Hormonal Environment Research Articles

COMPARING THE MOLECULAR PROPERTIES OF ENVIRONMENTAL HORMONES WITH HEARTBEAT CHANGES IN DAPHNIA MAGNA

Rationale: Environmental hormones (EH) disrupt the integrity of the endocrine system. Many chemical compounds act as endocrine disruptors, such as insecticides, herbicides, plasticizers. If these chemical compounds spread outside their area of intended use, they can stay in the environment and flow down into local bodies of water and wreak havoc upon ecosystems in the area. So, understanding the underlying relationship of the EHs with the physiology of an organism may be important for the design of chemical structures that could minimize the adverse effects for the future compounds.
 Methods: For this study, we chose 10 environmental hormones of BFR, DMT, LCH, DMA, TTS, MLT, ANN, CFT, GPS and GCH to examine the acute cardiac effects for 30 minute incubation in 1:10 serial dilution solutions. The heartbeat rates and their differences were evaluated at pre- and post-incubation, which was then converted into their heartbeat change% based on the pre-heartbeat rates. Then, the heartbeat change % for the individual EH was put on a regression analysis with molecular properties such as molecular weight, XlogP, topological polar surface area (TPSA), complexity, solubility and heavy atom count.
 Results: The leading coefficient of polynomial function showed relationship with those molecular properties with regression coefficient R2 from 0.1163 to 0.3182. The study should be significantly recognized in that the relationship of acute cardiac effects to the molecular properties were able to quantify as a unique attempt to elucidate. More study might be needed for in-depth clarification in the constants of the polynomial relationship.

The hormonal environment and estrogen receptor signaling alters Chlamydia muridarum infection in vivo.

Genital Chlamydia is the most common bacterial sexually transmitted infection in the United States and worldwide. Previous studies indicate that the progression of chlamydial infection is influenced by various factors, including the female sex hormones estrogen and progesterone. Sex hormone levels naturally fluctuate in women throughout their menstrual cycle. Varying concentrations of estrogen and progesterone may impact the progression of chlamydial infection and the host's immune response to Chlamydia. Estrogen signals through estrogen receptors (ERs), ERα and ERβ. These receptors are similar in structure and function, but are differentially expressed in tissues throughout the body, including the genital tract and on cells of the immune system. In this study, we used ovariectomized (OVT) BALB/c mice to investigate the impact of long-term administration of physiologically relevant concentrations of estrogen (E2), progesterone (P4), or a combination of E2/P4 on the progression of and immune response to C. muridarum infection. Additionally, we used ERα and ERβ knockout C57/BL6 mice to determine the how ERs affect chlamydial infection and the resulting immune response. Estrogen exposure prevented C. muridarum infection in vaginally infected OVT mice exposed to E2 alone or in combination with P4, while OVT or Sham mice exposed to hormone free, P4 or depo-medroxyprogesterone acetate shed similar amounts of chlamydiae. The hormonal environment also altered T cell recruitment and IFNϵ production the genital tracts of infected OVT and Sham mice on day 10 post infection. The absence of ERα, but not ERβ, in ER knockout mouse strains significantly changed the timing of C. muridarum infection. ERαKO mice shed significantly more chlamydiae at day 3 post infection and resolved the infection faster than WT or ERβKO animals. At day 9 post infection, flow cytometry showed that ERαKO mice had more T cells present and targeted RNA sequencing revealed increased expression of CD4 and FOXP3, suggesting that ERαKO mice had increased numbers of regulatory T cells compared to ERβKO and WT mice. Mock and chlamydia-infected ERαKO mice also expressed more IFNϵ early during infection. Overall, the data from these studies indicate that sex hormones and their receptors, particularly ERα and ERβ, differentially affect C. muridarum infection in murine models of infection.

