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Development of the follicular basement membrane during human gametogenesis and early folliculogenesis.

Heeren AM, van Iperen L, Klootwijk DB, de Melo Bernardo A, Roost MS, Gomes Fernandes MM, Louwe LA, Hilders CG, Helmerhorst FM, van der Westerlaken LA, Chuva de Sousa Lopes SM - BMC Dev. Biol. (2015)

Bottom Line: In adults, in the primary and secondary follicles, collagen IV, laminin and to a lesser extent fibronectin were prominent in the follicular BM.The ECM-molecular niche compartimentalizes the female gonads from the time of germ cell colonization until adulthood.This knowledge may contribute to improve methods to recreate the environment needed for successful folliculogenesis in vitro and that would benefit a large number of infertility patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333, Leiden, ZC, The Netherlands. marijneheeren@gmail.com.

ABSTRACT

Background: In society, there is a clear need to improve the success rate of techniques to restore fertility. Therefore a deeper knowledge of the dynamics of the complex molecular environment that regulates human gametogenesis and (early) folliculogenesis in vivo is necessary. Here, we have studied these processes focusing on the formation of the follicular basement membrane (BM) in vivo.

Results: The distribution of the main components of the extracellular matrix (ECM) collagen IV, laminin and fibronectin by week 10 of gestation (W10) in the ovarian cortex revealed the existence of ovarian cords and of a distinct mesenchymal compartment, resembling the organization in the male gonads. By W17, the first primordial follicles were assembled individually in that (cortical) mesenchymal compartment and were already encapsulated by a BM of collagen IV and laminin, but not fibronectin. In adults, in the primary and secondary follicles, collagen IV, laminin and to a lesser extent fibronectin were prominent in the follicular BM.

Conclusions: The ECM-molecular niche compartimentalizes the female gonads from the time of germ cell colonization until adulthood. This knowledge may contribute to improve methods to recreate the environment needed for successful folliculogenesis in vitro and that would benefit a large number of infertility patients.

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Related in: MedlinePlus

Collagen IV expression in human fetal female and male gonads during first and second trimester. (A-C) Longitudinal sight of W9 (A,A’) and transversal sight of W10.5 (B,B’) female gonad showed a distinctive expression pattern of collagen IV (green). (C,C’) Collagen IV (green) detected in the BM surrounding the developing seminiferous tubes in male gonad of first trimester (W10). (D-F) Collagen IV (green) expression in the BM of ovarian cords in female gonads (D,D’,E,E’) and in the BM of seminiferous tubes in male gonads (F,F’). Germ cells (red) were identified by the early marker OCT4 (nuclear) and late marker VASA (cytoplasmatic). The same secondary antibody was used to detect OCT4 and VASA, because the two proteins localize to different cellular compartments (nucleus and cytoplasm, respectively) and their expression can therefore be clearly distinguished. Red arrows point to the BM of the OSE, yellow arrows point to the BM of the primordial follicles, green arrows show the BM of the seminiferous tubes and ovarian cords, white arrows to the BM of blood vessels, and white asterisks marked individual germ cells expressing collagen IV. Note that occasional autofluorescent red blood cells are visible as red/orange cells inside blood vessels. Scalebars are 100 μm.
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Fig2: Collagen IV expression in human fetal female and male gonads during first and second trimester. (A-C) Longitudinal sight of W9 (A,A’) and transversal sight of W10.5 (B,B’) female gonad showed a distinctive expression pattern of collagen IV (green). (C,C’) Collagen IV (green) detected in the BM surrounding the developing seminiferous tubes in male gonad of first trimester (W10). (D-F) Collagen IV (green) expression in the BM of ovarian cords in female gonads (D,D’,E,E’) and in the BM of seminiferous tubes in male gonads (F,F’). Germ cells (red) were identified by the early marker OCT4 (nuclear) and late marker VASA (cytoplasmatic). The same secondary antibody was used to detect OCT4 and VASA, because the two proteins localize to different cellular compartments (nucleus and cytoplasm, respectively) and their expression can therefore be clearly distinguished. Red arrows point to the BM of the OSE, yellow arrows point to the BM of the primordial follicles, green arrows show the BM of the seminiferous tubes and ovarian cords, white arrows to the BM of blood vessels, and white asterisks marked individual germ cells expressing collagen IV. Note that occasional autofluorescent red blood cells are visible as red/orange cells inside blood vessels. Scalebars are 100 μm.

Mentions: By W9-W12, the female gonad showed a higher density of germ cells in the cortex, with the occasional germ cell in the medulla and absent from the ovarian surface epithelium (OSE) (Figure 2A and 2B). Unexpectedly, already at W9, collagen IV showed a distinctive expression pattern, strongly reminiscent of the BM surrounding the developing male seminiferous tubes in gonads of similar developmental age (Figure 2C), suggesting that in females the organization of germ cells in ovarian cords occurred much earlier than previously reported [16]. Konishi and colleagues (1986) have showed by electron microscopy that germ cells were in ovarian cords in the human ovary by W15, but not at W12. Immunostaining for the ECM component collagen IV revealed that this organization in ovarian cords is in fact occurring much earlier in human development, in a process that may be common between males and females.Figure 2


Development of the follicular basement membrane during human gametogenesis and early folliculogenesis.

