Abstract
Primordial follicle assembly is a process that occurs when oocyte nests break down to form individual primordial follicles. The size of this initial pool of primordial follicles in part determines the reproductive lifespan of the female. Connective tissue growth factor (CTGF) was identified as a potential regulatory candidate for this process in a previous microarray analysis of follicle development. The current study examines the effects of CTGF and associated transforming growth factor beta 1 (TGFβ-1) on follicle assembly. Ovaries were removed from newborn rat pups and placed in an organ culture system. The ovaries treated with CTGF for two days were found to have an increased proportion of assembled follicles. CTGF was found to regulate the ovarian transcriptome during primordial follicle assembly and an integrative network of genes was identified. TGFβ-1 had no effect on primordial follicle assembly and in combination with CTGF decreased oocyte number in the ovary after two days of culture. Over ten days of treatment only the combined treatment of CTGF and TGFβ-1 was found to cause an increase in the proportion of assembled follicles. Interestingly, treatment with TGFβ-1 alone resulted in fewer total oocytes in the ovary and decreased the primordial follicle pool size after ten days of culture. Observations indicate that CTGF alone or in combination with TGFβ-1 stimulates primordial follicle assembly and TGFβ-1 can decrease the primordial follicle pool size. These observations suggest the possibility of manipulating primordial follicle pool size and influencing female reproductive lifespan.
Highlights
Oocytes in newborn rodents are present in ‘nests’ that are composed of many adjacent oocytes with no intervening cells
The inhibitory actions of progesterone on primordial follicle assembly was found to coincide with a dramatic increase in connective tissue growth factor (CTGF) gene expression [33]
CTGF and transforming growth factor beta 1 (TGFb-1) were selected as candidates to investigate experimentally as being involved in the regulation of primordial follicle assembly
Summary
Oocytes in newborn rodents are present in ‘nests’ that are composed of many adjacent oocytes with no intervening cells. During the developmental process of follicle assembly primordial follicles are formed from oocyte nests [3,4,5,6,7]. In the embryonic ovary oogonia undergo mitotic proliferation and enter the first meiotic division to become oocytes. These unassembled oocytes are present directly adjacent to one another in nest structures which are surrounded by somatic cells (i.e. precursor granulosa cells) [3,4,5,6,7,9]. The primordial follicles formed constitute a pool of follicles having oocytes arrested in prophase I of meiosis [3,4,5,6]. It is possible that if the size of the follicle pool could be manipulated the reproductive capacity and fertile lifespan of the organism may change
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