Pregnancy Hormones Research Articles

Multiplying Meanings of Pregnancy Through Personal Accounts of Gestational Trophoblastic Disease

In cultures where reproduction is highly medicalised, pregnancy is often understood in terms of foetal development and an anticipated baby. This is connected to a wider privileging of the ‘foetal subject’ in these settings, which has had implications for reproductive autonomy. In this article, I disrupt dominant understandings of pregnancy by engaging with qualitative accounts of gestational trophoblastic disease. This rare condition can entail experiences of pregnancy without foetal development, allowing for scholarly attention to the wider biological, affective and relational constituents of this corporeal event. In this article, I pay particular attention to the ‘pregnancy hormone’ human chorionic gonadotropin (hCG), which in the context of gestational trophoblastic disease becomes a biomarker for disease. My research extends feminist science studies perspectives destabilising understandings of maternal and foetal bodies as bounded and distinct entities. The article de-centres foetal development as the most significant consequence of conception and enriches feminist discussions of reproductive politics.

Daily Subcutaneous injections of Relaxin is a therapy for heart failure with preserved ejection fraction

Abstract Background and Significance: Relaxin (RLX), a hormone of pregnancy has engendered a great deal of excitement as a therapy for cardiovascular diseases. Clinical trials treated patients with acute decompensated Heart Failure (HF) with RLX (i.v. 30µg/kg/day-2 days) and reported a 37% decrease in mortality during a 6-months follow up. This led the FDA to declare RLX a ‘break-through’ therapy. However, a larger trial failed to meet the sought-after end points. Here, we propose that periodic subQ RLX pulses are more effective. We measured the pharmacokinetics of serum RLX following subQ injections of RLX in Sprague Dawley rats. Further, we treated rats with confirmed HFpEF with daily subQ RLX (2-weeks) to reverse the diastolic dysfunction (DD), arrhythmia and fibrotic profile. Methods Sprague-Dawley (250 g, n=20, either sex) received 2-subQ injections 12 hrs apart of RLX (from Relaxera) or the vehicle. Serial blood samples were drawn following each injection to measure [RLX]. ZSF1 rats (9-weeks old, either sex) were placed on a high fat diet (HFD) and serial echos tracked the DD. Once severe DD was established (25-35 weeks of HFD), rats received daily subQ injections of RLX (100µg/kg) or vehicle. After 2-weeks, hearts were perfused to optically map action potentials and Ca2+ transients, and analyze the arrhythmia profile. IF and Westerns were used to measure changes in fibrosis (collagen 1), Nav1.5, connexin 43, Wnt1 and β-catenin. Results After an injection, RLX reached a peak in ~60 min, fell to 50% in 5-6 hours. Injections of 0, 30, 100 or 500 µg/kg yielded peak levels of 0, 11.26±3.52, 58.33±16.10, and 209.42±29.04 ng/ml and residual levels after 24-hrs of 0, 4.9, 45.1 and 156 pg/ml, respectively. The 30µg/kg injections had no effect and 100 µg/kg increased Nav1.5 (25%), Cx43 (30%) and β-catenin (90%). The 500 µg/kg injections increased Nav1.5 and Cx43 but upregulated β-catenin, only slightly. In ZSF1 HFpEF rats that received the vehicle (n=12), a premature stimulus (at 30 ms) elicited arrhythmia in 67% of the hearts. RLX injections reversed DD, suppressed sustained atrial and ventricular arrhythmias (n=0/12) but not self-terminating arrhythmias, lasting < 10sec. RLX improved the conduction velocity (CV), particularly at fast rates (100ms) from 0.74 to 0.9 m/s (p<0.001, n=12). RLX significantly increased Cx43 expression, Nav1.5 and β-catenin at intercalated disks. RLX reduced collagen deposition in HFpEF rats, to normal levels and increased Wnt1 compared to control HFpEF rats. Conclusions The ZSF1 diabetic rat on a HFD recapitulates human HFpEF, high blood pressure, fibrosis, DD, AF and VF. SubQ RLX injections reversed DD i.e. enlarged Left Atrium, E/e’ ratio, fibrosis, and the arrhythmia vulnerability by increasing CV, Cx43, and Nav1.5. Daily subQ RLX injections were highly effective as a therapy for HFpEF.Echo parameterHFpEF + RLX

Effects of thiacloprid, a neonicotinoid pesticide, on rat reproductive system: Pregnancy hormone disruption and abortion trends

