Ovarian Secretion Research Articles

Behavioral characterization of co-exposure to cannabinoids and hormonal contraceptives in female rats

Hormonal contraceptives are among the most widely used drugs by young healthy women to block ovulation and avoid pregnancy. They reduce the ovarian secretion of estradiol and progesterone, hormones that also modulate neuronal plasticity, cognitive functions, emotions and mood. Cannabis is the most commonly used illicit drug worldwide and its use is increasing among young women, many of which regularly take the “pill”. Despite evidence of a bidirectional interaction between the endocannabinoid system and gonadal hormones, only very few studies have examined the consequences of cannabis consumption in young females under hormonal contraceptives treatment. To fill this gap, this study evaluated the behavioral effects of co-exposure to chronic 1) hormonal contraceptives, i.e., ethinyl estradiol (EE) plus levonorgestrel (LNG), one of the synthetic estrogen-progestin combinations of hormonal contraceptives, and 2) cannabinoid receptor agonist, i.e., WIN 55,212–2 (WIN), on motor activity, emotional state and cognitive functions in young adult female rats (8–11/experimental group). Hormonal and cannabinoid treatment started at post-natal day (PND) 52 and 56, respectively, while behavioral testing occurred between PND 84–95. The results show that chronic EE-LNG treatment, at doses (0.020 and 0.060 mg/rat, respectively) known to drastically reduce plasma progesterone levels, and the contextual exposure to WIN, at a dose (12.5 μg/kg/infusion) known to be rewarding in the rat, alters the hormonal milieu but does not cause further changes in locomotor activity compared to EE-LNG or WIN alone, and does not modify anxiety-like state (as measured by the elevated plus maze and the marble burying tests) and cognitive abilities (as measured by the novel object recognition and the prepulse inhibition tests) in young adult female rats. Although exposure to EE-LNG and WIN tends to increase the duration of immobility and to reduce the time spent swimming in the forced swimming test, there was not a significant additive effect suggestive of a depressive-like state. These findings allow deepening the current knowledge on the interaction between cannabinoid agonists and hormonal contraceptives and suggest that low, rewarding doses of cannabinoids do not significantly alter the motor and cognitive skills and do not induce anxiety or depressive-like states in females that use hormonal contraceptives.

Prostaglandin E2 receptor Ptger4b regulates female-specific peptidergic neurons and female sexual receptivity in medaka

In vertebrates, female receptivity to male courtship is highly dependent on ovarian secretion of estrogens and prostaglandins. We recently identified female-specific neurons in the medaka (Oryzias latipes) preoptic area that express Npba, a neuropeptide mediating female sexual receptivity, in response to ovarian estrogens. Here we show by transcriptomic analysis that these neurons express a multitude of neuropeptides, in addition to Npba, in an ovarian-dependent manner, and we thus termed them female-specific, sex steroid-responsive peptidergic (FeSP) neurons. Our results further revealed that FeSP neurons express a prostaglandin E2 receptor gene, ptger4b, in an ovarian estrogen-dependent manner. Behavioral and physiological examination of ptger4b-deficient female medaka found that they exhibit increased sexual receptivity while retaining normal ovarian function and that their FeSP neurons have reduced firing activity and impaired neuropeptide release. Collectively, this work provides evidence that prostaglandin E2/Ptger4b signaling mediates the estrogenic regulation of FeSP neuron activity and female sexual receptivity.

P-636 Use of Desogestrel as an alternative to GnRH antagonists to inhibit the LH surge: a prospective randomized controlled observational study