Crosstalk between Nutrition, Insulin, Juvenile Hormone, and Ecdysteroid Signaling in the Classical Insect Model, Rhodnius prolixus

The rigorous balance of endocrine signals that control insect reproductive physiology is crucial for the success of egg production. Rhodnius prolixus, a blood-feeding insect and main vector of Chagas disease, has been used over the last century as a model to unravel aspects of insect metabolism and physiology. Our recent work has shown that nutrition, insulin signaling, and two main types of insect lipophilic hormones, juvenile hormone (JH) and ecdysteroids, are essential for successful reproduction in R. prolixus; however, the interplay behind these endocrine signals has not been established. We used a combination of hormone treatments, gene expression analyses, hormone measurements, and ex vivo experiments using the corpus allatum or the ovary, to investigate how the interaction of these endocrine signals might define the hormone environment for egg production. The results show that after a blood meal, circulating JH levels increase, a process mainly driven through insulin and allatoregulatory neuropeptides. In turn, JH feeds back to provide some control over its own biosynthesis by regulating the expression of critical biosynthetic enzymes in the corpus allatum. Interestingly, insulin also stimulates the synthesis and release of ecdysteroids from the ovary. This study highlights the complex network of endocrine signals that, together, coordinate a successful reproductive cycle.

Evaluation of Level of Pesticide Residue in Blood and its Effects on Hormonal Levels of Crossbred Bulls

Background: The pesticides are potentially toxic compounds that have become omnipresent in the environment. These toxicants modulate and/or disrupt the reproductive and hormonal environment by acting on hypothalamus, pituitary and reproductive organs. Fewer studies have been carried out on pesticide residues in body fluids especially blood and semen in breeding bulls. Method: Study was done to assess the pesticide residues in blood in relation to the endocrine profile in crossbred breeding bulls. Nineteen blood samples were collected and were allowed to clot overnight; serum was separated and stored at -20°C until analysis. The samples were analyzed for the pesticide residues using gas chromatography (GC) for seven organochlorine pesticides (OCPs) namely Heptachlor epoxide, Chlordane, Fipronil, Lindane, Methoxychlor, op-DDT and Endrin and eleven organophosphorus pesticides (OPPs) namely Chorpyrifos, Dichlorovos, Ethion, Monocrotophos, Malathion, Parathion-methyl, Profenphos, Phorate, Triazophos, Quinalphos and Phosalone and four synthetic pyrethroids (SPs) namely Cypermethrin, Permethrin, Deltamethrin, Cyhalothrin. Result: The blood samples of these bulls were found positive for organophosphate-phosalone and around 73.68% of the bulls were positive for phosalone at a retention time of 13.837 min. The concentration of phosalone in the blood of crossbred breeding bulls was found to be 1.89±0.98 ng/ml. In the present study, the blood hormonal profile of pesticide residues was analyzed and it showed a significant increase in the level of Estrogen thereby decreasing the testosterone: estrogen ratio. The decreased testosterone: estrogen ratio may be attributed to the detection of phosalone in blood.

Estrogen receptors mediate the antidepressant effects of aerobic exercise: A possible new mechanism.

This study aimed to examine whether aerobic exercise exerts mood-modulating effects through an estrogen signaling mechanism. The experiment was divided into two parts. The first part is to compare the three modeling methods to obtain the most obvious method of depression-like phenotype for further study in the second part. The first part of ovariectomized rats (age, 13 weeks) was tested when rats were 14 or 22 weeks old or in the sixth week after 3 weeks of chronic restraint stress. The second part was to treat the animals with the most obvious depression-like phenotype in different ways, placebo treatment or estradiol (E2) replacement therapy was administered, aerobic training, or estrogen receptor antagonist treatment. The cognitive (Barnes maze and 3-chamber social tests), anxiety-like (open-field and elevated plus maze tests) and depression-like (sucrose preference and forced swim tests) behaviors of rats in both parts were analyzed to study the effects of estrogen depletion and aerobic exercise. Rats did not develop depressive symptoms immediately after ovariectomy, however, the symptoms became more pronounced with a gradual decrease in ovarian hormone levels. Compared with the placebo or control groups, the exercise and E2 groups showed improved performance in all behavioral test tasks, and the antidepressant effects of aerobic exercise were comparable to those of estrogen. Moreover, the estrogen receptor antagonist has markedly inhibited the antidepressant effects of aerobic exercise. Estrogen receptors may mediate the antidepressant effects of aerobic exercise. In addition, an increasingly fragile ovarian hormonal environment may underlies chronic restraint stress-induced depression.