Thiacloprid (TCL), commonly known as Biscaya, is among the most widely used pesticides in agriculture, designed to eliminate insects by targeting their nicotinic receptors. This study explores the effects of orally administering TCL (at a dose of 50 mg/kg) on the hormone secretion crucial for pregnancy and the factors influencing abortion throughout the early, middle, and late stages of pregnancy in female rats.Following TCL exposure, there were significant increases in levels of 17β-Estradiol, prostaglandins F2α and E2, and serum oxytocin hormone in different stages of pregnancy. In contrast, progesterone and endothelin-1 serum levels notably decreased during the initial and final stages of pregnancy. Additionally, TCL led to a substantial rise in lipid peroxidation levels and a decrease in total thiol molecules and total antioxidant capacity, especially in uterine tissue. Although TCL did not significantly affect the morphological characteristics of the delivered fetuses, it notably increased the number of abortions, especially during the second and third stages of pregnancy.In summary, our findings suggest that TCL elevates the risk of abortion in pregnant rats by disrupting the secretion of hormones crucial for fertility (such as 17β-Estradiol/progesterone) and by increasing the secretion of abortion-inducing hormones like prostaglandins and oxytocin. Furthermore, these effects may be associated with disruptions in the oxidant/antioxidant balance within the ovaries and uterus.

Maternal hypothyroidism and subsequent metabolic outcomes in children: a systematic review and meta-analysis

IntroductionAs the fetus relies on maternal thyroid hormones in early pregnancy, maternal hypothyroidism plays an important role in fetal development. However, the association between maternal hypothyroidism and metabolic disease in offspring is unclear.ObjectiveTo examine the association between maternal hypothyroidism in pregnancy and metabolic outcomes (obesity, hypertension, type 2 diabetes mellitus, and dyslipidemia) in children < 18 years.MethodsWe systematically searched 5 databases from inception to May 2023. Eligible studies included cohort, case-control, and randomized controlled trials involving children born to mothers with or without hypothyroidism in pregnancy. Data were pooled across studies using random-effects models for outcomes reported in at least three studies. Quality assessment was performed using the ROBINS-E tool for observational studies and the Cochrane Risk of Bias tool for trials.ResultsThe search identified 3221 articles, of which 7 studies were included (1 trial, 6 observational). All studies were conducted outside of North America and ranged in size from 250 to > 1 million children. The follow-up time ranged from 6 to 20 years. Included studies support an increased risk of hypertension and glucose dysregulation in offspring exposed to maternal hypothyroidism (hypertension: OR 1.08, 95% CI 0.75, 1.57 and HR 1.81, 95% CI 1.21, 2.69; diabetes: RR 2.7, 95% CI 0.7, 10). In the pooled analysis, maternal hypothyroidism was not associated with obesity in offspring (OR 1.04, 95% CI 0.64, 1.70).ConclusionThis study found inconsistent evidence on the association between maternal hypothyroidism in pregnancy and metabolic outcomes in offspring, though associations with hypertension and glucose dysregulation are possible.

Comparative analysis of the syncytiotrophoblast in placenta tissue and trophoblast organoids using snRNA sequencing.

The outer surface of chorionic villi in the human placenta consists of a single multinucleated cell called the syncytiotrophoblast (STB). The unique cellular ultrastructure of the STB presents challenges in deciphering its gene expression signature at the single-cell level, as the STB contains billions of nuclei in a single cell. There are many gaps in understanding the molecular mechanisms and developmental trajectories involved in STB formation and differentiation. To identify the underlying control of the STB, we performed comparative single nucleus (SN) and single cell (SC) RNA sequencing on placental tissue and tissue-derived trophoblast organoids (TOs). We found that SN was essential to capture the STB population from both tissue and TOs. Differential gene expression and pseudotime analysis of TO-derived STB identified three distinct nuclear subtypes reminiscent of those recently identified in vivo . These included a juvenile nuclear population that exhibited both CTB and STB marker expression, a population enriched in genes involved in oxygen sensing, and a fully differentiated subtype. Notably, suspension culture conditions of TOs that restore the native orientation of the STB (STB out ) showed elevated expression of canonical STB markers and pregnancy hormones, along with a greater proportion of the terminally differentiated mature STB subtype, compared to those cultivated with an inverted STB polarity (STB in ). Gene regulatory analysis identified novel markers of STB differentiation conserved in tissue and TOs, including the chromatin remodeler RYBP, that exhibited STB-specific RNA and protein expression. Finally, we compared STB gene expression signatures amongst first trimester tissue, full-term tissue, and TOs, identifying many commonalities but also notable variability across each sample type. This indicates that STB gene expression is responsive to its environmental context. Our findings emphasize the utility of TOs to accurately model STB differentiation and the distinct nuclear subtypes observed in vivo , offering a versatile platform for unraveling the molecular mechanisms governing STB functions in placental biology and disease.