Abstract Study question To describe whether desogestrel is as effective as GnRH antagonists in inhibiting the LH surge during controlled ovarian stimulation. Summary answer We conclude that although we can obtain fewer oocytes,desogestrel is effective as GnRH antagonists to inhibit the LH surge during controlled ovarian stimulation. What is known already It is known that ovarian secretion of progesterone has the ability to modulate the secretory pattern of LH of a natural menstrual cycle. Because exposure to high levels of progesterone can generate a phase shift between embryonic development and endometrial receptivity, this was not an option when performing HOC in conventional IVF-ICSI. New technologies and constant advances in vitrification techniques for both gametes and embryos have allowed us to think of different strategies when performing a HOC. This is why a new concept, progestagen priming, was introduced as a safe and comparable alternative to conventional ovarian stimulation with GnRH antagonists. Study design, size, duration We conducted a prospective, observational, randomized, controlled study at our institution IFER affiliated with the University of Buenos Aires, from August 2020 to December 2021. A total of 74 patients were included. Our main objective was to evaluate the efficacy of desogestrel as an LH surge inhibitor in patients undergoing egg donation, medical and social fertility preservation, and controlled ovarian stimulation without fresh embryo transfer. Participants/materials, setting, methods Patients under 39 years of age who underwent controlled ovarian stimulation for egg donation cycles, fertility preservation for medical and social reasons, and IVF-ICSI cycles without fresh transfer (risk of OH,PGS) The patients were separated into two groups. Both groups received conventional HOC.In the DESOGESTREL group received 75mg/day from the start of stimulation to the day of CGH, in the control group, received antagonists 0.25mg/day with follicles 14 mm until the day of CGH.ther parameters Main results and the role of chance We divided the Desogestrel Goup : > 35-35 y (GI) 32 p, 36-39 y (GII) 42p, Control Group : 35-35 y (GIII) 29 p,36-39 y (GIV) 45p. total dose of gonadotrophins used: GI: 1600 UI ± 300 UI, GIII: 1800 UI ± 400 UI ( NS) GII:1900 UI ± 400 UI, G IV : 2200 UI ± 400 UI (NS).Length of HOC: G I: 12 d ± 2 , G III: 13 d ± 2, G II: 14 d ± 2 , G IV: 15 d ± 2 ( NS). MII retrieved: GI: 10 ±3, GIII: 12± 3 (NS), GII : 7± 3, G IV: 7± 2 ( NS).The number of oocytes obtained may be a little lower than those obtained in the control group, but not statistically significant, the same as in the number of doses of gonadotrophins used, nor in the number of days of stimulation. Limitations, reasons for caution Size of study group Wider implications of the findings Although the study group is small, we have shown that the use of desogestrel is similar shown with the use of other gestagens during COH. We believe that desogestrel is a patient-friendly alternative due to its route of administration, price, and longer half-life, compared to antagonist analogs. Trial registration number NA

O-163 Hyperandrogenaemia in early adulthood is an independent risk factor for abnormal glucose metabolism in later life

Abstract Study question What is the role of androgen excess as a contributing factor to insulin resistance and abnormal glucose metabolism (AGM) in women? Summary answer There was a positive association between early adulthood hyperandrogenaemia with AGM. Serum SHBG levels could help identifying women at risk for disordered glucose metabolism. What is known already It is commonly recognised that insulin resistance induces compensatory hyperinsulinaemia which promotes ovarian androgen secretion. Studies in rodents have also suggested that testosterone causes prolonged activation of androgen receptor in pancreatic islet β-cells, inducing insulin hypersecretion and eventually secondary β-cell failure, thus predisposing to type 2 diabetes (T2D). However, the exact physiology behind the association between androgens, insulin resistance and T2D in women is not well understood. Many previously published studies are limited by cross-sectional study design, unrepresentative clinic populations, as well as variying steroid hormone measurement methods and definitions of androgen excess. Study design, size, duration A prospective longitudinal population-based cohort (n = 5,889) to investigate whether serum levels of testosterone (T, measured using LC-MS/MS) and free androgen index (FAI) at ages 31 and 46 associated with AGM at age 46 years. After exclusion of pregnant women, users of hormonal intrauterine device, contraceptive pills, hormone therapy, minipills and statins, there were 4,421 women at age 31 and 4,457 women at age 46. At age 46 a two-hour OGTT was performed in 2,780 women. Participants/materials, setting, methods Serum fasting glucose and insulin, insulin resistance (HOMA–IR) and pancreatic β-cell function (HOMA–B) assessments were performed at ages 31 and 46. Elevated T levels (age 31: >2.3nmol/l; age 46: >1.7nmol/l) were defined according to the 97.5% percentile. T2D diagnoses were gathered from postal questionnaire at age 46, and verified and completed from the hospital discharge and national medication reimbursement registers. Impaired fasting glucose, impaired glucose tolerance or T2D were categorised as AGM. Main results and the role of chance At age 31, hyperandrogenic (HA) women displayed increased insulin resistance estimated by HOMA-IR (1.35±0.96 vs. 1.03±0.44, P = 0.05), increased insulin secretion estimated by HOMA-B (115.05±34.67 vs. 99.25±25.47, P = 0.006), and higher fasting insulin level (10.48±7.54 mU/l vs. 7.93±3.42 mU/l, P = 0.034) compared with normoandrogenic (NA) women, after BMI adjustment. At age 46, HA women had comparable HOMA-B levels (98.04±60.03 vs. 96.27±65.89, P = 0.93) but their fasting glucose (5.57±1.06 mmol/l vs. 5.37±0.77 mmol/, P = 0.07) and glycated haemoglobin levels (37.47±7.83 mmol/mol vs. 36.18±4.99 mmol/mol, P = 0.07) tended to be higher. Women in the highest T quartile (Q4 odds ratio [OR]=1.77, 95%CI: [1.14–2.76]) and in the two highest FAI quartiles at age 31 (Q4: OR = 3.61 [2.16–6.03] and Q3: OR = 2.11 [1.24–3.59]) had increased risk for AGM at age 46, independently of BMI, when compared with women in the lowest quartile. Similarly, women in the two highest FAI quartiles at age 46 had increased risk for AGM (Q4: OR = 2.91 [1.82–4.64]) when compared with women in the lowest quartile, after BMI adjustment. The three highest sex hormone-binding globulin (SHBG) quartiles inversely associated with AGM, both at ages 31 and 46, independently of BMI (at age 31: Q4: OR = 0.38 [0.24–0.62], at age 46: Q4: OR = 0.27 [0.17–0.44]). Limitations, reasons for caution We used only serum T as a marker of HA, even though other androgens, such as androstenedione and adrenal androgens have a place in the evaluation of androgenicity in women. Further studies of other large populations are needed to confirm our results. Wider implications of the findings This is the first longitudinal, general population based study to confirm a positive association between early adulthood hyperandrogenaemia with AGM in middle adulthood independently of confounding factors. Our results further suggest that SHBG levels could help to identify women at risk for AGM. Trial registration number NA

