Melatonin facilitates oocyte growth in goats and mice through increased nutrient reserves and enhanced mitochondrial function.

Oogenesis involves two phases: initial volumetric growth driven by nutrient accumulation and subsequent nuclear maturation. While melatonin (MLT) has been employed as a supplement to enhance the quality of fully grown oocytes during nuclear maturation phase, its impact on oocyte growth remains poorly studied. Here, we provide in vivo evidence demonstrating that follicle-stimulating hormone increases MLT content in ovary. Administration of MLT improves oocyte growth and quality in mice and goats by enhancing nutrient reserves and mitochondrial function. Conversely, MLT-deficient mice have smaller oocytes and dysfunctional mitochondria. Exploring the clinical implications of MLT in promoting oocyte growth, we observe that a brief 2-day MLT treatment enhances oocyte quality and reproductive performance in older mice. These findings highlight the role of MLT in regulating oocyte growth and provide a specific treatment window for optimizing oocyte quality and reproductive performance in female animals.

The FSH-mTOR-CNP signaling axis initiates follicular antrum formation by regulating tight junction, ion pumps, and aquaporins.

The initial formation of the follicular antrum (iFFA) serves as a dividing line between gonadotropin-independent and gonadotropin-dependent folliculogenesis, enabling the follicle to sensitively respond to gonadotropins for its further development. However, the mechanism underlying iFFA remains elusive. Herein, we reported that iFFA is characterized by enhanced fluid absorption, energy consumption, secretion, and proliferation and shares a regulatory mechanism with blastula cavity formation. By use of bioinformatics analysis, follicular culture, RNA interference, and other techniques, we further demonstrated that the tight junction, ion pumps, and aquaporins are essential for follicular fluid accumulation during iFFA, as a deficiency of any one of these negatively impacts fluid accumulation and antrum formation. The intraovarian mammalian target of rapamycin-C-type natriuretic peptide pathway, activated by follicle-stimulating hormone, initiated iFFA by activating tight junction, ion pumps, and aquaporins. Building on this, we promoted iFFA by transiently activating mammalian target of rapamycin in cultured follicles and significantly increased oocyte yield. These findings represent a significant advancement in iFFA research, further enhancing our understanding of folliculogenesis in mammals.

Phosphine-Catalyzed [3 + 2] Annulation of Morita-Baylis-Hillman Carbonates with Isoxazole-Based Alkenes.

A phosphine-catalyzed [3 + 2] annulation of Morita-Baylis-Hillman (MBH) carbonates with 3-methyl-4-nitro-5-styrylisoxazoles has been developed to afford various multifunctional isoxazoles in moderate to good yields with moderate to excellent diastereoselectivities. With a spirocyclic chiral phosphine as the catalyst, up to 89% ee was obtained.

Palladium-catalyzed stereoselective (3 + 2) cycloaddition of vinylethylene carbonates with cyclic N-sulfonyl ketimines.

A diastereoselective (3 + 2) cycloaddition of N-sulfonyl ketimines with vinylethylene carbonates (VECs) in the presence of Pd2dba3·CHCl3 and PPh3 has been developed. The reaction of various substituted VECs and diverse cyclic N-sulfonyl ketimines proceeded smoothly under mild conditions, giving highly functionalized oxazolidine frameworks in good to excellent yields with moderate to good diastereoselectivities. With the use of spiroketal-based diphosphine SKP as a chiral ligand, an asymmetric version of the current (3 + 2) cycloaddition was achieved, and chiral products were obtained in >99% ee in most cases.

Organocatalytic Asymmetric C(sp2 )-H Allylic Alkylation: Enantioselective Synthesis of Tetrasubstituted Allenoates.

Herein we describe the first organocatalytic asymmetric C(sp2 )-H allylation of racemic trisubstituted allenoates with Morita-Baylis-Hillman (MBH) carbonates to access axially chiral tetrasubstituted allenoates. Various trisubstituted allenoates and MBH carbonates were well tolerated under mild reaction conditions, providing novel chiral tetrasubstituted allenoates with adjacent axial chirality and tertiary carbon stereocenters in high yields with good to excellent diastereoselectivities and enantioselectivities.

Granulosa Cell-Layer Stiffening Prevents Escape of Mural Granulosa Cells from the Post-Ovulatory Follicle.

