ResearchPad - female-reproduction:-basic-mechanisms https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[MON-001 Peripartum Sertraline (Zoloft®) Increases Pup Mortality Immediately Postpartum]]> https://www.researchpad.co/article/elastic_article_8805 Peripartum and postpartum depression can be detrimental to both the mother and the developing child. Use of antidepressants, such as selective serotonin reuptake inhibitors (SSRIs), is common during the peripartal period and SSRIs have been the leading prescribed antidepressant to treat maternal depression. One of the most commonly prescribed SSRIs is sertraline (Zoloft®) because of the limited fetal teratogenic effects observed, unlike maternal paroxetine (Paxil®) usage which can manifest in fetal cardiovascular defects. Fluoxetine (Prozac®), like sertraline, has previously been shown to have limited teratogenic effects, however, we have shown treatment with fluoxetine for the entire period of pregnancy and lactation in mice compromises pup bones at weaning resulting in decreased long bone length and head circumference. Furthermore, maternal fluoxetine usage results in a sustained reduction in maternal bone mineral density post weaning, which may lead to long-term osteopenia, putting the mother at risk for bone-related disorders later in life. We hypothesized sertraline, like fluoxetine, will compromise maternal bone postpartum and fetal bone development at weaning. Treatment with sertraline in C57BL/6 dams throughout pregnancy and lactation reduced litter size (5.4 pups/dam) and increased pup mortality during the first 24 hours postpartum (20% dead pups/litter) compared to controls (6.8 pups/dam, 5% dead pups/litter, respectively; P < 0.018). Maternal calcium transporters (Orai1 and Serca2) were downregulated in the mammary gland in sertraline-treated dams on day 21 of lactation (P < 0.0032). Together, our data suggests in utero pharmacological exposure to sertraline may induce a failure to thrive in the pups and alters calcium metabolism in the dam. SSRI exposure during pregnancy and lactation may adversely affect the developing neonate(s) as well as have lasting impacts on the mother.

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<![CDATA[MON-003 Uterine Contractility in Pregnancies Complicated by Obesity: The Effects of Adipokines on the in Vitro Functional Contractility of Isolated Uterine Samples]]> https://www.researchpad.co/article/elastic_article_8674 Objectives: The onset of parturition in pregnant women with obesity is frequently delayed. Without induction, these women are nearly twice as likely as normal-weight to have prolonged pregnancy (≥41 weeks gestation) which is concerning because of associated two-fold increased risk of third-trimester stillbirth. Data from vascular studies have shown that different adipokines have different effects on smooth muscle contractility; either as relaxants or constrictors. However, only few studies have investigated their role in uterine contractility, a relationship that we sought to investigate. Materials and Methods: Total of 22 pregnant women scheduled for term cesarean delivery (CD) were recruited. Strips from the first two participants were used to identify dose response effects for each adipokine, and 20 participants’ data were included in the final analysis. Study groups consisted of normal-weight (N=10) and women with obesity (N=10). Myometrial strips were obtained from the hysterotomy incision at the time of the CD. Muscle strips were mounted within experimental recording baths. Both spontaneous and oxytocin induced contractions were recorded by a custom-build data acquisition software. Adipokines of interest included adiponectin, TNFα, resistin, and omentin. Adipokines were added to the muscle baths after muscle equilibration was achieved. Contractions outcomes of interest included forces, durations, and frequencies. Data comparisons were conducted using Wilcoxon Rank-Sum tests; medians and ranges are presented. Results: Forces of contractions in normal-weight participants were double those studied from participants with obesity (13.9 [9.3-34.3] vs. 8.9 [4.8-23.6], p=0.05). There were no statistically significant differences between contractility outcomes of interest after adding adiponectin, TNFα, and resistin to the muscle baths within and between the study groups. In participants with obesity, compared to baseline, omentin significantly reduced the force of spontaneous induced contractions (p=0.002) and prolonged the period between contractions (p=0.01). Importantly, that effect was not seen in normal-weight participants or in oxytocin induced contractions. Omentin also significantly reduced the forces of spontaneous induced contractions (2.9 [2.2-4.6] vs. 14.4 [4.8-33.6]; p=0.01) and prolonged the period (790.6 [753.0-832.0] vs. 611.4 [128.3-702.7]; p=0.04) in participants with obesity compared to normal-weight participants. Differences were no longer observed after adding oxytocin. Conclusion: In vitro, uterine contractions were reduced in muscle samples prepared from pregnant women with obesity compared to normal-weight counterparts. Omentin may have a role in reduced uterine contractility in pregnant women with obesity and that effect may be corrected by oxytocin administration.

