Age-specific values of Access anti-Müllerian hormone immunoassay carried out on Japanese patients with infertility: a retrospective large-scale study.

BACKGROUND: The ovarian reserve in women is known to correlate with anti-Müllerian hormone (AMH) levels, and currently the latest, third-generation, fully-automated AMH immunoassays, such as Access and Cobas, are beginning to be used for measuring AMH levels. However, the age-specific reference values obtained for AMH levels have been based on samples from an American population, measured using first-generation immunoassays. In this study, we attempted to determine the age-specific AMH reference values based on a large set of samples taken from Japanese infertile women measured by Access so that they could be used by infertility centers treating Japanese and those with similar racial and life-style characteristics. METHODS: The study included 5483 Japanese patients who enrolled in infertility treatment programs at two in-vitro fertilization centers, Shimbashi YUME Clinic and Natural ART Clinic Nihombashi in Tokyo, and who had their serum AMH levels measured between December 2015 and November 2017 by Access. Each patient was represented only once in the study. The mean, median, and standard deviation values were obtained from the measured values for single-year intervals from 28 through 48 years of age (21 age groups in total). The 3D-fitted curve of age-specific mean and median values measured by Access was obtained by regression analysis. RESULTS: The mean and median values decreased with advancing age (mean: R2 = 0.9864; median: R2 = 0.9926). In all age groups, the mean values were higher than the median values; however, the differences between these values decreased with increasing age. CONCLUSIONS: The age-specific AMH reference values measured by Access in this study may serve as a useful diagnostic marker in infertility centers, especially those treating Japanese patients or patients with similar characteristics.

Levothyroxine supplementation improves serum anti-Müllerian hormone levels in infertile patients with Hashimoto's thyroiditis.

AIM: Thyroid dysfunction and autoimmunity are associated with an adverse effect on fertility. An aberrant high thyroid stimulating hormone level is associated with diminished ovarian reserve in women of reproductive age; however, the utility of levothyroxine (LT4) replacement for infertile patients with subclinical hypothyroidism is still under discussion. The aim of this study was to investigate whether LT4 supplementation for infertile patients with subclinical hypothyroidism improves impaired ovarian function. METHODS: We measured levels of serum thyroid-related hormones and a biomarker of ovarian function, anti-Müllerian hormone (AMH) in infertile women from 2014 to 2015. Out of a consecutive 1431 infertile patients, 311 patients with an elevated thyroid stimulating hormone level (≥ 2.5 µIU/mL) underwent detailed thyroid examinations, including blood tests of thyroid antibodies. We recruited 174 infertile patients, excluding patients with factors impacting ovarian and thyroid function. We evaluated alterations in AMH and thyroid related hormone levels during LT4 supplementation and infertility treatment with assisted reproductive technology. RESULTS: After LT4 supplementation, no significant change in the average AMH level was detected overall. However, the AMH level in 35 patients with Hashimoto's disease increased significantly after treatment (1 month 1.3 ± 0.5 fold, P = 0.007; 3 months 1.3 ± 0.4 fold, P = 0.040). The AMH level in patients with thyroglobulin antibody-positive and thyroid peroxidase antibody-negative also significantly increased after LT4 treatment (1 and 3 months 1.5 fold; P = 0.023). CONCLUSION: In the patients with Hashimoto's disease, preconception LT4 treatment may relieve adverse effects, including autoimmune antibodies, and support follicular development.

Cytogenetic analysis of the retained products of conception after missed abortion following blastocyst transfer: a retrospective, large-scale, single-centre study.

Cytogenetic analysis of the retained products of conception (POC) is the most effective test for identifying miscarriage causes. However, there has been no large-scale study limited to blastocyst transfer. This study retrospectively reports the findings of 1030 cases in which POC analysis was performed after missed abortion following single blastocyst transfer performed at the Shinbashi Yume Clinic. We identified 19.4% as normal karyotypes and 80.6% as aneuploid. These cases broke down into: 62.3% trisomy; 7.8% double trisomy; 0.5% triple or quadruple trisomy; 1.3% monosomy 21; 3.2% monosomy X; 0.1% 47,XXY; 1.0% polyploidy; 1.0% mixed; 1.1% embryonic mosaicism; and 2.4% structural anomalies. In samples with normal karyotypes, 49.5% were female while 50.5% were male. The occurrence of trisomy and double trisomy were both significantly more frequent in the ≥38 years group than in the ≤37 years group (P < 0.01). Trisomy was significantly more frequently associated with fetal heartbeat (P < 0.01); double trisomy, polyploidy and normal karyotype were significantly more frequent with no fetal heartbeat (P < 0.01). There was no significant difference in the frequency of chromosomal abnormalities between the number of miscarriages or blastocyst quality. Thus, POC cytogenetic testing is highly valuable for ascertaining the cause of miscarriage.

