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Human Reproduction Update Jul 2023Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as... (Review)
Review
BACKGROUND
Regulated cell death is a fundamental component of numerous physiological processes; spanning from organogenesis in utero, to normal cell turnover during adulthood, as well as the elimination of infected or damaged cells throughout life. Quality control through regulation of cell death pathways is particularly important in the germline, which is responsible for the generation of offspring. Women are born with their entire supply of germ cells, housed in functional units known as follicles. Follicles contain an oocyte, as well as specialized somatic granulosa cells essential for oocyte survival. Follicle loss-via regulated cell death-occurs throughout follicle development and life, and can be accelerated following exposure to various environmental and lifestyle factors. It is thought that the elimination of damaged follicles is necessary to ensure that only the best quality oocytes are available for reproduction.
OBJECTIVE AND RATIONALE
Understanding the precise factors involved in triggering and executing follicle death is crucial to uncovering how follicle endowment is initially determined, as well as how follicle number is maintained throughout puberty, reproductive life, and ovarian ageing in women. Apoptosis is established as essential for ovarian homeostasis at all stages of development and life. However, involvement of other cell death pathways in the ovary is less established. This review aims to summarize the most recent literature on cell death regulators in the ovary, with a particular focus on non-apoptotic pathways and their functions throughout the discrete stages of ovarian development and reproductive life.
SEARCH METHODS
Comprehensive literature searches were carried out using PubMed and Google Scholar for human, animal, and cellular studies published until August 2022 using the following search terms: oogenesis, follicle formation, follicle atresia, oocyte loss, oocyte apoptosis, regulated cell death in the ovary, non-apoptotic cell death in the ovary, premature ovarian insufficiency, primordial follicles, oocyte quality control, granulosa cell death, autophagy in the ovary, autophagy in oocytes, necroptosis in the ovary, necroptosis in oocytes, pyroptosis in the ovary, pyroptosis in oocytes, parthanatos in the ovary, and parthanatos in oocytes.
OUTCOMES
Numerous regulated cell death pathways operate in mammalian cells, including apoptosis, autophagic cell death, necroptosis, and pyroptosis. However, our understanding of the distinct cell death mediators in each ovarian cell type and follicle class across the different stages of life remains the source of ongoing investigation. Here, we highlight recent evidence for the contribution of non-apoptotic pathways to ovarian development and function. In particular, we discuss the involvement of autophagy during follicle formation and the role of autophagic cell death, necroptosis, pyroptosis, and parthanatos during follicle atresia, particularly in response to physiological stressors (e.g. oxidative stress).
WIDER IMPLICATIONS
Improved knowledge of the roles of each regulated cell death pathway in the ovary is vital for understanding ovarian development, as well as maintenance of ovarian function throughout the lifespan. This information is pertinent not only to our understanding of endocrine health, reproductive health, and fertility in women but also to enable identification of novel fertility preservation targets.
Topics: Adult; Animals; Female; Humans; Apoptosis; Granulosa Cells; Mammals; Oocytes; Ovarian Follicle; Ovary; Regulated Cell Death; Homeostasis
PubMed: 36857094
DOI: 10.1093/humupd/dmad005 -
American Journal of Obstetrics and... Dec 2023We conducted a systematic review and meta-analysis of the effects of Mediterranean diet on female reproductive health outcomes over the life-course. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
We conducted a systematic review and meta-analysis of the effects of Mediterranean diet on female reproductive health outcomes over the life-course.
DATA SOURCES
We searched PubMed, Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), and ClinicalTrials.gov to identify eligible studies published till February 2022. Eligible references from identified studies and review articles were also considered.
STUDY ELIGIBILITY CRITERIA
Randomized controlled trials, prospective cohort studies, or nested case-control studies examining Mediterranean diet and major female reproductive outcomes over the lifespan, including clinical outcomes from childhood to adulthood (menarche, polycystic ovary syndrome, endometriosis, and outcomes related to fertility, pregnancy, and menopause), were included for review.
METHODS
Two independent reviewers screened and performed data extraction and risk-of-bias assessment. We performed random-effects meta-analysis to obtain summary relative risks and 95% confidence intervals for major female reproductive outcomes. Subgroup analyses were performed for several pregnancy outcomes according to timing of the interventions for randomized controlled trials and timing of the dietary assessment for observational studies.
