Luteal Research Articles

Investigating genotype by environment interaction for beef cattle fertility traits in commercial herds in northern Australia with multi-trait analysis

BackgroundGenotype by environment interactions (GxE) affect a range of production traits in beef cattle. Quantifying the effect of GxE in commercial and multi-breed herds is challenging due to unknown genetic linkage between animals across environment levels. The primary aim of this study was to use multi-trait models to investigate GxE for three heifer fertility traits, corpus luteum (CL) presence, first pregnancy and second pregnancy, in a large tropical beef multibreed dataset (n = 21,037). Environmental levels were defined by two different descriptors, burden of heat load (temperature humidity index, THI) and nutritional availability (based on mean average daily gain for the herd, ADWG). To separate the effects of genetic linkage and real GxE across the environments, 1000 replicates of a simulated phenotype were generated by simulating QTL effects with no GxE onto real marker genotypes from the population, to determine the genetic correlations that could be expected across environments due to the existing genetic linkage only. Correlations from the real phenotypes were then compared to the empirical distribution under the null hypothesis from the simulated data. By adopting this approach, this study attempted to establish if low genetic correlations between environmental levels were due to GxE or insufficient genetic linkage between animals in each environmental level.ResultsThe correlations (being less than <0.8) for the real phenotypes were indicative of GxE for CL presence between ADWG environmental levels and in pregnancy traits. However, none of the correlations for CL presence or first pregnancy between ADWG levels were below the 5th percentile value for the empirical distribution under the null hypothesis from the simulated data. Only one statistically significant (P < 0.05) indication of GxE for first pregnancy was found between THI environmental levels, where rg = 0.28 and 5th percentile value = 0.29, and this result was marginal.ConclusionsOnly one case of statistically significant GxE for fertility traits was detected for first pregnancy between THI environmental levels 2 and 3. Other initial indications of GxE that were observed from the real phenotypes did not prove significant when compared to an empirical null distribution from simulated phenotypes. The lack of compelling evidence of GxE indicates that direct selection for fertility traits can be made accurately, using a single evaluation, regardless of environment.

Roe Deer Reproduction in Western Poland: The Late Autumn Rut Phenomenon

Roe deer (Capreolus capreolus L.) populations in Poland are characterized by low productivity, which is why their reproductive potential was investigated. The presence of corpora lutea (CL) on the ovaries of females hunted in autumn and winter in the years 2015 and 2016 was assessed. Most animals were post-rut and most often had multiple ovulations. However, in early autumn 2015, 60% of the females had no CL. Therefore, they did not participate in mating at the turn of July/August. Those that did ovulate were found to have one CL. In late autumn, 97% of the females were post-rut, mostly with twin ovulations. This confirmed the occurrence of a late autumn rut. This phenomenon had been suggested in studies but not confirmed. In contrast, almost 100% of roe deer ovulated in summer in 2016. It was hypothesized that the reason for the low mating activity of roe deer in the summer of 2015 was heat stress and limited food resources. The summer was exceptionally hot, with many days in July and August when temperatures exceeded 30 °C. The heat combined with low rainfall led to extreme drought. Meanwhile, July and August are the months of mating activity for roe deer. The late autumn rut allowed the roe deer—a monoestrous species—to limit the consequences of a decrease in mating activity or fertility during the hot summer. Global warming may affect roe deer reproduction, so climatic conditions should be considered in population studies, not only in terms of food availability.

Expression and localization of Uhrf1 in the major reproductive organs of yaks during different reproductive cycles

Uhrf1 is a multi-domain and multifunctional epigenetic regulator playing key roles in DNA methylation, cell metabolism, and cell proliferation. To investigate the role of Uhrf1 in the reproductive physiology of female yaks, we collected three reproductive organs (ovaries, oviducts, and uteri) from healthy yaks during three reproductive phases (follicular, luteal, and gestational phases), with a total of nine groups. Real-time fluorescence quantitative PCR (RT-qPCR), Western blotting, and immunohistochemistry (IHC) were employed to determine the expression levels of Uhrf1 and the subcellular localization of this protein. RT-qPCR and Western blotting results showed that Uhrf1 was expressed highest in the oviduct during the follicular phase, moderate expression in the uterus during the gestational phase, and the lowest expression in the uterus during the luteal phase (P < 0.05). IHC results showed that Uhrf1 was mainly expressed in the ovarian germinal epithelium, theca follicular, follicular granulosa, luteal cells, oviduct mucosal epithelial cells, and uterine glands (UG) of yaks. In conclusion, Uhrf1 was differentially expressed in the major reproductive organs during the reproductive cycle of female yaks, indicating its important regulatory role in the reproductive physiology of yaks.