The Effects of Elaeagnus angustifolia L. on the Thyroid-Stimulating Hormone, Dehydroepiandrosterone-Sulfate, Prolactin and Cortisol Levels in Post-Menopausal Women: A Double-Blind, Randomized, and Placebo-Controlled Study.

Menopause is the last menstrual period associated with a decline in ovarian steroid secretion and follicular loss. Hormone profile changes during menopause include a decrease in the production of estrogen, dehydroepiandrosterone (DHEA), and prolactin (PRL), and an increase in thyroid-stimulating hormone (TSH) and cortisol. Herbal medicines are considered as alternatives to hormone therapy. The studies on postmenopausal women have shown that Elaeagnus angustifolia L. (called “Senjed” in Persian) has some efficacy in improving sex hormone and lipid profiles, joint pain, and cardiovascular function, as the decrease in luteinizing hormone, low-density lipoprotein, and heart rate was significant. The aim of the present study was to evaluate the effects of E. angustifolia on TSH, DHEA-S, PRL, and cortisol levels and their ratios in postmenopausal women. It is assumed that the eventual effects of hormones on the brain and other tissues are determined by the balance between interdependent hormones. In the present randomized double-blinded placebo-controlled trial (https://en.irct.ir/search/result?query=IRCT20170227032795N4), fifty-eight postmenopausal women were randomly assigned to one of two medicinal herb (15 g of the whole E. angustifolia fruit powder) and placebo (7.5 g isomalt + 7.5 g cornstarch) groups. After 10 weeks of the treatment, the serum levels of TSH, DHEA-S, PRL, cortisol hormones, and their ratios were measured. The increase in the TSH, and cortisol levels, and cortisol/DHEA-S ratio and the decrease in prolactin and DHEA-S and the PRL/TSH, PRL/cortisol, and DHEA-S/TSH ratios after E. angustifolia consumption were significant only based on within-group but not on the between-group analysis. Based on between-group analyses, the changes in the hormone profile were not significant in the placebo group. According to Iranian tradition and folklore, E. angustifolia fruit is a symbol of female fertility. Therefore, its consumption is highly recommended to maintain health in the elderly, especially women. However, the observed outcomes about the effect of E. angustifolia on menopause were not completely in line with the Iranian folklore. E. angustifolia consumption did not significantly affect the hormone profile and ratios at the end of the ten-week trial, possibly due to the small sample size, short time, and the fact that our participants were postmenopausal women.