A controlled clinical trial to evaluate the efficacy of Tilanala Kshara in the management of Vatashteela vis-a-vis Benign Prostatic Hyperplasia

Background: Benign prostatic hyperplasia is the most common urological disease among elderly men, which is characterized by hypertrophic nodular changes of the prostate gland, which is located at the base of the bladder surrounding the proximal urethra. Gland grows at the rate of 2.4cm3/year after the age of 40 owing to the change in hormonal environment. In India, the prevalence rate is around 50% in men above the age of 65 years. The condition can be corelated to Vatashteela in Ayurveda based on the symptomatology. Objective of the study: To evaluate the efficacy of Tila Nala Kshara in the management of Muthraghata vis-a-vis BPH. Materials and Methods: A double arm open labelled clinical study with pre-post-test design was carried out at Government Ayurveda Medical College and Hospital, Mysuru. Data was collected as per the proforma prepared for the purpose of the study. Tila Nala Kshara was administered as intervention in 54 subjects and the control drug was Gokshuradi Guggulu. The data was analysed using SPSS descriptive and inferential statistics. Results: Among the objective parameters, change in prostate volume was significant between the groups with a P value 0.024. But for postvoid residual volume, the difference between the groups was not statistically significant. For subjective parameters which includes IPSS total and Quality of life scale, the difference between the groups was statistically nonsignificant. Conclusion: Tilanala Kshara when used along with Gokshuradi Guggulu was observed to improve general condition of the subjects to greater extent, which clearly implies the added effect of the trial drug.

Androgens and low density lipoprotein-cholesterol interplay in modulating prostate cancer cell fate and metabolism.

Androgens, the known drivers of prostate cancer (PCa), have been indicated as important metabolic regulators with a relevant role in stimulating lipid metabolism. Also, the relationship between obesity and the aggressiveness of PCa has been established. However, it is unknown if the androgenic hormonal environment may alter the response of PCa cells to lipid availability. The present study evaluated the effect of 5α-dihydrotestosterone (DHT) in regulating lipid metabolism, and the interplay between this hormone and low-density lipoprotein (LDL)-cholesterol in modulating PCa cells fate. Non-neoplastic and neoplastic PCa cells were treated with 10nM DHT, and the expression of fatty acids transporter, fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A) evaluated. PCa cells were also exposed to LDL (100μg/ml) in the presence or absence of DHT. Treatment with DHT upregulated the expression of FASN and CPT1A in androgen-sensitive PCa cells. In contrast, LDL supplementation suppressed FASN expression regardless of the presence of DHT, whereas augmenting CPT1A levels. Our results also showed that LDL-cholesterol increased PCa cells viability, proliferation, and migration dependently on the presence of DHT. Moreover, LDL and DHT synergistically enhanced the accumulation of lipid droplets in PCa cells. The obtained results show that androgens deregulate lipid metabolism and enhance the effects of LDL increasing PCa cells viability, proliferation and migration. The present findings support clinical data linking obesity with PCa and first implicate androgens in this relationship. Also, they sustain the application of pharmacological approaches targeting cholesterol availability and androgens signaling simultaneously.