RESULTS
Thirty-two studies (9 randomized controlled trials, 22 prospective cohort studies, and 1 nested case-control study) involving 103,204 predominantly White women (>95%) were included. The pooled relative risk (95% confidence interval) comparing randomization to Mediterranean diet vs a control diet based on 7 randomized controlled trials was 0.74 (0.55-0.99) for gestational diabetes mellitus, 0.45 (0.26-0.76) for preterm birth, 0.71 (0.51-1.00) for gestational hypertension, and 0.82 (0.54-1.22) for preeclampsia; the effect sizes for preterm birth were greater in randomized controlled trials that initiated the interventions in first trimester vs after first trimester (P heterogeneity=.02). We observed inverse associations for all the above-mentioned pregnancy outcomes based on 9 cohort studies. There was suggestive evidence of favorable associations between Mediterranean diet adherence with fertility and gestational weight management. Limited studies suggested associations between higher Mediterranean diet adherence and later time to menarche and fewer vasomotor menopausal symptoms, null associations for polycystic ovary syndrome-like phenotype and pregnancy loss, and positive associations for luteal phase deficiency.
CONCLUSION
Adherence to Mediterranean diet may lower risks of adverse pregnancy outcomes among predominantly White populations. For fertility-related outcomes, available evidence supporting potential beneficial effects is suggestive yet limited. For other reproductive outcomes across the lifespan, data remains sparse.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Child; Adolescent; Young Adult; Polycystic Ovary Syndrome; Diet, Mediterranean; Premature Birth; Reproductive Health; Longevity; Case-Control Studies; Prospective Studies
PubMed: 37506751
DOI: 10.1016/j.ajog.2023.05.030 -
BMC Endocrine Disorders Oct 2023Many studies have investigated the impact of precocious puberty on cardiovascular disease (CVD) outcomes and the association between lipid profile levels and precocious... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Many studies have investigated the impact of precocious puberty on cardiovascular disease (CVD) outcomes and the association between lipid profile levels and precocious puberty. However, the results have been inconsistent. The aim of this meta-analysis was to evaluate whether triglyceride (TG), total cholesterol (TC), high density lipoprotein (HDL)and low density lipoprotein (LDL) levels were altered in girls with precocious puberty compared with healthy controls.
METHODS
References published before June 2022 in the EMBASE, Cochrane Library, PubMed and Web of Science databases were searched to identify eligible studies. A DerSimonian-Laird random-effects model was used to evaluate the overall standard mean difference (SMD) between precocious puberty and healthy controls. Subgroup analyses and sensitivity analyses were preformed, and publication bias was assessed.
RESULTS
A total of 14 studies featuring 1023 girls with precocious puberty and 806 healthy girls were selected for analysis. The meta-analysis showed that TG (SMD: 0.28; 95% CI: 0.01 to 0.55; P = 0.04), TC (SMD: 0.30; 95% CI: 0.01 to 0.59; P = 0.04), LDL (SMD: 0.45; 95% CI: 0.07 to 0.84; P = 0.02)levels were significantly elevated in girls with precocious puberty. HDL levels did not change significantly (SMD: -0.06; 95% CI: -0.12 to 0.61; P = 0.62). Subgroup analyses revealed that the heterogeneity in the association between lipid profile and precocious puberty in this meta-analysis may arise from disease type, region, sample size, chronological age, body mass index difference and drug usage.
CONCLUSION
Lipid profile levels altered in girls with precocious puberty compared with healthy controls. In order to minimize the risk of CVD morbidity and mortality, early interventions were needed to prevent obesity in children and adolescents, especially those with precocious puberty.
Topics: Female; Child; Adolescent; Humans; Lipids; Pediatric Obesity; Puberty, Precocious; Cholesterol, HDL; Cholesterol, LDL; Triglycerides; Cardiovascular Diseases
PubMed: 37848909
DOI: 10.1186/s12902-023-01470-8 -
Frontiers in Pediatrics 2023The aim of this study was to evaluate the potential association between early onset puberty and the risk of different forms of obesity in children. (Review)
Review
OBJECTIVES
The aim of this study was to evaluate the potential association between early onset puberty and the risk of different forms of obesity in children.
METHODS
The databases PubMed, EMBASE, Web of Science and Cochrane Library were systematically searched for relevant studies. The odds ratio (OR) and 95% confidence interval (CI) of obesity in precocious puberty were calculated using Stata software 14.0. A fixed-effects model was used if > 0.1 and ≤ 50%. Otherwise, a random-effects model was used. Publication bias was assessed using funnel plots and Egger's test.