The mechanism of NF-κB-TERT feedback regulation of granulosa cell apoptosis in PCOS rats.

Patients with Polycystic ovary syndrome (PCOS) have chronic low-grade ovarian inflammation. Inflammation can cause telomere dysfunction, and telomere and telomerase complex are also involved in regulating inflammation. However, the specific mechanisms of inflammatory signaling feedback and telomere-telomerase mutual regulation remain to be discovered. This study elucidates the role of Nuclear factor kappa-B (NF-κB)-Telomerase reverse transcriptase (TERT) feedback in PCOS granulosa cell apoptosis. Using letrozole and a high-fat diet, a PCOS rat model was established, along with a Lipopolysaccharide (LPS) -treated KGN cell inflammation model was established. NF-κB and TERT inhibitors (BAY 11-7082 and BIBR1532) were then administered to LPS-induced KGN cells. PCOS rats displayed disrupted estrous cycles, increased weight, elevated serum testosterone, cystic follicles, granulosa cell layer thinning, and reduced corpora lutea count (P are all less than 0.05). In PCOS rat ovaries, NF-κB, Interleukin-6 (IL-6), Tumor Necrosis Factor α (TNF-α), TERT, Bax, and Caspase-3 exhibited notable upregulation, while Bcl-2 decreased, with telomere elongation (P are all less than 0.05). There were significant correlations among NF-κB-related inflammatory factors, TERT and apoptotic factors, and they were positively correlated with Bax and Caspase-3, and negatively correlated with Bcl-2 (P are all less than 0.05). LPS-treated KGN cells demonstrated increased expression of inflammatory and pro-apoptotic factors, later restored post-treatment with NF-κB and TERT inhibitors (P are all less than 0.05). In conclusion, TERT may induce granulosa cell apoptosis by participating in the regulation of the NF-κB signaling pathway, thereby mediating the chronic inflammatory response of PCOS through downstream inflammatory factors IL-6 and TNF-α.

Embryo production by Holstein heifers superovulated with a recombinant long-acting follicle stimulating hormone analog.

This study aimed to evaluate embryo yield in Holstein heifers superovulated with a single injection of recombinant, long-acting human follicle-stimulating hormone (rFSH) versus multiple injections of pituitary-derived follicle-stimulating hormone (FSH). In Experiment 1, heifers were assigned randomly to one of 4 experimental groups: Control (280mg of pituitary derived FSH; six injections of 40mg and two injections of 20mg, each ~12h apart, n = 16); rFSH1 (50 μg of FSH analog protein, n = 16); rFSH2 (75 μg of FSH analog protein, n = 16) or; rFSH3 (100 μg of FSH analog protein, n = 16). The rFSH was administered as a single injection. Estrous cycles were presynchronized with gonadorelin acetate (GnRH) and an intra-vaginal progesterone insert (CIDR) on d -8, followed by cloprostenol sodium (PGF2α) on d -3 and d -2 with removal of the CIDR, and GnRH on d 0. On d 5, ovarian follicles ≥ 5mm in diameter were ablated by transvaginal ultrasound-guided aspiration. On d 6.5, heifers received a CIDR and the rFSH or the first injection of pituitary-derived FSH. On d 9, heifers received two injections of PGF2α, 12h apart. On d 10.5, the CIDR was removed, and on d 11, heifers received a GnRH injection. Heifers were AI-inseminated 12- and 24-hours post-GnRH injection, and uterine contents were flushed trans-cervically on day 18 (7 d after the GnRH injection). Ovarian follicles ≥ 5mm and corpora lutea were counted via ultrasound on days 5, 9, and 18. In Experiment 1, group did not affect (P = 0.52) the number of follicles ≥ 5mm (Control = 15.9 ± 1.2; rFSH1 = 17.5 ± 1.3; rFSH2 = 17.1 ± 1.3; rFHS 3 = 18.6 ± 1.4 follicles) or the number of corpora lutea (P = 0.96) on d 9 (Control = 1.1 ± 0.3; rFSH1 = 1.1 ± 0.3; rFSH2 = 1.1 ± 0.3; rFSH3 = 0.9 ± 0.2). Furthermore, there was no effect (P = 0.28) of rFSH dose on freezable embryos (grade 1 and 2 embryos) collected on d 18 (Control = 4.7 ± 1.1; rFSH1 = 4.7 ± 1.2; rFSH2 = 4.4 ± 1.1; rFSH3 = 2.6 ± 0.7 embryos). In Experiment 2, Control (n=8) and rFSH1 (n=16) groups were repeated in 3 replicates using the same protocols as Experiment 1. Consequently, Results showed that rFSH produced fewer total number of ova/embryos (Control = 9.9 ± 1.5 vs. rFHS1 = 5.9 ± 0.9, P = 0.04) and fewer freezable embryos (Control = 5.3 ± 1.0 vs. rFSH1 = 1.4 ± 0.3, P < 0.01). In conclusion, the single rFSH injection effectively induced superovulation; however, its repeated use reduced embryo production.