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<![CDATA[MON-028 Chronic Resveratrol Exposure Improves Glucose Homeostasis and Cardiac Function in a Rat Model of Polycystic Ovarian Syndrome]]> https://www.researchpad.co/article/elastic_article_8660 Polycystic ovary syndrome (PCOS) is the commonest endocrinopathy in women of reproductive age, with a prevalence of 5-8%. Long-term complications seen in PCOS include cardiovascular disease and type 2 Diabetes Mellitus. Current therapies do not completely address the cardiometabolic perturbations seen in women with PCOS. Resveratrol (RSV), a natural polyphenol, is shown to have beneficial cardio-metabolic effects in various pathological conditions including that on insulin sensitivity, cardiovascular function. In-vitro studies suggest it’s beneficial effects on ovarian function as well. Therefore, we hypothesized that chronic exposure to RSV would improve both cardiovascular and metabolic phenotypes in PCOS. To test this hypothesis we used an established rat model of PCOS that develops metabolic derangement and irregular cycles. A 7.5 mg (90-day release) dihydrotestosterone (DHT) pellet providing a daily dose of 83 mcg was implanted in 5-week-old female rats. Studies were also conducted on littermate matched controls (C) with no DHT implant. A subgroup of the control and DHT treated rats (n=6 per group) received a 0.84 g/kg dose of resveratrol (RSV) in their chow starting at age 5 weeks. At 8 weeks, animals were weighed weekly (n=6 per group). Oral glucose tolerance test (OGTT n=6 per group) and cardiac echocardiogram (C n=12, C+RSV n=6, DHT n=10, DHT+RSV n=6) were conducted at 16-weeks of age. Body weight increased significantly in DHT treated rats compared to C between 8 and 16 weeks (40 vs 22 grams, p <0.001). RSV treatment did not mitigate the effects of DHT on body weight (34 vs 40 grams, p>0.5). There was significantly higher glucose excursion at 30 minutes post glucose load in both DHT (148± 7.4 mg/dl) and DHT+RSV (139± 7.4 mg/dl) compared to C group (121± 13 mg/dl, p<0.001, p=0.03 respectively). However, by 60 and 90 minutes only DHT group had a significantly higher glucose excursion compared to both DHT+RSV and C groups (131± 4.1,124± 5.7,110 ± 5.9 mg/dl, p=0.015,p=0.21 respectively); 90min (118±5.8,110±4.7,96±4.2 mg/dl, p<0.01,p=0.09 respectively). By 120 minutes, no significant difference in glucose levels existed between groups. Cardiac echocardiogram showed significantly lower mitral valve E/A ratio (and increased MV isovolumic relaxation time (IVRT) in DHT group compared to C. RSV treatment reversed these changes. In conclusion, RSV improved glucose homeostasis and diastolic dysfunction in the DHT induced rodent model of PCOS and may serve as a novel treatment option targeting the cardiometabolic derangement seen in PCOS. Further studies elucidating the mechanisms underlying the beneficial effects of RSV on cardio-metabolic phenotype in this PCOS rodent model is warranted.