A review of progesterone roles in implantation

Implantation failure constitutes one of the major causes of pregnancy loss in all mammalian species. The complexity of implantation mechanism involves series of hormones, macromolecules, cytokines, chemokines, growth factors and repertoire of genes, however, progesterone receptor through which physiological responses to progesterone are initiated is the most essential for implantation across all mammalian species. Progesterone is also known as hormone of pregnancy because of its crucial roles to establish and sustain pregnancy and implantation. Progesterone facilitates blastocyst implantation to the maternal endometrium by promoting uterine secretion for conceptus growth and development, initiating window of receptivity, inducing quiescence and non-contractility of endometrium to avoid abortion and protection of embryo against maternal immune system. The aforementioned roles of progesterone and their mechanisms are the subject matter of this review.

Sirenian (manatees and dugongs) reproductive endocrinology

Reproductive hormones are essential to mating systems, behavior, fertility, gestation, parturition, and lactation in mammals and understanding the role of hormones in these processes is essential for species conservation. Sirenia is a unique order of marine mammals that include manatees, dugongs, and the extinct Steller’s sea cow. Extant Sirenian species are all listed as vulnerable due to habitat loss, cold stress, boat strike trauma, harmful algal bloom toxicity, entanglements, and illegal hunting. Therefore, successful reproduction is essential to maintaining and increasing Sirenian populations. Understanding Sirenian reproductive behavior, endocrinology, and mating strategies will aid conservation and management efforts to protect and provide the proper conditions for successful reproduction. The objectives of this review were to synthesize the current knowledge regarding reproductive cycles and endocrinology of Sirenians and identify knowledge gaps for future investigation. The current literature on Sirenian reproductive physiology reports reproductive seasonality, sexual maturation, estrous cyclicity and acyclicity, pregnancy, and sex differences. However, there remain significant knowledge gaps on the cyclicity and pulsatile release of gonadotropins, maturation in females, and characterization of pregnancy hormone profiles throughout gestation. To date, there is no explanation for confirmed pattern for ovarian acyclicity, nor understanding of the function of the numerous accessory corpus luteum described in manatees. Research including a greater number of longitudinal and postmortem studies on a wider variety of wild manatee populations are important first steps. Taken together, understanding the reproductive endocrinology of these vulnerable and threatened species is critical for policy and management decisions to better inform protection initiatives.

Association Between Dietary Phytochemical Index and Neonatal Thyroid Function.

Background: Thyroid hormones regulate fetal growth and differentiation of several tissues. Maternal dietary patterns may be correlated with changes in the level of neonatal thyroid-stimulating hormone (TSH). We hypothesized that since maternal nutrition affects birth weight and offspring growth, it may also impact endocrine patterns in offspring. This study is aimed at assessing the relationship between maternal dietary phytochemical index (DPI) in the first trimester of pregnancy and neonatal cord blood thyroid hormone levels. Methods: This cross-sectional study is a substudy of a birth cohort. Overall, 216 mothers, aged 16-45 years, were recruited in their first trimester of pregnancy. To calculate DPI, the daily energy percentage of phytochemical-rich foods was divided by the total daily energy intake. At delivery time, TSH and free thyroxine (FT4) levels were measured in cord blood samples using chemiluminescence immunoassay. Results: The mean (standard deviation (SD)) age of mothers was 29.56 (5.50) years, and 47% of newborns were girls. The mean (SD) of DPI in the first, second, third, and fourth quartiles was 25.03 ± 4.67, 33.87 ± 2.18, 40.64 ± 2.10, and 51.17 ± 4.98, respectively. There was not any significant correlation between DPI score with cord serum TSH and FT4 levels in crude and adjusted analysis. Conclusion: No significant relationship between maternal DPI with cord serum TSH and FT4 levels was shown. Limited experience exists about the effect of maternal diet quality indices on neonatal thyroid function, and further studies are needed in this regard.