Cardiovascular disease risk in offspring of polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder affecting women at reproductive age. PCOS diagnosis (Rotterdam criteria) is based on the presence of two out of three criteria; clinical and/or biochemical hyperandrogenism, oligo- or an-ovulation and polycystic ovaries. PCOS women suffer from a constellation of reproductive and metabolic abnormalities including obesity and insulin resistance. PCOS women also have increased blood pressure and increased risk of cardiovascular diseases (CVD). In-utero, offspring of PCOS women are exposed to altered maternal hormonal environment and maternal obesity (for most of PCOS women). Offspring of PCOS women could also be subject to genetic susceptibility, the transgenerational transmission of some of the PCOS traits or epigenetic changes. Offspring of PCOS women are commonly reported to have an abnormal birth weight, which is also a risk factor for developing CVD and hypertension later in life. Although studies have focused on the growth pattern, reproductive and metabolic health of children of PCOS women, very limited number of studies have addressed the risk of hypertension and CVD in those offspring particularly as they age. The current narrative review is designed to summarize the available literature (both human studies and experimental animal studies) and highlight the gaps in addressing hypertension and CVD risks in offspring of PCOS women or hyperandrogenemic female animal models.

The effect of oestradiol and progesterone on chemerin system expression in the porcine endometrium during early pregnancy and the mid-luteal phase of the oestrous cycle

Chemerin is an adipokine which is the product of the RARRES2 gene expressed mainly in adipose tissue. This hormone exerts biological effects via three metabotropic receptors: chemokine like receptor 1 (CMKLR1), G protein-coupled receptor 1 (GPR1), and C–C chemokine receptor-like 2 (CCRL2). Chemerin exerts pleiotropic effects and participates in the regulation of many processes, such as blood pressure control, immune system regulation, inflammation, and angiogenesis. There is a growing body of evidence to indicate that chemerin is involved in the regulation of reproductive system functions. However, little is known about the regulation of chemerin system (chemerin and its receptors) expression. The authors hypothesized that steroid hormones affect the expression of the chemerin system in the uterus of domestic pigs. Thus, the aim of this study was to investigate the influence of steroids, oestradiol (E2), and progesterone (P4), on the gene (qPCR) and protein (Western blot) expression of chemerin receptors, RARRES2 gene expression as well as chemerin secretion (ELISA) by endometrial slices during early pregnancy (days 10 to 11, 12 to 13, 15 to 16, and 27 to 28) and the mid-luteal phase of the oestrous cycle (days 10 to 11). Both steroid hormones modulated the expression of chemerin receptor genes and proteins, as well as the abundance of RARRES2 mRNA transcripts. The study also demonstrated that E2 increased chemerin protein secretion by endometrial cells during the maternal recognition of pregnancy (days 12 to 13) and decreased its release during embryo implantation (days 15 to 16). P4 had no significant effect on chemerin levels during the studied periods of gestation and the oestrous cycle. These observations suggest that the effects of E2 and P4 on the chemerin system are dependent on the period of gestation or the oestrous cycle. Our results support the hypothesis that the hormonal environment could modulate the expression of the chemerin system in the endometrium.

Obesity-derived alterations in the lactating mammary gland: Focus on prolactin

Obesity is a modern pandemic with negative consequences in women's reproductive health. Women with overweight and obesity can develop mammary gland alterations that unable exclusive breastfeeding. Obesity associates with a disturbed lactating mammary gland endocrine environment including a decreased action of the hormone prolactin (PRL), the master regulator of lactation. The PRL receptor and the action of PRL are reduced in the mammary gland of lactating rodents fed an obesogenic diet and are contributing factors to impaired lactation in obesity. Also, treatment with PRL improves milk yield in women with lactation insufficiency. This review focuses on the impact of diet-induced obesity in the lactating mammary gland and how obesity impairs the lactogenic action of PRL. Although obesity alters lactation performance in humans and rodents, the responsible mechanisms have been mainly addressed in rodents.

