{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nStudies on the PATE-like family of proteins reveal that founding members—such as those related to PATE2—are secreted proteins characterized by ten conserved cysteine residues arranged in three‐fingered (TFP)/Ly-6/uPAR domains. These proteins are predominantly expressed in the male genital tract, with transcripts being highly enriched in the prostate and testis. Their localization to structures such as the sperm acrosome, along with pharmacological evidence demonstrating modulation of nicotinic acetylcholine receptors, supports a role for PATE-like proteins in the fine tuning of both fertility-related processes and neural transmission."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn parallel studies targeting the molecular underpinnings of gametogenesis, CHTF18—a conserved component of the Replication Factor C-like complex—has emerged as critical for the maintenance of genomic integrity during meiosis. In the male germline, loss of CHTF18 leads to gross abnormalities in spermatogenesis, premature separation of homologous chromosomes during prophase I, and markedly reduced sperm counts, pointing to its essential participation in ensuring the proper repair of DNA double-strand breaks and the establishment of crossovers."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurther investigations into female reproductive biology have shown that CHTF18 is equally indispensable for oocyte development and quality. Genetic ablation of CHTF18 in females results in diminished ovarian follicle pools, persistent DNA damage, impaired crossover formation, and a high incidence of aneuploidy in the resulting oocytes, ultimately leading to age-dependent subfertility. These findings underscore the dual and complementary roles played by secreted factors like PATE-like proteins in modulating reproductive function and by cell cycle regulators like CHTF18 in safeguarding meiotic fidelity across both sexes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Fiana Levitin, Mordechai Weiss, Yoonsoo Hahn, et al. "}, {"type": "b", "children": [{"type": "t", "text": "PATE gene clusters code for multiple, secreted TFP/Ly-6/uPAR proteins that are expressed in reproductive and neuron-rich tissues and possess neuromodulatory activity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2008)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M801454200"}], "href": "https://doi.org/10.1074/jbc.M801454200"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "18387948"}], "href": "https://pubmed.ncbi.nlm.nih.gov/18387948"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "M Margalit, L Yogev, H Yavetz, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Involvement of the prostate and testis expression (PATE)-like proteins in sperm-oocyte interaction."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Hum Reprod (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/humrep/des064"}], "href": "https://doi.org/10.1093/humrep/des064"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22402205"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22402205"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Karen M Berkowitz, Aislinn R Sowash, Lydia R Koenig, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Disruption of CHTF18 causes defective meiotic recombination in male mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS Genet (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pgen.1002996"}], "href": "https://doi.org/10.1371/journal.pgen.1002996"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23133398"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23133398"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Rebecca A Holton, Abigail M Harris, Barenya Mukerji, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CHTF18 ensures the quantity and quality of the ovarian reserve†."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biol Reprod (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1093/biolre/ioaa036"}], "href": "https://doi.org/10.1093/biolre/ioaa036"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32219340"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32219340"}]}]}]}