Follicle-intrinsic and spatially distinct molecular programs drive follicle rupture and luteinization during ex vivo mammalian ovulation

During ovulation, the apical wall of the preovulatory follicle breaks down to facilitate gamete release. In parallel, the residual follicle wall differentiates into a progesterone-producing corpus luteum. Disruption of ovulation, whether through contraceptive intervention or infertility, has implications for women’s health. In this study, we harness the power of an ex vivo ovulation model and machine-learning guided microdissection to identify differences between the ruptured and unruptured sides of the follicle wall. We demonstrate that the unruptured side exhibits clear markers of luteinization after ovulation while the ruptured side exhibits cell death signals. RNA-sequencing of individual follicle sides reveals 2099 differentially expressed genes (DEGs) between follicle sides without ovulation induction, and 1673 DEGs 12 h after induction of ovulation. Our model validates molecular patterns consistent with known ovulation biology even though this process occurs in the absence of the ovarian stroma, vasculature, and immune cells. We further identify previously unappreciated pathways including amino acid transport and Jag-Notch signaling on the ruptured side and glycolysis, metal ion processing, and IL-11 signaling on the unruptured side of the follicle. This study yields key insights into follicle-inherent, spatially-defined pathways that underlie follicle rupture, which may further understanding of ovulation physiology and advance women’s health.

Diagnosis of Menopause in a Captive Sumatran Orangutan (Pongo abelii).

Humans were long thought to be the only mammal to experience menopause, the permanent cessation of reproduction followed by a long post-reproductive lifespan. More recently, evidence has been found for the existence of menopause in other long-lived mammals, including chimpanzees and gorillas. However, orangutans, which have the longest interbirth interval of any primate, have rarely been studied in this period of their lives. In this paper, we describe clinical, ultrasound, endocrine, and histological evidence consistent with a natural menopause in a captive, previously fertile, Sumatran orangutan (Pongo abelii), aged approximately 50. Consecutive serum samples showed low levels of estradiol and high levels of follicle-stimulating hormone. Transvaginal ultrasound revealed an atrophic uterus with an antero-posterior diameter of 2.36 cm, an endometrial thickness of 2 mm, and inactive ovaries. Following this female's death from a subdural hematoma, histological examination of the ovaries showed a dense stroma with corpora albicantia, in comparison to the numerous primordial follicles seen in the ovaries of a stillborn infant female orangutan. These multiple lines of evidence suggest that Sumatran orangutans can now be added to the list of mammals which undergo a true menopause, which may ensure that females' final offspring can be reared to independence.

The lifespan of corpora lutea in nonpregnant females is positively correlated with gestation length

Abstract In mammals, a temporary endocrine gland called the corpus luteum forms on the ovary shortly after ovulation and is required for the initiation and maintenance of early pregnancy. However, the corpus luteum persists even when fertilization or pregnancy does not occur, and species-specific variation in the length of this persistence remains enigmatic. Here we perform a comparative evolutionary study across 72 species and show that corpus luteum lifespan in nonpregnant females is positively correlated with gestation length. We argue that the most likely explanation for this correlation is physiological inertia. The corpus luteum begins secreting progesterone prior to implantation, and when pregnancy does not occur it takes time for females to degrade it and prepare the next reproductive cycle. Our study suggests that this physiological inertia is stronger in species with long gestation times.

