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Objective: Female Mcoln1 -/- mice (5-6 months old) with exogenous P4 treatment on days 1.5 post-coitum (D1.5), D2.5, and D3.5, and observed partially restored luteal cell morphology on D4.5, but unexpectedly found 17β-estradiol (E Mcoln1 ) contamination in the P4 working solution. In this study, we aim to investigate exogenous P4 and/or E -/- mice (5-6 months old) with exogenous P4 treatment on days 1.5 post-coitum (D1.5), D2.5, and D3.5, and observed partially restored luteal cell morphology on D4.5, but unexpectedly found 17β-estradiol (E 2 ) contamination in the P4 working solution. In this study, we aim to investigate exogenous P4 and/or E 2 for the partial recovery of luteal cell morphology in infertile Mcoln1 -/- mice., Methods: Control and non-virgin Mcoln1 mice (5-6 months old) were treated with newly ordered vehicle, P4, E -/- , or P4 + E 2 on D1.5 and D2.5 and dissected on D3.5 for P4 and E 2 on D1.5 and D2.5 and dissected on D3.5 for P4 and E 2 measurements, ovary histology, immunofluorescence, lipid droplet staining, and transmission electron microscopy., Results: E 2 treatment significantly increased serum P4 levels in D3.5 Mcoln1 mice. E -/- and P4 + E 2 and P4 + E 2 treatments, but not P4 treatment alone, largely improved the morphology of D3.5 Mcoln1 luteal cells, while in E -/- corpora lutea, indicated by a more contiguous web-like collagen IV expression pattern, increased heat shock protein 60 expression, and reduced accumulation of large lipid droplets. Transmission electron microscopy revealed extremely enlarged autophagosomes and lipid droplets, lysosomes with lamellar structures, and mitochondria with reduced cristae in vehicle-treated D3.5 Mcoln1 -/- luteal cells, while in E 2 -treated D3.5 Mcoln1 -/- luteal cells, extremely enlarged autophagosomes and lipid droplets were reduced, indicating improved luteal cell ultrastructure., Conclusion: These findings reveal protective effects of high levels of exogenous E 2 on P4 production and lysosomal function in Mcoln1 -/- luteal cells., Competing Interests: All authors declare no conflicts of interest., (Copyright © 2024 Reproductive and Developmental Medicine, Published by Wolters Kluwer Health, Inc.)

The phytochemical investigation of the hydromethanolic extract of Carica papaya Linn. leaves (Caricaceae) resulted in the isolation and characterization of ten compounds, namely; carpaine (1), methyl gallate (2), loliolide (3), rutin (4), clitorin (5), kaempferol-3- O -neohesperidoside (6), isoquercetin (7), nicotiflorin (8) and isorhamnetin-3- O -β-d-glucopyranoside (9). The compounds 2, 3, 5-7 and 9 were isolated for the first time from the genus Carica . An in vitro breast cancer cytotoxicity study was evaluated with an MCF-7 cell line using the MTT assay. Methyl gallate and clitorin demonstrated the most potent cytotoxic activities with an IC 50 of 1.11 ± 0.06 and 2.47 ± 0.14 μM, respectively. Moreover, methyl gallate and nicotiflorin exhibited potential EGFR wt kinase inhibition activities with an IC 50 of 37.3 ± 1.9 and 41.08 ± 2.1 nM, respectively, compared with the positive control erlotinib (IC 50 = 35.94 ± 1.8 nM). On the other hand, clitorin and nicotiflorin displayed the strongest aromatase kinase inhibition activities with an IC 50 of 77.41 ± 4.53 and 92.84 ± 5.44 nM, respectively. Clitorin was comparable to the efficacy of the standard drug letrozole (IC 50 = 77.72 ± 4.55). Additionally, molecular docking simulations of the isolated compounds to EGFR and human placental aromatase cytochrome P450 (CYP19A1) were evaluated. Methyl gallate linked with the EGFR receptor through hydrogen bonding with a pose score of -4.5287 kcal mol -1 and RMSD value of 1.69 Å. Clitorin showed the strongest interaction with aromatase (CYP19A1) for the breast cancer receptor with a posing score of -14.2074 and RMSD value of 1.56 Å. Compounds (1-3) possessed a good bioavailability score with a 0.55 value., Competing Interests: The authors declare no conflict of interest., (This journal is © The Royal Society of Chemistry.)