Embryo implantation involves a complex interaction between the embryo and the endometrium of the mother, the study of which faces a variety of problems. The modeling of endometrial epithelial organoids and endometrial assembloids provides a new way to study the process of embryo implantation in vitro. This paper summarized the latest research progress in embryo implantation, the regulation mechanism of endometrial receptivity by estrogen- progesterone coordination and embryo-derived signals, the establishment of endometrial organoids, and the development and application of endometrial assembloids in the research on mother-embryo interaction, providing new strategies for studying the communication between embryo and maternal uterus during implantation.
Endometrium/physiology* ; Organoids/cytology* ; Embryo Implantation/physiology* ; Female ; Animals ; Progesterone/pharmacology* ; Pregnancy ; Estrogens/metabolism* ; Humans

BACKGROUND: Steroid receptor-associated and regulated protein (SRARP) suppresses tumor progression and modulates steroid receptor signaling by interacting with estrogen receptors and androgen receptors in breast cancer. In endometrial cancer (EC), progesterone receptor (PR) signaling is crucial for responsiveness to progestin therapy. The aim of this study was to investigate the role of SRARP in tumor progression and PR signaling in EC. METHODS: Ribonucleic acid sequencing data from the Cancer Genome Atlas, Clinical Proteomic Tumor Analysis Consortium, and Gene Expression Omnibus were used to analyze the clinical significance of SRARP and its correlation with PR expression in EC. The correlation between SRARP and PR expression was validated in EC samples obtained from Peking University People's Hospital. SRARP function was investigated by lentivirus-mediated overexpression in Ishikawa and HEC-50B cells. Cell Counting Kit-8 assays, cell cycle analyses, wound healing assays, and Transwell assays were used to evaluate cell proliferation, migration, and invasion. Western blotting and quantitative real-time polymerase chain reaction were used to evaluate gene expression. The effects of SRARP on the regulation of PR signaling were determined by co-immunoprecipitation, PR response element (PRE) luciferase reporter assay, and PR downstream gene detection. RESULTS: Higher SRARP expression was significantly associated with better overall survival and disease-free survival and less aggressive EC types. SRARP overexpression suppressed growth, migration, and invasion in EC cells, increased E-cadherin expression, and decreased N-cadherin and Wnt family member 7A ( WNT7A ) expression. SRARP expression was positively correlated with PR expression in EC tissues. In SRARP -overexpressing cells, PR isoform B (PRB) was upregulated and SRARP bound to PRB. Significant increases in PRE-based luciferase activity and expression levels of PR target genes were observed in response to medroxyprogesterone acetate. CONCLUSIONS This study illustrates that SRARP exerts a tumor-suppressive effect by inhibiting the epithelial-mesenchymal transition via Wnt signaling in EC. In addition, SRARP positively modulates PR expression and interacts with PR to regulate PR downstream target genes.
Female ; Humans ; Receptors, Progesterone/metabolism* ; Proteomics ; Cell Line, Tumor ; Endometrial Neoplasms/metabolism* ; Cell Proliferation/genetics* ; Luciferases/pharmacology* ; Gene Expression Regulation, Neoplastic/genetics*