#1437 Renal expression pattern of the relaxin receptor, RXFP1, and effects of the RXFP1 agonist, AZD5462, on renin in non-human primates and humans

Abstract Background and Aims RXFP1 is a G protein-coupled receptor (GPCR) for the pregnancy hormone, relaxin. While preclinical studies, performed primarily in rodent, describe beneficial effects of this pleiotropic peptide across several organ systems, there has been a disappointing lack of success in translating these observations into clinical benefit. To provide a potential pharmacological explanation accounting for this translational gap, the aim of this study was thus to thoroughly evaluate RXFP1 expression across species and tissues as well as to evaluate the renal-intrinsic effects of the RXFP1 agonist, AZD5462. Method Unbiased bioinformatic analysis of several gene expression databases was used as a first approach to compare RXFP1 tissue-level expression between rodent and human. Experimental validation was subsequently performed using scRNAseq, RNAscope and immunohistochemistry on mouse, rat, non-human primate (NHP) and human kidney. The putative renal target engagement effects of RXFP1 agonism were assessed by determining the acute and chronic effects of the RXFP1-selective small molecule agonist, AZD5462, on plasma renin concentrations in both NHPs and in a Phase 1 randomized, single-blind, placebo-controlled study in healthy humans. Results RXFP1 was identified as one of the most highly expressed GPCRs in human and NHP kidney glomeruli. Specifically, by multiple assays, we identified glomerular endothelial cells as the principal cell type expressing RXFP1. This observation is in stark contrast to mouse and rat kidney, where RXFP1 was not readily detected. AZD5462 administered orally to NHPs and healthy human participants elicited an early and sustained dose-dependent increase in plasma renin concentration, and in humans an additional decline in serum creatinine. Conclusion Human RXFP1 kidney glomerular expression is conserved with NHPs but not rodent, thus highlighting the translational and pharmacological challenges in studying RXFP1/relaxin biology across species. The concordant ability of AZD5462 to induce elevations in renin and reduction in serum creatinine, together with relaxin's reported renal-hemodynamic activity in humans, may underlie a previously unappreciated renal-intrinsic RXFP1 target engagement mechanism driving its hemodynamic and renal effects. The potential therapeutic benefits of RXFP1 agonism are the subject of on-going clinical trials in heart failure patients.

STAT5B SH2 variants disrupt mammary enhancers and the stability of genetic programs during pregnancy.

During pregnancy, mammary tissue undergoes expansion and differentiation, leading to lactation, a process regulated by the hormone prolactin through the JAK2-STAT5 pathway. STAT5 activation is key to successful lactation making the mammary gland an ideal experimental system to investigate the impact of human missense mutations on mammary tissue homeostasis. Here, we investigated the effects of two human variants in the STAT5B SH2 domain, which convert tyrosine 665 to either phenylalanine (Y665F) or histidine (Y665H), both shown to activate STAT5B in cell culture. We ported these mutations into the mouse genome and found distinct and divergent functions. Homozygous Stat5bY665H mice failed to form functional mammary tissue, leading to lactation failure, with impaired alveolar development and greatly reduced expression of key differentiation genes. STAT5BY665H failed to recognize mammary enhancers and impeded STAT5A binding. In contrast, mice carrying the Stat5bY665F mutation exhibited abnormal precocious development, accompanied by an early activation of the mammary transcription program and the induction of otherwise silent genetic programs. Physiological adaptation was observed in Stat5bY665H mice as continued exposure to pregnancy hormones led to lactation. In summary, our findings highlight that human STAT5B variants can modulate their response to cytokines and thereby impact mammary homeostasis and lactation.

Proportion of Newly Detected Hypothyroidism among the Diabetic and Nondiabetic Pregnant Ladies and Correlation of Different Parameters with Thyroid Stimulatory Hormone in Pregnancy Attending a Tertiary Care Hospital

