Endometrial Estrogen Receptor Research Articles

Bushen Zhuyun Decoction Improves Endometrial Receptivity by Inhibiting NF-κB/NLRP3 Signaling Pathway.

Bushen Zhuyun Decoction (BSZY), a traditional Chinese herbal prescription has shown promising effects on gynecological infertility, but the mechanism for endometrial receptivity is still unclear. This study aimed to investigate the regulatory effects of BSZY on endometrial receptivity, which plays a key role in colonization of embryo, and its regulatory mechanisms associated with NF- κB/NLRP3 pathway. SD rats at reproductive age with affected endometrial receptivity was established using mifepristone (RU486), and the regulatory effects of BSZY on endometrial receptivity were evaluated by H&E staining, and changes in sex hormones by ELISA and Western blot. Moreover, human endometrial RL95-2 cells were treated with H2O2, and inflammatory cytokines in rats and RL95-2 cells were analyzed by ELISA. The activation of NF-κB/NLRP3 signaling pathway in RL95-2 cells were characterized using immunofluorescence and Western blot. Mitochondrial morphology and function in RL95-2 cells were observed by transmission electron microscope and cell mitochondrial stress test. BSZY increased uterine endometrial thickness and attenuate histopathological changes induced by RU486. BSZY can regulate endometrial estrogen receptor and progesterone receptor, and the levels of sex hormones and inflammatory cytokines in pregnant rats. BSZY-containing serum also showed strong anti-inflammatory and cytoprotective effects in vitro. In addition, BSZY-containing serum inhibited the activation of NF-κB/NLRP3 signaling pathway, and improve mitochondrial morphology and function in RL95-2 cells. BSZY can improve endometrial receptivity, potentially by improving mitochondrial morphology and function to inhibit the activation of NF-κB/NLRP3 signaling pathway in endometrial cells, thus regulate inflammation to improve endometrial receptivity.

Nandrolone treatment of adolescent female rats alters reproductive tissue and gonadal steroid profile

Anabolic androgenic steroids (AAS) are drugs that mimic the chemical structure of testosterone. The most commonly AAS used by young adults is nandrolone. In the USA, more than 20 % of AAS users started using steroids before the age of 20. This is alarming as most female users are unaware of the detrimental reproductive effects of AAS use such as amenorrhea, anovulation and clitoromegaly. An additional detrimental effect of AAS is their addictive liability. Previous studies indicate that animals self-administer AAS. Furthermore, AAS can cross-sensitize with other drugs of abuse such as cocaine. Our goal was to elucidate the effects of both AAS and cocaine in the reproductive system of female rats. Our hypothesis is that AAS will have a detrimental effect on the reproductive system of female rats. Adolescent female rats were divided into two large groups, one that received nandrolone decanoate (20mg/kg/sc) and another that received sesame oil (vehicle) for 10 successive days starting on day 28. Animals were further subdivided into groups that received saline or cocaine injections (0.01cc/10g) for a total of 4 groups: Oil-Saline, ND-Saline, Oil-Cocaine and ND-Cocaine. One cohort (Day 40) received cocaine or saline injections (0.01cc/10g) from days 40 to 44 and on days 52 and day 62. The other cohort (Day 65) received cocaine or saline injections from days 65 to 69 and on days 77 and 87. Our data show that administration of nandrolone during adolescence increased body weight of female rats. Ovarian weight was decreased, and ovarian tissue presented multiple cysts with fewer follicles. Nandrolone also disrupted uterine morphology. The uterine lumen was increased, the endometrial thickness reduced and thickness of myometrial tissue, as well as uterine weight, was increased. In addition, nandrolone reduced both endometrial estrogen and androgen receptors, an effect lost by day 88. In contrast, uterine tissue at day 63 showed an increase in progesterone receptor (PR) immunoreactivity, whereas PR immunoreactivity decreased in tissue obtained at Day 88 regardless of whether animals had received cocaine. Cocaine also increased PR receptors in uterine tissue at day 63 and 88. Animals treated with nandrolone had higher serum concentrations of testosterone and estradiol and a lower level of progesterone. These data show that nandrolone when administered in supraphysiologic doses during adolescence, has long lasting effects on the reproductive system of the female rat due to the depot effects and long half-life of this drug. These data warrant further research in this area to determine the long-term consequences of early nandrolone exposure on the female reproductive system, as well as fertility. Financial assistance was provided by the Offce of International Science and Engineering (OISE) of NSF through the Partnerships for Research and Education (PIRE) Program (OISE-#1545803). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Uterine ageing