Effect of Gonadotropin-Releasing Hormone Treatment on Superovulation Response and Embryo Recovery in Holstein Heifers: A Field Trial at Zagros Milk and Meat Company, Iran

Background: Superovulation is a crucial component of assisted reproductive technology. Inducing superovulation with Gonadotropin-releasing hormone (GnRH) can lead to ovarian hyperstimulation, potentially affecting reproductive outcomes. Objectives: This study aimed to examine the effects of GnRH treatment on superovulation response and embryo recovery in Holstein heifers. Methods: Twenty-one Holstein heifers (age: 135.15 months; weight: 361.05 kg) were selected based on their general health status and ovarian function. All heifers received two consecutive doses of prostaglandin F2α and underwent superovulation. The heifers were inseminated twice: Once at the onset of standing estrus and again 12 hours later. In the treatment group (13 heifers), a single dose of GnRH was administered simultaneously with the second insemination. The superovulation response was evaluated based on the number of corpus luteum (CL), unovulated follicles (UoF), total recovered embryos/ova, and the number of transferable embryos, using logistic regression with the GENMOD procedure in SAS. Results: The mean number of CL was not significantly greater in the control group (13.6) compared to the GnRH group (11.4). The average number of UoF was similar between the two groups (P = 0.1853). However, the control group had a significantly higher average total number of recovered embryos/ova (7.7) compared to the GnRH group (2.1). Additionally, the control group produced more transferable embryos, with an average of 2.5, while the GnRH group averaged 0.7 (P &lt; 0.0062). Conclusions: Gonadotropin-releasing hormone likely deactivated the oviduct by disrupting the balance of estradiol and estrogen, leading to a reduction in both the total number of embryos and the number of transferable embryos in heifers.

The metabolomic composition of the oviductal fluid is controlled by the periovulatory hormonal context in Bos indicus cows.

In cattle, oviductal function is controlled by the ovarian sex-steroids estradiol and progesterone. Here, we tested the hypothesis that the exposure to contrasting sex-steroid milieus differentially impacts the oviductal fluid composition. Estrous cycles of non-lactating, multiparous Nelore cows were pre-synchronized and then synchronized with a protocol designed two induce ovulation of large (LF group) or small (SF group) follciles. Larger preovulatory follicle (day 0) and corpora lutea (day 4) and greater estradiol (day 0) and progesterone (day 4) concentrations were observed in the LF group. Four days after induced ovulation, oviductal fluid was collected post-mortem. Quantitative mass spectrometry was used to determine the concentration of amino acids, biogenic amines, acylcarnitines, phosphatidylcholines, lysophosphatidylcholines, sphingomyelins, hexoses, prostaglandins and related compounds. Multivariate analyses (OPLS-DA) were conducted to compare the metabolomic signatures of oviductal fluids. Correlation network analysis was conducted to measure the strength and hierarchy of associations among metabolites. Of the 205 metabolites quantified, 171 were detected in at least 50% of the samples and were included in further data analysis. After OPLS-DA analysis, samples of the LF and SF were divided clearly into two non-overlapping clusters. Twenty metabolites had different or tended to have different concentrations in the oviductal fluid when comparing groups. Seven of these 20 analytes had greater concentrations in LF cows. Moreover, total sum of biogenic amines, phosphatidylcholines, and prostaglandins were higher in the SF group. The correlation network showed that the LF group metabolites' concentrations were highly intercorrelated, which was not observed in the SF group. We concluded that the periovulatory endocrine milieu regulates the composition of the oviductal fluid.

A new species of the pill millipede genus Rhopalomeris Verhoeff, 1906 (Diplopoda, Glomerida, Glomeridae) from Myanmar, and notes on Rhopalomeriscarnifex (Pocock, 1889).

The taxonomy of the pill millipede genus Rhopalomeris Verhoeff, 1906, which is restricted to Indochina and currently comprises six described species, is refined and updated. An integrative taxonomic approach was employed that combines morphological examination with DNA barcoding using the cytochrome c oxidase subunit I (COI) gene for species identification and delineation. The first objective was to confirm the identity of Rhopalomeriscarnifex (Pocock, 1889), a charismatic species known as the "candy pill millipede" due to its vivid coloration, based on specimens collected near the type locality in Myanmar. The second objective was to describe a new species, Rhopalomerisnigroflava Likhitrakarn, sp. nov., discovered in Linno Gu, Kayin State, Myanmar. This new species is distinguished by its small body size (5.1-9.7 mm long) and yellow body with contrasting brown to blackish markings on certain terga. In addition, the position of the telopod syncoxital lobe relative to the lateral syncoxite horns separates it from other Rhopalomeris species. The interspecific divergence between R.nigroflava Likhitrakarn, sp. nov. and other congeners ranges from 10.85% to 16.13%, based on uncorrected COI p-distances, while the intraspecific divergence was 0%-7.44%. A distribution map of and a revised identification key to all known species of Rhopalomeris are also provided.

