Analysis of Expression and Functional Activity of Aromatic L-Amino Acid Decarboxylase (DDC) and Serotonin Transporter (SERT) as Potential Sources of Serotonin in Mouse Ovary.

Denis A Nikishin,Maria L Semenova,Nina M Alyoshina,Yuri B Shmukler

doi:10.3390/ijms20123070

Abstract

The origin of serotonin in the ovary is the key question for understanding mechanisms of serotonergic regulation of reproductive function. We performed a study of the expression and functional activity of the serotonin transporter (SERT) and the enzyme for the synthesis of serotonin, aromatic l-amino acid decarboxylase (DDC) in mouse ovary. A pronounced peak of SERT mRNA expression occurs at the age of 14 days, but serotonin synthesis enzymes are expressed at the maximum level in the ovaries of newborn mice. SERT is detected immunohistochemically in all cellular compartments of the ovary with a maximum level of immunostaining in the oocytes of growing ovarian follicles. DDC immunolocalization, in contrast, is detected to a greater extent in primordial follicle oocytes, and decreases at the later stages of folliculogenesis. Serotonin synthesis in all cellular compartments occurs at very low levels, whereas specific serotonin uptake is clearly present, leading to a significant increase in serotonin content in the oocytes of growing primary and secondary follicles. These data indicate that the main mechanism of serotonin accumulation in mouse ovary is its uptake by the specific SERT membrane transporter, which is active in the oocytes of the growing ovarian follicles.

Highlights

Serotonin (5-hydroxytryptamine, 5HT) is found in the reproductive system of female mammals, including the ovaries [1], follicular fluid [2], mature oocytes and cumulus cells [3]
We performed a quantitative study of the gene expression of components presumably responsible for the synthesis and uptake of serotonin in postnatal mouse ovaries in order to identify the dynamics of their expression and draw conclusions about the period of folliculogenesis during which these mechanisms may be active (Figure 1)
The expression of the DDC gene is maximal in the ovaries of newborn mice, when the vast majority of the follicles are in the primordial stage, and it decreases slightly in the later stages

Summary

Introduction

Serotonin (5-hydroxytryptamine, 5HT) is found in the reproductive system of female mammals, including the ovaries [1], follicular fluid [2], mature oocytes and cumulus cells [3]. Serotonin affects the functional activity of follicular cells, which play an important role in the process of maturation of the egg but are the main source of oestrogen in the female body [5,6,9,10]. The enzyme in the first step of serotonin biosynthesis, tryptophan hydroxylase, TPH1, is expressed in cumulus cells [3] and TPH2 is expressed in mature oocytes [11]. Because the tryptophan hydroxylase is a rate-limiting enzyme, it is believed that a local system of serotonin synthesis is present in the ovary. The expression and the activity of the serotonin membrane transporter SERT are shown both in cumulus cells and in isolated oocytes [3]

Methods

Results

Conclusion