ABCC5, a gene that influences the anterior chamber depth, is associated with primary angle closure glaucoma.

Anterior chamber depth (ACD) is a key anatomical risk factor for primary angle closure glaucoma (PACG). We conducted a genome-wide association study (GWAS) on ACD to discover novel genes for PACG on a total of 5,308 population-based individuals of Asian descent. Genome-wide significant association was observed at a sequence variant within ABCC5 (rs1401999; per-allele effect size =  -0.045 mm, P = 8.17 × 10(-9)). This locus was associated with an increase in risk of PACG in a separate case-control study of 4,276 PACG cases and 18,801 controls (per-allele OR = 1.13 [95% CI: 1.06-1.22], P = 0.00046). The association was strengthened when a sub-group of controls with open angles were included in the analysis (per-allele OR = 1.30, P = 7.45 × 10(-9); 3,458 cases vs. 3,831 controls). Our findings suggest that the increase in PACG risk could in part be mediated by genetic sequence variants influencing anterior chamber dimensions.

Histological assessment of impact of ovarian endometrioma and laparoscopic cystectomy on ovarian reserve.

AIM: The rate of oocyte decline follows a biphasic pattern, characterized by acceleration between 32 and 38 years old. Ovarian reserve is also affected by external factors, including ovarian disease and iatrogenic damage. The aim of this study was to histologically evaluate the impact of ovarian endometriomas, laparoscopic cystectomy, and age on follicle reserve in healthy ovarian tissues and in surgically resected cyst walls. MATERIAL AND METHODS: Sixty-one patients were found to have ovarian endometriomas and 42 patients non-endometriotic cysts. A small amount of normal ovarian tissue was obtained during ovarian cystectomy. The follicles in normal ovarian tissue and resected cyst walls were histologically evaluated. RESULTS: The density of follicles in ovarian tissues correlated with the age of the patients in both groups. In women aged <35 years, the relative density of follicles in healthy ovarian tissues was consistently lower in the endometriotic cyst group compared to the non-endometriotic cyst group, with the relative ratio at age 20, 30 and 35 years calculated to be 35.4%, 46.8% and 62.7%, respectively. There was no significant difference between the groups in patients over the age of 35. The resection rate of normal ovarian tissue in cystectomy specimen of the endometriosis group was significantly higher than in the non-endometriotic cyst group (P < 0.001). CONCLUSIONS: Our data suggest that ovarian endometriomas have a detrimental impact on follicle reserve in younger patients. Further, laparoscopic cystectomy for endometriomas may accelerate the rate of oocyte loss associated with aging.

Use of magnetic resonance analysis for clinical evaluation of the peripheral area of gestational sac in bleeding and non-bleeding ectopic pregnancy cases.

PURPOSE: To evaluate preoperative magnetic resonance (MR) imaging features of bleeding and non-bleeding ectopic pregnancy (EP) by comparison with surgical findings. METHODS: Eighteen suspected EP cases underwent preoperative MR imaging. We classified 8 cases as the bleeding group and 7 cases as the non-bleeding group with or without intra-abdominal bleeding and/or hematoma at the site of EP, and compared, retrospectively, gestational sac (GS)-like structure, particularly the peripheral area of the GS via MR analysis. Excluded were 3 cases that were insufficient for assessing extrauterine GS-like structure: ruptured tubal pregnancy and uterine horn pregnancy. RESULTS: GS-like structures were typically observed as low intensity on T1-weighted image (T1WI) and as high intensity on T2-weighted image (T2WI). In non-bleeding cases, most peripheral areas of the GS were of intermediate intensity on T1WI and high intensity on T2WI. Most bleeding cases were of high intensity on T1WI and low to high intensity on T2WI. Furthermore, the peripheral area of the GS was of higher intensity on T1WI with fat suppression than on T1WI. CONCLUSIONS: It is clear that MR imaging is effective for diagnosis of cases of suspected EP. EP conditions may be predicted by signal intensity of the peripheral area of the GS via MR analysis.

[A case of Oguchi disease with disappearance of golden tapetal-like fundus reflex after vitreous resection].