Selecting optimal progestational agents either alone or in combination in common pediatric endocrine settings: challenges of unmet needs.

Progesterone is a natural hormone, mainly produced by the corpus luteum, with the foremost endocrine function on the secretory glands of the endometrium. Since being isolated, both natural and synthetic forms have been produced and are utilized for several purposes, including regulating the menstrual cycle and preventing endometrial hyperplasia. Specifically, the use of progestational agents is essential in the treatment of many common endocrine conditions, including Polycystic Ovary Syndrome, Congenital Adrenal Hyperplasia, Turner Syndrome, and Functional Hypothalamic Amenorrhea. Although these agents are essential for disease management, literature that focuses on the benefits of specific progestins as well as the effects on glucocorticoid receptors (GR), mineralocorticoid receptors (MR), and androgenic receptors (AR) is limited. In this review, we provide a disease specific summary of the available literature and highlight where more information is needed.

The Potential Health Risks of Catha edulis Forsk (Khat) Consumption on Some Vital Organs

Abstract Introduction/Objective Introduction: Catha edulis Forsk (Khat) leaves are widely chewed by adults in the Arabian Peninsula and the Horn of Africa for their mild stimulating properties. Objectives To investigate the impact of an aqueous extract of Catha edulis Forsk leaves on the proper functioning of vital organs. Methods/Case Report Methods: Materials and methods: Twenty-five female albino rats were divided into two groups: a control group and a treated group which received a daily gavage of 1 ml of aqueous Khat extract with a concentration of 700 mg/kg body weight for four weeks. The effects of this treatment on selected organs, including the brain, hippocampus, heart, and ovaries, were assessed using various measurements and analyses. Results (if a Case Study enter NA) Results: Results: The antioxidant evaluation showed a significant increase in MDA levels in the khat group and a significant decrease in GSH, SOD, and CAT levels compared to the control group. There was a significant decrease in IL-4 and a significant increase in TNF-α and TGF-β1 compared to the control group. In contrast, the cardiac enzymes; Troponin, CK, CPK, and GOT showed a significant increase compared to the control group. The results of the hormonal assay indicated a significant increase in LH, FSH, and testosterone levels, along with a significant decrease in estrogen in the khat group compared to the control group. Furthermore, the histological investigations revealed significant changes in tissue architecture in the studied organs. In the heart, the treated group exhibited an intact, thick pericardium, along with markedly apoptotic cardiac muscle fibers and others with pyknotic nuclei and mildly congested blood vessels and capillaries. The examination of brain tissues in the treated group showed thick meninges with mild inflammatory infiltrate, marked astrogliosis with degenerated neurons in the cerebral cortex, inflammatory infiltrate with abscess formation and mildly congested blood vessels and eosinophilic plaque-like area in the deep cortex, and scattered degenerated neurons and some neurons with nuclear vacuoles and average glial cells in the white matter. In the ovaries, sections showed primary, secondary, and antral follicles, scattered cystically dilated follicles with atrophied lining, and multiple corpora lutea in the edematous stroma with scattered apoptotic stromal cells. Conclusion Based on these findings, long-term use of khat as a chewing material may harm vital organs.

Genetic architecture of meat traits in Large White sows

Currently, genome-wide association analysis is a modern and reliable method for analyzing genomic information about animals, as well as determining the “genotype — phenotype” relationship. This study aims to use the GWAS method to identify significant SNPs located within or linked to genes for meat traits in Large White pigs — backfat thickness over the 6–7th and 10–12th vertebrae, and loin muscle depth. The conducted GWA analysis revealed 60 genes, of which 17 are associated with biological functionality, annotated using the DAVID program. Three genes were found to have codification in the Pig QTL database. The genes were divided into 10 groups based on gene ontology (GO). Of all the genes, the AUTS2 gene, located on chromosome 3 and predicting the number of corpora lutea in sows, is of greatest interest. The results of this scientific work will contribute to the development of a genetic evaluation system and improvement of meat qualities in pigs.

Small extracellular vesicles derived from the crosstalk between early embryos and the endometrium potentially mediate corpus luteum function.