Maturation of ovarian follicles in the prepubertalgilt

Summary. The processes of follicle development and puberty are closely related, and both are associated with maturation of the hypothalamic—pituitary—ovarian axis. Prenatal development of the ovary is independent of gonadotrophic stimulation. Beyond 60 days of age (postnatally), tertiary follicles develop and gonadotrophins begin to influence ovarian follicular development. Negative feedback regulation of pituitary gonadotrophins by ovarian secretions develops between 60 and 100 days of age. In the prepubertal gilt, no consistent changes in peripheral FSH, oestrogen or progesterone concentrations have been identified which are associated with recruitment of the first set or preovulatory follicles. Whether LH secretion increases before this recruitment remains equivocal. Few details are available on how gonadotrophic hormones stimulate ovarian function in the prepubertal gilt. On the basis of a follicular maturation model that has been described for the rat, the actions of FSH, LH and oestrogens on follicular cell receptors and the regulation of aromatase activity seem paramount. Aromatization of androgens to oestrogens has been proposed as a central regulator for follicular maturation.

Human embryonic stem cell-derived mesenchymal stem cells improved premature ovarian failure.

BACKGROUNDPremature ovarian failure (POF) affects many adult women less than 40 years of age and leads to infertility. According to previous reports, various tissue-specific stem cells can restore ovarian function and folliculogenesis in mice with chemotherapy-induced POF. Human embryonic stem cells (ES) provide an alternative source for mesenchymal stem cells (MSCs) because of their similarities in phenotype and immunomodulatory and anti-inflammatory characteristics. Embryonic stem cell-derived mesenchymal stem cells (ES-MSCs) are attractive candidates for regenerative medicine because of their high proliferation and lack of barriers for harvesting tissue-specific MSCs. However, possible therapeutic effects and underlying mechanisms of transplanted ES-MSCs on cyclophosphamide and busulfan-induced mouse ovarian damage have not been evaluated.AIMTo evaluate ES-MSCs vs bone marrow-derived mesenchymal stem cells (BM-MSCs) in restoring ovarian function in a mouse model of chemotherapy-induced premature ovarian failure.METHODSFemale mice received intraperitoneal injections of different doses of cyclophosphamide and busulfan to induce POF. Either human ES-MSCs or BM-MSCs were transplanted into these mice. Ten days after the mice were injected with cyclophosphamide and busulfan and 4 wk after transplantation of the ES-MSCs and/or BM-MSCs, we evaluated body weight, estrous cyclicity, follicle-stimulating hormone and estradiol hormone concentrations and follicle count were used to evaluate the POF model and cell transplantation. Moreover, terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling, real-time PCR, Western blot analysis and immunohistochemistry and mating was used to evaluate cell transplantation. Enzyme-linked immunosorbent assay was used to analyze vascular endothelial growth factor, insulin-like growth factor 2 and hepatocyte growth factor levels in ES-MSC condition medium in order to investigate the mechanisms that underlie their function.RESULTSThe human ES-MSCs significantly restored hormone secretion, survival rate and reproductive function in POF mice, which was similar to the results obtained with BM-MSCs. Gene expression analysis and the terminal deoxynucleotidyl transferase mediated 2-deoxyuridine 5-triphosphate nick end labeling assay results indicated that the ES-MSCs and/or BM-MSCs reduced apoptosis in the follicles. Notably, the transplanted mice generated new offspring. The results of different analyses showed increases in antiapoptotic and trophic proteins and genes.CONCLUSIONThese results suggested that transplantation of human ES-MSCs were similar to BM-MSCs in that they could restore the structure of the injured ovarian tissue and its function in chemotherapy-induced damaged POF mice and rescue fertility. The possible mechanisms of human ES-MSC were related to promotion of follicular development, ovarian secretion, fertility via a paracrine effect and ovarian cell survival.