Ovulation is vital for successful reproduction. Following ovulation, cumulus cells and oocyte are released, while mural granulosa cells (mGCs) remain sequestered within the post-ovulatory follicle to form the corpus luteum. However, the mechanism underlying the confinement of mGCs has been a longstanding mystery. Here, in vitro and in vivo evidence is provided demonstrating that the stiffening of mGC-layer serves as an evolutionarily conserved mechanism that prevents mGCs from escaping the post-ovulatory follicles. The results from spatial transcriptome analysis and experiments reveal that focal adhesion assembly, triggered by the LH (hCG)-cAMP-PKA-CREB signaling cascade, is necessary for mGC-layer stiffening. Disrupting focal adhesion assembly through RNA interference results in stiffening failure, mGC escape, and the subsequent development of an abnormal corpus luteum characterized by decreased cell density or cavities. These findings introduce a novel concept of "mGC-layer stiffening", shedding light on the mechanism that prevents mGC escape from the post-ovulatory follicle.

Copper/Lewis base cooperatively catalyzed asymmetric allylic alkylation of Morita-Baylis-Hillman carbonates with azomethine ylides.

In this paper, an asymmetric allylic alkylation of easily available azomethine ylides with Morita-Baylis-Hillman (MBH) carbonates through a copper (i)/Lewis base cooperative catalysis strategy has been realized. The co-catalyzed asymmetric allylic alkylation provided the corresponding amino acid derivatives in up to 90% yields with up to 99% ee as well as good to excellent regioselectivity.

Phosphine-Catalyzed (4 + 2) Annulation of δ-Sulfonamido-Substituted Enones with 1,1-Dicyanoalkenes: Synthesis of Piperidine Derivatives.

The δ-sulfonamido-substituted enones were employed as phosphine acceptor in phosphine-catalyzed (4 + 2) annulation of 1,1-dicyanoalkenes. They served as a four-membered synthon to react with 1,1-dicyanoalkenes under mild reaction conditions, producing piperidine derivatives in moderate to excellent yields with good to excellent diastereoselectivities.

Base-Catalyzed Sequential 1,4-Addition/Intramolecular Cyclization/Aromatization Reaction: Synthesis of Benzofuro[3,2-b]pyridines.

An efficient K2CO3-catalyzed 1,4-addition/intramolecular cyclization/aromatization reaction of aurone-derived 1-azadienes with trisubstituted allenoates has been developed, giving a series of benzofuro[3,2-b]pyridines in moderate to excellent yields. The reaction proceeded efficiently under an air atmosphere without the use of transition metal catalysts. This protocol provides a concise approach to benzofuro[3,2-b]pyridines.

Synthesis of heterocyclic compounds through nucleophilic phosphine catalysis.

Nucleophilic phosphine catalysis is a practical and powerful tool for the synthesis of various heterocyclic compounds with the advantages of environmentally friendly, metal-free, and mild reaction conditions. The present report summarizes the construction of four to eight-membered heterocyclic compounds containing nitrogen, oxygen and sulphur atoms through phosphine-catalyzed intramolecular annulations and intermolecular [2+2], [3+2], [4+1], [3+1+1], [5+1], [4+2], [2+2+2], [3+3], [4+3] and [3+2+3] annulations of electron-deficient alkenes, allenes, alkynes and Morita-Baylis-Hillman carbonates.

Multifunctional chiral phosphine-catalyzed [3+2] annulation of Morita-Baylis-Hillman carbonates with cyclopentenones: asymmetric synthesis of 4-oxo-hexahydropentalenes.

A multifunctional chiral phosphine-catalyzed enantioselective [3+2] annulation of Morita-Baylis-Hillman carbonates with cyclopentenones provides a direct approach to access functional 4-oxo-1,3a,4,5,6,6a-hexahydropentalene compounds. Moderate to good yields and excellent enantioselectivities (>90% ee) were obtained for a series of substrates under mild reaction conditions.

Phosphine-Catalyzed [4 + 2] Annulation of Allenoate with Sulfamate-Derived Cyclic Imines: A Reaction Mode Involving γ'-Carbon of α-Substituted Allenoate.

A phosphine-catalyzed [4 + 2] cycloaddition of cyclic α-substituted allenoates with sulfamate-derived cyclic imines has been reported. Using dibenzylphenylphosphine as the nucleophilic catalyst, the reaction worked efficiently to yield various fused multicyclic heterocyclic compounds in high yields with excellent diastereoselectivities. It undergoes a new reaction mode involving γ'-carbon of α-substituted allenoate.

Palladium-Catalyzed [5 + 2] Cycloaddition of Vinyloxiranes with Sulfamate-Derived Cyclic Imines To Construct 1,3-Oxazepine Heterocycles.

Palladium-catalyzed [5 + 2] cycloaddition of 2-aryl-2-vinyloxiranes with sulfamate-derived cyclic imines is described. The zwitterionic allylpalladium intermediates act as five-membered synthon to react with sulfamate-derived cyclic imines to furnish [5 + 2] cycloaddition, giving 1,3-oxazepine derivatives in moderate to excellent yields with excellent regioselectivities.