BACKGROUND: Oguchi disease is a form of congenital stationary night-blindness characterized by a golden tapetal fundus reflex. This reflex is known to disappear in the dark-adapted state ("Mizuo-Nakamura phenomenon"). The origin of the reflex is not clear. We report a case of Oguchi disease with the disappearance of the golden tapetal reflex after vitreous resection. CASE: An 80-year-old man was referred for rhegmatogenous retinal detachment of the left eye. Golden tapetal reflex was observed in both eyes. Negative b-wave in the electroretinogram and mutation in the SAG gene indicated Oguchi disease. Pars plana vitrectomy and posterior hyaloid membrane peeling were performed. The tapetal reflex in the all regions of the fundus in the operated eye disappeared after the retina was reattached. The reflex partially recovered 2 years after the operation. CONCLUSION: It is suggested that the change in vitreo-retinal interface after a vitreous operation leads to the disappearance of the reflex. This report presents a hypothesis on the origin of the golden tapetal reflex in Oguchi disease.

Alterations in endometrial vascular density via hysteroscopy evaluated by vascular analysis software during laparoscopic myomectomy on an infertile woman with submucous myoma.

Submucous myomas cause infertility and recurrent pregnancy loss. Several studies have reported successful reproductive outcomes after hysteroscopic myomectomy (HM), but the risk of postoperative intrauterine adhesion is present. We performed laparoscopic myomectomy (LM) for a submucous myoma and second look laparoscopy under observation using a hysteroscope to evaluate the alteration in endometrial vascular density during surgery using vascular analysis software. The patient was a 33-year-old nulliparous infertile woman. She had one submucous myoma of 4 cm in diameter and 50-60% penetration into the myometrium (class T:II; the European Society of Hysteroscopy classification). The surface vascular density of the submucous myoma was 68.6% before the start of surgery, decreased to 51.4% upon vasopressin injection and increased to 67.6% at the end of LM. Intraabdominal and intrauterine adhesions were not seen at second look laparoscopy. The vascular density was 70.8%, and the rate of endometrial blood flow was increased to 112.5% by comparison with the vascular density before the start of surgery. HM is a safe and effective procedure, but carries the risk of scarring the uterine cavity with uterine adhesions. We have to consider LM for women of reproductive age who have a submucous myoma with penetration >50% into the myometrium (class T:II).

A new instrument: a flexible hysteroscope with narrow band imaging system: optical quality comparison between a flexible and a rigid hysteroscope.

There are two different types of hysterocopes available: Flexible and rigid. Flexible scopes have the ability to observe the whole intrauterine cavity, but it is difficult to perform an operation on endometrial lesions. Rigid hysteroscopes provide superior optical qualities due to higher pixel count. We report the use of a new flexible hysteroscope with narrow band imaging (NBI) system (HYF-V EndoEYE Flexible Video Hysteroscope) and compared the optical qualities of this flexible to those of a rigid hysteroscope using the vascular analysis software "SolemioENDO ProStudy". Twenty-four images of endometrium in eight cases, and 12 images of submucous myoma in six cases were each photographed by two the hysteroscopes. The vascular densities of both endometrium and myoma under conventional light in the flexible scope were significantly higher than with the rigid scope. However the vascular densities under narrow-band light in the two scopes were not significantly different. The vascular densities of the images taken by flexible scope were higher than the images taken by rigid scopes under conventional light. With the rigid scope, microvascular structure may be crumpled by high water pressure. A flexible hysteroscope with NBI system has superior ability to observe the intrauterine cavity and measure vascular density compared to a rigid scope.

The phenotype and genotype experiment object model (PaGE-OM): a robust data structure for information related to DNA variation.

Torrents of genotype-phenotype data are being generated, all of which must be captured, processed, integrated, and exploited. To do this optimally requires the use of standard and interoperable "object models," providing a description of how to partition the total spectrum of information being dealt with into elemental "objects" (such as "alleles," "genotypes," "phenotype values," "methods") with precisely stated logical interrelationships (such as "A objects are made up from one or more B objects"). We herein propose the Phenotype and Genotype Experiment Object Model (PaGE-OM; www.pageom.org), which has been tested and implemented in conjunction with several major databases, and approved as a standard by the Object Management Group (OMG). PaGE-OM is open-source, ready for use by the wider community, and can be further developed as needs arise. It will help to improve information management, assist data integration, and simplify the task of informatics resource design and construction for genotype and phenotype data projects.

The impact of endometriosis, endometrioma and ovarian cystectomy on assisted reproductive technology.