OBJECTIVE: This study aimed to compare 9 perfluoroalkyl sulfonic acids (PFSA) with carbon chain lengths (C4-C12) to inhibit human placental 3β-hydroxysteroid dehydrogenase 1 (3β-HSD1), aromatase, and rat 3β-HSD4 activities. METHODS: Human and rat placental 3β-HSDs activities were determined by converting pregnenolone to progesterone and progesterone secretion in JEG-3 cells was determined using HPLC/MS-MS, and human aromatase activity was determined by radioimmunoassay. RESULTS: PFSA inhibited human 3β-HSD1 structure-dependently in the order: perfluorooctanesulfonic acid (PFOS, half-maximum inhibitory concentration, IC ₅₀: 9.03 ± 4.83 μmol/L) > perfluorodecanesulfonic acid (PFDS, 42.52 ± 8.99 μmol/L) > perfluoroheptanesulfonic acid (PFHpS, 112.6 ± 29.39 μmol/L) > perfluorobutanesulfonic acid (PFBS) = perfluoropentanesulfonic acid (PFPS) = perfluorohexanesulfonic acid (PFHxS) = perfluorododecanesulfonic acid (PFDoS) (ineffective at 100 μmol/L). 6:2FTS (1H, 1H, 2H, 2H-perfluorooctanesulfonic acid) and 8:2FTS (1H, 1H, 2H, 2H-perfluorodecanesulfonic acid) did not inhibit human 3β-HSD1. PFOS and PFHpS are mixed inhibitors, whereas PFDS is a competitive inhibitor. Moreover, 1-10 μmol/L PFOS and PFDS significantly reduced progesterone biosynthesis in JEG-3 cells. Docking analysis revealed that PFSA binds to the steroid-binding site of human 3β-HSD1 in a carbon chain length-dependent manner. All 100 μmol/L PFSA solutions did not affect rat 3β-HSD4 and human placental aromatase activity. CONCLUSION Carbon chain length determines inhibitory potency of PFSA on human placental 3β-HSD1 in a V-shaped transition at PFOS (C8), with inhibitory potency of PFOS > PFDS > PFHpS > PFBS = PFPS = PFHxS = PFDoS = 6:2FTS = 8:2FTS.
Humans ; Pregnancy ; Female ; Rats ; Animals ; Placenta ; Progesterone/pharmacology* ; Aromatase/pharmacology* ; Cell Line, Tumor ; Fluorocarbons ; Alkanesulfonic Acids ; Structure-Activity Relationship ; Hydroxysteroid Dehydrogenases/pharmacology*

The acrosome reaction is a prerequisite for fertilization, and its signaling pathway has been investigated for decades. Regardless of the type of inducers present, the acrosome reaction is ultimately mediated by the elevation of cytosolic calcium. Inositol 1,4,5-trisphosphate-gated calcium channels are important components of the acrosome reaction signaling pathway and have been confirmed by several researchers. In this study, we used a novel permeabilization tool BioPORTER^® and first demonstrated its effectiveness in spermatozoa. The inositol 1,4,5-trisphosphate type-1 receptor antibody was introduced into spermatozoa by BioPORTER^® and significantly reduced the calcium influx and acrosome reaction induced by progesterone, solubilized zona pellucida, and the calcium ionophore A23187. This finding indicates that the inositol 1,4,5-trisphosphate type-1 receptor antibody is a valid inositol 1,4,5-trisphosphate receptor inhibitor and provides evidence of inositol 1,4,5-trisphosphate-gated calcium channel involvement in the acrosome reaction in human spermatozoa. Moreover, we demonstrated that the transfer of 1,4,5-trisphosphate into spermatozoa induced acrosome reactions, which provides more reliable evidence for this process. In addition, by treating the spermatozoa with inositol 1,4,5-trisphosphate/BioPORTER^® in the presence or absence of calcium in the culture medium, we showed that the opening of inositol 1,4,5-trisphosphate-gated calcium channels led to extracellular calcium influx. This particular extracellular calcium influx may be the major process of the final step of the acrosome reaction signaling pathway.
Acrosome Reaction/physiology* ; Calcimycin/pharmacology* ; Calcium/pharmacology* ; Calcium Ionophores/pharmacology* ; Drug Delivery Systems ; Humans ; Inositol 1,4,5-Trisphosphate Receptors/metabolism* ; Male ; Progesterone/pharmacology* ; Spermatozoa/metabolism* ; Zona Pellucida/metabolism*