Studies using animal models, have investigated the influence of increasing age on uterine factors that might lead to abnormal decidualization and reduced implantation and defective placentation. The decidual response to a standardized estrogen /progesterone stimulus was reduced in the older animals; whereas, in young rodents decidual response closely resembled the normal decidual response during implantation. Furthermore in rodents, there was a decrease in the expression of endometrial estrogen and progesterone receptor in older ones. Several microRNAs have been associated with the fibrosis process in mice causing age-related uterine dysfunction. Aging of the uteri lead to the downregulation of several genes associated with cell proliferation in mice, indicating impaired proliferation in the presence of senescent cells.

Ovine endometrial estrogen receptor expression is altered following PG-600 administration.

Dysregulation of the estrogen receptor 1 (ESR1) expression during the establishment of pregnancy could contribute to reduce fertility reported in ewes treated with PG-600. The objective of this study was to evaluate the effect of treatment with PG-600 on ESR1 expression in the ovine endometrium during early diestrus. Polypay ewes (n = 24) that had exhibited an oestrous cycle of normal duration (16-18 days) were treated with intravaginal progesterone-releasing device (CIDR) for 9 days. Cloprostenol was administrated two days before CIDR withdrawal. On the day of CIDR withdrawal (day 0), ewes received a 5mL intramuscular injection of PG-600 (400 IU equine chorionic gonadotropin and 200 IU human chorionic gonadotropin) or saline. Blood samples were collected before treatment and on the day of tissue collection to determine serum estradiol-17β and progesterone concentrations using radioimmunoassay. On days 4 and 7, six ewes from each treatment group were anaesthetised and a laparotomy was performed to obtain intercaruncular endometrial samples. Endometrial samples were collected ipsilateral to the ovary bearing the highest number of corpora lutea. An estradiol exchange assay was used to determine ESR1 concentration. Estradiol concentrations did not differ by time or treatment, but progesterone concentrations were significantly higher in the PG-600-treated group on day 7 despite a similar number of corpora lutea. Endometrial ESR1 concentration was significantly reduced on day 7 in the PG-600 group. In conclusion, although progesterone was higher than controls on day 7, ESR1 did not differ from controls suggesting that treatment with PG600 is unlikely to impair reproductive potential.

Endometrial receptivity in women of reproductive age with "thin" and "absolutely thin" endometrium

Aim. To evaluate the expression of steroid receptors (estrogen [ER] and progesterone [PR]) in the endometrium during the implantation window in females with a history of fertility disorders in "thin" and "absolutely thin" endometrium versus healthy females.
 Materials and methods. A prospective comparative study was conducted. The study group (n=42) included patients with "thin" endometrium (7 mm M-echo 5 mm at cycle days 1113 according to ultrasound); the comparison group (n=10) included females with "absolutely thin" (5 mm according to ultrasound in the pre-ovulatory days) endometrium (females in both groups had a history of infertility and miscarriage of unclear reasons in the anamnesis); the control group included 16 healthy fertile females. A Pipelle biopsy of the uterine mucosa was performed on day 68 after ovulation, and a peripheral blood sample was obtained to measure the concentration of sex steroids (estradiol [E2] and progesterone [P]). Endometrial samples were examined by histological and immunohistochemical methods (ER, PR expression).
 Results. All study participants had an ovulatory cycle of P16.1 nmol/L (day 68 after ovulation) and normal estrogen levels (E2, pmol/L). E2/P was similar in all cohorts (p0.05 for all measures). ER and PR expression in the endometrium similar to those in healthy females was detected in 20% of patients in the study and comparison groups (M-echo = 4.83.1 mm): 21% (9/42) and 20% (2/10), respectively. ER and PR expression in the endometrial glands and ER expression in the endometrial stroma were significantly different (p0.05) from healthy females in 79% (41/52) of patients with "thin" endometrium and 80% (8/10) of patients with "absolutely thin" endometrium. No differences in the ER or PR expression in the endometrium in females with hypoplastic endometrium were found (p0.05).
 Conclusion. The M-echo value does not accurately determine endometrial hormonal-receptor abnormalities: 20% of the study participants with hypoplastic endometrium had ER and PR expression comparable to those in healthy females. No differences were found in the expression of endometrial estrogen and progesterone receptors in females with "thin" and "absolutely thin" endometrium.

