Biology subjects

Yamano, M.

Publications and source records attributed to Yamano, M..

5 recordsLinked to original sources

bioRxiv2026

Membrane progesterone receptors PAQR6 and PAQR8 in the ruminant uterus and ovary

Progesterone governs the establishment and maintenance of pregnancy in ruminants, acting through the nuclear progesterone receptor (PGR) and, potentially, through membrane progesterone receptors (mPRs) of the PAQR family. The cellular distribution of mPRs in ruminant reproductive tissues, however, remains undefined. We generated and validated rabbit polyclonal antibodies against the intracellular C-terminal peptides of bovine PAQR6 (mPR{delta}) and PAQR8 (mPR{beta}), and used them, with quantitative PCR of the uterus and conceptus, to map these receptors in the ovine uterus and conceptus and in the bovine ovary. Both antisera showed high ELISA titer against their immunizing peptides, negligible preimmune reactivity, and complete loss of tissue signal after peptide pre-absorption. By qPCR, PAQR6, PAQR8 and PGR transcript levels did not change significantly across the peri-implantation period in either the conceptus or the endometrium; in contrast, the progesterone-responsive gene ZBTB16 increased markedly in the conceptus (up to ~45-fold by day 21, p < 0.05 at days 17, 19 and 21), whereas FKBP5 showed a numerical increase without reaching statistical significance. Both genes remained relatively stable in the endometrium, indicating conceptus-specific changes in progesterone-responsive gene expression. At the protein level, PAQR6 and PAQR8 localized to the luminal and glandular epithelium of the endometrium across the cycle and early pregnancy, and to follicular (granulosa) and luteal cells of the ovary. Dual immunofluorescence in the ovine endometrium showed that both PAQR6 and PAQR8 are enriched at the apical surface of the luminal epithelium and are spatially distinct from the basolateral adherens-junction marker E-cadherin. These results provide a protein-level map of PAQR6 and PAQR8 in the ruminant reproductive tract, identify the apical epithelial surface as a site of receptor enrichment, and show that the endometrial epithelium retains membrane progesterone receptors while progesterone-responsive gene expression changes dynamically in the conceptus during the peri-implantation period. The validated ruminant-reactive antibodies provide a resource for future functional studies.

developmental biology↗

bioRxiv2026

Maternal progesterone signaling establishes lifelong oral homeostasis

Pregnancy is accompanied by profound endocrine remodeling, yet the mechanisms by which maternal hormonal signals establish long-term tissue homeostasis remain largely unknown. Here we identify maternal progesterone signaling as a developmental cue that establishes lifelong oral homeostasis through a hormone-lipid-microbiome axis. We show that the membrane progesterone receptor mPR{delta} is selectively expressed in the developing and maternal submandibular glands, where it mediates non-genomic progesterone signaling to promote epithelial differentiation by driving the selective mobilization of docosahexaenoic acid (DHA). Loss of this pathway disrupts salivary gland maturation, reshapes the oral microbial ecosystem through the selective expansion of Pasteurellaceae, and causes local inflammation as well as systemic metabolic dysfunction. Mechanistically, antibiotic treatment abolishes these phenotypes, whereas transfer of the oral microbiota recapitulates disease, demonstrating that developmental defects in the host are translated into long-term pathology through the oral microbiome. Remarkably, maternal--but not adult--DHA supplementation restores salivary gland development and microbial homeostasis and prevents adult disease phenotypes, identifying a critical developmental window during which oral homeostasis is durably established. Collectively, these findings reveal a previously unrecognized maternal endocrine mechanism that establishes lifelong host-microbiome homeostasis and identify developmental programming as a fundamental principle linking maternal physiology to adult health. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=188 SRC="FIGDIR/small/743932v1_ufig1.gif" ALT="Figure 1"> View larger version (56K): org.highwire.dtl.DTLVardef@178cc90org.highwire.dtl.DTLVardef@1be04beorg.highwire.dtl.DTLVardef@29759dorg.highwire.dtl.DTLVardef@1e89994_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2025

The pivotal role of a novel free fatty acid receptor GPR164 in the intestinal barrier function