ABSTRACT Background: Subclinical hypothyroidism and gestational diabetes are the two most common endocrinopathy encountered in daily clinical practice. Many literature showed a higher frequency of hypothyroidism in the persons with diabetes but others did not find it. Objectives: The study was intended to compare the proportion of newly detected hypothyroidism in persons with diabetes and without diabetes in pregnancy (DIP). Materials and Methods: This cross-sectional, observational study enrolled 175 pregnant women by convenient sampling from the Department of Obstetrics and Gynecology, BIRDEM General Hospital, with or without diabetes after IRB clearance. According to the study protocol, Thyroid function test (TFT) and oral glucose tolerance test were done in the participants. Thyroid stimulatory hormone (TSH), free thyroxin, and antithyroid antibodies were tested using the chemiluminescent technique by the ADVIA centaur, Siemens. Plasma glucose was analyzed by Advia-1800, SIEMENS, USA by glucose oxidase method. Data were analyzed by SPSS version 25. Nonparametric tests were chosen for statistical analysis. Results: The median maternal age was 30 years, and half of the participants had a family history of diabetes mellitus (DM). Hundred patients had diabetes either gestational DM or DIP or preexisting diabetes. Among the persons with diabetes, 34% had hypothyroidism, and in euglycemic patients, 29.3% had hypothyroidism. There was no statistically significant (P = 0.785) difference in the median values of TSH across the glycemic status among the hypothyroid subjects. TSH had a positive correlation with thyroid peroxidase antibody (P = 0.174) within the hypothyroid patients. In the study subjects, TSH was inversely correlated with hemoglobin (P &lt; 0.001). Conclusions: There is no statistically significant concordance in diagnosing hypothyroidism in pregnancy between the persons with diabetes and without diabetes.

Increased risk of preterm birth due to heat exposure during pregnancy: Exploring the mechanism of fetal physiology

BackgroundHeat exposure during pregnancy can increase the risk of preterm birth (PTB) through a range of potential mechanisms including pregnancy complications, hormone secretion and infections. However, current research mainly focuses on the effect of heat exposure on pathophysiological pathways of pregnant women, but ignore that maternal heat exposure can also cause physiological changes to the fetus, which will affect the risk of PTB. ObjectiveIn this study, we aimed to explore the mediating role of fetal heart rate (FHR) in the relationship between maternal heat exposure and PTB incidence. MethodsWe assigned heat exposure to a multi-center birth cohort in China during 2015–2018, which included all 162,407 singleton live births with several times FHR measurements during the second and third trimesters. We examined the associations between heat exposure, FHR and PTB in the entire pregnancy, each trimester and the last gestational month. The inverse odds ratio-weighted approach applied to the Cox regression was used to identify the mediation effect of heat exposure on PTB and its clinical subtypes via FHR. FindingsExposure to heat significantly increased the risk of PTB during the third trimester and the entire pregnancy, hazard ratios and 95 % CIs were 1.266 (1.161, 1.379) and 1.328 (1.218, 1.447). Heat exposure during the third trimester and entire pregnancy increased FHR in the third trimester by 0.24 bpm and 0.14 bpm. The proportion of heat exposure mediated by FHR elevation on PTB and its subtype ranged from 3.68 % to 24.06 %, with the significant mediation effect found for both medically indicated PTB and spontaneous PTB. ConclusionsThis study suggests that heat exposure during pregnancy has an important impact on fetal health, and FHR, as a surrogate marker of fetal physiology, may mediate the increased risk of PTB caused by extreme heat. Monitoring and managing physiological changes in the fetus would constitute a promising avenue to reduce adverse birth outcomes associated with maternal heat exposure.

Management of Garbhini Mukhpaka with Kavala Dharana

It is well known that in pregnancy various physiological and pathological changes occurs. Most of which are reversible after delivery. Due to hormonal changes during pregnancy the changes in oral mucosa are also seen. The reasons for these changes are not well known established. Of all the changes the one most well-known is stomatitis. In Pregnancy hormone fluctuation causes changes in saliva making mouth more susceptible to ulcer. Physical and emotional stress of pregnancy aggravates the factor for mouth ulcer. In Ayurveda this condition is known as Mukhpaka, Acharya Sushruta has described under Mukhroga. Among 65 Mukhroga it comes in Sarvasara Roga and these are of three types. In modern science it is treated by maintaining oral hygiene and by using tropical anaesthetics, antibacterial and anti-inflammatory drugs. Many of these drugs are of unknown adverse effect that cannot be frequently used in pregnant women. In Ayurveda it is treated by various methods like Kwatha, Gandusha, etc. In Kashyapa Samhita this Garbhini Vikara is treated with the administration of Kavala of Haridra and Daruharidra. Then Kavala of Sneha/Sugar added water and of Lodhra Kwath Kawal and at the end dusting of Lodhra Choorna is done, and with intake of powder of Manjistha, Ghrashi, Sariva, Mochras, with honey.