Local embryo-mediated changes in endometrial gene expression during embryo mobility in mares

Prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) are involved in equine embryo mobility throughout the uterus on Days 11–15 (ovulation = Day 0). On a day (Day 12) of maximal embryo mobility in pregnant mares (n = 13) and before luteolysis in nonbred mares (n = 10), gene expressions were compared between the uterine horns that did and did not contain the mobile embryo and between pregnant and nonbred mares. A cytobrush was used to collect an endometrial sample from the middle of each uterine horn. In nonbred mares, there was no difference for any of the considered gene expressions between the uterine horn ipsilateral and contralateral to the CL or for side (left vs right). For endometrial estrogen receptors, ESR1 was lower (P < 0.03) and ESR2 was greater (P < 0.04) for pregnant than nonbred mares. The mRNA abundance for PGE2 synthase (PTGES) was greater (P < 0.05) in the horn with (1.40 ± 0.10) than without (0.89 ± 0.10) the embryo and was greater (P < 0.05) in the horn with the embryo than in the combined horns of nonbred mares (1.06 ± 0.10). The hypothesis that the embryo locally upregulates PGE2 and PGF2α synthesis in the endometrium adjacent to the embryo in the pregnant group but not in the uterine horns of the nonbred group, was partially supported; only PGE2 synthase (PTGES) was locally upregulated in the endometrium adjacent to the mobile embryo.

Patterns of sex hormone receptor expression in stimulated endometrium from oocyte donors

In patients with high serum E2 embryo transfer is often postponed, as high E2 levels adversely affect embryo transfer outcome. We aimed to determine if stratified serum oestradiol (E2) and progesterone (P4) levels differentially affect endometrial histology and endometrial oestrogen and progesterone receptor protein levels. Endometrial biopsies were collected from oocyte donors. Samples were divided based on peak serum E2 levels into three groups: (i) low-E2 (n = 33) E2≤2999pg/mL; (ii) mid-E2 (n = 40) E2 3000–4999 pg/mL; and (iii) high-E2 (n = 15) E2≥5000 pg/mL. Oestrogen receptor alpha (ERα) and progesterone receptors A and B (PR) protein levels in endometrial stroma (S), glandular (GE) and luminal (LE) epithelia were assessed by immunohistochemistry. Samples in high-E2 group demonstrated strongest association with accelerated endometrial maturation (2 (1–2); 2 (1–3); and 3 (2.8–3) median days of advancement of endometrial maturation respectively in low, mid, high-E2 groups, p = 0.046). There were significant differences in ERα and PR immunoexpression in S, GE and LE among the groups (p < 0.05). Higher E2 levels were associated with decreased ERα expression (p < 0.017) in GE and LE, and increased PR expression in S and GE (p < 0.011 and p < 0.0001, respectively). Higher serum E2 levels were associated with impaired endometrial steroid hormone receptor expression, higher serum P4 and more advancement of endometrial maturation.

Estrogen and progesterone receptor expression and blood vessel density in abnormal uterine bleeding

Aim: The aim of present study was to analyse endometrial estrogen and progesterone receptor expression and blood vessel density in cases of abnormal uterine bleeding. Material and method: The present study was conducted in the department of Pathology at SMS Medical College, Jaipur among specimens received from 266 patients presenting with abnormal uterine bleeding in reproductive age group (18-45 years) on endometrial biopsies and hysterectomy specimens. The intensity and distribution of ER, PR was evaluated using a semi-quantitative method Allred score. Also density of blood vessels /10 HPF was evaluated. Results: Neoplastic cases were found among 9.4% (25) of the subjects whereas non-neoplastic lesions were present in 90.6% (241) of the subjects. Mean Allred scoring of estrogen and progesterone receptor in glandular component was highest among endometrial carcinoma. Mean Allred scoring of estrogen receptor in stromal component was highest among Hyperplasia without atypia (5.13±1.58). Mean progesterone receptor in stroma component was highest among Hyperplasia without atypia followed by disordered maturation and endometrial carcinoma. Conclusion: The results of the present study showed that ER and PR expression are useful investigations. There expression varies in various causes of abnormal bleeding. Future studies with clinical trials could be done to try medical treatment of AUB.