PSII-5 Endotoxin-Induced Inflammation on Immune Markers and Steroidogenesis in Granulosa Cells

Abstract Reproductive performance is central to profitability in beef cattle operations. Pathogenic stress can result from gram-negative bacteria release of the lipopolysaccharide (LPS) endotoxin which has the potential to accumulate in follicular fluid and impair folliculogenesis and steroidogenesis, leading to reduced fertility. Elevated LPS concentrations observed in acute clinical bacterial infections are recognized to have detrimental effects on female fertility, however, definitive effects of low concentrations of LPS present in subclinical or undetectable infection remains to be fully elucidated. This study investigated the effect of varying concentrations of LPS on mechanisms regulating ovarian function and subsequent steroidogenesis. A granulosa cell line (KGN) was cultured with or without increasing doses of LPS (0.0001 to 10 µg/mL) for 30 min or 48 h. Cells collected 30 min after treatment were analyzed for abundance of phosphorylated proteins and cells collected 48 h after treatment were analyzed for total protein abundance and gene expression. Media were analyzed by radioimmunoassay for steroid hormone concentrations. Quantitative and semi-quantitative PCR was used to evaluate aromatase, beta-catenin, and cytokines IL-6 and IL-8, respectively. No differences were detected among LPS treatment groups compared to vehicle-treated controls for protein abundance of total beta-catenin (P = 0.99) or active beta-catenin lacking phosphorylation at serine 33/37 (P = 0.95) evaluated at 48 h. Similar results were observed in protein abundance of phosphorylated forms of beta-catenin at serine 552 (P = 0.98) and 675 (P = 0.85) evaluated at 30 min. Additionally, estradiol concentrations were not different at 0.0001 to 1.0 µg/mL LPS; however, estradiol was significantly decreased at 10 µg/mL LPS treatment compared to the vehicle-treated control (P = 0.03). Progesterone concentrations were also similar within 0.0001 to 1.0 µg/mL LPS treatment groups with a tendency to decrease at 10 µg/mL LPS treatment (P = 0.08) compared to the vehicle-treated control. Varying concentrations of LPS did not change mRNA expression of beta-catenin (P = 0.28), aromatase (P = 0.32), and IL-6 (P = 0.35). However, a significant increase in cytokine IL-8 mRNA expression was observed at 10 µg/mL LPS compared to the vehicle-treated control (P = 0.04). These findings suggest that inflammatory response against LPS at higher concentrations may influence distinct cytokine expression and steroidogenesis. Conversely, basal expression of key steroidogenic enzymes and ovarian steroidogenic modulators are less affected by low concentrations of LPS. Therefore, immune response of granulosa cells is dependent on concentration of LPS exposure that has the ability to impact fertility by modulating the ovarian hormonal and follicular environment.

Impact of Estrogen and Progesterone on Immune Cells and Host-Pathogen Interactions in the Lower Female Reproductive Tract.

Microbial infections are a threat to women's reproductive health. Although reproductive cycles and pregnancy are controlled by sex hormones, the impact of hormones on host-pathogen interactions and immune function in the female reproductive tract are understudied. Furthermore, the changing endocrine environment throughout pregnancy may influence how and when women are susceptible to ascending infection. Because most intrauterine microbial infections originate in the lower reproductive tract, it is vital that future studies determine how different hormonal conditions influence the lower reproductive tract's susceptibility to infection to understand temporal components of infection susceptibilities across pregnancy. These studies should also extend to nonpregnant women, as it is critical to establish how hormonal fluctuations across the menstrual cycle and hormonal contraceptives may influence disease susceptibility. This review summarizes current knowledge of how estrogen and progesterone impact vaginal and cervical mucosal immunity, barrier function, and interactions with microbial communities.

THE RATIO BETWEEN THE LENGTH OF THE SECOND AND FOURTH DIGIT (2D:4D RATIO) AS A BIOMARKER OF OVARIAN RESERVE IN INFERTILE PATIENTS

Ovarian reserve is established during intrauterine life, with a peak at 20 weeks of gestation. The 2D:4D ratio, which is also established during prenatal life, has been proposed as a non-invasive biomarker of the prenatal hormonal environment. It has been suggested that an intrauterine environment rich in androgens induces a development of the 2D:4D ratio < 1 while estrogen exposure during prenatal life leads to a higher 2D:4D ratio. However, whether 2D:4D ratio can be used to could predict ovarian reserve needs further investigation.

