in aging and age-related diseases like cancer, Alzheimer's, cardiovascular diseases, and neurodegenerative disorders, highlighting its involvement in various pathophysiological processes. However, its impact on female reproduction is not well understood. This review aims to bridge this knowledge gap by comprehensively exploring the complex interplay between NAD+ biology and female reproductive aging and providing valuable information that could help develop plans to improve women's reproductive health and prevent fertility issues.

Aberrant CD8+T cells drive reproductive dysfunction in female mice with elevated IFN-γ levels.

Interferon-gamma (IFN-γ) is pivotal in orchestrating immune responses during healthy pregnancy. However, its dysregulation, often due to autoimmunity, infections, or chronic inflammatory conditions, is implicated in adverse reproductive outcomes such as pregnancy failure or infertility. Additionally, the underlying immunological mechanisms remain elusive. Here, we explore the impact of systemic IFN-γ elevation on cytotoxic T cell responses in female reproduction utilizing a systemic lupus-prone mouse model with impaired IFN-γ degradation. Our findings reveal that heightened IFN-γ levels triggered the infiltration of CD8+T cells in the pituitary gland and female reproductive tract (FRT), resulting in prolactin deficiency and subsequent infertility. Furthermore, we demonstrate that chronic IFN-γ elevation increases effector memory CD8+T cells in the murine ovary and uterus. These insights broaden our understanding of the role of elevated IFN-γ in female reproductive dysfunction and suggest CD8+T cells as potential immunotherapeutic targets in female reproductive disorders associated with chronic systemic IFN-γ elevation.