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Reverse transcription–polymerase chain reaction (RT– PCR) expression analyses of leptin and leptin receptor (B219) isoforms in newly isolated human follicular cumulus oophorus (C) and granulosa cells (G). Molecular weight markers (MWM), 100 bp ladder are indicated.
Source publication
The expression of leptin and its receptors was examined by reverse transcriptase-polymerase chain reaction and immunofluorescence in granulosa and cumulus cells of pre-ovulatory follicles and in meiotically mature oocytes obtained from women undergoing in-vitro fertilization. Leptin concentrations were measured in newly aspirated follicular fluids...
Context in source publication
Context 1
... I also shows the leptin concentration in: (i) maternal RT-PCR analysis demonstrated that leptin and two forms serum at the time of ovulation induction (pre-HCG) and ovum of its receptor (B219 Types 1 and 3) are expressed at the retrieval (36.5-37 h post-HCG); and (ii) in the fluid aspirates mRNA level in granulosa and cumulus cells aspirated several of follicles from which an oocyte was retrieved. Leptin h prior to ovulation from fully-grown human ovarian follicles concentrations were determined by radioimmunoassay for 248 ( Figure 1). Anti-leptin immunofluorescence demonstrated the follicles of similar size (18-22 mm) and volumes (2.5-4.5 ml) ...
Similar publications
The objective of the study was to characterize the effect of the oestrous cycle stage on the yield, morphology and meiotic competence of porcine oocytes. A total of 46 cycling gilts, at 8.5–9 months of age, were used as oocyte donors. Their oestrous cycle was synchronized by Regumate and the onset of oestrus was checked (Day 0). The gilts were slau...
Citations
... Leptin is a neuroendocrinal protein that exists in excess in obese women. Integrating follicular fluid leptin in our study is rationalized by the following: first, leptin is a reflection of the oocyte microenvironment; second, leptin receptors and m-RNA are expressed in granulosa cells [28], oocytes [4,11] and pre-implantation embryos [4],third, leptin is depicted to regulate ovarian steroidogenesis, follicular growth and apoptosis, and oocyte maturation [12,47], Fourth: controversial reports exist for the impact of FF leptin on cycle outcomes in the studied infertile cohort [3,24,30]. ...
Background
Our research question is could follicular fluid (FF) leptin solely or contemporaneously with other clinical, biochemical, and sonographic adiposity measures predict the probability of having a live birth during ICSI cycles? This is a prospective cohort study that enrolled infertile women without polycystic ovary syndrome scheduled for ICSI. At baseline, women had an assessment of obesity using different metrics: clinical, serum biochemical, and sonographic. Clinical measures encompassed waist circumference and body mass index. Biochemical evaluation comprised an assessment of the homeostasis model for insulin resistance, visceral adiposity index, and lipid accumulation product. Preperitoneal and subcutaneous abdominal fat were measured using ultrasound and body fat index was calculated. On the day of oocyte retrieval, pooled FF was sampled to assess FF leptin. Our primary outcome was live birth after one fresh embryo transfer cycle.
Results
Out of 91 women analyzed in this study, 28 have a live birth (30.8%). No difference in FF leptin concentration was found between women with and without live birth (mean ± SD; 20336 ± 8006 vs 18493 ± 6655 pg/ml; P = 0.2). None of the assessed adiposity markers was a predictor for live birth. Substantially, follicular fluid leptin was positively correlated with insulin resistance in women with and without live birth ( r = 0.21, P = 0.04). In logistic regression analysis, the outcome of the prior cycle, the ability to have cryopreserved embryos, and the oocyte maturation index were the predictors for live birth in our study.
Conclusions
The present work could not find evidence that follicular fluid leptin, preperitoneal fat, and other evaluated adiposity measures could impact live births after ICSI cycles.
... Leptin is also involved in the direct regulation of ovarian function. Leptin is found in follicular fluid with levels in accordance with those reported in serum (Cioffi et al., 1997). ObRs have been found in interstitial, theca, and granulosa cells of the ovary in humans (Cioffi et al., 1997;Karlsson et al., 1997). ...