Is digit ratio (2D:4D) associated with a religious profession? An exploratory study on male Polish seminary students

Human females demonstrate higher religiosity than men in populations. Digit ratio (2D:4D), being a putative indicator of prenatal testosterone, is associated in varying degrees with characters that show sexual dimorphism. A small number of studies have indicated that religiosity may be associated with the biological basis of sex differences in humans. The objective of the present study was to ascertain whether 2D:4D in religiously oriented seminary students is different from individuals in other occupations. The study followed a cross-sectional design. Male participants of the study included 13 seminary students, 18 military chaplains and 91 control students from study courses relating to civil occupations. Lengths of second (2D) and fourth (4D) digits and their ratio (2D:4D) for each hand, height and weight were the variables and 2D:4D was the outcome measure. The results demonstrated that the seminary students had significantly higher 2D:4D than both the military chaplains and civil students. The military chaplains had the lowest 2D:4D. The study also revealed that the choice of religious occupation, and for that matter, religiosity, could be linked with the prenatal hormonal environment, particularly lower intrauterine testosterone compared to oestrogen.

A Rare Case: Genital Warts in Pregnancy

Genital wart is a benign lesion which is caused by Human Papillomavirus (HPV) type-6 or type-11 infection. Liu et al. found an overall HPV prevalence of 16.82% in pregnant women vs. 12.25% in non-pregnant women [1]. The persistence of HPV is arguably favored as the maternal hormonal environment and immune system undergo significant changes during pregnancy.[2] Here, we report an interesting case of 30 year old primigravida with vaginal warty growth. Keywords: human papillomavirus, genital warts, pregnancy, trichloroacetic acid

Age and Sex-Related Changes in Retinal Function in the Vervet Monkey.

Among the deficits in visual processing that accompany healthy aging, the earliest originate in the retina. Moreover, sex-related differences in retinal function have been increasingly recognized. To better understand the dynamics of the retinal aging trajectory, we used the light-adapted flicker electroretinogram (ERG) to functionally assess the state of the neuroretina in a large cohort of age- and sex-matched vervet monkeys (N = 35), aged 9 to 28 years old, with no signs of obvious ocular pathology. We primarily isolated the cone–bipolar axis by stimulating the retina with a standard intensity light flash (2.57 cd/s/m2) at eight different frequencies, ranging from 5 to 40 Hz. Sex-specific changes in the voltage and temporal characteristics of the flicker waveform were found in older individuals (21–28 years-old, N = 16), when compared to younger monkeys (9–20 years-old, N = 19), across all stimulus frequencies tested. Specifically, significantly prolonged implicit times were observed in older monkeys (p < 0.05), but a significant reduction of the amplitude of the response was only found in old male monkeys (p < 0.05). These changes might reflect ongoing degenerative processes targeting the retinal circuitry and the cone subsystem in particular. Altogether, our findings corroborate the existing literature in humans and other species, where aging detrimentally affects photopic retinal responses, and draw attention to the potential contribution of different hormonal environments.

