Cholesterol Accumulation in Ovarian Follicles Causes Ovulation Defects in Japanese Medaka ()

Overview

Journal Heliyon

Specialty Social Sciences

Date 2023 Feb 23

PMID 36816300

Authors

Ryota Futamata

Masato Kinoshita

Katsueki Ogiwara

Noriyuki Kioka

Kazumitsu Ueda

Affiliations

Soon will be listed here.

Abstract

ATP-binding cassette A1 (ABCA1) is a membrane protein, which exports excess cellular cholesterol to generate HDL to reduce the risk of the onset of cardiovascular diseases (CVD). In addition, ABCA1 exerts pleiotropic effects on such as inflammation, tissue repair, and cell proliferation and migration. In this study, we explored the novel physiological roles of ABCA1 using Japanese medaka ( a small teleost fish. Three genes were found in the medaka genome. ABCA1A and ABCA1C exported cholesterol to generate nascent HDL as human ABCA1 when expressed in HEK293 cells. To investigate their physiological roles, each -deficient fish was generated using the CRISPR-Cas9 system. female medaka was found to be infertile, while and female medaka were fertile. ovarian follicle culture suggested that deficiency causes ovulation defects. In the ovary, ABCA1A was expressed in theca cells, an outermost layer of the ovarian follicle. Total cholesterol content of ovary was significantly higher than that of the wild-type, while estrogen and progestin contents were compatible with those of the wild-type. Furthermore, cholesterol loading to the wild-type follicles caused ovulation defects. These results suggest that ABCA1A in theca cells regulates cholesterol content in the ovarian follicles and its deficiency inhibits successful ovulation through cholesterol accumulation in the ovarian follicle.

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