Our main research themes

      Our laboratory is primarily interested in understanding at the molecular level the functional roles of vertebrate reproductive organs, especially ovary. Our research particularly focuses on following themes using mice and medaka fish.　

 

     The primary functions of the ovary is to produce mature fertilizable oocyte(s) and to secret ovarian hormones. Ovary has many follicles. Oocytes, which are surrounded by a follicle layer, grow in the follicle (Fig. 1). Ovulation is the process that a part of the follicle layer of the follicle is degraded and that mature oocyte is released from an ovary into an ovarian cavity. The breakdown of the follicle layer is indispensable for ovulation, and the enzymes involved in the breakdown (ovulation enzyme) were identified for the first time in vertebrates using medaka. Subsequent studies are performed to reveal the whole mechanism of medaka ovulation, including the endocrine regulatory mechanism of ovulation. We have now come to the most interesting and exciting stage of the medaka ovulation studies. We are currently studying the following unknown issues using medaka fish and mouse.

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(1) Identification of ovulatory enzymes in mammals. Fig.1-(1)

Ovulation is a dynamic process that results in the liberation of a mature fertilizable ovum (oocyte) from the ovarian follicle. This process known as follicle rupture has been a subject of intensive investigation over the past century. Previous studies have established that the action of proteolytic enzymes (ovulation enzymes) are essential for this process. Despite much effort, the whole picture about ovulation is still not clear in mammals. Recently, for the first time in vertebrates, we succeeded in identifying the enzymes that are critically involved in ovulation using medaka fish. We strongly believe this discovery as a huge step forward for our efforts to identify mechanism of ovulation in mammals. We try to identify the mammalian ovulatory enzymes using mouse as an experimental model.

(2) Studies on the mechanism of tissue repair after ovulation. Fig.1-(2)

Ovulation is thought to be the process for degradation of folllcle tissue by proteolytic enzymes. After the oocytes iare released from the ovarian follicles on ovulation, the follicular tissues need to be repaired. A remarkably rapid repair of the tissue (within 24 hours) is observed in the medaka fish ovary because the fish ovulates (spawns) every day. We consider it to be a good experimental system to study the mechanism of tissue repair. In this research project, we explore how such a rapid tissue repair takes place, including an effort to search factors playing important roles in this event. If the mechanism is clear understood, it may be applicable to a rapid healing  of wounds caused by a surgical operation or injuries.

(3) Does follicle cells communicate with oocytes during ovulatory period? Fig.1-(3)

Mature medaka oocyte, which is ready to fertilization, is ovulated and fertilizes with sperm. If immature medaka oocytes are ovulated, it is disadvantage for the fish. This leads us to hypothesize that communication between oocyte and follicle layer determines the timing of oocyte maturation and ovulation. The objective of the project is to study whether oocyte and follicle layer have a communication with each other.

 

(4) Studies on the regulatory mechanism in medaka ovulation. Fig.1-(3) and (4)

As we have identified the mechanism of ovulation in the medaka, we intend to further expand our search for the regulation of expression of the hydrolytic enzymes (ovulation enzymes) and other factors involved in ovulation. To date, there are no available information about gene regulation during ovulation due to the lack of knowledge on ovulatory enzymes. In this study, to reveal the mechanisms for controlling the ovulation, we try to identify the regulatory proteins of the ovulatory enzyme genes. This becomes the first study of this kind in vertebrates and may elucidate a common mechanism to all vertebrates.

(5) Studies on the involvement of Growth hormone in ovulation in the medaka. Fig.1-(5)

Growth hormone (GH) affects cell growth, tissue repair (wound healing?) , metabolism as well as animal reproduction. In the ovary, GH plays some important roles in follicle growth and production of reproductive hormones.Our data suggest that GH is also required for the ovulation process in medaka. In this research project, we explore how GH affects on medaka ovulation.

(6) Study on the molecular mechanism of mouse follicle selection. Fig.1-(6)

A lot of primordial follicles, which are before starting the growth, are stocked in mammalian ovary. For example, human ovary has tens to hundreds of thousands of primordial follicles. Some of them (several tens to several hundreds of follicles in the human ovary) start to grow by unknown signal(s), but most of them die by apoptosis during the growth. Selected follicles go to the final step and ovulated (In human, only one oocyte is ovulated). This process is called “follicle selection”. Why are the follicle(s) selected? How is the mechanism by which the follicles are selected and start to grow from the stocked primordial follicles? How is the mechanism by which the ovulating follicles are selected from the growing follicles. We want to know the above questions.

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