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<![CDATA[MON-LB004 Understanding the Influence of Endometrial Cancer Risk Factors Using Human Primary Endometrial Organoids]]> https://www.researchpad.co/article/elastic_article_8616 It is unclear how endometrial cancer risk factors such as obesity, high serum testosterone, and high serum levels of the endocrine-disrupting compound bisphenol-A (BPA) influence hormone action to promote carcinogenesis. We hypothesized that obesity, high testosterone, and BPA exposure alters the protective progesterone response in the benign endometrium. Primary human benign endometrial organoids, consisting of both epithelial and stromal cells, were exposed to each of these risk factors in vitro in the presence of cyclic levels of estradiol, progesterone, and testosterone for 14 days. Progesterone response genes HSD17B2, IGFBP1, PAEP, and PRL were measured by real-time qPCR and IHC. First, to simulate obesity, endometrial organoids were cocultured with increasing numbers of human adipocyte spheroids during the hormone treatment. Real-time qPCR analysis revealed dysregulation of expression of HSD17B2 and IGFBP1 by approximately 20% when cocultured with 30 adipocyte spheroids. In addition, PRL protein levels were significantly lower in the stroma of the endometrial organoids. Second, increasing concentrations of BPA and 3nM testosterone individually or in combination were added to endometrial organoids together with the 14-day menstrual cycle hormones. Treatment with 0.6 ng/mL of BPA decreased expression of HSD17B2, IGFBP1, and PAEP by 50% to 80%. However, this effect was not seen in the context of high testosterone, indicating that there may be crosstalk between these two risk factors. In summary, this study demonstrated that adipocytes, BPA exposure, and high testosterone directly alter progesterone action in benign endometrial organoids, suggesting a diminution of the protective effects of progesterone and an increased risk of endometrial cancer.

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<![CDATA[MON-022 Dissecting the Interplay Between Diet and PCOS Pathology on Gut Microbiota in a PCOS Mouse Model]]> https://www.researchpad.co/article/elastic_article_8543 The gut microbiome has been implicated in the development of metabolic disorders such as obesity and type-2 diabetes, and more recently polycystic ovary syndrome (PCOS). PCOS is a heterogeneous disorder with reproductive, endocrine and metabolic irregularities, and clinical and animal studies have reported that PCOS causes a decrease in microbial diversity and composition. Diet is an important regulator of the gut microbiome, and a recent study identified that alterations in macronutrient balance impact gut microbial communities which correlate with different metabolic health outcomes (1). We have identified that macronutrient balance impacts the development of PCOS traits. Therefore, to investigate the interplay between macronutrient balance and a PCOS environment on the gut microbiome, we analyzed the intestinal microbiome from fecal pellets of control and DHT-induced PCOS mice exposed to 10 different diets that varied systematically in protein (P), carbohydrate (C) and fat (F) content. The amount of dietary P, C and F consumed significantly altered alpha and beta diversity of the gut microbiota of pooled control and PCOS mice (P<0.0001). Alpha diversity between control and PCOS mice on the same diet did not differ significantly, and hence was only affected by diet composition. However, beta diversity was significantly altered between control and PCOS mice (P<0.05). We performed DESeq2 analysis and identified an operational taxonomic unit (OTU) within Bacteroides (OTU3) to be the most differentially abundant OTU between control and PCOS mice, with a significant decrease in PCOS mice compared to controls (control: 7.88 and PCOS: 5.38; fold change = 1.464; P<0.0001). The consensus sequence of Bacteroides OTU3 was found to share 99.2% similarity to Bacteroides acidifaciens. B. acidifaciens is associated with obesity with elevated levels reported to prevent the onset of obesity (2). Thus, we then investigated the influence of P, C and F on the relative abundance of Bacteroides OTU3 and revealed an association with C consumption, with increasing levels of C leading to increased levels of Bacteroides OTU3 (Carb: r= 0.22, p=0.0028, q=0.015). These findings demonstrate that diet exerts a stronger influence over the gut microbiome than PCOS pathology. However, the hyperandrogenic PCOS environment does lead to changes in gut microbiota beta diversity, with a specific decrease in an obesity-associated (2) Bacteroides species in PCOS mice that is also responsive to levels of C consumption. Reference: (1) Holmes et al., Cell Metabolism. 2017; 25(1): 140-151. (2) Yang et al., Mucosal Immunology. 2017, 10 (1), 104-116.