The first interactions among the embryo, endometrium, and corpus luteum (CL) are essential for pregnancy success. Small extracellular vesicles (sEVs) are part of these interactions. We previously demonstrated that sEVs from in vivo- or in vitro-produced bovine embryos contain different miRNA cargos. Herein we show: 1) the presence and origin (in vivo or in vitro) of the blastocyst differentially reprograms endometrial transcriptional profiles; 2) the endometrial explant (EE) cultured with in vivo or in vitro embryos release sEVs with different miRNA contents, and; 3) the luteal explant (CLE) exposed to these sEVs have distinct mRNA and miRNA profiles. To elucidate this, the EE were cultured in the presence or absence of a single Day-7 in vivo (EE-AI) or in vitro (EE-IVF) embryo. After of culture we found, in the EE, 45 and 211 differentially expressed genes (DEGs) associated with embryo presence and origin, respectively. SEVs were recovered from the conditioned media (CM) in which EE and embryos were co-cultured. Four miRNAs were differentially expressed between sEVs from CM-EE-AI and CM-EE-IVF. Luteal explants exposed in culture to these sEVs showed 1360 transcripts, and fifteen miRNAs differentially expressed. The DEGs associated with embryo presence and origin, modulating cells' proliferation, and survival. These results demonstrate that in vivo- or in vitro-produced bovine embryos induce molecular alterations in the endometrium; and that the embryo and endometrium release sEVs capable of modifying the mRNA and miRNA profile in the CL. Therefore, the sEVs-mediated embryo-endometrium-CL interactions possibly regulate the CL viability to ensure pregnancy success.

Fertility and teratogenic study of the aqueous extract of Hibiscus sabdariffa L. in female Sprague Dawley rats

Hibiscus sabdariffa (roselle) has long been gaining attention in phytotherapy research due to its medicinal properties. Despite its benefits, there is very scarce information available on the reproductive toxicity of this plant. The aqueous extract of H. sabdariffa (AEHS) was tested in the present study to investigate its potential effects on fertility and teratogenicity in 40 female Sprague Dawley rats. AESH treatment was administered orally by gavage at four different dosages: 250, 500 and 1000 mg/kg/day or distilled water (control). Treatment began from pre-mating and continued through mating up to the 19th day of pregnancy periods. Throughout this study, the reproductive parameters were evaluated until the day of sacrifice (day 20th of pregnancy). Results obtained revealed no significant differences in general physical health, behaviours and maternal body weights throughout the treatment period. Furthermore, the mean length of the oestrous cycle was not statistically affected, even though a few rats displayed irregular cycles. In addition, there was no statistical significance in the mating and pregnancy indices, number of corpora lutea and implantation sites, percentages of pre-implantation loss and postimplantation death and reproductive organ weights. Foetal parameters such as the number of live foetuses, sex ratio and body weight were also not statistically affected by AESH. Ultimately, there were no signs of teratogenicity observed since none of the foetuses exhibited congenital malformations. In conclusion, these findings imply that the oral administration of AEHS up to 1000 mg/kg/day did not pose any significant toxicity on the fertility and teratogenicity but slightly affected the oestrous cycle in rats.

Antioxidant activity of self-nanoemulsifying drug delivery system (SNEDDS) of Curcuma longa in polycystic ovary syndrome rat model

Purpose: To investigate the effect of SNEDDS containing Curcuma longa extract on hormonal and histological improvement of polycystic ovary syndrome (PCOS) rat model. Method: A total of 36 female Wistar rats, aged between 8 and 10 weeks, were randomly divided into 6 groups, including control (normal rats), PCOS (untreated PCOS rats), PCOS + M (treated with 20 mg/kg bw/day metformin), PCOS + SC25, PCOS + SC50, and PCOS + SC100 (treated with Curcuma longa extract at 25, 50, and 100 mg/kg/day with SNEDDS, respectively). This study used a posttest-only control group design. The rats were euthanized on day 15, and blood samples were taken to examine malondialdehyde (MDA) and anti-mullerian hormone (AMH) levels. Ovarian tissue was prepared on a histological slide, and various follicles were observed. Data was analyzed using analysis of variance (ANOVA) and Kruskal-Wallis tests. Results: Curcuma longa extract, at 50 and 100 mg/kg, incorporated in SNEDDS resulted in a significant reduction in the corpus luteum number and width of the granulosa layer (p &lt; 0.05). Also, Curcuma longa significantly reduced malondialdehyde (MDA), anti-mullerian hormone (AMH), preantral follicles, and follicular cysts (p &lt; 0.05). Conclusion: Curcuma longa extract in SNEDDS reduces MDA and AMH levels and improves the histology of the ovaries in PCOS model rats. There is a need to conduct further studies of C. longa extract or isolates in SNEDDS using human cell lines of PCOS model.