The present study was conducted to explores the effects of short-term addition of 17β-E2 on the growth,gonad development and internal quality of overwintering Whitmania pigra. Before overwintering,0. 0,1. 0,10. 0,25. 0,50. 0,100. 0 μg·L~(-1) of 17β-E2 were added to the aquaculture water for 6 weeks and then hibernated for 60 days. The changes of growth performance,gonad index,morphological structure of spermary( ovary),endogenous steroid hormones level and internal quality were measured. The results showed that the body weight,weight gain rate,specific growth rate,female gonad index,oocyte development and endogenous estrogen level of the leech increased first and then decreased with the increase of the concentration of exogenous 17β-E2,which were higher than those of the control group. The body weight,weight gain rate and specific growth rate of the leech at the concentration of 25 μg·L~(-1)17β-E2 were significantly higher than those of the other groups( P<0. 05),oocyte development and endogenous estrogen levels were significantly higher than those of other groups at the concentration of 50 μg·L~(-1)( P<0. 05). When the concentration of exogenous 17β-E2 was higher than 50 μg·L~(-1),the levels of male gonad index,spermatocyte development,endogenous androgen and progesterone were significantly inhibited( P< 0. 05). There was no significant difference in endogenous corticosteroid levels among the groups. In conclusion,short-term addition of exogenous 17β-E2 of 10-25 μg·L~(-1) could promote the growth of overwintering leeches,oocyte development and antithrombin activity without inhibiting the development of male gonads.
Androgens ; analysis ; Animals ; Estradiol ; pharmacology ; Estrogens ; analysis ; Female ; Gonads ; drug effects ; growth & development ; Hibernation ; Leeches ; drug effects ; growth & development ; Male ; Progesterone ; analysis

OBJECTIVE: Yun Kang oral liquid is a listed proprietary Chinese Medicine. To further evaluate its efficacy, this experiment established a kidney deficiency and luteum inhibition threatened abortion rat model to observe the effects of Yun Kang oral liquid. METHODS: Sixty pregnant rats were randomly divided into normal control group (NC), model group (MG), dydrogesterone group (DT, 3.02 mg/kg), and Yun Kang oral liquid low-dose group (YK-L, 4 ml/kg), medium dose group (YK-M, 6 ml/kg), high dose group (YK-H, 9 ml/kg), 10 in each group. On the first day of pregnancy, each administration group was treated with the test drug at the prescribed dose every morning, and the NC group and the MG group were given an equal volume of purified water for 10 days; the rats were intragastrically administrated every afternoon, except for the NC group. In addition, the other groups were intragastrically administered with hydroxyurea at a dose of 450 mg/kg for 9 days, and mifepristone was administered at a dose of 4.0 mg/kg on the 10th day. On the 9th day of pregnancy, behavioral signs such as back temperature, grasping force, pain threshold, and autonomic activity were measured in each group. On the 11th day of pregnancy, blood was collected from the abdominal aorta in each group to determine serum levels of estradiol (E) , progesterone (P) and thromboxane B (TXB) . Ovary and fetal uterus were removed, the number and diameter of embryos were observed, and the ovary and uterus indexes were calculated. RESULTS: Compared with the NC group, the back temperature, grip, pain threshold, number of spontaneous activities, number of embryos, embryo diameter, uterus index and serum E, P, TXB levels in the MG group were decreased significantly (P＜0.05, 0.01). Compared with the MG group, the back temperature, grasping force, number of embryos, embryo diameter and serum E and P levels were increased significantly in each dose group (P＜0.05, 0.01); the pain threshold, autonomic activity, and uterus index of YK-M and YK-H group were increased significantly (P＜0.05); serum level of TXB in YK-H group were increased significantly (P＜0.05). CONCLUSION Yun Kang oral liquid has a clear kidney-filling effect on rats with threatened abortion caused by kidney deficiency-luteal suppression. The mechanism may be related to raising serum E, P, TXB levels, improving kidney deficiency and improving embryo quality.
Abortion, Spontaneous ; prevention & control ; Abortion, Threatened ; prevention & control ; Animals ; Drugs, Chinese Herbal ; pharmacology ; Estradiol ; Female ; Humans ; Kidney ; physiopathology ; Luteal Phase ; Pregnancy ; Progesterone ; Rats ; Uterus

OBJECTIVETo investigate the expression of 17 beta-hydroxysteroid dehydrogenase type 1 (17β-HSD1) in the kidney of rats and explore the capacity of the kidney for synthesizing sex hormones.

METHODSThe expressions of 17-HSD1 and sex hormones were detected by Western blotting and radioimmunoassay in rat renal cells in primary cultured for 24 and 48 h in the presence or absence of follicle-stimulating hormone (FSH) and luteinizing hormone (LH).