... Leptin is found in follicular fluid with levels in accordance with those reported in serum (Cioffi et al., 1997). ObRs have been found in interstitial, theca, and granulosa cells of the ovary in humans (Cioffi et al., 1997;Karlsson et al., 1997). Leptin plays a significant role in the maturation of ovarian follicles and oocytes (Childs et al., 2021). ...
Leptin, besides its role in regulating body weight, also plays a significant
part in various physiological functions, including reproduction. It acts as
a central player in the intricate signaling pathways of the hypothalamic-
pituitary-gonadal axis, influencing multiple regions. Leptin receptors are
found in the arcuate and ventromedial nucleus of the hypothalamus and
the adenohypophysis, suggesting that leptin can impact the brain and/or
anterior pituitary to modulate the secretion of GnRH and gonadotropins.
Particularly during puberty, leptin can act as a metabolic gate in both
males and females.
... 21 Studies on humans found at least four types of splice variants of OBR messenger ribonucleic acid (mRNA) encoding proteins. 22 Apart from action on energy metabolism, leptin also influence various reproductive functions. DNA polymorphisms in leptin gene (LEP) are linked to extreme obesity. ...
Gestational diabetes mellitus (GDM) is defined as impaired glucose tolerance that is discovered during pregnancy. It is associated with both maternal and various fetal and neonatal mobidity. Prevalence of gestational diabetes mellitus ranges from 3.8% to 17.8% in various studies done in different regions of Indian subcontinent. It has been observed in follow-up studies that both mother and child is more susceptible to develop type 2 diabetes mellitus later in life. Some studies have shown that pathogenesis of type 2 diabetes mellitus and GDM has many similar features and also observed that candidate genes involved in pathogenesis of type 2 DM might have role in pathogenesis of GDM. GDM is potentially induced by several etiologic factors such as genetic and environmental. Family, twins and trans-generational studies have provided evidence that GDM is heritable in some case. There is ample chance to develop GDM in subsequent pregnancies. In this review we will discuss the role of genes regulating insulin secretion ie KCNQ1 and two gene involved in insulin resistance and inflammatory processes ie Leptin and PPARᵞ2.
... Leptin is thought to be a link between diet and reproduction [40]. The hypothalamus-pituitary-ovarian (HPO) axis contains the leptin receptor and mRNA [41,42] Leptin mRNA and protein production is also established in granulosa cells, oocytes and early cleavage-stage embryos. [43]. ...
Background
Polycystic ovary syndrome (PCOS) is an endocrinopathy affecting women of reproductive age group at a global level. According to many community-based studies, the prevalence of PCOS in India ranges from 3.7 to 22.5% due to the country's enormous population. Upon ultrasound, it shows multiple cysts arranged in a bead of necklace-like appearance causing irregular menstrual cycles and infertility in most cases. It is manifested with abnormally raised testosterone and insulin levels and increased luteinizing hormone (LH)-to-follicle-stimulating hormone (FSH) ratio. Phenotypically, it is presented as obesity, hirsutism, acne and male pattern baldness, which impacts the self-esteem of young girls leading to depression and compromised quality of life.
Aim
Numerous potential genes have been shown to contribute to PCOS, and the genetic linkage of PCOS has been investigated in many studies. In this study we are looking into the candidate genes, the variants, and other responsible factors behind the genesis of PCOS. This will help in better understanding of its pathogenesis and, as a result, deciphering the mechanism by proper medication.
Method of the study
We comprehensively searched for publications including PCOS-relevant keywords in different areas in five different electronic databases: PubMed, Google Scholars, Elsevier, Springer Link and Science Direct up to March 2023 focusing on the new ones. We excluded non-English articles, conference papers and studies that were overlapping. Chosen articles were carefully read and further articles that were retrieved from their references were also reviewed so as to make the search complete with the inclusion criterion.
Result
This review summarizes PCOS as an polygenic and a multifactorial complex disease in which a vast array of genetic and environmental factors are involved. Genes that affect steroidogenesis (ovarian and adrenal), gonadotropin action and regulation, insulin action and secretion, body mass index and chronic inflammation are directly or indirectly associated with PCOS.