Outcome of laparoscopic uterine artery occlusion for uterine fibroids on ovarian function and complications in patients with uterine fibroid

Objective: The aim of this study is to investigate the outcome of laparoscopic uterine artery occlusion (LUAO) on ovarian function in the treatment of uterine fibroid and its influence on complications.Materials and Methods: A total of 61 patients with uterine fibroid accept LUAO from January 2013 to December 2015 were selected as the research objects. The changes of ovarian hormone secretion volume, internal blood supply of uterine fibroid, uterine volume, fibroid volume, and the occurrence of complications were observed before and 3, 6, 12, and 24 months after surgery. These results were compared with the outcomes of 63 patients with uterine fibroid accept myomectomy.Results: Compared with myomectomy treatment, the length of intraoperative blood loss, operation time, and hospitalization time of patients in the LUAO group were shorter (P < 0.05). Menstruation characteristics, uterine volume, and uterine fibroid volume postoperation were better than the prior ones in the LUAO group (P < 0.05). The ovarian secretion of luteinizing hormone, estradiol, and follicle-stimulating hormone levels in patients in the following 24 months after surgery were not statistically different in two groups (P > 0.05), and the pelvic floor function had similar results.Conclusion: Uterine fibroid treated by LUAO is effective, it can decrease the internal blood supply of uterine fibroid, narrow the volume of uterine fibroid, and little impaction on ovarian function. Hence, this kind of treatment is worthy of promotion.

124 Ovarian follicular development and steroid secretion during oestrous cycle of Lohi sheep

Pakistan has 30.9 million heads of sheep; however, little information is available on their reproductive aspects. The objective of this study was to document ovarian physiology and endocrinology of Lohi ewes during the oestrous cycle. Nine Lohi ewes, synchronized by administering single prostaglandin F2α (PGF2a; Cyclomate, Star Laboratories), were monitored for ovarian follicular dynamics using transrectal ultrasonography (7.5MHz, HS-1500, Honda) for two consecutive oestrous cycles during the breeding season (September to November 2018). Changes in plasma progesterone and oestradiol-17β concentrations of ewes (n=9) were also determined during the oestrous cycle using radioimmunoassay. The interovulatory interval of Lohi ewes averaged 17.0±0.1 days, and the duration of follicular and luteal phases was 4.6±0.2 and 11.3±0.2 days, respectively. Follicles emerged in either 3- or 4-wave patterns, but the frequency of the 3-wave pattern was higher than that of the 4-wave (87 vs. 13%, respectively; P=0.05). Following ovulation (Day 0), follicles (=3mm) in 3-wave cycles (n=14) emerged on Days 0.7, 5.2, and 10.5, whereas in 4-wave cycles (n=2) follicles emerged on Days 0.1, 4, 8.5, and 11.5. The maximum diameter of preovulatory follicles and corpora lutea (CL) were 5.4±0.3 and 10.4±0.3mm, respectively. Regardless of the wave pattern, single ovulation occurred in each cycle. The CL was first detectable on Day 4±0.1, it reached maximum diameter on Day 9±0.1, and luteolysis began on Day 12.2±0.2 of the cycle. The peak plasma oestradiol-17β concentration (42.5±2.6 pgmL−1) was observed 48h before ovulation and correlated with the diameter of the preovulatory follicle during the follicular phase (r=0.84; P&amp;lt;0.05). The peak plasma progesterone concentration (11.8±1.7ngmL−1) was observed on Day 9±0.1 and coincided with the diameter of CL throughout the oestrous cycle (r=0.93; P&amp;lt;0.05). In conclusion, the majority of oestrous cycles in Lohi ewes had a 3-wave pattern and were mono-ovulatory in nature.

Effect of Body Mass Index on Abnormal Ovarian Secretion Hormones among Iraqi Women with Polycystic Ovarian Syndrome (PCOS)

Polycystic ovarian syndrome (PCOS) is the most common and complex endocrine disorder affecting women in the reproductive age. The etiology of this syndrome is not completely known, so there is a developing proof that supports genetic basis, PCOS has a strong familial preference. This study was carried out to investigate the effect of body mass index (BMI) on ovarian hormones in women with PCOS and healthy women. Eighty-three women aged (17-40) years were divided into two groups for testing (BMI less than 25 and more than 25). Hormonal study of Luteinizing hormone (LH), Androgen, Estradiol (E2) was done for each patient, the results of these hormones in patients compared with controls in both BMI groups with E2/T ratio showed a significant increase in patients women compared to controls in (p<0.05), While the results of Follicle stimulating hormone (FSH) and Total Testosterone (TT) showed an increase with not statistically significant. it has been concluded that the increase in BMI doesn’t show to have an opposite effect on FSH, Androgen, E2, and TT levels but the result of LH shows a highly significant increase in PCOS groups compared to controls when BMI˃25.