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<![CDATA[MON-018 Fertility Rates in Rats Characterized by Increased Hypothalamic CRH Secretion]]> https://www.researchpad.co/article/elastic_article_7035 Certain strains of rats are characterized by hyperactive Hypothalamic-Pituitary-Adrenal axis responses to stress, increased hypothalamic Corticotropin-Releasing Hormone (CRH) production and decreased fertility rates. Activation of the HPA-axis and CRH secretion has been associated with suppression of the Hypothalamic-Pituitary-Ovarian axis primarily as a result of glucocorticoids. Here we examined the hypothesis that Fischer rats have decreased fertility rates because of hypothalamic CRH hypersecretion. Antalarmin, a CRH receptor type 1 antagonist, is known to suppress adrenocorticotropin hormone secretion and other CRH receptor type 1-mediated responses. Adult female Fischer rats were injected with antalarmin or placebo, twice a day, for 16 days. Mating was evidenced by the presence of spermatozoa in the vaginal smear performed every morning. After 16 days, 20% of rats (20%) treated with placebo became pregnant and 55% rats treated with antalarmin became pregnant. We have previously reported that administration of antalarmin after the first day of pregnancy does not affect blastocyst implantation in Fischer rats. Our data suggest that antalarmin improves fertility rates in Fischer rats by antagonizing the direct antireproductive role of hypothalamic CRH.

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<![CDATA[MON-024 Steroid Cell Tumor, Not Otherwise Specified; A Rare Case of Hyperandrogenism]]> https://www.researchpad.co/article/elastic_article_6368 BACKGROUND:

Steroid cell tumor is a rare sex cord stromal tumor. There are 3 types including steroid cell tumor not otherwise specified (NOS), stromal luteoma and leydig cell tumors.

Steroid cell tumor (NOS) is the most common of all the subtypes. About 75% of the steroid cell tumor (NOS) are secretory. They can secrete androgens and estrogens. In a few cases, cortisol and renin secretion have been reported. The patient’s clinical features depend on the hormone secreted.

CASE PRESENTATION

Here, we report a case of a 22-year-old woman who was seen at an outpatient clinic for hirsutism, irregular menstrual bleeding, and progressive weight gain. Examination revealed androgenic facial hair growth, clitoromegaly and obesity.

Initial differentials on presentation were PCOS, ovarian or adrenal pathology. Initial LH, FSH values were normal. Lab investigation showed elevated testosterone, DHEAS and 17-OH progesterone levels. Baseline labs showed Androstenedione of 3345 ng/dl (41-262 ng/dl), DHEAS of 595.5 ug/dl (110- 431.7 ug/dl), 17-OH progesterone was 2394 ng/dl (follicular: 15-70 ng/dl, Luteal: 35-290 ng/dl), total and free testosterone was 558 ng/dl (premenopausal; 10-55ng/dl) and 33.0 pg/ml, (0.8-1.4pg/ml), respectively. Patient subsequently had an ACTH stimulation test which showed an increase in 17-OH progesterone from 384 ng/dl to 657 ng/dl and a repeat showed an elevation from 204 to 322 ng/dl, ruling out a late onset CAH. She was then sent for pelvic sonogram which showed the presence of a left ovarian mass 4.9x 4.8x 4.8 cm and a pelvic CT scan confirmed a left ovarian mass measuring 6.8x5.5x 5.5 cm and an unremarkable right ovary. She underwent a laparoscopic unilateral salpino-oophorectomy and histology confirmed the diagnosis of an ovarian steroid cell tumor (NOS). Post-surgery, the androgen levels returned to normal. The patient is now being followed for recurrence.

CONCLUSION

Women who present with virilism should be evaluated adequately with comprehensive history taking and physical examination along with appropriate biochemical tests and imaging studies to confirm tumor location and plan for surgery.