Endometrial estrogen and progesterone receptors in infertility and abnormal uterine bleeding

Introduction: Evaluation of endometrial histology can be made more meaningful with the study of Estrogen and Progesterone receptor (ER and PR) status. Present study aimed at studying ER and PR status of normal endometrium and endometrium in infertility and abnormal uterine bleeding and elucidating its relevance and utility. Materials and Methods: This case control study was carried out on prospectively registered patients. It included 12 cases of infertility, 24 cases of abnormal uterine bleeding, 14 cases of uterine leiomyoma and 22 cases of age matched controls undergoing endometrial sampling for causes other than above mentioned conditions. The cases were subjected to thorough clinical evaluation. The study of endometrium was done with routine histology. Endometrial ER and PR expression was studied immunohistochemically. The data collected was analyzed to find out the variability of expression of endometrial ER and PR in normal and abnormal endometrium with student’s t-test and correlation t-test (SPSS software version 11). Results: The ER and PR expression in normal endometrium showed cyclical variation. It was highest in the proliferative phase followed by the periovulatory phase followed by a significant decline in the late secretory phase. In cases of infertility and abnormal uterine bleeding with endometrial dysfunction; late secretory endometrium showed increased ER expression as compared to controls. Conclusion: Variations noted in endometrial ER and PR expression in infertility and abnormal uterine bleeding provided insight in its pathogenesis and helped in contemplating treatment options. Keywords: ER, PR, Endometrium, Infertility, Abnormal uterine bleeding, Uterine leiomyoma

The fungicide Mancozeb reduces spheroid attachment onto endometrial epithelial cells through downregulation of estrogen receptor β and integrin β3 in Ishikawa cells

Mancozeb is a metal-containing ethylene bis-dithiocarbamate fungicide widely used in agriculture. Ethylene thiourea (ETU) is the primary metabolite of Mancozeb. Mancozeb has been associated with spontaneous abortions and abnormal menstruation in women. However, the effects of Mancozeb and ETU on embryo attachment remain unknown. The human blastocyst surrogate trophoblastic spheroids (JEG-3), endometrial epithelial surrogate adenocarcinoma cells (Ishikawa), or human primary endometrial epithelial cells (EECs) monolayer were used in the spheroid attachment models. Ishikawa and EECs were pretreated with different concentrations of Mancozeb or ETU for 48 h before the attachment assay. Gene expression profiles of Ishikawa cells were examined to understand how Mancozeb modulates endometrial receptivity with Microarray. The genes altered by Mancozeb were confirmed by qPCR and compared with the ETU treated groups. Mancozeb and ETU treatment inhibited cell viability at 10 μg/mL and 5000 µg/mL, respectively. At non-cytotoxic concentrations, Mancozeb at 3 μg/mL and ETU at 300 μg/mL reduced JEG-3 spheroid attachment onto Ishikawa cells. A similar result was observed with human primary endometrial epithelial cells. Mancozeb at 3 μg/mL modified the transcription of 158 genes by at least 1.5-fold in Microarray analysis. The expression of 10 differentially expressed genes were confirmed by qPCR. Furthermore, Mancozeb decreased spheroid attachment possibly through downregulating the expression of endometrial estrogen receptor β and integrin β3, but not mucin 1. These results were confirmed in both overexpression and knockdown experiments and co-culture assay. Mancozeb but not its metabolite ETU reduced spheroid attachment through modulating gene expression profile and decreasing estrogen receptor β and integrin β3 expression of endometrial epithelial cells.

Endometrial Estrogen and Progesterone Receptor Expression and Blood Vessel Density in Abnormal Uterine Bleeding

Background: The aim of present study was to analyse endometrial estrogen and progesterone receptor expression and blood vessel density in cases of abnormal uterine bleeding. Material and Method: The present study was conducted on specimens received from 266 patients presenting with abnormal uterine bleeding in reproductive age group (18-45 years) on endometrial biopsies and hysterectomy specimens. The intensity and distribution of ER, PR was evaluated using a semi-quantitative method Allred score. Also density of blood vessels /10 HPF was evaluated. Results: Neoplastic cases were found among 9.4% (25) of the subjects whereas non-neoplastic lesions were present in 90.6% (241) of the subjects. Mean Allred scoring of estrogen and progesterone receptor in glandular component was highest among endometrial carcinoma. Mean Allred scoring of estrogen receptor in stromal component was highest among Hyperplasia without atypia (5.13±1.58). Mean progesterone receptor in stroma component was highest among Hyperplasia without atypia followed by disordered maturation and endometrial carcinoma. Conclusion: The results of the present study showed that ER and PR expression are useful investigations. There expression varies in various causes of abnormal bleeding. Future studies with clinical trials could be done to try medical treatment of AUB.

