As women age, oocytes are susceptible to a myriad of dysfunctions, including mitochondrial dysfunction, impaired DNA repair mechanisms, epigenetic alterations, and metabolic disturbances, culminating in reduced fertility rates among older individuals. Ferredoxin (FDX) represents a highly conserved iron-sulfur (Fe-S) protein essential for electron transport across multiple metabolic pathways. Mammalian mitochondria house two distinct ferredoxins, FDX1 and FDX2, which share structural similarities and yet perform unique functions. In our investigation into the regulatory mechanisms governing ovarian aging, we employed a comprehensive multi-omics analysis approach, integrating spatial transcriptomics, single-cell RNA sequencing, human ovarian pathology, and clinical biopsy data. Previous studies have highlighted intricate interactions involving excessive lipid peroxide accumulation, redox-induced metal ion buildup, and alterations in cellular energy metabolism observed in aging cells. Through a multi-omics analysis, we observed a notable decline in the expression of the critical gene FDX1 as ovarian age progressed. This observation prompted speculation regarding FDX1's potential as a promising biomarker for ovarian aging. Following this, we initiated a clinical trial involving 70 patients with aging ovaries. These patients were administered oral nutritional supplements consisting of DHEA, ubiquinol CoQ10, and Cleo-20 T3 for a period of two months to evaluate alterations in energy metabolism regulated by FDX1. Our results demonstrated a significant elevation in FDX1 levels among participants receiving nutritional supplementation. We hypothesize that these nutrients potentiate mitochondrial tricarboxylic acid cycle (TCA) activity or electron transport chain (ETC) efficiency, thereby augmenting FDX1 expression, an essential electron carrier in metabolic pathways, while concurrently mitigating lipid peroxide accumulation and cellular apoptosis. In summary, our findings underscore the potential of nutritional intervention to enhance in vitro fertilization outcomes in senescent cells by bolstering electron transport proteins, thus optimizing energy metabolism and improving oocyte quality in aging women.
Meconium aspiration syndrome (MAS), possibly resulting from fetal hypoxia, is a respiratory distress disorder in the infant. Pregnancy-induced hypertension (PIH) can cause placental dysfunction and lead to fetal hypoxia, which may induce the development of MAS. Therefore, the aim of this study was to determine the association between PIH and MAS and to identify the predictive risk factors.This was a retrospective cohort study. We selected patients with newly diagnosed PIH and a matched cohort group from the Taiwan National Health Insurance Research Database (NHIRD), from January 1, 2000 till December 31, 2013. For each patient in the PIH cohort, 4 subjects without PIH, matched for age and year of delivery, were randomly selected as the comparison cohort. The incidence of meconium aspiration syndrome was assessed in both groups.Among the 23.3 million individuals registered in the NHIRD, 29,013 patients with PIH and 116,052 matched controls were identified. Patients who experienced PIH had a higher incidence of MAS than did those without PIH. According to a multivariate analysis, PIH (odds ratio [OR] = 1.70, 95% confidence interval [CI] = 1.49-1.93, p < 0.0001) was independently associated with increased risk of MAS. Additionally, age ≥30 years (OR = 1.26, 95% CI = 1.12-1.42, p = 0.0001), nulliparity (OR = 1.13, 95% CI = 1.01-1.27, p = 0.0367) and patients with diabetes mellitus (OR = 3.09, 95% CI = 1.35-7.09, p = 0.0078) were also independent risk factors of MAS.Patients with PIH obtained higher subsequent risk for the development of MAS than those without PIH. Besides, age ≥30 years, nulliparity and patients with diabetes mellitus are the independent risk factors of developing MAS.
To determine the association between pregnancy-induced hypertension (PIH) and transient tachypnea of the newborn (TTN) and to identify the predictive risk factors.Pregnant women with a newly diagnosed PIH (between 2000 and 2013) from the Taiwan National Health Insurance Research Database (NHIRD) were compared with a matched (with respect to age and year of delivery) cohort of pregnant women without PIH. The occurrence of TTN was evaluated in both cohorts.Among the 23.3 million individuals registered in the NHIRD, 29,013 patients with PIH and 116,052 matched controls were identified. According to a multivariate analysis, PIH (odds ratio [OR] = 1.85, 95% confidence interval [CI] = 1.69-2.03, p < 0.0001), age ≥ 30 years (OR = 1.38, 95% CI = 1.26-1.51, p < 0.0001), primiparity (OR = 1.37, 95% CI = 1.24-1.5, p < 0.0001), preterm birth (OR = 3.4, 95% CI = 3.09-3.75, p < 0.0001), multiple births (OR = 2.54, 95% CI = 2.24-2.89, p < 0.0001), and cesarean section (OR = 1.71, 95% CI = 1.56-1.88, p < 0.0001) were independent risk factors for the development of TTN.Women with PIH have an increased risk of having infants who develop TTN compared with those without PIH. Additionally, age ≥30 years, primiparity, preterm birth, multiple births, and cesarean section were independent risk factors for the development of TTN.