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<![CDATA[MON-017 Effect of Estradiol Therapy on Depressive like Behavior in an Ovarian Intact Rat Model of Perimenopause]]> https://www.researchpad.co/article/elastic_article_6318 In women, perimenopause is a period of high vulnerability to mood disorders which are associated with vasomotor symptoms, sleep disorders and several changes in the reproductive cycle. The general clinical practice to ameliorate these symptoms strongly relies on the use of estradiol therapy (E2T), although perimenopausal women are not estradiol deficient and it is not known whether E2T provides beneficial effects to all perimenopausal symptoms experienced. Our aim was to investigate the effect of E2T on depressive like behavior in rats treated with 4-vinylcycloxene diepoxide (VCD), which accelerates the natural process of ovarian follicular atresia modelling perimenopause in women. For this, prepubertal female rats (PND 28) were injected daily with VCD or oil for 15 days; 55-65 days after the first injection, pellets of 17β-estradiol (VCD+E) or oil (VCD+O and O+O) were inserted subcutaneously. Around 20 days later, the rats underwent 5 min open field (OFT) test followed by 5 min forced swimming test (FST; O+O and VCD+O rats on diestrus). Next, the animals were anesthetized, a blood sample was withdrawn from cardiac puncture for hormonal radioimmunoassay. The liver, adrenal glands, ovaries, kidney and uterus were removed and weighted. Another set of animals were submitted to the same experimental protocol described above; on the day of the experiment the rats were decapitated for noradrenaline (NA) measurement in brain punches of Hippocampus (HP). In the OFT there were no significant differences in the total distance travelled and the time spent in the periphery and central zone among the groups, showing that neither VCD nor E2 treatment were able to alter the locomotor activity. In the FST, on the other hand, VCD rats displayed increased immobility time and decreased climbing (CT) and swimming times compared to the Oil treated animals. VCD+E displayed similar results to VCD+O with an additional stronger effect in decreasing CT, demonstrating a negative effect of E2T in depressive like behavior in VCD-periestropausal rats. Associated to these behavioral responses we found that the content of NA in the HP of VCD+E was reduced compared to O+O and VCD+O. Plasma levels of LH and FSH were similar among the groups. Progesterone plasma levels were decreased in VCD+O compared to O+O rats and E2T increased progesterone and decreased testosterone in VCD+E compared to O+O and VCD+O groups. The weight of the liver, kidney and adrenal glands did not vary among the groups. As expected, in the VCD+E rats, the weight of the ovaries was decreased and that of the uterus increased in response to E2T. In conclusion, we showed that progressive ovarian failure triggers depressive like behavior in VCD-periestropausal rats associated with low progesterone plasma levels. Although progesterone levels are improved by E2T, depressive like behavior is intensified possibly due to a reduction in NA transmission in the hippocampus.

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<![CDATA[MON-026 Estradiol Triggering Extracellular Matrix Degradation Leading Signalling Cascades Succeeding a Feedback Loop as Contributing Factor to Develop Endometriosis in Females of Reproductive Age]]> https://www.researchpad.co/article/elastic_article_6284 INTRODUCTION: Endometriosis is common gynaecological disorder that leads to infertility in females of reproductive age. It is characterized by endometrial glands and stromal tissues outside the wall of uterus. Upregulation of estradiol is responsible for the cell proliferation, adhesion and invasion in endometriosis. It enhances prostaglandins (PGE-2) that triggers the formation of matrix metalloproteinases (MMPs), Tumor necrosis factor-α (TNF-α) and nuclear factor kappa B (NF-kB). Whereas, levels of progesterone are reported to be decreased in the patients with endometriosis. Less production of progesterone activity of 17β-hydroxysteroid dehydrogenase-II (17β-HSD-II) decreases that converts estradiol to less potent estrone. Intake of excess trans-fats and deficiency of vitamin D raises level of arachidonic acid and converts PGE-2 by the action cyclooxygenase (COX-2). PGE2 in theca cells of ovaries increases cAMP and activity of liver receptor homologue-1/steroidogenic factor-1(LRH-1/SF-1) thus leading to the stimulation of aromatase enzyme. MATERIALS AND METHODS: Two hundred eighty-eight (n=288) females with endometriosis and hundred (n=100) controls were enrolled. Informed consent was obtained before the collection of samples. Levels of estradiol, progesterone, aromatase enzymes, 17β-HSD-II, COX-2, PGE-2, MMPs (2, 7, 9), vitamin D and lipopolysaccharides (LPO) were estimated by respective protocols. RESULTS: Findings suggests significant increase in the levels of estradiol, aromatase enzymes, COX-2, PGE-2, MMPs (2,7,9) and LPO (67.08±5.55 pg/ml, 7.16±1.28 ng/ml, 1.56±0.144 ng/ml, 4.89±0.61 pg/ml, 995.2±8.15 ng/ml, 105.2±7.19 ng/ml, 109.2±12.25 ng/ml and 125.25±11.26 pg/ml) in patients as compared to (21.08±3.65 pg/ml, 2.08±0.15 ng/ml, 0.61±0.056 ng/ml, 1.158±0.18 pg/ml, 388.26±14.26 ng/ml, 66.29±5.26 ng/ml, 38.29±15.2 ng/ml and 17.25±1.26 pg/ml) controls respectively. Whereas, levels of progesterone, 17β-HSD-II and vitamin D remained significantly low in the endometrial patients (3.07±1.08 ng/ml, 0.183±0.024 ng/ml and 17.17±2.3 ng/ml) as compared to healthy females (29.22±3.29 ng/ml, 1.43±0.153 ng/ml and 36.26±3.09 ng/ml). CONCLUSION: Current study suggests the role of estradiol in triggering ECM degradation and initiating signalling cascades that following a feedback loop enhances the levels of estradiol and contributes in the development and progression of endometriosis. Hence, therapies with supplementation of vitamin D and progesterone may help in regressing the role estradiol and other contributing factors that are involved in the development and progression of endometriosis in the patients. Keyword: Endometrial glands, Stromal tissues, Estrogen, Progesterone, Endometriosis, Vitamin D