Uterine glycolytic enzyme expression is affected by knockout of different estrogen receptor subtypes.

The estrogen signaling pathway via nuclear estrogen receptors (ER) α and β is considered to be the master regulator of the cellular glucose metabolism in the uterus. While in vivo animal studies have demonstrated that 17β-estradiol (E2) treatment increases the expression levels and activities of several glycolytic enzymes in the uterus, the specific ER subtype-dependent regulation of key glycolytic enzymes in the uterus has not been experimentally verified. In this study, the localization of ERα and ERβ in human and mouse endometria were evaluated using immunohistology. Given that ERα and ERβ are not functionally equivalent, ERα, ERβ and ERαβ knockout (ERα-/-, ERβ-/- and ERαβ-/-) mice were utilized to determine the expression pattern of glycolytic enzymes in the uterus. It was found that the level of ERα was higher than that of ERβ in the human and mouse endometrial epithelial and stromal cells, and both receptors were downregulated by E2 treatment in the mouse uterus. The expression of the hexokinase 1 and GAPDH was increased in ERα-/- and ERβ-/- mice compared with wild-type controls. Increased phosphofructokinase expression was observed in ERα-/- and ERαβ-/- mice, whereas increased pyruvate kinase isozyme M2 and pyruvate dehydrogenase expression was observed in ERβ-/- and ERαβ-/- mice. The findings indicated for the first time that while estrogen regulates ERα and ERβ expression in the uterus, ERα and ERβ selectively regulate uterine glycolytic enzyme expression during glycolysis. Additionally, the link between endometrial ER subtypes and glycolysis in women with polycystic ovary syndrome (PCOS) is discussed. The findings suggested that the E2-dependent ER-mediated regulation of glycolysis may be involved in the disturbance of the glucose metabolism in patients with PCOS with endometrial dysfunction.

Effects of l-arginine on endometrial estrogen receptor α/β and progesterone receptor expression in nutrient-restricted sheep

This study aimed to determine the effects of l-arginine (L-Arg) supplementation on steroid hormone receptors in non-pregnant ovine endometrium. All experimental ewes were randomly assigned to either a control group (n = 6), a nutrient-restricted group (n = 6), or an L-Arg supplemented nutrient-restricted group (n = 6). The effects of L-Arg on estrogen receptor α/β (ERα/β) and progesterone receptor (PGR) expression in the ovine endometrium were assessed. Our results showed that levels of ERβ and PGR expression were significantly increased by nutrient restriction, but L-Arg counteracted the effect of nutrient restriction on ERβ and PGR expression (p < 0.05). Also, expression of endometrial ERα was substantially increased (p < 0.05) by L-Arg supplementation. Furthermore, ERα/β and PGR were mainly detected in the endometrial luminal epithelium and glandular epithelium. Therefore, we isolated and identified endometrial epithelial cells (EECs) from sheep. Different concentrations of L-Arg were added to investigate the effects on ERα/β and PGR in EECs. The expression levels of endothelial nitric oxide synthase, ERβ, and PGR were significantly increased in response to low-concentration (200 μmol) L-Arg supplementation, which subsequently decreased with a high concentration (800 μmol) (p < 0.05). Otherwise, ERα expression was remarkably increased at both L-Arg concentrations in EECs (p < 0.05). Overall, the results indicated that L-Arg performed crucial roles in the regulation of ovine steroid hormone receptor expression in the endometrium. The results of this study provide a theoretical basis and technical means for the normal function of endometrium in response to low nutrient levels.

