Ovarian mast cells migrate toward ovary-fimbria connection in neonatal MRL/MpJ mice.

Teppei Nakamura,Masataka Chihara,Saori Otsuka-Kanazawa,Yaser Hosny Ali Elewa,Osamu Ichii,Ken-Ichi Nagasaki,Yasuhiro Kon,Osamu Tatsumi

doi:10.1371/journal.pone.0196364

Teppei Nakamura, Masataka Chihara + Show 6 more

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https://doi.org/10.1371/journal.pone.0196364

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Abstract

MRL/MpJ mice have abundant ovarian mast cells (MCs) as compared with other strains at postnatal day 0 (P0); however, they sharply decrease after birth. These ovarian MCs, particularly beneath the ovarian surface epithelium (SE), which express mucosal MC (MMC) marker, might participate in early follicular development. This study investigated the changes in spatiotemporal distribution of MCs in the perinatal MRL/MpJ mouse ovaries. At P0 to P7, the MCs were densely localized to the ovary, especially their caudomedial region around the ovary-fimbria connection. The neonatal ovarian MCs showed intermediate characteristics of MMC and connective tissue MC (CTMC), and the latter phenotype became evident with aging. However, the expression ratio of the MMC to CTMC marker increased from P0 to P4 in the MRL/MpJ mouse ovary. Similarly, the ratio of MCs facing SE to total MC number increased with aging, although the number of ovarian MCs decreased, indicating the relative increase in MMC phenotypes in the early neonatal ovary. Neither proliferating nor apoptotic MCs were found in the MRL/MpJ mouse ovaries. The parenchymal cells surrounding MCs at ovary-fimbria connection showed similar molecular expression patterns (E-cadherin+/Foxl2-/Gata4+) as that of the ovarian surface epithelial cells. At P2, around the ovary-fimbria connection, c-kit- immature oocytes formed clusters called nests, and some MCs localized adjacent to c-kit- oocytes within the nests. These results indicated that in postnatal MRL/MpJ mice, ovarian MCs changed their distribution by migrating toward the parenchymal cells composing ovary-fimbria connection, which possessed similar characteristics to the ovarian surface epithelium. Thus, we elucidated the spatiotemporal alterations of the ovarian MCs in MRL/MpJ mice, and suggested their importance during the early follicular development by migrating toward the ovary-fimbria connection. MRL/MpJ mice would be useful to elucidate the relationship between neonatal immunity and reproductive systems.

Highlights

Mast cells (MCs) are derived from the bone marrow and migrate into the local tissues where they mature depending on their microenvironments [1]
In the adult uterus and ovary of mice and rats where the number of MCs vary over the estrous cycles, the MCs are morphologically heterogeneous by alcian blue (AB)/safranin O (SO) staining, and the majority of AB-positive MCs depends on the estrus cycles [4, 5]
In rats treated with partial hepatectomy, the mucosal MC (MMC) marker (RMCP-2) expressing MCs increased in the regenerating liver [6]

Summary

Introduction

Mast cells (MCs) are derived from the bone marrow and migrate into the local tissues where they mature depending on their microenvironments [1]. MMCs are migratory cells, and possess chondroitin sulfate, stained with alcian blue (AB), and express mast cell protease 1 (Mcpt1) and Mcpt. CTMCs are characteristically non-migratory cells, and possess heparin and histamine, stained with safranin O (SO), and express Mcpt, chymase 1 (Cma1), tryptase beta 2 (Tpsb2), tryptase alpha/beta 1 (Tpsab1), and carboxypeptidase A3 (Cpa3), but lack the MMC markers Mcpt and Mcpt. MCs have plasticity to change their phenotypes depending on the microenvironments of tissues [3], and MCs possessing both MMC and CTMC phenotypes increase under certain circumstances [4,5,6]. A recent study demonstrated that MCs contribute to female reproductive processes [10]

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