scholarly journals Ablation of TGFBR3 (betaglycan) in oocytes does not affect fertility in female mice

Reproduction ◽  
2020 ◽  
Author(s):  
Yining Li ◽  
Yeu-Farn Lin ◽  
Xiang Zhou ◽  
Hugh J Clarke ◽  
Daniel J. Bernard

Ovarian follicle development is regulated by locally produced TGFβ superfamily members. The TGFβ type III receptor (TGFBR3, or betaglycan), which regulates the actions of diverse TGFβ ligands, including inhibins, is expressed in different ovarian cell types. However, its functional roles in the ovary have not been investigated in vivo. Here, we ablated Tgfbr3 in murine oocytes using the Cre-loxP system. Oocyte-specific Tgfbr3 knockout (cKO) females were fertile, producing litters of similar size and frequency as controls. Their ovarian weights and histology were also normal. Though we confirmed efficient recombination of the floxed alleles, we did not detect Tgfbr3 mRNA in purified oocytes from superovulated cKO or control mice. These results challenge earlier observations of betaglycan protein expression in this cell type. Regardless, Tgfbr3 in the murine oocyte is clearly dispensable for female fertility.

2019 ◽  
Author(s):  
Beatriz Peñalver Bernabé ◽  
Teresa Woodruff ◽  
Linda J Broadbelt ◽  
Lonnie D Shea

SUMMARYReliably producing a competent oocyte entails a deeper comprehension of ovarian follicle maturation, a very complex process that includes meiotic maturation of the female gamete, the oocyte, together with the mitotic divisions of the hormone-producing somatic cells. In this report, we investigate mice ovarian folliculogenesis in vivo using publically available time-series microarrays from primordial to antral stage follicles. Manually curated protein interaction networks were employed to identify autocrine and paracrine signaling between the oocyte and the somatic cells (granulosa and theca cells) and the oocyte and cumulus and mural cells at multiple stages of follicle development. We established protein binding interactions between expressed genes that encoded secreted factors and expressed genes that encoded cellular receptors. Some of computationally identified signaling interactions are well established, such as the paracrine signaling from the oocyte to the somatic cells through the secreted oocyte growth factor Gdf9; while others are novel connections in term of ovarian folliculogenesis, such as the possible paracrine connection from somatic secreted factor Ntn3 to the oocyte receptor Neo1. Additionally, we identify several of the likely transcription factors that might control the dynamic transcriptome during ovarian follicle development, noting that the YAP/TAP signaling is very active in vivo. This novel dynamic model of signaling and regulation can be employed to generate testable hypotheses regarding follicle development, guide the improvement of culture media to enhance in vitro ovarian follicle maturation and possibly as novel therapeutic targets for reproductive diseases.


2000 ◽  
Vol 21 (2) ◽  
pp. 200-214 ◽  
Author(s):  
Elizabeth A. McGee ◽  
Aaron J. W. Hsueh

Abstract Mammalian ovaries consist of follicles as basic functional units. The total number of ovarian follicles is determined early in life, and the depletion of this pool leads to reproductive senescence. Each follicle develops to either ovulate or, more likely, to undergo degeneration. The dynamics of ovarian follicle development have interested endocrinologists and developmental biologists for many years. With the advent of assisted reproductive techniques in humans, the possibility of regulating follicle development in vivo and in vitro has gained clinical relevance. In this review, we focus upon key branching points during the development of ovarian follicles as well as factors involved in determining the eventual destiny of individual follicles. We discuss inconsistencies in the literature regarding the definitions of follicle recruitment and selection and propose to name the two major steps of follicle development as initial and cyclic recruitment, respectively. Because some of these disparities have arisen due to differences in the animal systems studied, we also compare the development of the ovarian follicles of both humans and rats. We also review the status of knowledge of several puzzling clinical issues that may provide important clues toward unlocking the mechanisms of follicle development.