Heeren AM, van Iperen L, Klootwijk DB, de Melo Bernardo A, Roost MS, Gomes Fernandes MM, Louwe LA, Hilders CG, Helmerhorst FM, van der Westerlaken LA, Chuva de Sousa Lopes SM - BMC Dev. Biol. (2015)

Collagen IV expression in human fetal female and male gonads during first and second trimester. (A-C) Longitudinal sight of W9 (A,A’) and transversal sight of W10.5 (B,B’) female gonad showed a distinctive expression pattern of collagen IV (green). (C,C’) Collagen IV (green) detected in the BM surrounding the developing seminiferous tubes in male gonad of first trimester (W10). (D-F) Collagen IV (green) expression in the BM of ovarian cords in female gonads (D,D’,E,E’) and in the BM of seminiferous tubes in male gonads (F,F’). Germ cells (red) were identified by the early marker OCT4 (nuclear) and late marker VASA (cytoplasmatic). The same secondary antibody was used to detect OCT4 and VASA, because the two proteins localize to different cellular compartments (nucleus and cytoplasm, respectively) and their expression can therefore be clearly distinguished. Red arrows point to the BM of the OSE, yellow arrows point to the BM of the primordial follicles, green arrows show the BM of the seminiferous tubes and ovarian cords, white arrows to the BM of blood vessels, and white asterisks marked individual germ cells expressing collagen IV. Note that occasional autofluorescent red blood cells are visible as red/orange cells inside blood vessels. Scalebars are 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4307144&req=5

Fig2: Collagen IV expression in human fetal female and male gonads during first and second trimester. (A-C) Longitudinal sight of W9 (A,A’) and transversal sight of W10.5 (B,B’) female gonad showed a distinctive expression pattern of collagen IV (green). (C,C’) Collagen IV (green) detected in the BM surrounding the developing seminiferous tubes in male gonad of first trimester (W10). (D-F) Collagen IV (green) expression in the BM of ovarian cords in female gonads (D,D’,E,E’) and in the BM of seminiferous tubes in male gonads (F,F’). Germ cells (red) were identified by the early marker OCT4 (nuclear) and late marker VASA (cytoplasmatic). The same secondary antibody was used to detect OCT4 and VASA, because the two proteins localize to different cellular compartments (nucleus and cytoplasm, respectively) and their expression can therefore be clearly distinguished. Red arrows point to the BM of the OSE, yellow arrows point to the BM of the primordial follicles, green arrows show the BM of the seminiferous tubes and ovarian cords, white arrows to the BM of blood vessels, and white asterisks marked individual germ cells expressing collagen IV. Note that occasional autofluorescent red blood cells are visible as red/orange cells inside blood vessels. Scalebars are 100 μm.
Mentions: By W9-W12, the female gonad showed a higher density of germ cells in the cortex, with the occasional germ cell in the medulla and absent from the ovarian surface epithelium (OSE) (Figure 2A and 2B). Unexpectedly, already at W9, collagen IV showed a distinctive expression pattern, strongly reminiscent of the BM surrounding the developing male seminiferous tubes in gonads of similar developmental age (Figure 2C), suggesting that in females the organization of germ cells in ovarian cords occurred much earlier than previously reported [16]. Konishi and colleagues (1986) have showed by electron microscopy that germ cells were in ovarian cords in the human ovary by W15, but not at W12. Immunostaining for the ECM component collagen IV revealed that this organization in ovarian cords is in fact occurring much earlier in human development, in a process that may be common between males and females.Figure 2

Bottom Line: In adults, in the primary and secondary follicles, collagen IV, laminin and to a lesser extent fibronectin were prominent in the follicular BM.The ECM-molecular niche compartimentalizes the female gonads from the time of germ cell colonization until adulthood.This knowledge may contribute to improve methods to recreate the environment needed for successful folliculogenesis in vitro and that would benefit a large number of infertility patients.

View Article: PubMed Central - PubMed

Affiliation: Department of Anatomy and Embryology, Leiden University Medical Center, Einthovenweg 20, 2333, Leiden, ZC, The Netherlands. marijneheeren@gmail.com.

ABSTRACT

Background: In society, there is a clear need to improve the success rate of techniques to restore fertility. Therefore a deeper knowledge of the dynamics of the complex molecular environment that regulates human gametogenesis and (early) folliculogenesis in vivo is necessary. Here, we have studied these processes focusing on the formation of the follicular basement membrane (BM) in vivo.

Results: The distribution of the main components of the extracellular matrix (ECM) collagen IV, laminin and fibronectin by week 10 of gestation (W10) in the ovarian cortex revealed the existence of ovarian cords and of a distinct mesenchymal compartment, resembling the organization in the male gonads. By W17, the first primordial follicles were assembled individually in that (cortical) mesenchymal compartment and were already encapsulated by a BM of collagen IV and laminin, but not fibronectin. In adults, in the primary and secondary follicles, collagen IV, laminin and to a lesser extent fibronectin were prominent in the follicular BM.

Conclusions: The ECM-molecular niche compartimentalizes the female gonads from the time of germ cell colonization until adulthood. This knowledge may contribute to improve methods to recreate the environment needed for successful folliculogenesis in vitro and that would benefit a large number of infertility patients.

Show MeSH
Related in: MedlinePlus