Age-Specific Peripheral Anti-Mullerian Hormone (AMH) Concentration: A Candidate Endocrine Marker for Fertility Assessment in Cattle

Anti- Mullerian hormone (AMH) emerges as the most reliable endocrine marker in assessing the fertility potential over the ages. The age-specific reference range for peripheral AMH concentrations in cattle is lacking. The present study thus aimed (i) to address the question whether ovarian secretion of AMH would be affected by gonadotrophic status after gonadotrophin releasing hormone (GnRH) challenge in cattle and (ii) to establish age-specific plasma AMH concentrations in Holstein Friesian crossbred cattle (n= 151) using an enzyme immune-assay technique. Data on hormonal concentrations over time in GnRH-treated animals were analyzed by nonparametric one-way repeated measure ANOVA. GnRH challenge could not bring any change (P>0.05) in plasma AMH concentrations, while plasma FSH and LH concentrations changed significantly (P

Inhibition of TMEM16A impedes embryo implantation and decidualization in mice.

Recent studies revealed that TMEM16A is involved in several reproductive processes, including ovarian estrogen secretion and ovulation, sperm motility and acrosome reaction, fertilization and myometrium contraction. However, little is known about the expression and function of TMEM16A in embryo implantation and decidualization. In this study, we focused on the expression and regulation of TMEM16A in mouse uterus during early pregnancy. We found that TMEM16A is upregulated in uterine endometrium in response to embryo implantation and decidualization. Progesterone treatment could induce TMEM16A expression in endometrial stromal cells through progesterone receptor/c-Myc pathway, which is blocked by progesterone receptor antagonist or the inhibitor of c-Myc signaling pathway. Inhibition of TMEM16A by small molecule inhibitor (T16Ainh-A01) resulted in impaired embryo implantation and decidualization in mice. Treatment with either specific siRNA of Tmem16a or T16Ainh-A01 inhibited the decidualization and proliferation of mouse endometrial stromal cells. In conclusion, our results revealed that TMEM16A is involved in embryo implantation and decidualization in mice, compromised function of TMEM16A may lead to impaired embryo implantation and decidualization.

Age-specific peripheral anti-müllerian hormone concentrations in goats (capra hircus)

Anti- Mullerian hormone (AMH) appears to be the best biochemical-endocrine marker in assessing the age-related decline of the ovarian follicular reserve. There is inadequate information on age-related changes in peripheral AMH concentrations in goats (Capra hircus). The present study thus aimed (i) to investigate the responsiveness of the ovary to gonadotrophin releasing hormone (GnRH) challenge to release plasma AMH into circulation in view of addressing the question whether ovarian secretion of AMH would be affected by gonadotrophic status in goats and (ii) to determine plasma AMH concentrations at different ages in goats (n= 82) using enzyme immune-assay technique. Data on hormonal concentrations in GnRH-treated animals as well as in different ages of animals were analyzed by nonparametric one-way repeated measure ANOVA and one-way ANOVA, respectively. There was no change (P greater than 0.05) of plasma AMH concentrations after GnRH challenge in experimental goats. Plasma AMH concentrations changed significantly (P less than 0.05) between the mean rank of the related groups over the time (age) in goats. Plasma AMH concentration at 3 months of age was 0.36 ± 0.04 ng/ ml and thereafter it started increasing and reached³ 2 ng/ ml between 3 and 4 years of age and then showed a progressive decline from 5 years of age and reached at 0.30 ± 0.07 ng/ ml at 10 years of age. A cubic model was found to be the best fitted model that delineated the change of plasma AMH level with age. Hence, the present study indicated that peripheral AMH concentration could be a useful management tool for the selection of goats in breeding programmes.

Calf presence and estrous response, ovarian follicular activity and the pattern of luteinizing hormone in postpartum Bos indicus cows.