RESULT
The pooling analysis showed that precocious puberty in girls was associated with a higher risk of obesity (OR = 1.98; 95% CI: 1.76-2.24; = 0.00%, < 0.001). Girls with a history of precocious puberty were found to have an increased risk of general obesity (OR = 2.03; 95% CI: 1.62-2.55; = 22.2%, < 0.001), central obesity (OR = 1.96; 95% CI: 1.70-2.26; = 0.00%, < 0.001), and overweight (OR = 2.03; 95% CI: 1.68-2.46; = 5.1%, < 0.001). The pooled analysis showed that precocious puberty in boys was not associated with an increased risk of obesity (OR = 1.14; 95% CI: 0.86-1.51; = 50.6%, = 0.369). In boys, the occurrence of precocious puberty was not associated with an elevated risk of general obesity (OR = 0.96; 95% CI: 0.40-2.27; = 79.6%, = 0.922), central obesity (OR = 1.17; 95% CI: 0.96-1.43; = 0.00%, = 0.125), or overweight (OR = 1.03; 95% CI: 0.56-1.88; = 74.4%, = 0.930).
CONCLUSION
This meta-analysis suggests that the onset of puberty at an early age in girls is associated with an increased risk of obesity, however precocious puberty in boy was not associated with an increased risk of obesity. These findings highlight that precocious puberty should be considered an independent risk factor for obesity in girls.
SYSTEMATIC REVIEW REGISTRATION
CRD42023404479.
PubMed: 37635793
DOI: 10.3389/fped.2023.1226933 -
Early Human Development Aug 2023A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship... (Review)
Review
BACKGROUND
A secular trend towards earlier age at menarche has been reported, but the trend in breast development is less clear. We reviewed the evidence on the relationship between in utero and early life events and breast onset/development.
METHODS
Eligible studies were identified in PubMed and Embase databases. We selected studies in which female human exposure during fetal or the first years of life was measured or estimated, and associations with breast onset or development were evaluated.
RESULTS
Of the 49 cohort studies and 5 cross-sectional studies identified, 43 provided sufficient data to assess associations. High maternal weight, primiparity, and early weight gain, were related to an increased risk of early breast onset/development in most of the studies that analysed these associations, whereas late breast onset/development was associated with preterm birth. Results were inconsistent for smoking in pregnancy, maternal hypertensive disorders, breastfeeding, diabetes, and small for gestational age. No association emerged for maternal age at delivery, alcohol drinking, and selected drug use during pregnancy, and low birth weight.
CONCLUSIONS
The results of this review show that high maternal weight, primiparity and early weight gain were associated with an increased risk of early breast onset/development. Late breast onset/development was associated with preterm birth. Breast development is a key physical marker of puberty onset, and early puberty development is linked to consequences that can reverberate throughout life. Answering the questions about the interconnections between pre/postnatal environmental exposures and their impact on puberty, represents an important area of multidisciplinary research.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Premature Birth; Cross-Sectional Studies; Prenatal Care; Maternal Age; Weight Gain
PubMed: 37421688
DOI: 10.1016/j.earlhumdev.2023.105816 -
Endocrine Practice : Official Journal... Apr 2024This study aims to explore the significant impact of environmental chemicals on disease development, focusing on their role in developing metabolic and endocrine... (Review)
Review
OBJECTIVE
This study aims to explore the significant impact of environmental chemicals on disease development, focusing on their role in developing metabolic and endocrine diseases. The objective is to understand how these chemicals contribute to the increasing prevalence of precocious puberty, considering various factors, including epigenetic changes, lifestyle, and emotional disturbances.
METHODS
The study employs a comprehensive review of descriptive observational studies in both human and animal models to identify a degree of causality between exposure to environmental chemicals and disease development, specifically focusing on endocrine disruption. Due to ethical constraints, direct causation studies in human subjects are not feasible; therefore, the research relies on accumulated observational data.
RESULTS
Puberty is a crucial life period with marked physiological and psychological changes. The age at which sexual characteristics develop is changing in many regions. The findings indicate a correlation between exposure to endocrine-disrupting chemicals and the early onset of puberty. These chemicals have been shown to interfere with normal hormonal processes, particularly during critical developmental stages such as adolescence. The research also highlights the interaction of these chemical exposures with other factors, including nutritional history, social and lifestyle changes, and emotional stress, which together contribute to the prevalence of precocious puberty.