Investigation of Phosphorylated and O-Glycosylated Proteins in Gestational Diabetes Mellitus

Gestational Diabetes Mellitus (GDM) is a common but temporary type of diabetes that develops among 10-20% of all pregnant women. It is a major cause of several pre- and post-pregnancy diseases in both mother and offspring. The main causative is altered pregnancy hormones that lead to deficient glucose metabolism. Complications can be preeclampsia, caesarean sections and cardiovascular diseases. This study was designed to determine the phosphorylated and glycosylated proteins present in GDM and to investigate the role of their post-translational modifications (PTMs) in the pathogenesis of GDM. The study was performed on 30 blood samples from pregnant diabetic women (diseased), 30 pregnant non-diabetic women (control) and 30 women without pregnancy and gestational diabetes (normal). Protein extraction was done from blood plasma, and phosphorylated and glycosylated proteins were determined by Enzyme-Linked Immuno-Sorbent Assay (ELISA) by use of specific antibodies. This study showed that proteins found in GDM are highly phosphorylated and O-glycosylated (p&lt;0.01). Furthermore, a bioinformatic investigation was done, which showed that blood coagulation proteins such as the Fibrinogen alpha chain and lipid metabolism-regulating proteins apolipoprotein E, L1 and C-III showed a high potential for phosphorylation, which suggests that phosphorylation can be used as a therapeutic marker in GDM.

Periodic injections of Relaxin 2, its pharmacokinetics and remodeling of rat hearts

Relaxin-2 (RLX), a critical hormone in pregnancy, has been investigated as a therapy for heart failure. In most studies, the peptide was delivered continuously, subcutaneously for 2 weeks in animals or intravenously for 2-days in human subjects, for stable circulating [RLX]. However, pulsatile hormone levels may better uncover the normal physiology.This premise was tested by subcutaneously injecting Sprague Dawley rats (250 g, N = 2 males, 2 females/group) with human RLX (0, 30, 100, or 500 µg/kg), every 12 h for 1 day, then measuring changes in Nav1.5, connexin43, and β-catenin, 24 h later. Pulsatile RLX was measured by taking serial blood draws, post-injection.After an injection, RLX reached a peak in ∼ 60 min, fell to 50 % in 5–6 h; injections of 0, 30, 100 or 500 µg/kg yielded peak levels of 0, 11.26 ± 3.52, 58.33 ± 16.10, and 209.42 ± 29.04 ng/ml and residual levels after 24-hrs of 0, 4.9, 45.1 and 156 pg/ml, respectively. The 30 µg/kg injections had no effect and 100 µg/kg injections increased Nav1.5 (25 %), Cx43 (30 %) and β-catenin (90 %). The 500 µg/kg injections also increased Nav1.5 and Cx43 but were less effective at upregulating β-catenin (up by 25 % vs. 90 %).Periodic injections of 100 µg/kg were highly effective at increasing the expression of Nav1.5 and Cx43 which are key determinants of conduction velocity in the heart and the suppression of arrhythmias. Periodic RLX is effective at eliciting changes in cardiac protein expression and may be a better strategy for its longer-term delivery in the clinical setting.

The rhizomes of Atractylodes macrocephala Koidz improve gastrointestinal health and pregnancy outcomes in pregnant mice via modulating intestinal barrier and water-fluid metabolism