The main objective of the present experiment was to assess the effect of temporary weaning on the onset of estrus, ovarian follicular activity and secretion of luteinizing hormone in Bos indicus cows. Forty six mature cows were divided into three groups 1) calves were weaned for 72 h allowing auditory, olfactory and visual contact with their dams (VISUAL, n = 17), 2) calves without contact with their dams for 72 h (NC, n = 17) and 3) calves not weaned and in constant contact with their dams (CTRL, n = 12). Estrus was synchronized in all cows using CIDR for 9 days plus 2 mg of estradiol benzoate given at CIDR insertion. The VISUAL group had a greater (P < 0.05) proportion of cows in estrus (76.5%) compared to the CTRL group (16.7%), but no differences were found when compared to the NC group (58.8%). The VISUAL group had a greater proportion of animal that ovulated (76.5%) compared to CTRL (33.3%) and NC groups (64.7%; P = 0.059). Duration of estrus was shorter (P = 0.04) in the VISUAL (8.4 ± 4.4 hours) than in the NC (12.9 ± 13.4 hours) however, CTRL treatment (11 ± 1.4 hours) was not different from either of these two groups. LH concentration after implant removal was similar among treatments and started to increase at 36 h post CIDR removal. Only in the CTRL group was there an obvious increase by 54 h after implant removal. Follicular size increased in diameter from 36 h and were evident in treatments and control groups by 60 h (P < 0.05). The VISUAL treatment increased the number of cows ovulating and shortened the length of estrus. VISUAL and NC groups showed a similar response in follicular growth and pattern of circulating LH because of treatment.

Urinary metabolomic study of the antagonistic effect of P. ginseng in rats with estrogen decline using ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry.

Estrogens are biologically active steroid hormones mainly released from the ovary by ovarian secretion of estrogen into the circulating blood to regulate or function at the distal target. Estrogens play an important role in the central nervous system, cardiovascular system and immune system, especially for post-menopausal women. Panax ginseng Mayer has been reported to relieve women's menopausal symptoms and affect estrogen activities. However, the mechanism of its estrogen regulation has not yet been clearly investigated. In this work, ovariectomized rats were administered a P. ginseng decoction intragastrically for 8 weeks. Urine samples were analyzed by ultra performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS) to identify metabolites. The estrous cycle, body weight, uterine weight index and serum hormone levels were measured. The results showed that P. ginseng significantly prolonged the estrus stage, decreased the body weight and serum luteinizing hormone (LH) levels and increased the uterine weight index and serum estradiol (E2) levels of ovariectomized rats. A total of twelve potential biomarkers for which levels changed markedly upon treatment have been identified based on metabolomics. A systematic network analysis of their corresponding pathways indicates that the antagonistic effect of P. ginseng on ovariectomized rats occurs mainly through regulating steroid hormone metabolism, fatty acid biosynthesis, the citric acid cycle and tryptophan metabolism. In conclusion, this study validated the antagonistic effect of P. ginseng in rats with estrogen decline and explored the metabolic and biochemical mechanisms involved.

Ovarian steroid hormone secretion activity examined after supplementation of green tea extract.

This study aimed at examining the secretion activity of steroid hormones progesterone and 17beta-estradiol by porcine ovarian granulosa cells after addition of green tea extract. Granulosa cells were incubated with green tea extract (at doses of 0.01, 0.1, 1, 10 and 100 microg.ml(-1). Another set of cells were incubated with green tea extract at the above doses along with additional supplementation of follicle stimulating hormone (FSH) at 10 microg.ml(-1). Release of hormones by granulosa cells was assessed by EIA after 24 h exposure. Secretion of steroid hormones was not affected either by green tea extract alone or after FSH supplementation with green tea extract. Results indicate that ovarian steroidogenesis is not affected by green tea under conditions used in the experiment.

Lack of Ovarian Secretions Reverts the Anabolic Action of Olanzapine in Female Rats.

BackgroundOlanzapine is an orexigenic antipsychotic drug associated with serious metabolic adverse effects in humans. Development of valid rodent models for antipsychotic-induced metabolic adverse effects is hampered by the fact that such effects occur in females only. Estradiol is a predominant female hormone that regulates energy balance. We hypothesized that the female-specific hyperphagia and weight gain induced by olanzapine in the rat are dependent on the presence of estrogens.MethodsFemale sham-operated or ovariectomized rats were treated with a single injection of olanzapine depot formulation. Food intake, body weight, plasma lipids, lipogenic gene expression, energy expenditure, and thermogenic markers including brown adipose tissue uncoupling protein 1 protein levels were measured. Olanzapine was also administered to ovariectomized rats receiving estradiol replacement via the subcutaneous (peripheral) or intracerebroventricular route.ResultsOrexigenic effects of olanzapine were lost in ovariectomized female rats. Ovariectomized rats treated with olanzapine had less pronounced weight gain than expected from their food intake. Accordingly, brown adipose tissue temperature and protein levels of uncoupling protein 1 were elevated. Replacement in ovariectomized rats with either peripherally or centrally administered estradiol reduced food intake and body weight. Cotreatment with olanzapine blocked the anorexigenic effect of peripheral, but not central estradiol.ConclusionsOur results indicate that the ovarian hormone estradiol plays an important role in olanzapine-induced hyperphagia in female rats and pinpoint the complex effects of olanzapine on the balance between energy intake and thermogenesis.