PURPOSE: To assess outcomes in assisted reproductive technology (ART) in infertile women with endometriosis with respect to their concomitant endometrioma status and surgical history in our department. METHODS: This is a retrospective case control study which analyzes informational data obtained at a university hospital. The study drew from a patient pool of 332 cases (877 cIVF/ICSI cycles) that took place in our department from 2006 to 2008. Sixty-one cases (97 cycles) had major indications for cIVF/ICSI with endometriosis. We classified groups from these 61 cases as follows: an unoperated endometrioma group (A) with 31 cycles, a postoperative endometrioma group (B) with 51 cycles, and a no endometrioma group (C) with 15 cycles. We analyzed and compared these three groups and also included a non-endometriosis tubal infertility group (D) with 27 cycles. RESULTS: In the control group (D), serum FSH levels and the cancellation rates were significantly lower than those of other groups, and the number of developing follicles was higher. E2 levels before oocyte aspiration in the postoperative endometrioma group (B) was lower. Implantation, pregnancy, delivery and miscarriage rates were not significantly different among the four groups. CONCLUSION: The results suggest that endometriosis causes a decrease in endocrinologic ovarian function whether or not an endometrioma is also present. As for E2 level before oocyte aspiration, our results suggest that ovarian reserves might be reduced by endometrioma excision, but this is difficult to evaluate. In the endometriosis groups, cancellation rates were significantly higher, although when embryos were transferred the pregnancy rates were not significantly different when compared with the non-endometriosis group. As for infertile women with endometriomas, our results suggest that preexisting ovarian reserve is reduced by the presence of endometriosis, and ovarian reserve might also be reduced by excision of endometriomas.

Erratum to: The impact of endometriosis, endometrioma and ovarian cystectomy on assisted reproductive technology.

[This corrects the article DOI: 10.1007/s12522-009-0021-1.].

An in vitro model of a retinal prosthesis.

Epiretinal prostheses are being developed to bypass a degenerated photoreceptor layer and excite surviving ganglion and inner retinal cells. We used custom microfabricated multielectrode arrays with 200-microm-diameter stimulating electrodes and 10-microm-diameter recording electrodes to stimulate and record neural responses in isolated tiger salamander retina. Pharmacological agents were used to isolate direct excitation of ganglion cells from excitation of other inner retinal cells. Strength-duration data suggest that, if amplitude will be used for the coding of brightness or gray level in retinal prostheses, shorter pulses (200 micros) will allow for a smaller region in the area of the electrode to be excited over a larger dynamic range compared with longer pulses (1 ms). Both electrophysiological results and electrostatic finite-element modeling show that electrode-electrode interactions can lead to increased thresholds for sites half way between simultaneously stimulated electrodes (29.4 +/- 6.6 nC) compared with monopolar stimulation (13.3 +/- 1.7 nC, p < 0.02). Presynaptic stimulation of the same ganglion cell with both 200- and 10-microm-diameter electrodes yielded threshold charge densities of 12 +/- 6 and 7.66 +/- 1.30 nC/cm2, respectively, while the required charge was 12.5 +/- 6.2 and 19 +/- 3.3 nC.

A genome-wide association study identified a novel genetic loci STON1-GTF2A1L/LHCGR/FSHR for bilaterality of neovascular age-related macular degeneration.

Bilateral neovascular age-related macular degeneration (AMD) causes much more handicaps for patients than unilateral neovascular AMD. Although several AMD-susceptibility genes have been evaluated for their associations to bilaterality, genome-wide association study (GWAS) on bilaterality has been rarely reported. In the present study, we performed GWAS using neovascular AMD cases in East Asian. The discovery stage compared 581,252 single nucleotide polymorphisms (SNPs) between 803 unilateral and 321 bilateral Japanese cases but no SNP showed genome-wide significance, while SNPs at six regions showed P-value < 1.0 × 10-5, STON1-GTF2A1L/LHCGR/FSHR, PLXNA1, CTNNA3, ARMS2/HTRA1, LHFP, and FLJ38725. The first replication study for these six regions comparing 36 bilateral and 132 unilateral Japanese cases confirmed significant associations of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR), rs2284665 (ARMS2/HTRA1), and rs8002574 (LHFP) to bilaterality. In the second replication study comparing 24 bilateral and 78 unilateral cases from Singapore, rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) only showed significant association. Meta-analysis of discovery and replication studies confirmed genome-wide level significant association (P = 2.61 × 10-9) of rs4482537 (STON1-GTF2A1L/LHCGR/FSHR) and strong associations (P = 5.76 × 10-7 and 9.73 × 10-7, respectively) of rs2284665 (ARMS2/HTRA1) and rs8002574 (LHFP). Our GWAS for neovascular AMD bilaterality found new genetic loci STON1-GTF2A1L/LHCGR/FSHR and confirmed the previously reported association of ARMS2/HTRA1.