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<![CDATA[MON-004 Ovarian Steroid Cell Tumor, Not Otherwise Specified (NOS): A Case Report and Clinical Review]]> https://www.researchpad.co/article/elastic_article_6030 Background: Ovarian tumors are divided into non functioning and functioning, within the last group, we can find those with endocrine activity that produce androgenization. Ovarian cell tumors, not otherwise specified (SCT-NOS) is a rare type of ovarian sex cordomal tumor and represents the 60% of this tumors, which compromise less than 0.1% of the ovarian tumors. (1)

Clinical Case: We here present a 28 year old woman who was referred to the Endocrine Clinic due to secondary amenorrhea and virilization signs. At the age of twelve a diagnosis of polycystic ovarian syndrome (POS) was made and treated with combined oral anticonceptive (COA). Menses became regular only with medication. Six months after she stopped medication, amenorrhea and virilization signs worsened. Biochemically she had levels of serum total testosterone 6.8 ng/mL (0.02-0.45) and free testosterone 42 pg/mL (0.1-6.4) since only pelvic ultrasonography has been made by physician, a transvaginal ultrasound and abdomen – pelvic CT scan showed a anexial tumor. After analysis of biochemical and imaging results a multidisciplinary team performed a surgical extirpation of the primary lesion, which was diagnosed by histopathology as a tumor of lipoidic cells NOS. A month after the surgery, menses became regular.

Conclusion: The purpose of this article is to present the available information about this kind of tumors and the treatment recommended. It is mandatory to follow a correct approach among a multidisciplinary team, in order to get the correct diagnosis at the proper time.

(1) Zang L, Ye M, Yang G, Li J, Liu M, Du J et al. Accessory ovarian steroid cell tumor producing testosterone and cortisol. Medicine. 2017;96(37):e7998.