Dysregulation of the immune system plays a role in the pathogenesis of both, pregnancy-induced hypertension (PIH) and systemic lupus erythematosus (SLE). It is well known that SLE predisposes to be complicated with PIH. However, few studies have attempted to investigate whether PIH increased subsequent SLE risk. The objectives of this study were to assess the association between PIH and subsequent SLE risk and identify predictive risk factors. Patients with newly diagnosed PIH were selected from the Taiwan National Health Insurance Research Database (NHIRD) and compared with a matched cohort without PIH based on age and the year of delivery. The incidence of new-onset SLE was evaluated in both cohorts. The overall observational period was from January 1, 2000 to December 31, 2013. Among the 23.3 million individuals registered in the NHIRD, 29,091 patients with PIH and 116,364 matched controls were identified. The incidence of SLE was higher among patients with PIH than in the matched controls (incidence rate ratio [IRR] = 4.02, 95% confidence interval [CI] 3.98–4.05, P < 0.0001). The IRR for subsequent SLE development remained significantly higher in all stratifications during the follow-up years. The multivariate Cox regression model was performed and the results showed that PIH may be an independent risk factors for the development of subsequent SLE (hazard ratio [HR] = 2.87, 95% CI 2.07–3.98, P < 0.0001). Moreover, multivariate Cox regression model was used again among the PIH cohort only in order to identify the possible risk factors for subsequent SLE in the population with PIH. Patients with PIH may have higher risk of developing newly diagnosed SLE than those without PIH. In addition, among individuals who have experienced PIH, those younger than 30 years, having experienced preeclampsia/eclampsia, single parity, preterm birth, or chronic kidney disease, may display an increased subsequent risk of SLE.
Advanced maternal age is associated with decreased oocyte quantity and quality and in vitro fertilization (IVF) success rates. This study aimed to investigate whether melatonin supplementation can improve IVF outcomes in women of advanced maternal age by modulating cuproptosis and ferroptosis.
Adolescent pregnancy (teenage pregnancy) is a high-risk condition associated with adverse outcome, not only for the mother but also for the newborn child.1 One report showed that teenage pregnancy was associated with adverse maternal outcomes, because teenage mothers had a higher risk of severe perineal tear during labor than adult mothers [odds ratio (OR) 1.6; 95% confidence interval (CI) 0.95–2.70].2 Another report showed that younger pregnant women had a significantly increased risk of development of striae gravidarum than older pregnant women.3 Striae gravidarum results in itching and discomfort and produces significant psychological burden in affected women.1 In terms of adverse fetal outcomes, teenage mothers were more likely to have infants with low body weight (<2500 g; OR 2.8; 95% CI 1.3–6.1, p < 0.006), preterm babies (<37 weeks of gestational age; OR 1.9; 95% CI 1.0–3.4, p < 0.003), and lower 5-minute Apgar scores (OR 1.7, 95% CI 0.9–3.0, p = 0.05) compared to adult mothers.2 These reports reinforce the assertion that pregnant adolescents are at an increased risk for adverse outcomes. Palpably worse outcomes for both infant and mother have been noted in adolescent pregnancy by many studies, including: (1) an increase of fetal death, neonatal death, low birth weight, intrauterine growth retardation, prematurity; and (2) an increase of severe perineal laceration and a tendency to result in permanent body image changes, such as occurrence of striae gravidarum, and an increase of maternal mortality.2–5 The results of these studies all suggest that health during and after adolescent pregnancy is an important issue that requires additional efforts to improve outcomes. Major underlying causes for worse outcome of both mothers and fetuses include: (1) unintended, unwanted, and unsupported pregnancy; (2) poor maternal nutrition; (3) not securing adequate care during the course of pregnancy; (4) labor without assistance by experienced obstetricians; and (5) not securing proper postpartum maternal and newborn care.4 In addition, adolescent mothers were more likely to be unemployed, unmarried, and less educated than the adult mothers, and low socioeconomic status subsequently results in inadequate prenatal care, including poor nutrition support.2 In fact, malnutrition might be very common in adolescent pregnancy. A recent review article focusing on adolescent pregnancy and the first 1000 days after childbirth found that >35% of adolescent pregnancies were considered nutritionally at-risk.4 The seventh National Nutrition Survey showed that >25% of female adolescents were underweight. In addition, based on the criteria which defined nutritionally at-risk pregnant women as those with body mass index-for-age
Background: Dehydroepiandrosterone (DHEA) supplementation has been reported to have beneficial effects on the in vitro fertilization (IVF) outcomes of patients with poor ovarian response or diminished ovarian reserve. The Patient-Oriented Strategies Encompassing IndividualizeD Oocyte Number (POSEIDON) stratification is a set of newly established criteria for low prognosis patients. The aim of this study was to examine the potential effects of DHEA supplementation on the IVF outcomes of patients who fulfill the POSEIDON group 4 criteria. Methods: This retrospective cohort study investigated 297 cycles that fulfilled the POSEIDON group 4 criteria and underwent IVF treatment using the gonadotropin-releasing hormone antagonist protocol. The study group contained 159 cycles that received DHEA (30 mg three times per day) daily for 12 weeks before their IVF cycles. The control group included 138 cycles that underwent IVF cycles but did not receive DHEA. The baseline characteristics and cycle parameters as well as the IVF outcomes of both groups were compared. Results: In terms of baseline characteristics, more previous IVF attempts and lower AMH levels were found in the study group than in the control group. Regarding IVF outcomes, patients in the study group had significantly higher follicular oocyte index and higher numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day 3 embryos and top-quality day 3 embryos than those in the control group. Besides, a higher cumulative pregnancy rate and lower cancellation rate were observed in the study group than in the control group although clinical pregnancy rate, live birth rate, and cumulative live birth rate did not differ between the two groups. Whether patients are aged ≤ 40 years or aged > 40, higher numbers of oocytes and embryos were observed in the study group than in the control group. In patients aged > 40, cumulative pregnancy rate was significantly higher in the study group than in the control group. Conclusions: Our data suggest that DHEA supplementation might increase both oocyte and embryo yields, as well as cumulative pregnancy rates, in patients fulfilling the POSEIDON group 4 criteria.