Стрес та вісь мозок-кишечник

The purpose of the review was to study the effects of stress on the gut microbiota. Results and discussion. The gut microbiota forms a complex microbial community that has a significant impact on human health. The composition of the microbiota varies from person to person, and it changes throughout life. It is known that the microbiome can be altered due to diet, various processes, such as inflammation and/or stress. Like all other areas of medicine, microbiology is constantly growing. The gut microbiota lives in a symbiotic relationship with the human host. It is now believed to interact with almost all human organs, including the central nervous system, in the so-called «gut-brain-microbiome axis». Recently, a growing level of research is showing that microbes play a much bigger role in our lives than previously thought, and can have a myriad of effects on how we behave and think, and even on our mental health. The relationship between the brain and the microbiota is bidirectional and includes endocrine, neuronal, immune, and metabolic pathways. The microbiota interacts with the brain through various mechanisms and mediators, including cytokines, short-chain fatty acids, hormones, and neurotransmitters. According to the hypothalamic-pituitary-adrenocortical axis imbalance theory, hormonal imbalances are closely related to psychiatric illness, anxiety, and stress disorders. Therefore, the gut microbiome is closely related to the development and functioning of this axis. The microbiota can influence neurotransmitter levels in a variety of ways, including the secretion of gamma-aminobutyric acid, norepinephrine, dopamine, and serotonin, and can even regulate serotonin synthesis. These neurotransmitters can influence the hormonal status of the body, and the hormones themselves can influence the formation of the qualitative and quantitative composition of the microbiota. Accordingly, a change in the composition of the intestinal microbiota may be responsible for modifying the hormonal levels of the human body. The endocrine environment in the gut can also be modulated through the neuro-enteroendocrine system. Conclusion. Today, it is known that microbiota changes can be associated with several disorders of the nervous system, such as neuropsychiatric, neurodegenerative and neuroinflammatory processes. Research in recent decades has shown that disorders of the nervous system and mood disorders are associated with changes in the balance of neurotransmitters in the brain. Therefore, understanding the role of microbiota in the development and functioning of the brain is of great importance

Multimodal 3-D/2-D human islet and duct imaging in exocrine and endocrine lesion environment: associated pancreas tissue remodeling.

Pancreatic intraepithelial neoplasia (PanIN) and islet cell microadenoma are exocrine and endocrine neoplasms of human pancreas that have been linked to pancreatic ductal adenocarcinoma (PDAC) and neuroendocrine tumor, respectively. However, in health and at the surgical margin of pancreatic cancer, it remains unresolved how to simultaneously characterize duct and islet remodeling to investigate the exocrine-endocrine association in the lesion microenvironment. Here, we develop a new vibratome-based approach to detect, confirm, and analyze the two types of pancreas remodeling via stereo/three-dimensional (3-D) and classic/two-dimensional (2-D) histology. Surgical margins of PDAC (n = 10, distal) and cadaveric donor pancreases (n = 10, consecutive cases) were fixed, sectioned by vibratome (350 µm), and surveyed for PanIN and microadenoma via stereomicroscopy. After lesion detection, PanIN and microadenoma were analyzed with 3-D fluorescence imaging and clinical microtome-based histology for confirmation and assessment of microenvironment. Multimodal imaging of PDAC surgical margins and cadaveric donor pancreases detected the peri-PanIN islet aggregation with duct-islet cell clusters. Organ-wide survey of cadaveric donor pancreases shows a marked 2.3-fold increase in the lesion size with the PanIN-islet association vs. without the association. In the survey, we unexpectedly detected the islet cell microadenoma adjacent to (<2 mm) PanIN. Overall, among the 53 early lesions in the cadaveric donor pancreases (PanINs and microadenomas), 81% are featured with the associated exocrine-endocrine tissue remodeling. Multimodal 3-D/2-D tissue imaging reveals local and simultaneous duct and islet remodeling in the cancer surgical margin and cadaveric donor pancreas. In the cadaveric donor pancreas, the peri-PanIN islet aggregation and PanIN-microadenoma association are two major features of pancreas remodeling in the early lesion microenvironment.NEW & NOTEWORTHY We develop a new multimodal 3-D/2-D imaging approach (matched stereomicroscopic, fluorescence, and H&E signals) to examine human duct-islet association in the PDAC surgical margin and cadaveric donor pancreas. In both conditions, peri-PanIN islet aggregation with duct-islet cell clusters was identified. The PanIN-islet cell microadenoma association was unexpectedly detected in the donor pancreas. Our work provides the technical and morphological foundations to simultaneously characterize human islets and ducts to study their association in health and disease.

The Endocrine–Metabolic Axis Regulation in Offspring Exposed to Maternal Obesity—Cause or Consequence in Metabolic Disease Programming?