JSNP: a database of common gene variations in the Japanese population.

JSNP is a repository of Japanese Single Nucleotide Polymorphism (SNP) data, begun in 2000 and developed through the Prime Minister's Millennium Project. The aim of this undertaking is to identify and collate up to 150 000 SNPs from the Japanese population, located in genes or in adjacent regions that might influence the coding sequence of the genes. The project has been carried out by a collaboration between the Human Genome Center (HGC) in the Institute of Medical Science (IMS) at the University of Tokyo and the Japan Science and Technology Corporation (JST). JSNP serves as both a storage site for the Japanese SNPs obtained from the ongoing project and as a facility for public dissemination to allow researchers access to high quality SNP data. A primary motivation of the project is the construction of a basic data set to identify relationships between polymorphisms and common diseases or the reaction to drugs. As such, emphasis has been placed on the identification of SNPs that lie in candidate regions which may affect phenotype but which would not necessarily directly cause disease. Unrestricted access to JSNP and any associated files is available at http://snp.ims.u-tokyo.ac.jp/.

Structural visualization of expert nursing: Expert nursing care for a patient undergoing outpatient radiotherapy.

In the past, almost all patients underwent radiotherapy during the hospital stay. So nurses took care of patients after radiotherapy in the hospital where patients could receive nursing care 24 hours a day. However, recently more and more patients have undergone radiotherapy at clinics as outpatients. This benefits them in enabling them to receive the therapy with improving QOL and maintaining their style of living--on the other hand this requires much self-care ability on their part and patient compliance of outpatient visits depends on their own positive decision-making. Nurses are considered to make decisions or take implementation of various kinds of intervention in the limited time of pre and post proceedings of the therapy when they accommodate patients directly. The process of their intervention has not so far been clarified so that the quality of the care depends on the degree of each individual's capacity or devotion. In addition, with the trend in decreasing hospitalized days, it is predicted that more and more patients will undergo outpatient radiotherapy. So it is significant to clarify the process for quality assurance of nursing.

The Contribution of Genetic Architecture to the 10-Year Incidence of Age-Related Macular Degeneration in the Fellow Eye.

PURPOSE: To correlate a genetic risk score based on age-related macular degeneration (AMD) susceptibility genes with the risk of AMD in the second eye. METHODS: This is a retrospective, open cohort study consisting of 891 unilateral AMD patients, who were followed for at least 12 months and recruited from three institutes. DNAs were genotyped using Illumina OmniExpress, HumanOmni2.5-8, and/or HumanExome. Survival analyses and Cox proportional hazard models were used to examine the association between 11 AMD susceptibility genes and the duration until second-eye involvement in 499 samples from Kyoto University, which were replicated in two other cohorts. Genetic risk score (GRS) was also evaluated. RESULTS: The ARMS2 rs10490924 recessive model (hazard ratio [HR]meta = 2.04; Pmeta = 3.4 × 10⁻³) and CFH rs800292 additive model (HRmeta = 1.77; Pmeta = 0.013) revealed significant associations with second-eye involvement. The dominant model of TNFRSF10A rs13278062, VEGFA rs943080, and CFI rs4698775 showed consistent effects across three datasets (I² = 0%; HRmeta = 1.46, 1.30, 1.51, respectively). The GRS using these five single nucleotide polymorphisms (SNPs) was also significantly associated (HRmeta [per score] = 2.42; P = 2.2 × 10⁻5; I² = 0%). After 10 years from the first visit, the patients within the top 10% by GRS showed a 51% hazard rate, in contrast to 2.3% among patients within the lowest 10% by GRS. CONCLUSIONS: We demonstrated that the GRS using ARMS2, CFH, TNFRSF10A, VEGFA, and CFI was significantly associated with second-eye involvement. Genetic risk has high predictive ability for second-eye involvement of AMD.

Purification, characterization and gene cloning of thermostable O-acetyl-L-serine sulfhydrylase forming beta-cyano-L-alanine.

