A Review on Electrochemical and Optical Nanobiosensor for the Detection of Progesterone and Estradiol

Electrochemical and optical biosensors for the detection of E. Coli

Implementation of 3D printing technologies to electrochemical and optical biosensors developed for biomedical and pharmaceutical analysis

H2O2 is a reactive oxygen species (ROS), which can diffuse away from its site of generation and may act as a cell-to-cell signaling factor. The mechanisms responsible for the generation of H2O2 in human ovarian follicles and possible signaling role(s) of H2O2 are not well known. We identified a source of H2O2, the enzyme NADPH oxidase (NOX) 4, in isolated differentiated, in-vitro fertilisation-derived human granulosa-lutein cells (GCs), in proliferating human granulosa tumour cells (KGN), as well as in situ in cells of growing ovarian follicles. H2O2 was readily detected in the supernatant of cultured GCs and KGN cells. H2O2 levels were significantly lowered by the NOX4 blocker GKT137831, indicating a pronounced contribution of NOX4 to overall H2O2 generation by these cells. We provide evidence that extracellular H2O2 is taken up by GCs, which is facilitated by aquaporins (peroxiporins). We thus conclude that GC-derived H2O2 might act as autocrine/paracrine factor. Addition of H2O2 increased MAPK-phosphorylation in GCs. Moreover, reducing H2O2 production with GKT137831 slowed proliferation of KGN cells. Our results pinpoint NOX4 and H2O2 as physiological players in the regulation of GC functions.