Mechanism of physical stress-induced inhibition of ovarian estradiol secretion in anesthetized rats.

This study examined the site of main integration center in the physical stress-induced inhibition of ovarian estradiol secretion because of ovarian sympathetic nerve (superior ovarian nerve: SON) activation in anesthetized rats. In central nervous system-intact rats, electrical stimulation of the tibial afferent nerve at 10V increased the efferent activity of the SON by 39±13% and reduced the ovarian secretion of estradiol by 34±7%. These responses were observed in decerebrate rats but were abolished in spinal rats. Thus, the main integration center for this ovarian hormonal response is located in the brain stem.

Metabolic status and ghrelin regulate plasma levels and release of ovarian hormones in layer chicks.

The aim of the present study was to examine the role of nutritional status, the metabolic hormone ghrelin and their interrelationships in the control of chicken hormones involved in the regulation of reproduction. For this purpose, we identified the effect of food deprivation, administration of ghrelin 1-18 and their combination on plasma levels of testosterone (T), estradiol (E), arginine-vasotocin (AVT) and growth hormone (GH) as well as the release of these hormones by isolated and cultured ovarian fragments. It was observed that food deprivation reduces plasma T and E and increases plasma AVT and GH levels. Food restriction also reduced the amount of E produced by isolated ovaries, but it did not affect the ovarian secretion of T and AVT. No ovarian GH secretion was detected. Ghrelin administered to ad libitum fed chickens did not affect plasma T and E levels, but it did increase plasma GH and AVT concentrations. Moreover, it partially prevented the effect of food deprivation on plasma E and AVT levels, but not on T or GH levels. Ghrelin administration to control birds promoted ovarian T, but not E or AVT release and reduced T and no other hormonal outputs in birds subjected to food restriction. Our results (1) confirmed the ovarian origin of the main plasma T and E and the extra-ovarian origin of the main blood AVT and GH; (2) showed that food deprivation-induced suppression of reproduction may be caused by suppression of T and E and the promotion of AVT and GH release; (3) suggest the involvement of ghrelin in control chicken E, AVT and GH output; and (4) indicates that ghrelin can either mimic or modify the effect of the intake of low calories on chicken plasma and ovarian hormones, i.e. it can mediate the effect of metabolic state on hormones involved in the control of reproduction.

Neonatal Androgen Exposure Causes Persistent Gut Microbiota Dysbiosis Related to Metabolic Disease in Adult Female Rats.

Alterations of gut microbiome have been proposed to play a role in metabolic disease, but the major determinants of microbiota composition remain ill defined. Nutritional and sex hormone challenges, especially during early development, have been shown to permanently alter adult female phenotype and contribute to metabolic disturbances. In this study, we implemented large-scale microbiome analyses to fecal samples from groups of female rats sequentially subjected to various obesogenic manipulations, including sex hormone perturbations by means of neonatal androgenization or adult ovariectomy (OVX), as a model of menopause, to establish whether these phenomena are related to changes in gut microbiota. Basic metabolic profiles concerning glucose/insulin homeostasis were also explored. The effects of the sex hormonal perturbations, either developmentally (androgenization) or in adulthood (OVX), clearly outshone the impact of nutritional interventions, especially concerning the gut microbiota profile. Notably, we observed a lower diversity in the androgenized group, with the highest Firmicutes to Bacteroidetes ratio, supporting the occurrence of durable alterations in gut microbiota composition, even in adulthood. Moreover, the elimination of adult ovarian secretions by OVX affected the richness of gut microbiota. Our data are the first to document the durable impact of sex steroid manipulations, and particularly early androgenization, on gut microbiota composition. Such dysbiosis is likely to contribute to the metabolic perturbations of conditions of obesity linked to gonadal dysfunction in the female.