RESULTSAfter cell culture for 24 h, the primary rat renal cells expressed a low level of 17β-HSD1 (0.1843±0.076), which increased to 1.6651±0.044 (P<0.01) in response to co-stimulation by FSH and LH. Low levels of estradiol, progesterone and testosterone were also detected in rat renal cells (3.30±3.78, 62.60±12.33, and 22.12±3.36, respectively), and co-stimulation of FSH and LH significantly increased their levels to 8.50±2.64, 117.80±9.79, and 45.04±4.39, respectively (P<0.05). The levels of these hormones showed no significant differences between cells cultured for 24 h and 48 h (P>0.05).

CONCLUSIONThe rat renal cells express 17β-HSD1 and are capable of stably secreting sex hormones in response to co-stimulation with FSH and LH, suggesting the capacity of the rat kidneys for synthesizing sex hormones. These findings enrich the understanding of the endocrine function of the kidney.

17-Hydroxysteroid Dehydrogenases ; metabolism ; Animals ; Cells, Cultured ; Estradiol ; biosynthesis ; Follicle Stimulating Hormone ; pharmacology ; Kidney ; enzymology ; Luteinizing Hormone ; pharmacology ; Progesterone ; biosynthesis ; Rats ; Testosterone ; biosynthesis

OBJECTIVETo observe protective effects of Schisandra extract (SE) on embryotoxicity and reproductive toxicity of early pregnant rats exposed to Benzo[a]pyrene (Bap).

METHODSPregnant rat model was prepared using periodic screening cage method. Totally 50 female pregnant SD rats were divided into five groups by randomized block design according to the weight, i.e., the BaP model group, the low dose SE group, the middle dose SE group, the high dose SE group, the normal control group, 10 rats in each group. Rats in the BaP model group were administered with BaP at a daily dose of 2 mg/kg by gastrogavage. Rats in low, middle, and high dose SE groups were administered by gastrogavage with BaP (at a daily dose of 2 mg/kg) plus SE at a daily dose of 40, 200, and 1 000 mg/kg, respectively. Equal volume of olive oil was administered to rats in the normal control group by gastrogavage. All medication was performed for 8 successive days. Changes of rat body weight in each period were observed. The uterus embryonic total quality and ovary quality were measured, and organ index calculated. The number of corpus luteum, the number of embryo implantation, and the number of absorbed embryo were statistically calculated respectively. The implantation rate and the absorbed embryos rate were calculated. Serum levels of human chorionic gonadotrophin β (β-HCG) and progesterone (PROG) were detected by ELISA.

RESULTSCompared with the normal control group, the weight of 9-day pregnant rats, the number of embryo implantation, the uterus embryonic total index, ovary index, serum levels of β-HCG and PROG all decreased in the Bap model group with significant difference (P < 0.05, P < 0.01). Compared with the Bap model group, body weight, the uterus embryonic total index, and the PROG level increased in 3 dose SE groups (P < 0.05, P < 0.01). Ovary index and serum β-HCG increased in middle and high dose SE groups (P < 0.05, P < 0.01). The number of implantation obviously increased in the high dose SE groups (P < 0.01).

CONCLUSIONSE could reduce the embryotoxicity and reproductive toxicity of early pregnant rats exposed to Benzo[a]pyrene.

Animals ; Benzo(a)pyrene ; toxicity ; Chorionic Gonadotropin ; blood ; Embryo Implantation ; drug effects ; Female ; Ovary ; drug effects ; Plant Extracts ; pharmacology ; Pregnancy ; Progesterone ; blood ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Reproduction ; drug effects ; Schisandra ; chemistry ; Uterus ; drug effects

OBJECTIVETo observe the effect of Qingre Yangyin Recipe (QRYYR) on sex hormones and insulin resistance (IR) in polycystic ovary syndrome (PCOS) patients.

METHODSTotally 90 PCOS patients were randomly assigned to the Chinese herbs group,the Western medicine group, the combined group, 30 in each group. Patients in the Chinese herbs group took QRYYR, one dose per day in two portions, once in the morning and once in the evening. Patients in the Western medicine group took Metformin 500 mg, twice per day for 3 consecutive months. Patients in the combined group took QRYYR and Metformin (the same as the former said two groups) in the 1st month, and took QRYYR for the following two months. Fasting blood glucose (FPG) and postprandial 2 h blood glucose (2 h GLU) were determined using hexokinase method before and after treatment. Fasting insulin (FINS), postprandial 2 h insulin (2 h INS), luteinizing hormone (LH), follicle stimulating hormone (FSH), estradiol (E2), progesterone (P), prolactin (PRL), and testosterone (T) were detected using chemiluminescent method. Leptin and adiponectin (APN) were determined using ELISA. Homeostasis model assessment of insulin resistance (HOMA-IR) was calculated. Body weight and height were measured once before treatment and once after treatment to calculate body mass index (BMI). The total two-phase basal body temperature (BBT) actually obtained within 3 months was statistically collected to calculate the two-phase BBT rate. Scores for Chinese medical syndromes were compared between the two groups before and after treatment.