From 1977 to 2013, the average age of thelarche, the first sign of puberty in girls, decreased by nearly 3 months per decade.1 This trend, along with rising rates of precocious puberty in girls, has significant implications for girls’ physical and psychosocial development, especially because early puberty has been linked to future health risks.2,3In 1997, the Pediatric Research in Office Setting study introduced race into the discourse surrounding pubertal timing trends.4 In a study of approximately 17 000 girls, Black girls at every age had more advanced breast development compared with White girls. Breast development had begun at age 6 years for 6.4% of Black and 2.8% of White girls and, by 8 years, 37.8% of Black and 10.5% of White girls.4 Because of these findings, the Pediatric Endocrine Society Drugs and Therapeutic Committee recommended new race-based criteria for defining precocious puberty.5 Proposed recommendations stated that breast development should be considered precocious in Black girls younger than 6 years and White girls younger than 7 years.5 Although these guidelines were never formally recognized, race has become widely accepted as a factor in the pubertal timing of girls and has been included in recent American Academy of Pediatrics (AAP) clinical reports6 and Pediatric Endocrine Society guidelines.7 As a result, many patients, caregivers, medical students, and physicians have been taught that Black girls experience puberty at earlier ages. In addition, in scientific and educational resources8,9 and the lay media,10,11 race continues to be associated with precocious puberty without considering the potential causes of this association, including the impact of racism.12 Although the AAP has made it clear that race-based medicine is faulty and detrimental, its eradication from everyday practice remains a challenge.13 This article will examine the inclusion of Black race in discussions surrounding puberty, the implications of these race-based approaches to pubertal norms, and recommendations for reframing these notions.The most recent AAP clinical report on precocious puberty6 includes that race/ethnicity, among other factors, should be taken into account when evaluating early puberty in girls. Race is a social construct, without any biological or genetic basis,14 and it may inadvertently be used as a proxy for variables including obesity, environmental exposures, psychological stress, and, importantly, racism itself.Food insecurity and lower socioeconomic status are factors that affect rates and trajectories of obesity in youth,15 which may be related to the higher rates of obesity observed in Black girls.16 Obesity can influence differences in pubertal timing because increased adipose tissue is associated with more estrogen.5,17 However, the association between obesity and early puberty remains under investigation.18 One recent study reported that total body fat has a variable influence on puberty because girls with more total body fat had slower progression of breast development, yet achieved menarche earlier than girls with lower total body fat levels.19 In addition, a recent review suggests that obesity alone does not explain early puberty, and girls with obesity should continue to have a full workup for precocious puberty despite elevated body mass index.20Environmental racism, a phenomenon that describes the disproportionate exposure to and impact of environmental hazards on minority populations, must also be considered.21 Endocrine disrupting chemicals (EDCs) interfere with hormone signaling22 and have been linked to increased obesity rates and early puberty.23 One EDC is bisphenol A,24 a chemical found in plastic bottles. Studies have demonstrated that Black communities have higher exposures to bisphenol A and other EDCs.25 Hair products marketed to Black communities are another environmental exposure that may influence earlier pubertal onset26–28 because they have been shown to contain estrogens, human/bovine placenta, and EDCs.29–31 One study reported that 49.4% of Black people used products containing EDCs compared with 7% of White people.30Early childhood stress may also affect pubertal timing. The Weathering Hypothesis posits that the cumulative effects of social, economic, and political adversity fuel the early health deterioration of Black women.32 Early life stress may disproportionately affect Black girls33; studies have shown associations between household stress34 and both earlier puberty35 and menarche.35,36The idea that racial health disparities exist because of biological differences between racial groups perpetuates a tradition of race pathologization.37 Race pathologization is the practice of attributing poor health outcomes to an individual race rather than to the sociopolitical factors that influence such outcomes and perpetuating false ideas that health disparities are due to biological differences. In working toward health equity, it is essential to recognize that the burden of disease affects certain racial groups more than others and to acknowledge the roles of institutional and structural racism in fueling health inequities when identifying such disparities.The notion that Black girls achieve puberty at earlier ages may perpetuate adultification bias, a form of racial prejudice in which Black children are treated and judged as more mature than others of the same age.38 This bias has important implications for Black children across social structures. Black girls may be subject to unwanted sexual advances, harsher punishment by educators in schools, and experience greater use of force and/or harsher penalties in the criminal justice system.38–40Race-based medicine can lead to the inappropriate withholding of diagnostic and therapeutic interventions from patients. If physicians and other providers are taught that Black girls “naturally” achieve puberty at earlier times, they may fail to ask important questions, provide appropriate counseling, and unmask diagnoses. Precocious puberty can be caused by central nervous system tumors and genetic conditions such as McCune-Albright syndrome.41 Commonly held biases and expectations about pubertal timing in Black girls may prevent physicians from implementing a thorough workup on their patients, leading to missed or delayed diagnoses.In evaluating pubertal timing disparities, it is important to move away from race-based medicine and adopt principles of race-conscious medicine.42 Race-conscious medicine decenters race and identifies racism as a primary driver of disparities.42Pediatricians can prioritize the judicious evaluation of all girls who present with early puberty, despite commonly taught principles of what is “natural” for Black girls. Pediatricians must also attend to Black girls’ psychosocial development and needs. An expectation of early maturity among Black girls can have long-lasting implications on physical and emotional health.38 Earlier pubertal maturation has been associated with higher rates of unwanted sexual advances and sexual harassment.39,43 It is essential that clinicians are aware of these risks and support their patients by asking questions, providing age-appropriate guidance, and reiterating the importance of consent.In the short term, pediatricians are uniquely positioned to counsel patients and their parents about environmental factors affecting early puberty. One example is helping families identify and avoid personal care products that contain EDCs, estrogens, and placental materials. Pediatricians must continue to advocate for legislation to combat childhood obesity, including neighborhood and city-wide initiatives that increase green space and eliminate food deserts.Further research is essential in understanding recent trends in pubertal development. Relying on race as an explanation for differences in pubertal timing halts the intellectual curiosity and questioning needed to further scientific inquiry. Although many studies have identified differences in pubertal timing by race, few have focused on why these differences may exist. The effects of stress and weathering on Black girls’ pubertal presentation must be further elucidated. Additionally, investigating how to best support the psychosocial needs of girls undergoing early puberty will provide a more holistic approach to patient care.Transforming our approach to disparities in pubertal timing can lead to improved patient care for Black girls. From a population health perspective, studying factors that influence pubertal timing can help researchers gain a better understanding of pubertal trends and ways to halt the drift toward earlier puberty. Individualizing care rather than categorizing care based on race allows for optimal diagnostic evaluation, age-appropriate counseling, and works toward dismantling harmful structures such as adultification bias, leading to a more equitable and accessible health care system for all.