Endocrine actions of interferon-tau in ruminants

The ovine conceptus releases interferon-tau (IFNT), which prevents upregulation of the endometrial estrogen receptor (ESR1) and, consequently, oxytocin receptor (OXTR), thereby disrupting pulsatile release of prostaglandin F2alpha (PGF) in response to oxytocin. IFNT, through paracrine action on the endometrium, protects the corpus luteum (CL) during maternal recognition of pregnancy. Pregnancy also induces IFN stimulated genes (ISGs) in peripheral blood mononuclear cells (PBMCs), which is interpreted to reflect a prompted antiviral and immune cell response peripherally in ruminants. IFNT was recently demonstrated to be released from the uterus in amounts of 200 microg (2 x 10(7) U)/24 h via the uterine vein and to induce ISGs in the CL during maternal recognition of pregnancy. Delivery of recombinant ovine (ro) IFNT into the uterine vein in a location that is upstream of the utero-ovarian plexus from Day 10 to 17 maintained serum progesterone concentrations and extended normal 16-17 d estrous cycles to beyond 32 d. It is concluded from these studies that IFNT is released into the uterine vein and initiates a peripheral antiviral response to protect pregnancy from maternal viral infection. It also may have endocrine action through inducing luteal resistance to PGF and longer-term survival of the CL and maintenance of pregnancy.

Estrogen and progesterone receptors show distinct patterns in differentendometrial cells of oocyte donors after ovarian stimulation

Controlled ovarian hyperstimulation is associated with accelerated endometrial maturation and altered gene expression in the subsequent luteal phase. We aimed to evaluate the correlation between different serum levels of sex hormones, endometrial histology and endometrial estrogen and progesterone receptor protein levels at the time of oocyte retrieval after controlled ovarian stimulation (COS) in young healthy oocyte donors.

Uterine Cavity Assessment and Endometrial Hormonal Receptors in Women with Peri and Post Menopausal Bleeding

Objectives: To compare the accuracy of 2D-Transvagfinal ultrasound (TVUS), saline infused sonohysterography (SIS) and hysteroscopy (DH) in assessment of the uterine cavity in women with peri- and postmenopausal bleeding and to study the expression of endometrial estrogen receptors (ER) and progesterone receptors (PR) in them. Study design: 100 women with abnormal uterine bleeding (peri and postmenopausal) were subjected to TVUS, SIS and DH and fractional curettage followed by histopathological examination and immunohistochemical analysis for ER and PR. Results: Measurement of endometrial thickness by TVUS showed a significant difference between normal and atrophic endometrium and between atrophic endometrium and endometrial polyp (P value 0.004 and 0.001 respectively) DH had the best sensitivity, specificity, PPV and NPV as a diagnostic procedure followed by SIS then TVUS (97.7, 100,100,99.4 % vs. 74,91.2,67.3,93.5 and 52.9,89.4,56.3, 88.1 respectively) Both ER and PR scoring among glands and stroma showed a significant difference between normal and abnormal endometrium. ER expression in glands showed a significant difference between endometrial polyp and surrounding endometrium (P value 0.006) Conclusions: Sonohysterography is superior to ultrasound and very close to hysteroscopy, especially with intra-cavitary lesions. Hysteroscopy remains the gold standard for uterine cavity assessment, but cannot replace the histopathology. The expression of endometrial steroid receptors is important in the pathogenesis of endometrial polyps and endometrial hyperplasia.

Endometrial dysfunction: an algorithm for histological and immunohistochemical studies

It is advisable to conduct a comprehensive study of the morphological assessment of the expression of endometrial estrogen and progesterone receptors, inflammatory markers in the second phase of the menstrual cycle in patients with impaired reproductive function (infertility, miscarriage, failed IVF attempts). The optimal period for investigation of endometrial dysfunction via endometrial biopsy is the second phase of the cycle (the period of “implantation window”). Creating a diagnostic algorithm, histological and immunohistochemical studies in the endometrial dysfunction will allow to justify the optimal choice of therapy.