8354 OVARIAN HYPERTHECOSIS: AN UNCOMMON CAUSE OF HYPERANDROGENISM IN A POSTMENOPAUSAL WOMAN

Abstract Disclosure: M.D. Severino: None. F.P. Silva: None. M.V. Lopes: None. C. Nunes: None. M.I. Alexandre: None. M.J. Bugalho: None. Introduction: Severe hirsutism in postmenopausal women demands a careful clinical evaluation to exclude a malignant cause, such as adrenal or ovarian androgen-secreting tumors. Ovarian hyperthecosis is an uncommon and benign cause of hyperandrogenism and, consequently, hirsutism. It is caused by persistent testosterone synthesis due to proliferation of ovarian stromal cells and nests of luteinized theca cells. It occurs more often in postmenopausal women, as aromatization of testosterone to estradiol decreases due to the loss of granulosa cells. It is also frequently associated with obesity and insulin resistance. Clinical case: We present the case of a 61-year-old woman, with a history of hypertension and dyslipidemia, referred to Endocrinology Clinic due to a year long history of hirsutism, most severe on her face, chest, and abdomen. She also mentioned slight clitoromegaly. She had no other virilization symptoms such as acne, male-pattern alopecia, voice deepening or mammary atrophy. Her menarche occurred at the age of 14 and she had regular menses until menopause, at the age of 51. She had a BMI of 32 kg/m2 and an uncharacteristic phenotype. At observation, she had a mild hirsutism (Ferriman-Gallwey score of 9). This contrasted with the biochemical findings of severe androgenism - total testosterone of 366 ng/dL (reference values [RV] for women between 5-48) with free testosterone 7.8 pg/mL and SHBG 74 nmol/L (RV 32-128), resulting in a Free Androgen Index of 17,16 (RV &amp;lt;6.6). DHEAS, androstenedione, 17-hydroxyprogesterone and prolactin were normal, and gonadotropins were in the menopausal range. Blood tests also showed hyperinsulinemia and pre-diabetes with HbA1c 6,2%. She denied exposure to steroids in the form of new medication, supplements, or creams/gels (including second-hand exposure through her partner) and she had no exposure to other drugs with androgenic effect. Abdominal and pelvic CT scan, as well as transvaginal ultrasound, showed no adrenal or ovarian lesions. An ovarian cause was deemed the most likely and laparoscopic diagnostic bilateral salpingo-oophorectomy was performed. Gross pathology revealed ovaries of regular size, while histology showed bilateral ovarian stromal hyperthecosis. Testosterone levels returned to normal one month after surgery (14,2 ng/dL). Conclusion: Benign, ovarian causes of hyperandrogenism are uncommon in postmenopausal women, requiring a high index of suspicion. The diagnosis is difficult, and laparoscopic bilateral salpingo-oophorectomy is essential as both a diagnostic and therapeutic tool. Presentation: 6/2/2024