C-type natriuretic peptide signaling in human follicular environment and its relation with oocyte maturation

Environmental context Endocrine disrupting compounds (EDCs) are among the most recently targeted micropollutants detected in wastewater treatment plant (WWTP) effluents and in aquatic environments. There is a need for the development of robust analytical methods for most relevant estrogenic EDCs. This study provides optimisation of analytical techniques and addresses several relevant aspects that are often overlooked in the literature. The method was finally successfully employed for the analysis of WWTP effluents. Abstract Two analytical approaches – liquid chromatography–tandem mass spectrometry (LC-MS/MS) and gas chromatography–tandem mass spectrometry (GC-MS/MS) methods – were compared for the simultaneous determination of the 19 most important oestrogenic endocrine disrupting chemicals (EDCs), such as 17β-oestradiol, oestrone, 17α-ethinyloestradiol, bisphenol A and triclosan in wastewater treatment plant effluents. To lower the instrument limits of detection (ILODs), a derivatisation step preceded detection in both methods. The stability, sensitivity and ease of use of dansylation (Dns) for LC-MS/MS and trimethylsilylation (TMS) for GC-MS/MS derivatives were evaluated before method validation. TMS derivatisation products were highly unstable over time. Parameters such as susceptibility to matrix effects and the stability of monodansylated and didansylated derivatisation products of phytohormones are discussed. Lower ILODs of highly potent EDCs (0.11 ng mL−1 for 17β-oestradiol, 0.01 ng mL−1 for 17α-ethinyloestradiol and 0.22 ng mL−1 for oestrone) and stability of derivatisation products within 7 days were achieved using LC–MS/MS; therefore, further validation of this method at environmentally relevant concentrations was conducted. The method limits of detection (MLODs) met the requirements of the European Union defined in Directive 2008/105/ES for 17α-ethinyloestradiol (0.035 ng L−1) and 17β-oestradiol (0.4 ng L−1). Twenty samples of wastewater treatment plant effluent from the Czech Republic were screened using LC-MS/MS. Fifteen of the EDCs were detected in at least one sample. The most abundant EDCs were bisphenol A, with a concentration up to 1107 ng L−1, and triclosan, with a concentration up to 76 ng L−1. No seasonal trend between late spring and autumn samples was observed in the frequency or quantity of analytes.

Endocrine disrupting chemicals (EDCs) are environmental contaminants that interfere with the hormonal system, posing significant risks to human health. Found in everyday items such as plastics, pesticides, cosmetics, and industrial materials, EDCs include both persistent chemicals, for example, dichlorodiphenyltrichloroethane (DDT), polychlorinated biphenyls (PCBs), and per- and polyfluoroalkyl substances (PFAS) and non-persistent ones, for example, bisphenol A (BPA), phthalates, and parabens. Mechanistically, EDCs mimic or block natural hormones, affecting processes such as glucose metabolism, lipid metabolism, and insulin signaling. These disruptions elevate the risk of obesity, type 2 diabetes mellitus, metabolic syndrome, and cardiovascular diseases, especially when exposure occurs during prenatal and early life stages. The detrimental cardiovascular impact of EDCs extends beyond their diabetogenic and obesogenic effects. EDCs such as BPA and heavy metals disrupt estrogen and androgen signaling, leading to hypertension, endothelial dysfunction, and arterial stiffness. In addition, EDCs further promote oxidative stress, which contributes to atherosclerosis and cardiovascular events. EDCs significantly impact reproductive health, causing precocious puberty, infertility, polycystic ovarian syndrome, endometriosis, and uterine fibroids in females and precocious puberty, delayed puberty, and infertility in males. The health ramifications of EDCs extend beyond the individual and can affect ensuing generations. EDCs cause epigenetic changes that can be passed down to future generations, compounding long-term impact on quality of life and healthcare spending. Intrauterine EDC exposure is associated with profound impact on fetal growth, potentially leading to low birth weight and intrauterine growth restriction, which predispose these individuals to life-long metabolic and cardiovascular challenges. Mitigation of EDC exposure requires a comprehensive prevention strategy to minimize the widespread health impacts, starting from the individual and the family unit. These include making simple swaps in daily life such as minimizing use of plastic, processed food items, scrutinizing cosmetics, and paints for possible presence of EDCs and avoiding exposure to direct and second-hand smoking. However, broader regulatory actions need to be initiated on a global level to implement stricter safety standards, minimize production of EDCs and their entry into the ecosystem and exploring safer alternatives.