CONCLUSION
Environmental chemicals significantly contribute to the development of certain metabolic and endocrine diseases, particularly in the rising incidence of precocious puberty. Although the evidence is mainly observational, it adequately justifies regulatory actions to reduce exposure risks. Furthermore, these findings highlight the urgent need for more research on the epigenetic effects of these chemicals and their wider impact on human health, especially during vital developmental periods.
Topics: Adolescent; Animals; Humans; Endocrine Disruptors; Endocrine System; Endocrine System Diseases; Puberty; Puberty, Precocious; Observational Studies as Topic
PubMed: 38185329
DOI: 10.1016/j.eprac.2024.01.006 -
Frontiers in Endocrinology 2023Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital...
BACKGROUND
Noonan syndrome (NS) is a genetic multisystem disorder characterised by variable clinical manifestations including dysmorphic facial features, short stature, congenital heart disease, renal anomalies, lymphatic malformations, chest deformities, cryptorchidism in males.
METHODS
In this narrative review, we summarized the available data on puberty and gonadal function in NS subjects and the role of the RAS/mitogen-activated protein kinase (MAPK) signalling pathway in fertility. In addition, we have reported our personal experience on pubertal development and vertical transmission in NS.
CONCLUSIONS
According to the literature and to our experience, NS patients seem to have a delay in puberty onset compared to the physiological timing reported in healthy children. Males with NS seem to be at risk of gonadal dysfunction secondary not only to cryptorchidism but also to other underlying developmental factors including the MAP/MAPK pathway and genetics. Long-term data on a large cohort of males and females with NS are needed to better understand the impact of delayed puberty on adult height, metabolic profile and well-being. The role of genetic counselling and fertility related-issues is crucial.
Topics: Male; Child; Adult; Female; Humans; Noonan Syndrome; Cryptorchidism; Gonads; Puberty; Mitogen-Activated Protein Kinases
PubMed: 37576960
DOI: 10.3389/fendo.2023.1213098 -
American Journal of Obstetrics and... Mar 2024Accelerated female reproductive events represent the early onset of reproductive events involving puberty, menarche, pregnancy loss, first sexual intercourse, first... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
Accelerated female reproductive events represent the early onset of reproductive events involving puberty, menarche, pregnancy loss, first sexual intercourse, first birth, parity, and menopause. This study aimed to explore the association between childhood adversity and accelerated female reproductive events.
DATA SOURCES
PubMed, Web of Science, and Embase were systematically searched from September 22, 2022 to September 23, 2022.
STUDY ELIGIBILITY CRITERIA
Observational cohort, cross-sectional, and case-control studies in human populations were included if they reported the time of reproductive events for female individuals with experience of childhood adversity and were published in English.
METHODS
Two reviewers independently screened studies, obtained data, and assessed study quality, and conflicts were resolved by a third reviewer. Dichotomous outcomes were evaluated using meta-analysis, and pooled odds ratios and 95% confidence intervals were generated using random-effects models. Moderation analysis and meta-regression were used to investigate heterogeneity.
RESULTS
In total, 21 cohort studies, 9 cross-sectional studies, and 3 case-control studies were identified. Overall, female individuals with childhood adversity were nearly 2 times more likely to report accelerated reproductive events than those with no adversity exposure (odds ratio, 1.91; 95% confidence interval, 1.33-2.76; I=99.6%; P<.001). Moderation analysis indicated that effect sizes for the types of childhood adversity ranged from an odds ratio of 1.61 (95% confidence interval, 1.23-2.09) for low socioeconomic status to 2.13 (95% confidence interval, 1.14-3.99) for dysfunctional family dynamics. Among the 7 groups based on different reproductive events, including early onset of puberty, early menarche, early sexual initiation, teenage childbirth, preterm birth, pregnancy loss, and early menopause, early sexual initiation had a nonsignificant correlation with childhood adversity (odds ratio, 2.70; 95% confidence interval, 0.88-8.30; I=99.9%; P<.001). Considerable heterogeneity (I>75%) between estimates was observed for over half of the outcomes. Age, study type, and method of data collection could explain 35.9% of the variance.
CONCLUSION
The literature tentatively corroborates that female individuals who reported adverse events in childhood are more likely to experience accelerated reproductive events. This association is especially strong for exposure to abuse and dysfunctional family dynamics. However, the heterogeneity among studies was high, requiring caution in interpreting the findings and highlighting the need for further evaluation of the types and timing of childhood events that influence accelerated female reproductive events.