8354 Ovarian Hyperthecosis: an Uncommon Cause of Hyperandrogenism in a Postmenopausal Woman

Abstract Disclosure: M.D. Severino: None. F.P. Silva: None. M.V. Lopes: None. C. Nunes: None. M.I. Alexandre: None. M.J. Bugalho: None. Introduction: Severe hirsutism in postmenopausal women demands a careful clinical evaluation to exclude a malignant cause, such as adrenal or ovarian androgen-secreting tumors. Ovarian hyperthecosis is an uncommon and benign cause of hyperandrogenism and, consequently, hirsutism. It is caused by persistent testosterone synthesis due to proliferation of ovarian stromal cells and nests of luteinized theca cells. It occurs more often in postmenopausal women, as aromatization of testosterone to estradiol decreases due to the loss of granulosa cells. It is also frequently associated with obesity and insulin resistance. Clinical case: We present the case of a 61-year-old woman, with a history of hypertension and dyslipidemia, referred to Endocrinology Clinic due to a year long history of hirsutism, most severe on her face, chest, and abdomen. She also mentioned slight clitoromegaly. She had no other virilization symptoms such as acne, male-pattern alopecia, voice deepening or mammary atrophy. Her menarche occurred at the age of 14 and she had regular menses until menopause, at the age of 51. She had a BMI of 32 kg/m2 and an uncharacteristic phenotype. At observation, she had a mild hirsutism (Ferriman-Gallwey score of 9). This contrasted with the biochemical findings of severe androgenism - total testosterone of 366 ng/dL (reference values [RV] for women between 5-48) with free testosterone 7.8 pg/mL and SHBG 74 nmol/L (RV 32-128), resulting in a Free Androgen Index of 17,16 (RV &amp;lt;6.6). DHEAS, androstenedione, 17-hydroxyprogesterone and prolactin were normal, and gonadotropins were in the menopausal range. Blood tests also showed hyperinsulinemia and pre-diabetes with HbA1c 6,2%. She denied exposure to steroids in the form of new medication, supplements, or creams/gels (including second-hand exposure through her partner) and she had no exposure to other drugs with androgenic effect. Abdominal and pelvic CT scan, as well as transvaginal ultrasound, showed no adrenal or ovarian lesions. An ovarian cause was deemed the most likely and laparoscopic diagnostic bilateral salpingo-oophorectomy was performed. Gross pathology revealed ovaries of regular size, while histology showed bilateral ovarian stromal hyperthecosis. Testosterone levels returned to normal one month after surgery (14,2 ng/dL). Conclusion: Benign, ovarian causes of hyperandrogenism are uncommon in postmenopausal women, requiring a high index of suspicion. The diagnosis is difficult, and laparoscopic bilateral salpingo-oophorectomy is essential as both a diagnostic and therapeutic tool. Presentation: 6/2/2024

7617 Two Cases of Severe Beta-hCG-Mediated Hyperthyroidism with Gestational Trophoblastic Disease

Abstract Disclosure: A. Morvant: None. M. Mashayekhi: None. Introduction: Hyperthyroidism is most commonly caused by Graves’ disease and toxic nodules and affects 2.5% of the world’s population. Hyperthyroidism due to elevations in beta-hCG (b-hCG), which has thyroid-stimulating activity due to homology with TSH, is a rare process that requires high clinical suspicion. We present two cases of hyperthyroidism caused by severely elevated b-hCG due to gestational trophoblastic disease (GTD), with rapid resolution of hyperthyroidism after treatment of the underlying conditions. Clinical Cases Case 1: A 35-year-old at 28-weeks gestation presented with dyspnea, palpitations, and 6-pound weight loss over the prior month. Labs revealed b-hCG 5.2 million (0-5 mIU/mL), TSH &amp;lt;0.015 (0.35-3.6 mcU/mL), and free T4 2.42 (0.7-1.37 ng/dL). Imaging revealed extensive pulmonary lesions concerning for metastatic disease and a 2.4 cm ovarian mass. Due to worsening respiratory distress and the need to start chemotherapy urgently, she underwent Cesarean section to deliver the viable infant and take out the ovarian mass. Pathology confirmed choriocarcinoma. Methimazole was started post-operatively, and she started chemotherapy. Labs after cycle one of chemotherapy showed b-hCG 1.3 million, TSH &amp;lt;0.015, and free T4 1.46. The methimazole dose was decreased and ultimately stopped as free T4 levels decreased with subsequent chemotherapy cycles. After three cycles, labs showed b-hCG 4,652, TSH 1.55, and free T4 0.68. She was discharged without thyroid-targeting therapy. Case 2: A 33-year-old woman at 12-weeks gestation presented with nausea, vomiting, and 10-pound weight loss over 1 month. Labs showed TSH &amp;lt;0.015, free T4 2.39, and total T3 351 (58-160 ng/dL), which were thought to be due to hyperemesis gravidarum. Two months later she presented with vaginal bleeding and imaging showed an enlarged placenta with a moth-eaten appearance and theca lutein cysts concerning for partial molar pregnancy. Beta-hCG level was 3.3 million, TSH &amp;lt;0.015, free T4 1.76, and total T3 289. She underwent dilation and evacuation and pathology confirmed partial hydatidiform mole. Beta-hCG level decreased to 1.8 million and free T4 normalized after surgery, with b-hCG 3,300, normal TSH, and normal total T3 one month later. Conclusion: These cases highlight the importance of considering possible GTD when evaluating a patient with hyperthyroidism, particularly in women of childbearing age and cases of early pregnancy when the degree of hyperthyroidism seems out of proportion to that expected. Clinicians should consider checking a b-hCG level in consultation with an obstetrician when indicated. Treatment is aimed at the GTD and can yield rapid resolution of hyperthyroidism.