Ethnopharmacological relevanceBaizhu (BZ) is the dried rhizome of Atractylodes macrocephala Koidz (Compositae), which invigorates the spleen, improves vital energy, stabilizes the fetus, and is widely used for treating spleen deficiency syndrome. However, the impact of BZ on gastrointestinal function during pregnancy remains unexplored. Aim of the studyThis study elucidated the ameliorative effects of BZ on gastrointestinal health and pregnancy outcomes in pregnant mice with spleen deficiency diarrhea (SDD). MethodsTo simulate an irregular human diet and overconsumption of cold and bitter foods leading to SDD, a model of pregnant mice with SDD was established using an alternate-day fasting and high-fat diet combined with oral administration of Sennae Folium. During the experiment, general indicators and diarrhea-related parameters were measured. Gastric and intestinal motility (small intestinal propulsion and gastric emptying rates) were evaluated. Serum motilin (MTL), ghrelin, growth hormone (GH), gastrin (Gas), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-c), chorionic gonadotropin β (β-CG), progesterone (P), and estradiol (E2) were quantified using an enzyme-linked immunosorbent assay. Pathological changes were examined by hematoxylin and eosin staining (H&E) and alcian blue periodic acid Schiff staining (AB-PAS). Immunohistochemistry and immunofluorescence were used to measure the expression levels of the intestinal barrier and water metabolism-related proteins in colonic tissues. The pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, small size, average fetal weight, and body length of fetal mice were calculated. ResultsThe results showed that BZ significantly improved general indicators and diarrhea in pregnant mice with SDD, increased gastric emptying rate and small intestinal propulsion rate, elevated the levels of gastrointestinal hormones (AMS, ghrelin, GH, and Gas) in the serum, and reduced lipid levels (TC and LDL-c). It also improved colonic tissue morphology, increased the number of goblet cells, and promoted the mRNA and protein expression of occludin, claudin-1, ZO-1, AQP3, AQP4, and AQP8 in colonic tissues, downregulating the mRNA and protein expression levels of claudin-2, thereby alleviating intestinal barrier damage and regulating the balance of water and fluid metabolism. BZ also held the levels of pregnancy hormones (β-CG, P, and E2) in the serum of pregnant mice with SDD. Moreover, it increased the pregnancy rate, ovarian organ coefficient, uterus with fetus organ coefficient, litter size, average fetal weight, and body length of fetal mice. These findings indicate that BZ can improve spleen deficiency-related symptoms in pregnant mice before and during pregnancy, regulate pregnancy-related hormones, and improve pregnancy outcomes.

(264) Prioritizing Sexual and Reproductive Health Research and Care for People with Cystic Fibrosis: A 2023 Workshop Report From the Cystic Fibrosis Foundation Sexual Health, Reproduction, and Gender Research (SHARING) Working Group

Abstract Introduction With therapy advances, people with cystic fibrosis (CF) are living longer, healthier lives, and thus increasingly have general and CF-specific sexual and reproductive health (SRH) questions. The CF Foundation is supporting the Sexual Health, Reproduction, and Gender Research (SHARING) Working Group to identify knowledge gaps, research priorities, and infrastructure needed for CF SRH research. SHARING includes pulmonologists, nurses, research coordinators, registered dieticians, psychiatrists, endocrinologists, reproductive urologists, and community members with CF. Objective In Spring 2023, SHARING developed and distributed a SRH prioritization survey for the CF community. During the annual in-person workshop, the group used these results to establish research priorities and develop studies that would address identified knowledge gaps. Methods SHARING partnered with Community Voice, a virtual platform for people with CF and their caregivers to share their perspectives on ongoing and future CF SRH research, care, and programming. We provided a list of 15 SRH research topics and asked respondents to rank the top five. We analyzed survey results using descriptive statistics. We also summarized discussions and future key directions for CF SRH research. Results A total of 303 respondents (85% people with CF and 15% caregivers) completed the survey. Sixty-five percent of people with CF were women and 37% of the people with CF for whom caregivers responded were women/girls. The majority (95% of adults, 98% of people with CF for whom caregivers responded) identified as White; 5% of adults and 10% of people with CF for whom caregivers responded were Hispanic/Latino. The majority (73%) of people with CF were &amp;gt;30 years old and 68% of those with CF for whom caregivers responded were &amp;lt;18 years old. Table 1 summarizes respondent demographics. The top five SRH topics were: 1) effects of CF modulator therapy (elexacaftor/tezacaftor/ivacaftor, ETI) on sex hormones; 2) effects of sex hormones on CF; 3) fertility; 4) pregnancy; and 5) SRH/mental health (Figure 1). People with CF prioritized pregnancy, sexual functioning, parenthood, and menopause, while caregivers prioritized ETI effects on sex hormones, fertility, mental health, and assisted reproductive technology (ART). SRH priorities differed by gender identity. Men and caregivers of men/boys prioritized fertility, mental health, SRH care provision, sexual functioning, and ART, while women and caregivers of women/girls prioritized the effect of sex hormones in CF, pregnancy, menopause, and contraception. During workshop proceedings, SHARING identified the need for further research on the interplay between sex hormones, CF pathophysiology, ETI, fertility, and ART, and a focus on the impact of infertility on mental health for males with CF. Conclusions SRH is an important and emerging area of research in CF. Research priorities are not uniform among people with CF and their caregivers, particularly across genders. Thoughtful consideration of such perspectives can ensure that future CF SRH research is relevant and responsive to CF community needs. SRH providers should be aware of the concerns in this understudied population from research and patient care perspectives. Disclosure No.