Conclusion
In this study, research of the genetic propensity to PCOS was made, though not in-depth. With the acquired knowledge of array of genes involved, targeted efforts can be made for the potential therapeutic management of the PCOS patients via the novel discovered routes. Moreover, understanding more about PCOS would be beneficial in prevention of the associated metabolic disorders, life-threatening morbidities, restoring fertility and raising the self-esteem of the young women.
... Leptin is one of the adipokines that is present both in mature follicles and in the earlier stages of follicle development, and its presence supports, among others, the development to the stage of primary follicles [16]. It has been confirmed that treatment with leptin administered in low doses provides a chance to accelerate the growth and maturation of ovarian follicles [17]. ...
It is a well-known fact that the reproductive organs in women, especially oocytes, are exposed to numerous regulatory pathways and environmental stimuli. The maternal age is one cornerstone that influences the process of oocyte fertilization. More precisely, the longer a given oocyte is in the waiting-line to be ovulated from menarche to menopause, the longer the duration from oogenesis to fertilization, and therefore, the lower the chances of success to form a viable embryo. The age of menarche in girls ranges from 10 to 16 years, and the age of menopause in women ranges from approximately 45 to 55 years. Researchers are paying attention to the regulatory pathways that are impacting the oocyte at the very beginning during oogenesis in fetal life to discover genes and proteins that could be crucial for the oocyte’s lifespan. Due to the general trend in industrialized countries in the last three decades, women are giving birth to their first child in their thirties. Therefore, maternal age has become an important factor impacting oocytes developmental competence, since the higher a woman’s age, the higher the chances of miscarriage due to several causes, such as aneuploidy. Meiotic failures during oogenesis, such as, for instance, chromosome segregation failures or chromosomal non-disjunction, are influencing the latter-mentioned aging-related phenomenon too. These errors early in life of women can lead to sub- or infertility. It cannot be neglected that oogenesis is a precisely orchestrated process, during which the oogonia and primary oocytes are formed, and RNA synthesis takes place. These RNAs are crucial for oocyte growth and maturation. In this review, we intend to describe the relevance of regulatory pathways during the oogenesis in women. Furthermore, we focus on molecular pathways of oocyte developmental competence with regard to maternal effects during embryogenesis. On the background of transcriptional mechanisms that enable the transition from a silenced oocyte to a transcriptionally active embryo, we will briefly discuss the potential of induced pluripotent stem cells.
... Leptin is another adipokine that can also be produced from granulosa cells (147). Leptin plays a key role in regulating appetite and energy expenditure (99). ...
Polycystic ovary syndrome (PCOS) affects up to 20% of women but remains poorly understood. It is a heterogeneous condition with many potential comorbidities. This review offers an overview of the dysregulation of the reproductive and metabolic systems associated with PCOS. Review of the literature informed the development of a comprehensive summarizing ‘wiring’ diagram of PCOS-related features. This review provides a justification for each diagram aspect from the relevant academic literature, and explores the interactions between the hypothalamus, ovarian follicles, adipose tissue, reproductive hormones and other organ systems. The diagram will provide an efficient and useful tool for those researching and treating PCOS to understand the current state of knowledge on the complexity and variability of PCOS.
... Sugeriu-se que a leptina poderia ser um sinal importante para a puberdade ( Chehab et al., 1996;Cheung et al., 1997;Strobel et al., 1998). Além disso, a leptina é também sintetizada nos oócitos, células da granulosa (Cioffi et al., 1997) e tecidos placentários (Masuzaki et al., 1997). ...
... The true effect of PCOS on serum leptin levels is unknown, as some researchers found no difference and others found higher leptin levels in PCOS patients than in healthy controls [3,6]. The granulosa and theca cells of ovarian follicles have leptin receptors, and elevated leptin levels can affect follicular growth [7]. Obestatin, a newly discovered hormone, is mainly synthesized by gastrointestinal organs [8]. ...
Objective:
In this study we aimed to assess anorexigenic peptide levels in patients with or without polycystic ovary syndrome (PCOS) and their effects on assisted reproductive treatment (ART) outcomes.