Endometrial expression of progesterone, estrogen, and oxytocin receptors and of 20α-hydroxysteroid dehydrogenase and cyclooxygenase II 2 and 5 days after ovulation in induced short and normal estrous cycles in dairy cows

The aim of this study was to investigate causes of the short estrous cycles that occur frequently in dairy cows after estrus synchronization using PGF2α and GnRH. Expression of oxytocin receptor (OR), progesterone receptor (PR), and estrogen receptor (ER); of cyclo-oxygenase II (COX-II) and 20α-hydroxysteroid dehydrogenase (20α-HSD); and of peripheral blood estradiol-17ß and progesterone (P4) concentrations were analyzed in estrous cycles of normal length and in induced short estrous cycles. On Day 8 (ovulation = Day 0), presynchronized dairy cows (n = 14) were given 0.15 mg of dexcloprostenol and 0.1 mg of gonadorelin 24 hours later. Animals were bled once daily for P4 and estradiol-17ß analyses, and endometrial biopsy specimens were taken on Days 2 and 5 for PR, ER, OR, 20α-HSD, and COX-II determinations with immunohistochemistry and/or real-time quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR). Ovulations and ovarian structures were monitored with transrectal ultrasound daily until the next ovulation. After excluding one case of incomplete luteal regression, short estrous cycles occurred in 8 of 13 cases (length from 8 to 12 days). No differences were established in endometrial ER, PR, or COX-II expression between the normal and short cycle groups in the semi-quantitative immunohistochemistry analysis. In qRT-PCR analysis, no differences were found in relative gene expression of endometrial ER, PR, OR, 20α-HSD, or COX-II between normal and short cycles. Despite evidence from previous studies that short estrous cycles are induced by premature prostaglandin release, differences in these receptors or in enzyme expression do not explain the release.

The effects of genistein on estrogen receptor expression, cell proliferation, and apoptosis in endometriosis cell culture

Objectives: This study aimed to investigate whether genistein is able to inhibit cell proliferation and expression of estrogenic receptors, and to induce apoptosis in endometriosis cells. Methods: Confluent primary endometriosis cells were divided into seven groups, including control group and genistein treatment group at doses of 5, 10, 20, 30, 40 and 50 µmol/l. The times of incubation were 6, 24 and 48 hours. Four replications are applied in each group. Expression of estrogen receptor-α and estrogen receptor-β and level of proliferation cells in cells were measured using flow cytometry. Level of apoptosis cells and Bax were measured by enzyme-linked immunosorbent technique. Results: In 6 hours of treatment, the expression of estrogen receptor-α and estrogen receptor-β significantly decreased at all doses of genistein compared with control group. The expression of estrogen receptor-α was significantly reduced in 5 until 40 µM of 24 hours genistein treatment groups in comparison to control group, but estrogen receptor-β was not significantly different. In 48 hours of treatment, the expression of estrogen receptor-α and estrogen receptor-β were significantly lower in genistein-treated groups at doses of 40 µM and 20-50 µM, respectively, compared to control group. With 6 hours of treatment, the level of KI-67 and apoptosis significantly decreased in 50 µM genistein treatment group compared to control group. The expression of KI-67 significantly reduced at all doses of 24 hours genistein treatment compared to control group. In 48 hours of treatment, the level of KI-67 and apoptosis were significantly lower in 40 µM genistein treatment group compared to control group. The level of apoptosis was significantly higher in genistein treatment group compared to control group in 24 hours 50 µM genistein treatment group. Level of Bax significantly increased in genistein treatment at the doses from 10 until 50 µM compared to that of control group. Conclusion: Genistein inhibits endometrial cell proliferation and estrogen receptor expression, and induces apoptosis in endometriosis cell culture.

The impact of luteal phase support on endometrial estrogen and progesterone receptor expression: a randomized control trial

BackgroundTo assess the impact of luteal phase support on the expression of estrogen receptor (ER) alpha and progesterone receptors B (PR-B) on the endometrium of oocyte donors undergoing controlled ovarian hyperstimulation (COH).MethodsA prospective, randomized study was conducted in women undergoing controlled ovarian hyperstimulation for oocyte donation. Participants were randomized to receive no luteal support, vaginal progesterone alone, or vaginal progesterone plus orally administered 17 Beta estradiol. Endometrial biopsies were obtained at 4 time points in the luteal phase and evaluated by tissue microarray for expression of ER alpha and PR-B.ResultsOne-hundred and eight endometrial tissue samples were obtained from 12 patients. No differences were found in expression of ER alpha and PR-B among all the specimens with the exception of one sample value.ConclusionsThe administration of progesterone during the luteal phase of COH for oocyte donor cycles, either with or without estrogen, does not significantly affect the endometrial expression of ER alpha and PR.