Exposures of human populations to pesticides and industrial pollutants, and to synthetic chemicals present in foods, beverages, and plastics, have raised concern that these substances can interfere with endogenous sex hormone function. Interference with sex hormone action can, in turn, result in a variety of developmental and reproductive anomalies. Compounds in this class are thus referred to as endocrine disruptors (EDs). EDs that affect reproductive processes in vertebrates act primarily by altering oestrogenic and antiandrogenic activities. The recent cloning of a second oestrogen receptor (ER) subtype (ERP) and its widespread tissue distribution pattern indicates that the first ER to be cloned, ERa, may not be the only, or even the primary, mediator of oestrogen action. It is anticipated that this discovery will lead to development of antagonist compounds specific to either ER subtype, and help to determine the function of each receptor subtype in reproductive and other tissues. Growing evidence suggests that EDs interfere with reproductive function at low exposure levels and cause distinct effects at different concentrations within the same organ. Developing organisms have increased susceptibility to the actions of EDs because differentiating tissues are more vulnerable to changes in hormonal milieu. Thus, children are at greater risk of toxicant-related illnesses than adults. However, most data are collected from laboratory studies, and it remains to be determined that the levels of chemicals in the environment can impair human reproductive health. There is also significant genetic variability between human and animal species in their reactions to chemicals. The effects of low-dose, chronic, and multiple chemical exposures warrant further investigation in order to characterize the risk of environmental agents to humans. The aims of this review, which will focus on male reproduction, are to: 1) identify synthetic chemicals in the environment that fall into the ED class; 2) describe their mechanisms of toxicity in reproductive tissues; and, 3) outline the direction of future research efforts with respect to EDs.

Sex hormone-binding globulin (SHBG), a hepatic carrier protein for sex steroids is expressed in different steroid-sensitive tissues, including Sertoli cells of the testis. It has been suggested that this protein may be one of the local regulators of spermatogenesis. The expression of SHBG in the ovary is currently unknown. We have previously demonstrated the synthesis of SHBG in granulosa-lutein cells from patients undergoing in vitro fertilization. In this study, the presence of SHBG in human ovarian follicles and corpora lutea is investigated, using immunohistochemistry on adult and fetal ovarian tissue sections. SHBG is localized in the whole granulosa layer at all stages of folliculogenesis, whereas, only isolated theca cells are immunostained. In primordial and primary follicles, the oocyte cytoplasm shows an intense immunostaining, which disappears after the secondary stage. In the microenvironment of the mature oocytes, SHBG is present in the surrounding cumulus cells, the perivitelline space, and nearby the oolemma. In the corpus luteum, SHBG is localized in large luteal cells, whereas, small luteal cells do not show any significant staining. By analogy with the testis, these results raise the question of an involvement of SHBG in the regulation of follicular maturation as well as in luteal function.

Endocrine disrupting chemicals (EDCs) are a growing global concern due to their widespread use and potential harm to human and animal health. Several EDCs have been linked to cancer, obesity, and diabetes in children and adults. EDCs come from manufacturers or everyday products like cookware, textile, cosmetic, furniture, and plastic. Some EDCs are volatile and may be inhaled by the inhabitants where indoor exposure to EDCs is considered worse than outdoor exposure due to the limited and confined area allowing dermal contact and ingestion of EDCs. During the COVID-19 pandemic in 2020–2021, all Malaysians were confined to their homes, prompting the goal of this study to investigate EDCs in household dust collected from Klang Valley homes. A total of 57 dust samples were collected, filtered, and extracted using methanol. EDCs including perfluoroalkyl and polyfluoroalkyl substances (PFAS), bisphenol and parabens were identified and quantified in dust samples by liquid chromatography mass tandem spectrometry (LCMS/MS). The presence of perfluorooctanoic acid (PFOA), perfluorooctane sulfonic acid (PFOS), butylparaben (BuP), methylparaben (MeP), ethylparaben (EtP), and propylparaben (PrP) was detected in 50–100% of dust samples, with range of concentration of 0.31–3693.96 ng/g, indicating that these compounds are common in indoor dust. Methylparaben was the most prevalent EDC in collected dust samples with mean concentration at 148. 18 ng/g, accounting for 54% of the concentration distribution, followed by BuP and PFOA. There were regional differences in EDC profiles, with higher PFAS and paraben levels in urban areas such as Putrajaya, Kuala Lumpur, and Petaling. The estimated daily intake (EDI) of EDCs from indoor dust ingestion varied by age, with infants having a significantly higher EDI (p < .01) than children and adults. Despite safe for consumption (Hazard Quotient, HQ < 1), these findings provide a baseline for assessing PFAS, bisphenol, and paraben in indoor dust from Malaysian homes.