Methods:
A prospective case-control study was conducted in a tertiary care university-based ART clinic. Eighty-three patients were included in the study. The PCOS group included 41 patients, and the non-PCOS group included 42 controls. The 2003 Rotterdam criteria were used for PCOS patient selection. The ART indications in the non-PCOS group were tubal factor or unexplained infertility. Venous blood samples were taken on the third day of the menstrual cycle to determine the serum anorexigenic peptide levels. The enzyme-linked immunosorbent assay method was used for laboratory analyses.
Results:
In the PCOS group, serum obestatin levels were significantly lower than in the control group, but serum anorexigenic peptide levels were similar in PCOS patients with or without clinical pregnancy. Ovarian hyperstimulation syndrome (OHSS) was diagnosed only in PCOS patients, and the obestatin levels of OHSS patients were significantly lower than those of other PCOS patients.
Conclusion:
Baseline anorexigenic peptide levels did not affect the clinical pregnancy rate in ART cycles. Obestatin may play a role in the pathophysiology of OHSS. This possibility should be confirmed in further research.
... The early stages of an oocyte and the surrounding cells contain significant amounts of leptin, and after ovulation, its concentration increases in the blood (Cioffi et al., 1997). Leptin and its receptor (LEP-R) are present in granulosa cells and modulate ovulatory functions in the ovary (Dupuis et al., 2013). ...
Obesity affects female fertility and fecundity through a complex set of mechanisms involving an imbalance of hormones, changes in the adipose tissue, reproductive system, adipokines, cytokines, metabolic perturbation, dysbiosis, and ovulatory and embryonic malfunction. Obesity is an important factor for hyperandrogenism, hyperinsulinemia, and the development of polycystic ovarian syndrome (PCOS). PCOS impairs the functioning of gut microbes which in turn interrupts inflammatory signaling in the hypothalamic-pituitary-gonadal (HPG) axis and oocyte development. It causes abnormalities in the reproductive cycle, an increase in the body mass index (BMI), and alters the outcome of assisted reproductive treatment. Furthermore, kisspeptin-dependent leptin pathways augment the regulation of gonadal releasing hormone (GnRH) secretion to maintain ovarian function. The level of ghrelin and leptin is associated with the onset of puberty and inflammatory factors, mainly tumor necrosis factor (TNF)-α and interleukin (IL)-6. These affect the fertility of females by exacerbating oocyte development, insulin resistance, and PCOS. This article highlights the effect of obesity on the female reproductive system with the involvement of the interaction of various hormones, binding protein, inflammatory agents, metabolic perturbation, dysbiosis, obesity-induced alteration in the hypothalamic-pituitary-ovarian (HPO) axis and sustainable goals to manage obesity.
... These findings are consistent with others, demonstrating that leptin is a principal cytokine that increases with BMI in human follicular fluid [28,29]. Leptin is produced by granulosa and cumulus cells of ovarian follicles [44] and can impair follicle development, ovulation, and oocyte maturation [45,46]. Like leptin, IL-8 is also part of the immunologic profile associated with excessive body weight [47]. ...
The female reproductive system ages before any other organ system in the body. This phenomenon can have tangible clinical implications leading to infertility, miscarriages, birth defects and systemic deterioration due to estrogen loss. “Fibroinflammation” is a hallmark of aging tissues; there is an increase in inflammatory cytokines and fibrotic tissue in the aging ovarian stroma. We systematically evaluated immunomodulatory factors in human follicular fluid, which, like the stroma, is a critical ovarian microenvironment directly influencing the oocyte. Using a cytokine antibody array, we identified a unique fibroinflammatory cytokine signature in follicular fluid across an aging series of women (27.7–44.8 years). This signature (IL-3, IL-7, IL-15, TGFβ1, TGFβ3 and MIP-1) increased with chronologic age, was inversely correlated to anti-Müllerian hormone (AMH) levels, and was independent of body mass index (BMI). We focused on one specific protein, TGFβ3, for further validation. By investigating this cytokine in human cumulus cells and ovarian tissue, we found that the age-dependent increase in TGFβ3 expression was unique to the ovarian stroma but not other ovarian sub-compartments. This study broadens our understanding of inflammaging in the female reproductive system and provides a defined fibroinflammatory aging signature in follicular fluid and molecular targets in the ovary with potential clinical utility.