Single-Cell Transcription Mapping of Murine and Human Mammary Organoids Responses to Female Hormones

During female adolescence and pregnancy, rising levels of hormones result in a cyclic source of signals that control the development of mammary tissue. While such alterations are well understood from a whole-gland perspective, the alterations that such hormones bring to organoid cultures derived from mammary glands have yet to be fully mapped. This is of special importance given that organoids are considered suitable systems to understand cross species breast development. Here we utilized single-cell transcriptional profiling to delineate responses of murine and human normal breast organoid systems to female hormones across evolutionary distinct species. Collectively, our study represents a molecular atlas of epithelial dynamics in response to estrogen and pregnancy hormones.

Estriol and commensal microflora strains regulate innate lymphoid cells functional activity in multiple sclerosis

Multiple sclerosis (MS) is an autoimmune neurodegenerative disease in which the immune system attacks myelin basic protein of nerve axons. Recently, there has been growing interest in studying the role of a newly described population of immunity cells – innate lymphoid cells (ILCs) in the pathogenesis of the disease. At the same time, it was found that during pregnancy there is a weakening of Th1-mediated autoimmune pathologies manifestations, including MS. In this work, we studied phenotypic characteristics of ILC in MS patients in comparison with healthy donors after 48 h incubation with pregnancy hormone estriol (E3) and commensal microflora cells. To activate ILC, strains of Ecsherichia coli K12 and Lactobacillus plantarum 8R-A3 were used. ILC phenotype was assessed by flow cytometry using monoclonal antibody staining. It has been established that E3 and bacterial factors are able to regulate the maturation of ILC subtypes and their cytokines in different ways. In general, the studied factors influence the phenotypic changes in ILC cells, leading to the transition from one type to another, both in healthy donors and in MS patients.

Associations of urinary non-persistent endocrine disrupting chemical biomarkers with early-to-mid pregnancy plasma sex-steroid and thyroid hormones

Background/ObjectivesPregnant women are exposed to numerous endocrine disrupting chemicals (EDCs) that can affect hormonal pathways regulating pregnancy outcomes and fetal development. Thus, we evaluated overall and fetal sex-specific associations of phthalate/replacement, paraben, and phenol biomarkers with sex-steroid and thyroid hormones. MethodsIllinois women (n = 302) provided plasma for progesterone, estradiol, testosterone, free T4 (FT4), total T4 (TT4), and thyroid stimulating hormone (TSH) at median 17 weeks gestation. Women also provided up-to-five first-morning urine samples monthly across pregnancy (8–40 weeks), which we pooled to measure 19 phthalate/replacement metabolites (reflecting ten parent compounds), three parabens, and six phenols. We used linear regression to evaluate overall and fetal sex-specific associations of biomarkers with hormones, as well as weighted quantile sum and Bayesian kernel machine regression (BKMR) to assess cumulative associations, non-linearities, and chemical interactions. ResultsIn women of relatively high socioeconomic status, several EDC biomarkers were associated with select hormones, without cumulative or non-linear associations with progesterone, FT4, or TT4. The biomarker mixture was negatively associated with estradiol (only at higher biomarker concentrations using BKMR), testosterone, and TSH, where each 10% mixture increase was associated with −5.65% (95% CI: −9.79, −1.28) lower testosterone and −0.09 μIU/mL (95% CI: −0.20, 0.00) lower TSH. Associations with progesterone, testosterone, and FT4 did not differ by fetal sex. However, in women carrying females, we identified an inverted u-shaped relationship of the mixture with estradiol. Additionally, in women carrying females, each 10% increase in the mixture was associated with 1.50% (95% CI: −0.15, 3.18) higher TT4, whereas in women carrying males, the mixture was associated with −1.77% (95% CI: −4.08, 0.58) lower TT4 and −0.18 μIU/mL (95% CI: −0.33, −0.03) lower TSH. We also identified select chemical interactions. ConclusionSome biomarkers were associated with early-to-mid pregnancy hormones. There were some sex-specific and non-linear associations. Future studies could consider how these findings relate to pregnancy/birth outcomes.