| First Author | Chang CL | Year | 2022 |
| Journal | Front Endocrinol (Lausanne) | Volume | 13 |
| Pages | 1047498 | PubMed ID | 36452323 |
| Mgi Jnum | J:348722 | Mgi Id | MGI:7397414 |
| Doi | 10.3389/fendo.2022.1047498 | Citation | Chang CL, et al. (2022) Oocyte-specific disruption of adrenomedullin 2 gene enhances ovarian follicle growth after superovulation. Front Endocrinol (Lausanne) 13:1047498 |
| abstractText | BACKGROUND: Adrenomedullin 2 (ADM2), adrenomedullin (ADM), and calcitonin gene-related peptides (alpha- and beta-CGRPs) signal through heterodimeric calcitonin receptor-like receptor/receptor activity-modifying protein 1, 2 and 3 (CLR/RAMP1, 2 and 3) complexes. These peptides are important regulators of neurotransmission, vasotone, cardiovascular development, and metabolic homeostasis. In rodents, ADM is essential for regulating embryo implantation, fetal-placental development, and hemodynamic adaptation during pregnancy. On the other hand, ADM2 was shown to affect vascular lumen enlargement, and cumulus cell-oocyte complex (COC) communication in rodent and bovine ovarian follicles. To investigate whether oocyte-derived ADM2 plays a physiological role in regulating ovarian folliculogenesis, we generated mice with oocyte-specific disruption of the Adm2 gene using a LoxP-flanked Adm2 transgene (Adm2 loxP/loxP) and crossed them with Zp3-Cre mice which carry a zona pellucida 3 (Zp3) promoter-Cre recombinase transgene. RESULTS: While heterozygous Adm2 +/-/Zp3-Cre and homozygous Adm2 -/-/Zp3-Cre mice were fertile, Adm2 disruption in oocytes significantly increased the number of ovulated oocytes following a superovulation treatment. Oocyte-specific Adm2 disruption also significantly impaired the developmental capacity of fertilized eggs and decreased the size of the corpus luteum following superovulation, perhaps due to a reduction of ovarian cyclin D2-associated signaling. CONCLUSIONS: The disruption of intrafollicular ADM2 signaling leads to follicular dysfunction. These data suggested that oocyte-derived ADM2 plays a facilitative role in the regulation of hormonal response and follicle growth independent of the closely related ADM and CGRP peptides, albeit in a subtle manner. |