Endocrinology ◽  
2001 ◽  
Vol 142 (11) ◽  
pp. 4891-4899 ◽  
Author(s):  
Alexandra L. L. Durlinger ◽  
Maria J. G. Gruijters ◽  
Piet Kramer ◽  
Bas Karels ◽  
T. Rajendra Kumar ◽  
...  

Abstract Although ovarian follicle growth is under the influence of many growth factors and hormones of which FSH remains one of the most prominent regulators. Therefore, factors affecting the sensitivity of ovarian follicles to FSH are also important for follicle growth. The aim of the present study was to investigate whether anti-Müllerian hormone (AMH) has an inhibitory effect on follicle growth by decreasing the sensitivity of ovarian follicles to FSH. Furthermore, the combined action of AMH and FSH on ovarian follicle development was examined. Three different experiments were performed. Using an in vitro follicle culture system it was shown that FSH-stimulated preantral follicle growth is attenuated in the presence of AMH. This observation was confirmed by an in vivo experiment showing that in immature AMH-deficient females, more follicles start to grow under the influence of exogenous FSH than in their wild-type littermates. In a third experiment, examination of the follicle population of 4-month-old wild-type, FSHβ-, AMH-, and AMH-/FSHβ-deficient females revealed that loss of FSH expression has no impact on the number of primordial and preantral follicles, but the loss of inhibitory action of AMH on the recruitment of primordial follicles in AMH-deficient mice is increased in the absence of FSH. In conclusion, these studies show that AMH inhibits FSH-stimulated follicle growth in the mouse, suggesting that AMH is one of the factors determining the sensitivity of ovarian follicles for FSH and that AMH is a dominant regulator of early follicle growth.


Development ◽  
1976 ◽  
Vol 36 (1) ◽  
pp. 13-18
Author(s):  
J. M. Legay

Ovarian follicle development, which accompanies morphogenesis of the silkworm egg has three distinct phases: spheric, ellipsoidal and flattened-ellipsoid. Transitions between phases are rapid and form-stability (characterized by length/width ratio) is preserved from the beginning of the ellipsoidal phase. The geometric stability of the follicle-oocyte-ovariole system, the polarity of the egg and the determinism in form changes reveal strikingly coordinated spatial and temporal organization.


2017 ◽  
Vol 114 (38) ◽  
pp. 10131-10136 ◽  
Author(s):  
Yahav Yosefzon ◽  
Cfir David ◽  
Anna Tsukerman ◽  
Lilach Pnueli ◽  
Sen Qiao ◽  
...  

The TET enzymes catalyze conversion of 5-methyl cytosine (5mC) to 5-hydroxymethyl cytosine (5hmC) and play important roles during development. TET1 has been particularly well-studied in pluripotent stem cells, butTet1-KO mice are viable, and the most marked defect is abnormal ovarian follicle development, resulting in impaired fertility. We hypothesized that TET1 might play a role in the central control of reproduction by regulating expression of the gonadotropin hormones, which are responsible for follicle development and maturation and ovarian function. We find that all three TET enzymes are expressed in gonadotrope-precursor cells, butTet1mRNA levels decrease markedly with completion of cell differentiation, corresponding with an increase in expression of the luteinizing hormone gene,Lhb. We demonstrate that poorly differentiated gonadotropes express a TET1 isoform lacking the N-terminal CXXC-domain, which repressesLhbgene expression directly and does not catalyze 5hmC at the gene promoter. We show that this isoform is also expressed in other differentiated tissues, and that it is regulated by an alternative promoter whose activity is repressed by the liganded estrogen and androgen receptors, and by the hypothalamic gonadotropin-releasing hormone through activation of PKA. Its expression is also regulated by DNA methylation, including at an upstream enhancer that is protected by TET2, to allowTet1expression. The down-regulation of TET1 relieves its repression of the methylatedLhbgene promoter, which is then hydroxymethylated and activated by TET2 for full reproductive competence.


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