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. 2007 Mar 21:5:12.
doi: 10.1186/1477-7827-5-12.

Semaphorin-4D (Sema-4D), the Plexin-B1 ligand, is involved in mouse ovary follicular development

Avital Regev  1 , Shlomit Goldman, Eliezer Shalev
Affiliations

Semaphorin-4D (Sema-4D), the Plexin-B1 ligand, is involved in mouse ovary follicular development

Avital Regev et al. Reprod Biol Endocrinol. .

Abstract

Background: Human Plexin-B1 is expressed in two truncated forms. The long form encodes a trans-membranal protein, while the short form, which is bound to the cell surface and partially secreted, possibly serves as a decoy receptor. Plexin receptors are trans-membrane proteins. The sema domain, found in the extracellular region, is common to all plexins, semaphorins, and the scatter factor receptors and is crucial for the biological activity and plexin receptor specificity. Semaphorin-4D/Plexin-B1 binding provides attractive and repulsive cues for the navigation of axonal growth cones, and new studies suggest that this system also plays a role in the regulation of the biological functions of endothelial cells, specifically in the control of angiogenesis. In a previous study, we have demonstrated the expression and possible role of Plexin-B1 in the mouse ovary. The present study was designed to test the hypothesis that Plexin-B1 effects are mediated by Semaphorin-4D.

Methods: In vivo expression and localization of mouse ovarian Sema-4D were tested by immunohisto-chemistry. The role of Sema-4D in follicular development was examined by in vitro growth of preantral follicles in the presence or absence of Semaphorin-4D, with or without neutralizing antibodies against Plexin-B1. Follicular growth and steroid hormone secretion rates were tested.

Results: Semaphorin-4D is expressed in the mouse ovary in vivo mostly in the granulosa cells and and its expression is modulated by PMSG and hCG. In the presence of Semaphorin-4D, in-vitro constant growth was observed as indicated by follicular diameter during the culture period and elevated steroid hormone secretion rates compared with control. These effects were abolished after addition of neutralizing antibodies against Plexin-B1.

Conclusion: In the ovarian follicle, the effect of Plexin-B1 is mediated by sema-4D.

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Figures

Figure 1
Figure 1
Immunohistochemical staining revealing the presence of Sema-4D in the mouse ovary at all stages: (A) un-stimulated (B) after PMSG administration, (C) 6 hours after hCG administration, and (D) 24 hours after hCG administration. Sema-4D was identified as red-brown membrane staining in ovarian sections counterstained with hematoxylin; magnification ×400. Bar graph describing the relative percentage of Sema-4D expression, representing, mean ± SEM from three independent experiments.
Figure 2
Figure 2
Diameter of follicles obtained from 12-day old ICR mice and grown in in-vitro cultures for 12 days in M-199 Medium containing gonadotropins (FSH and LH 100 mIU/ml) and with the addition of Sema-4D (50 ng/ml) in the presence or absence or of specific neutralizing antibodies against Plexin-B1 (200 ng/ml). On day 9 hCG was added to the culture. Blue diamond represents the follicular diameter in the control group, Pink square represents the follicular diameter in the Sema-4D group. Turquoise triangle represents follicle diameter in the group treated with Sema-4D and neutralizing antibodies against Plexin-B1.
Figure 3
Figure 3
Secretion of steroid hormones (A. Estradiol; B. Progesterone and C. Testosterone), obtained from conditioned media from cultured follicles over 12 days in the absence (Dark blue circles) or presence of Sema-4D (Pink square) or in combination with specific neutralizing antibodies against Plexin-B1 (turquoise triangles). The graph represents mean ± SEM of the steroid hormones secreted from three independent experiments in triplicate.
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