GPR164 is a novel free fatty acid receptor, activated by both short-chain fatty acids and medium-chain fatty acids, and expressed throughout the gastrointestinal tract. Although GPR164 is reported to be involved in the release of gut hormones, the physiological functions of this receptor in the maintenance of intestinal homeostasis remain unclear. In this study, we explored the role of GPR164 in regulating intestinal barrier function using mice lacking Gpr164 gene (Gpr164-/-). A loss-of-function mutation in GPR164 promoted cell proliferation and disrupted the intestinal barrier function in both Caco-2 cell line and mice. Genome-wide RNA-seq analysis revealed that GPR164 deletion caused aberrant wnt/{beta}-catenin signaling, and the intraperitoneal injection of wnt/{beta}-catenin inhibitor ameliorated a series of abnormalities of Gpr164-/- mice. Gpr164-/- mice also exhibited gut microbial dysbiosis and severe inflammation, indicating that deletion of Gpr164 causes similar pathologies observed in patients with inflammation bowel disease (IBD). Thus, our findings uncover the pivotal role of GPR164 in the maintenance of intestinal barrier function, providing an attractive clinical target for IBD.

physiology↗

bioRxiv2024

Maternal progesterone and adipose mPRε in pregnancy regulate the embryonic nutritional state

Sex steroid hormones such as progesterone play a pivotal role in reproductive functions and maintaining pregnancy; however, the impact of progesterone on the interaction between mother and embryo is unclear. Here, we demonstrate that the relationship between maternal progesterone and membrane progesterone receptor epsilon (mPR{varepsilon}) in adipose tissue regulates embryonic nutritional environment and growth after birth in mice. The activation of adipose mPR{varepsilon} by increased progesterone during pregnancy enhanced maternal insulin resistance through the production of prostaglandins, thereby efficiently providing glucose to embryos. The offspring of mPR{varepsilon}-deficient mothers exhibited metabolic dysfunction, whereas mPR{varepsilon}-deficient mothers with high-fat-diet-induced obesity exhibited improved insulin sensitivity. These findings establish the importance of progesterone as a nutritional regulator between mother and embryo, and suggest that mPR{varepsilon} modulators could be developed to treat pregnant glycemic control disorders such as gestational diabetes mellitus, as well as metabolic syndrome in offspring. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=139 SRC="FIGDIR/small/609823v1_ufig1.gif" ALT="Figure 1"> View larger version (29K): org.highwire.dtl.DTLVardef@1ecd968org.highwire.dtl.DTLVardef@b5492aorg.highwire.dtl.DTLVardef@1d692ecorg.highwire.dtl.DTLVardef@47de8a_HPS_FORMAT_FIGEXP M_FIG C_FIG

physiology↗

bioRxiv2020

Phosphorylation of Elovl5 changes its substrate preference to synthesize Mead acid in response to essential fatty acid deficiency

Polyunsaturated fatty acids (PUFAs) of the n-6 and n-3 series cannot be synthesized in mammals and therefore are called essential fatty acids (EFAs). Mead acid (20:3n-9) is an unusual n-9 PUFA, endogenously synthesized from oleic acid (18:1n-9) in an EFA-deficient state. Although Elovl5, a fatty acid elongase, has long been known to selectively elongate C18 and C20 PUFAs, it can use 18:1n-9 as a substrate for the synthesis of Mead acid under C20 PUFA-deficient, but not-sufficient, conditions. We found, by an in vitro enzyme assay, that the microsomal fraction obtained from PUFA-deficient, but not -sufficient, cells showed significant Elovl5 activity toward 18:1n-9, with no effect on its constitutive activity toward 18:3n-6, implying that Elovl5 acquires the activity toward 18:1n-9 under the PUFA-deficient conditions at the enzyme level. Further biochemical analysis revealed that Elovl5 was phosphorylated in the C20 PUFA-supplemented cells, and that treatment with an inhibitor of glycogen synthase kinase 3 (GSK3) completely abolished the phosphorylation of Elovl5 and retained the Elovl5 activity toward 18:1n-9, even in the presence of C20 PUFA. Finally, mutation of putative phosphorylation sites (T281A/S283A/S285A) on Elovl5 did not decrease the activity of Elovl5 toward 18:1n-9 by supplementation with C20 PUFA, suggesting that the phosphorylation of Elovl5 contributed to a change in substrate preference. Thus, by changing its substrate specificity in an EFA-deficient state, Elovl5 is able to regulate the synthesis of Mead acid to maintain levels of long-chain PUFAs.

biochemistry↗