Topics: Adolescent; Child; Female; Humans; Pregnancy; Adverse Childhood Experiences; Cross-Sectional Studies; Parturition; Premature Birth; Reproduction
PubMed: 37820985
DOI: 10.1016/j.ajog.2023.10.005 -
Nutrients Aug 2023In phenylketonuria (PKU), natural protein tolerance is defined as the maximum natural protein intake maintaining a blood phenylalanine (Phe) concentration within a... (Meta-Analysis)
Meta-Analysis Review
In phenylketonuria (PKU), natural protein tolerance is defined as the maximum natural protein intake maintaining a blood phenylalanine (Phe) concentration within a target therapeutic range. Tolerance is affected by several factors, and it may differ throughout a person's lifespan. Data on lifelong Phe/natural protein tolerance are limited and mostly reported in studies with low subject numbers. This systematic review aimed to investigate how Phe/natural protein tolerance changes from birth to adulthood in well-controlled patients with PKU on a Phe-restricted diet. Five electronic databases were searched for articles published until July 2020. From a total of 1334 results, 37 articles met the eligibility criteria ( = 2464 patients), and 18 were included in the meta-analysis. The mean Phe (mg/day) and natural protein (g/day) intake gradually increased from birth until 6 y (at the age of 6 months, the mean Phe intake was 267 mg/day, and natural protein intake was 5.4 g/day; at the age of 5 y, the mean Phe intake was 377 mg/day, and the natural protein intake was 8.9 g/day). However, an increase in Phe/natural protein tolerance was more apparent at the beginning of late childhood and was >1.5-fold that of the Phe tolerance in early childhood. During the pubertal growth spurt, the mean natural protein/Phe tolerance was approximately three times higher than in the first year of life, reaching a mean Phe intake of 709 mg/day and a mean natural protein intake of 18 g/day. Post adolescence, a pooled analysis could only be performed for natural protein intake. The mean natural protein tolerance reached its highest (32.4 g/day) point at the age of 17 y and remained consistent (31.6 g/day) in adulthood, but limited data were available. The results of the meta-analysis showed that Phe/natural protein tolerance (expressed as mg or g per day) increases with age, particularly at the beginning of puberty, and reaches its highest level at the end of adolescence. This needs to be interpreted with caution as limited data were available in adult patients. There was also a high degree of heterogeneity between studies due to differences in sample size, the severity of PKU, and target therapeutic levels for blood Phe control.
Topics: Child; Child, Preschool; Adolescent; Adult; Humans; Infant; Phenylalanine; Phenylketonurias; Databases, Factual; Immune Tolerance; Longevity
PubMed: 37630696
DOI: 10.3390/nu15163506 -
Acta Bio-medica : Atenei Parmensis Dec 2023The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to...
BACKGROUND
The relationship between precocious or early puberty and its treatment has received significant research attention, yielding diverse outcomes. This short review aims to comprehensively analyze and summarize research articles to elucidate the potential link between precocious or early pubertal onset (CPP) and crucial health factors.
METHODS
We conducted a systematic review of studies published from -January 2000 to March 2023, sourced from databases of Medline, PubMed, Google Scholar and Web of Science. We assessed the relationship between CPP and final adult height (FHt), bone health, reproductive function, body mass index, metabolic and cardiovascular abnormalities, and increased cancer risk.
RESULTS
Upon reviewing and analyzing selected studies, the following key findings emerged: (a) treating CPP in girls before age 6-7 and in boys before age 9 improves FHt; (b) bone mineral density (BMD) decreases during GnRHa treatment but normalizes afterward, with no lasting effects on peak bone mass during puberty; (c) GnRH treatment does not negatively affect menstrual cycles; however, untreated CPP increases the risk of premature or early-onset menopause; (d) the incidence of PCOS/hyperandrogenemia may be slightly elevated in women with a history of CPP, but overall reproductive function remains largely unaffected; (e) earlier thelarche and menarche may enhance susceptibility to breast carcinogenesis; (f) CPP contributes to an increased risk of obesity and type 2 diabetes in both genders; (g) early menarche may slightly increase the risk of coronary heart disease and ischemic strokes and (h) early pubertal timing increases the risk of depression and anxiety disorders.
CONCLUSION
Monitoring and early diagnosis of these conditions are of paramount importance for successful management.
Topics: Female; Humans; Male; Child; Diabetes Mellitus, Type 2; Gonadotropin-Releasing Hormone; Puberty, Precocious; Obesity; Puberty
PubMed: 38054666
DOI: 10.23750/abm.v94i6.15316