We have previously reported that membrane-bound amino- and carboxypeptidases were expressed on the human follicles and corpora lutea (CL), and we proposed that these peptidases are involved in ovarian functions, probably by regulating the extracellular peptide concentrations. In this study, we examined the expression of endothelin-converting enzyme-1 (ECE-1) on human follicles and CL, which is a membrane-bound endopeptidase and is known to convert big endothelin-1 to endothelin-1. In the preovulatory follicles, immunohistochemical study showed that ECE-1 was expressed, with moderate intensity, on the theca interna cells and weakly on the granulosa cells. In the menstrual and pregnant CL, ECE-1 was highly expressed on both large and small luteal cells, indicating that ECE-1 expression increases during luteinization. Western blotting analysis revealed that the molecular mass of the ECE-1 extracted from the menstrual CL was 130 kDa and that ECE-1 was more strongly expressed on the CL in early and midluteal phases than the CL in late luteal phases. In the isolated luteinizing granulosa cells obtained from patients undergoing in vitro fertilization, ECE-1 was immunohistochemically detected on their cell surface. The activity of ECE-1 was also detected on cultured luteinizing granulosa cells by measuring endothelin-1 production from its precursor. The activity of ECE-1 was significantly enhanced by the treatment of human CG (10 U/mL) and interleukin (IL)-1 (10 ng/mL) during 4-day culture, whereas no significant alteration was observed by IL-4 (10 ng/mL) and IL-10 (10 ng/mL) treatment. These results indicate that ECE-1 is a cell surface differentiation-related molecule of human granulosa and of theca interna cells and suggest that the expression of ECE-1 is regulated by LH/human CG and cytokines.

Endocrine disrupting chemicals (EDCs), proved to be potential carcinogenic threats to human health, have received great concerns in food field. It was essential to develop effective methods to detect EDCs in food samples. The present study proposed an efficient method to determine trace EDCs including estrone (E1), 17β-estradiol (E2), estriol (E3) and bisphenol A (BPA) based on magnetic solid-phase extraction (MSPE) coupled high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) in meat samples. Fe3 O4 @COF(TpBD)/TiO2 nanocomposites were synthesized via functionalization of magnetic covalent organic frameworks (COFs) with titanium dioxide (TiO2 ) nanoparticles, and used as absorbents of MSPE to enrich EDCs. The efficient EDCs enrichment relies on π-π stacking interaction, hydrogen bonding, and the interaction between titanium ions (IV, Ti4+ ) and hydroxyl groups in EDCs, which improves the selectivity and sensitivity. Under the optimized conditions, target EDCs were rapidly extracted through MSPE with 5 min. Combining Fe3 O4 @COF(TpBD)/TiO2 based MSPE and HPLC-MS/MS to determine EDCs, good linearities were observed with correlation coefficient (R2 ) ≥ 0.9989. The limits of detection (LODs) and limits of quantification (LOQs) were 0.13-0.41 μg kg-1 and 0.66-1.49 μg kg-1 , respectively. Moreover, the proposed method was successfully applied to real samples analysis. The established MSPE-HPLC-MS/MS method was successfully applied to determine EDCs in meat samples with rapidness, improved selectivity and sensitivity. It shows great prospects for EDCs detection in other complicated matrices. © 2020 Society of Chemical Industry.

Glucose is an indispensable substance in human’s body. A normal and stable blood glucose rate plays a significant role in leading a healthy living condition. Thus, an effective method to monitor glucose is what scientists are continuously studying to find. This work introduces the currently mainstream testing methods of glucose and a cutting-edge detecting equipment in this field. The mainstream methods include chromatography and biosensor methods. The biosensors are divided into two branches, optical and electrochemical biosensors. Colorimetric, fluorescence and chemiluminescence are three main principle of optical biosensor which already have a long-term development and are mutual for application. While for the electrochemical biosensor, enzyme-based biosensors are widely known and have already been introduced to the public. The non-enzyme, however, is the brand-new field of electrochemical biosensors, which have an ultra-high sensitivity and selectivity for glucose in blood. Carbon-based composites, noble metal-based composites, copper-based composites, and other metal-based materials can be the main function material of electrochemical non-enzyme biosensors. Here, carbon-based composites, noble metal-based composites, copper-based composites, and other metal-based materials biosensors are presented as the example to discuss the advanced aspects compared to other methods and the significance and feasibility of researching and applying this approach.

MCX based solid phase extraction combined with liquid chromatography tandem mass spectrometry for the simultaneous determination of 31 endocrine-disrupting compounds in surface water of Shanghai

Dietary exposure to endocrine disrupting chemicals in metropolitan population from China: A risk assessment based on probabilistic approach