RESULTSCompared with before treatment in the same group, BMI, FINS, 2 h INS, HOMA-IR, leptin, LH, PRL, T, and scores for Chinese medical syndromes obviously decreased, and APN levels increased (P < 0.05). FPG and 2 h FPG obviously decreased in the Western medicine group and the combined group (P < 0.05). E2 levels obviously decreased in the combined group with statistical difference (P < 0.05). Compared with the Chinese herbs group, the difference of BMI between pre-treatment and post-treatment was more in the combined group (P < 0.05). The difference of FPG,2 h GLU, 2 h INS, HOMA-IR, and APN between pre-treatment and post-treatment was more in the Chinese herbs group and the combined group (P < 0.05). Compared with the Western medicine group, the difference of PRL, T, and scores for Chinese medical syndromes was more in the Western medicine group and the combined group (P < 0.05); the difference of E2 and LH was even more in the combined group (P < 0.05). Compared with the combined group, the biphasic rate was obviously lowered in the Western medicine group (P < 0.05).

CONCLUSIONSQRYYR could improve IR but with weaker power to that of Metformin. It also could decrease serum levels of LH, T, PRL, and scores for Chinese medical syndromes, with superior effect to that of Metformin. The effect in the combined group was better.

Adiponectin ; Blood Glucose ; Body Mass Index ; Drugs, Chinese Herbal ; pharmacology ; therapeutic use ; Estradiol ; Female ; Follicle Stimulating Hormone ; Gonadal Steroid Hormones ; Humans ; Insulin ; Insulin Resistance ; Leptin ; Luteinizing Hormone ; Metformin ; Polycystic Ovary Syndrome ; drug therapy ; metabolism ; Progesterone ; Prolactin ; Testosterone

OBJECTIVETo observe the neurological protective effects of progesterone (PROG) on focal cerebral ischemia/reperfusion injury in rats and to explore its possible mechanism.

METHODSOne handred and twenty male SD rats were divided into three groups randomly: sham-operated group, middle cerebral artery occlusion ( MCAO ) group and PROG + MCAO group( n = 40). The right temporary MCAO model was established by the line-embolism method. The PROG + MCAO group rats were according to 8 mg/kg intraperitoneal injection PROG, after that 30 min, the rats were suffered ischemia/reperfusion. After rats were suffered ischemia for 2 h and reperfusion 0, 24, 48, 72 h stress, the nervous functional defect degree were evaluated by longe scoring, and the expression of two-pore domain K channel 3 (TASK3) mRNA in brain tissue were detected by the real-time PCR.

RESULTSPROG (8 mg/kg) could significantly reduced the nervous functional defect degree in rats after ischemia/reperfusion 24, 48, 72 h (P < 0.05). The results of real-time PCR showed that the TASK3 mRNA expression in the brain tissue at all time points significantly decreased in MCAO group compared with sham-operated group (P < 0.05). However, compared with MCAO group, the expression of TASK3 mRNA in brain tissue at all time points dramatically increased in PROG + MCAO group (P < 0.05).

CONCLUSIONPROG can improve the nervous functional defect degree after focal cerebral ischemia/reperfusion injury in rats, and the mechanism might be associated with up-regulating the expression of TASK3 mRNA in brain tissue.

Animals ; Brain ; drug effects ; pathology ; Brain Ischemia ; drug therapy ; Infarction, Middle Cerebral Artery ; Male ; Neuroprotective Agents ; pharmacology ; Potassium Channels, Tandem Pore Domain ; metabolism ; Progesterone ; pharmacology ; Rats ; Rats, Sprague-Dawley ; Real-Time Polymerase Chain Reaction ; Reperfusion Injury ; drug therapy