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<![CDATA[MON-005 Inhibition of Glucocorticoid Signaling in SRC-1/-2 Double-Deficient Mice Results in Impaired Lung Maturation and Delayed Parturition]]> https://www.researchpad.co/article/N2cdd85bf-8ff5-4976-9123-5e9a517daf76 The mechanisms that lead to the initiation of parturition are incompletely defined. Parturition timing is mediated by signals from both mother and fetus. Our previous findings using mice that were double-deficient in steroid receptor coactivators (Src)1 and 2 (Src-1/-2d/d) suggest that the fetus signals its mother when it is ready to be born through fetal lung production of surfactant components, surfactant protein A (SP-A) and platelet-activating factor (PAF). Notably, mice that are double knockout for Src-1/-2 die at birth of respiratory distress, due to decreased surfactant lipoprotein production. Intriguingly, we observed that wild-type (WT) mothers carrying Src-1/-2d/d fetuses manifested a ~38 h delay in parturition compared to WT mothers carrying WT fetuses. This was associated with decreased production of SP-A and PAF by the Src-1/-2d/d fetal lungs. Our findings suggested that these effects of Src-1/-2d/d were caused by impaired glucocorticoid receptor (GR) transcriptional activity in fetal lung cells. To identify other genes in fetal lung that were affected by Src-1/-2d/d, we conducted RNA-seq analysis of lungs from 18.5 days post-coitum Src-1/-2d/dvs. WT fetuses. We observed that one of the genes most highly downregulated in Src-1/-2d/d fetal lungs was 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1). 11β-HSD1 catalyzes the conversion of inactive cortisone or 11-dehydrocorticosterone into active cortisol or corticosterone, respectively, which are ligands for the glucocorticoid receptor (GR). We validated the RNA-seq results by RT-qPCR and immunoblotting and observed a striking reduction of 11β-HSD1 mRNA and protein in lungs of Src-1/2d/d fetuses, compared to WT. Others observed that glucocorticoids potently increased 11β-HSD1 expression in various cell types via activation of transcription factors C/EBPα and C/EBPβ, providing a potential positive feed-forward loop. Notably, we observed that C/EBPα and C/EBPβ mRNA and protein were markedly reduced in Src-1/-2d/d fetal lungs, compared to WT. Deletion of the Cebpa gene in respiratory epithelium of fetal mice caused respiratory failure at birth due to surfactant lipid and protein deficiency. This was associated with increased expression of TGF-β2, which inhibits fetal lung maturation. Notably, we observed that expression of TGF-β2 and TGF-β3 were increased in Src-1/-2d/d fetal lungs. Thus, impaired lung development, surfactant synthesis and delayed parturition in Src-1/-2d/d fetuses are likely caused by decreased 11β-HSD1 and GR signaling, resulting in decreased C/EBPα/β expression and increased TGF-β signaling.

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<![CDATA[MON-010 Effects of Delta-9-Tetrahydrocannabinol (THC) on Oocyte Competence and Early Embryonic Development]]> https://www.researchpad.co/article/Naaea8869-ffd5-4330-a962-bc3e2e8a819b <![CDATA[MON-LB001 Ovulation Induction Results in Altered Growth and Metabolic Dysfunction in Mice Offspring]]> https://www.researchpad.co/article/Na386edfc-665e-40e7-802f-c8d32575ffd2 <![CDATA[MON-015 Pregnancy Adapts Circadian Rhythms in the Reproductive Axis: Impact on Labor Regulating Drug Efficacy]]> https://www.researchpad.co/article/Nd74946e6-a6cf-4403-9680-a89f074c0db7 <![CDATA[MON-019 Maternal Behaviour in Mice Is Modified by a High Fat Diet in Pregnancy]]> https://www.researchpad.co/article/N546e7552-dc1e-4775-ba01-cc53c1ca03d3 <![CDATA[MON-LB003 Clinical Case Series of Augmented Fertility in Females After Administration of an Amino Acid Blend That Enhances Release of Human Growth Hormone]]> https://www.researchpad.co/article/N6ce63383-e5e3-43e2-9b0d-6cfc545d4614 <![CDATA[MON-012 The Direct Effect of Kisspeptin on Human Ovarian Granulosa Cells to Regulate Steroidogenesis]]> https://www.researchpad.co/article/Nd5395ea1-7148-438c-8432-8f607dfc97cb <![CDATA[MON-LB5 A Longitudinal Cohort Study of Serum Decorin Levels in Normal and Preeclamptic Pregnant Women]]> https://www.researchpad.co/article/Na479359d-a4c9-401e-a081-9f4712468119 <![CDATA[MON-006 Progesterone Receptor Expression in Endometrial Biopsies After 12 Weeks of Exposure to A 4-µg E2 Softgel Vaginal Insert or Placebo]]> https://www.researchpad.co/article/N0b5b1599-a3d6-456f-951d-25f4d5556208 <![CDATA[MON-011 NALCN Expression Is Regulated by Progesterone and Estrogen in Human Myometrial Smooth Muscle Cells]]> https://www.researchpad.co/article/N59d8ea9e-8f14-44a7-8d7f-f2ab62953752