Fertility is possibly the most important capability contained within living cells or species. Therefore, finding the most efficacious way to enhance or promote fertility is the main goal of all living things. To best manage nature's strong predisposition for fertility, plant-based traditional medicines for birth control have long been incorporated into medical practices throughout the world, including those in the rural populations of North-East India, China, and Africa.1–3 In this issue of the Journal of the Chinese Medical Association, Muhammad and Muhammad1 published a very interesting review article entitled "Anti-fertility activity of medicinal plants," introducing >60 species of plants that might possess antifertility activity. This article divided these antifertility plants into five categories, namely, plants exhibiting antiovulation activity, anti-implantation activity, antispermatogenic activity, antifertility activity by interfering with the action of hormones, and finally abortifacient activity. The authors claimed to have provided a comprehensive summary of medicinal plants from the literature, including results from Cochrane Central Register of Controlled Trials (CENTRAL), Embase, and PubMed searches using terms such as antifertility, anti-implantation, antiovulation, and antispermatogenic activity of plants. We applaud the authors on the success of this article, because their research and information-gathering task were not easy. However, given the size of the project that they undertook, it goes without saying that their review ultimately will omit certain important data. For example, information about the extract of Drynaria quercifolia (L.) J. Smith rhizome was missed in their review. This extract was proven to possess significant antifertility activity, not only showing a high efficacy for both abortifacient and anti-implantation activities, but also affecting sex-hormone release.2 In addition, the presence of an "adjuvant reagent," including that in solutions or solvents, could influence the final effect of antifertility activity of these medicinal plants. As noted earlier, the methanol extract of D. quercifolia (L.) J. Smith rhizome has shown higher efficacy for both abortifacient (p < 0.01) and anti-implantation performance (p < 0.01) than its aqueous extract dose.2 Furthermore, the effect of plant-derived products on antifertility may be dose dependent, reversible, and sex dependent. For example, Shaik and colleagues4 demonstrated the antifertility potential of methanolic leaf extract of Artemisia vulgaris, which showed a strong and significant decrease in implant formation (50% and 100%) at two dose levels, 300 mg/kg and 600 mg/kg, respectively. However, it also manifested a strong estrogenic effect resulting in a significant increase in uterine weight in immature ovariectomized rats.4 By contrast, although Solomon and coworkers5 showed that the methanolic root extract of Rumex steudelii could cause atrophic changes in the uterus and disruption of ovarian folliculogenesis by inhibiting further development of the recruited ovarian follicles, there was no effect in male albino rats. Dhanapal and coworkers6 showed the reversible effect of Enicostemma axillare leaves and Urena lobata root on inhibiting spermatogenesis and steroidogenesis, however, this effect appeared to have no significance in female Wistar albino rats. Once again, although we commend the publication of this review article, we also conducted an extensive literature review up to December 25, 2014, to investigate the relationship between fertility and plants using the following strategies to identify the publications addressing fertility and plants. The term "decrease, fertility and plants" was used to search PubMed (http://www.ncbi.nlm.nih.gov/pubmed/?term=anti-fertility%2C+plants), and the term "increase, fertility and plants" in place of the term "decrease, fertility and plants" was used to access relevant articles (http://www.ncbi.nlm.nih.gov/pubmed/?term=increase%2C+fertility%2C+plants). This search criteria identified 266 and 574 published articles, respectively, suggesting that many natural products, especially plants, are still promising targets to be investigated not only for fertility control but also for infertility treatment. This expansive approach is also highly recommended for other troublesome diseases, such as many chronic or aging diseases, including neoplasms, diabetes mellitus, hypertension, and similar maladies. Indeed, paclitaxel, one of the most famous antineoplastic agents extracted from plants, is now widely used in the management of various kinds of neoplastic diseases, including ovarian cancer and breast cancer.7,8 Conflicts of interest The authors declare that there are no conflicts of interest related to the subject matter or materials discussed in this article. Acknowledgments This article was supported by grants from the Ministry of Science and Technology, Executive Yuan (Grant No. MOST 103-2314-B-010-043-MY3) and Taipei Veterans General Hospital (Grant Nos. V102C-141; V103C-112; V104C-095; V102E4-003; and V103E4-003).
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