A thermophilic and cyanide ion-tolerant bacterium, Bacillus stearothermophilus CN3 isolated from a hot spring in Japan, was found to produce thermostable beta-cyano-L-alanine synthase. The enzyme catalyzes the synthesis of beta-cyano-L-alanine from O-acetyl-L-serine and cyanide ions. The purified enzyme has a molecular mass of approximately 70 kDa and consists of two identical subunits. It was stable in the pH range of 6.0 to 10.0 and up to 70 degrees C. The enzyme also catalyzes the synthesis of various beta-substituted-L-alanine derivatives from O-acetyl-L-serine and nucleophilic reagents. The gene encoding the beta-cyano-L-alanine synthase was isolated from B. stearothermophilus CN3. Sequence homology analysis revealed that the beta-cyano-L-alanine synthase of the bacterium is O-acetyl-L-serine sulfhydrylase. A recombinant plasmid, constructed by ligation of the cloned gene and an expression vector, pKK223-3, was introduced into E. coli JM109. The transformed E. coli cells overexpressed beta-cyano-L-alanine synthase. Heat stable beta-cyano-L-alanine synthase can be applied to the synthesis of [4-11C]l-2,4-diaminobutyric acid as a tracer for positron emission tomography.

Intraretinal hyperreflective foci on spectral-domain optical coherence tomographic images of patients with retinitis pigmentosa.

BACKGROUND: The purpose of this study was to observe the characteristic findings of spectral-domain optical coherence tomography (SD-OCT) images in the retinas of patients with retinitis pigmentosa and to evaluate their distribution patterns in the early and advanced stages of the disease. METHODS: A total of 184 patients (368 eyes) with retinitis pigmentosa were observed using SD-OCT. We studied the presence or absence of continuous inner/outer segment (IS/OS) lines, presence of thinning of the retinal pigment epithelium-Bruch's membrane complex, and distribution patterns of hyperreflective foci in the inner and outer nuclear layers (INL and ONL). RESULTS: The IS/OS junction had partially disappeared in 275 eyes, which were at the early stage of retinitis pigmentosa (group X), whereas the junction had totally disappeared in 93, which were at the advanced stage of retinitis pigmentosa (group Y). Hyperreflective foci in the INL were observed in a significantly larger proportion of the eyes in group X than in group Y (90% versus 61%, P<0.001), but hyperreflective foci in the ONL were observed in a significantly larger proportion of eyes in group Y than in group X (100% versus 69%, P<0.001). CONCLUSION: Hyperreflective foci in the INL were more frequently observed in retinas with the early stage of retinitis pigmentosa and hyperreflective foci in the ONL were more frequently observed in the advanced stage. Hyperreflective foci may be indicative of changes in the retinal structure at each stage of retinitis pigmentosa.

Induction of 11ß-HSD 1 and activation of distinct mineralocorticoid receptor- and glucocorticoid receptor-dependent gene networks in decidualizing human endometrial stromal cells.

The actions of glucocorticoids at the feto-maternal interface are not well understood. Here, we show that decidualization of human endometrial stromal cells (HESCs) in response to progesterone and cAMP signaling is associated with a strong induction of 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1) expression and enzyme activity. Decidualization also triggered a gradual decrease in glucocorticoid receptor (GR) expression and reciprocal increase in mineralocorticoid receptor (MR) levels. Gene expression profiling of differentiating HESCs after small interfering RNA (siRNA)-mediated knockdown of either GR or MR identified 239 and 167 significantly regulated genes, respectively. Interestingly, GR-repressed genes were enriched for Krüppel-associated box domain containing zinc-finger proteins, transcriptional repressors involved in heterochromatin formation. In agreement, GR knockdown was sufficient to enhance trimethylated H3K9 levels in decidualizing cells. Conversely, we identified several MR-dependent genes implicated in lipid droplet biogenesis and retinoid metabolism. For example, the induction in differentiating HESCs of DHRS3, encoding a highly conserved enzyme that catalyzes the oxidation/reduction of retinoids and steroids, was enhanced by aldosterone, attenuated in response to MR knockdown, and abolished upon treatment with the MR antagonist RU26752. Furthermore, we demonstrate that decidualization is associated with dynamic changes in the abundance and distribution of cytoplasmic lipid droplets, the formation of which was blocked by RU26752. In summary, progesterone drives local cortisol biosynthesis by decidual cells through induction of 11ß-hydroxysteroid dehydrogenase type 1 (11ßHSD1), leading to transcriptional regulation of distinct GR and MR gene networks involved in epigenetic programming and lipid and retinoid metabolism, respectively.