Obesity incidence is rising worldwide, including women of reproductive age, contributing to increased gestations in which Maternal Obesity (MO) occurs. Offspring born to obese mothers present an increased predisposition to develop metabolic (e.g., obesity, diabetes) and cardiovascular disease (CVD). The developmental programming of the metabolic dysfunction in MO offspring can initiate in utero. The different availability of metabolic substrates, namely glucose, can modulate cellular growth, proliferation, and differentiation, resulting in different levels of tissue maturation and function. We defined the remodelling of these early processes as the first hit of metabolic disease programming. Among these, adipocyte early differentiation and gut dysbiosis are initial repercussions occurring in MO offspring, contributing to -tissue-specific dysfunction. The second hit of disease programming can be related to the endocrine–metabolic axis dysregulation. The endocrine–metabolic axis consists of multi-organ communication through the release of factors that are able to regulate the metabolic fate of cells of organs involved in physiological metabolic homeostasis. Upon adipose tissue and gut early dysregulation, these organs’ endocrine function can be programmed to the disrupted release of multiple factors (e.g., adiponectin, leptin, glucagon-like peptide). This can be perceived as a natural mechanism to overcome metabolic frailty in an attempt to prevent or postpone organ-specific disease. However, the action of these hormones on other tissues may potentiate metabolic dysfunction or even trigger disease in organs (liver, pancreas, heart) that were also programmed in utero for early disease. A second phase of the endocrine–metabolic dysregulation happens when the affected organs (e.g., liver and pancreas) self-produce an endocrine response, affecting all of the involved tissues and resulting in a new balance of the endocrine–metabolic axis. Altogether, the second hit exacerbates the organ-specific susceptibility to disease due to the new metabolic environment. The developmental programming of the endocrine–metabolic axis can start a vicious cycle of metabolic adaptations due to the release of factors, leading to an endocrine response that can jeopardize the organism’s function. Diseases programmed by MO can be boosted by endocrine dysregulation, namely Non-Alcoholic Fatty Liver Disease, Non-Alcoholic Fatty Pancreas Disease, and the aggravation of the adipose tissue and gut dysfunction. Chronic metabolic dysregulation can also predispose MO offspring to CVD through the modulation of the endocrine environment and/or the metabolic status. To cease the vicious cycle of MO disease transmission among generations and-provide preventive and specialized prenatal and postnatal care to MO offspring, it is necessary to understand the molecular mechanisms underlying the MO-related disease development. In this review, we summarize most of the developmental programming molecular events of the endocrine–metabolic axis described on the offspring exposed to MO, providing a brief overview of the potential mechanisms that predispose MO offspring to metabolic disease, and discuss the programming of the endocrine–metabolic axis as a plausible mechanism for metabolic disease predisposition in MO offspring.

Luteinizing Hormone Dynamics in Menstruation.

Menstruation is a finely-controlled cycle that responds to the prevailing endocrine and paracrine environment. However, social stigma has led to inadequate menstrual literacy, both among academics and the larger public. The poorly understood mechanisms of menstruation ultimately lead to suboptimal healthcare treatment and services for biological females, culminating in a physical, financial, and emotional burden. Various hormones signal the beginning and end of each stage of menstruation. In particular, luteinizing hormone (LH) is a major player in ovulation, corpus luteum function, and the stimulation of other key hormones. A LH model could be used to understand the larger control system of menstruation if analyzed in conjunction with models for other major hormones (e.g., FSH, progesterone, and GnRH). Thus, exploring a smaller subsection of LH dynamics within the larger control system of menstruation can lead to a greater understanding of menstruation, contributing towards therapeutics and research for women's health. Using parameters and kinetic equations in the existing body of literature, a transfer function was derived to model LH dynamics. Analysis of system stability reveals overdamped dynamics in LH sensitization at baseline, and underdamped mildly resonant dynamics at the peak of the menstrual cycle, the strength of which depends on the values of the rate constants of LH receptor formation, binding, and desensitization.