Changes

==Introduction==

==Introduction==

The follicle is the functional unit of the ovary containing both gametes (Oocyte) and endocrine cells (Granulosa and Theca cells). A female is born with all the primordial follicles it is ever going to have i.e Primordial Follicles do not divide anymore, they either develop further into primary, secondary, and tertiary follicles or they degenerate. Therefore the number of follicles declines with age as follicles develop and degenerate during the [[Female_Reproductive_Tract_-Oestrous_Cycle_-_Anatomy_%26_Physiology|oestrus cycle]]. When the supply of follicles is depleted then reproductive senescence occurs. In humans this phenomenon is known as "The Menopause".  Prior to ovulation, [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oogenesis]] and hormone production both occur in the follicle. The process of follicular growth is known as '''Folliculogenesis'''.

The follicle is the functional unit of the ovary containing both gametes (Oocyte) and endocrine cells (Granulosa and Theca cells). A female is born with all the primordial follicles it is ever going to have i.e Primordial Follicles do not divide anymore, they either develop further into primary, secondary, and tertiary follicles or they degenerate. Therefore the number of follicles declines with age as follicles develop and degenerate during the [[Female_Reproductive_Tract_-Oestrous_Cycle_- Anatomy & Physiology|oestrus cycle]]. When the supply of follicles is depleted then reproductive senescence occurs. In humans this phenomenon is known as "The Menopause".  Prior to ovulation, [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oogenesis]] and hormone production both occur in the follicle. The process of follicular growth is known as '''Folliculogenesis'''.

==General Structure==

==General Structure==

*Made up from two cell types; Granulosa cells and Theca cells aranged in two different layers.  

*Made up from two cell types; Granulosa cells and Theca cells aranged in two different layers.  

**The Granulosa cell layer is the inner cell layer found closest to the [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]]

**The Granulosa cell layer is the inner cell layer found closest to the [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]]

**The Theca cell layer is the outer cell layer

**The Theca cell layer is the outer cell layer

*One primary oocyte surrounded by a Single layer of squamous cells known as pre-granulosal cells.

*One primary oocyte surrounded by a Single layer of squamous cells known as pre-granulosal cells.

*Development from the primordial follicle to the primary follicle is characterized by:

*Development from the primordial follicle to the primary follicle is characterized by:

**Increase in the size of the [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]]

**Increase in the size of the [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]]

**The surrounding of the [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]] by a single layer of cuboidal granulosa cells which are capable of hormone production.

**The surrounding of the [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]] by a single layer of cuboidal granulosa cells which are capable of hormone production.

**Separation of the [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]] from the granulosal cells by a thick layer of material known as the zona pellucida.

**Separation of the [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]] from the granulosal cells by a thick layer of material known as the zona pellucida.

* This development is driven by Gdf9 and BMP15. Knockouts of these genes result in the failure of primordial follicles to develop into primary follicles.  These are normally found within the [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]] itself.

* This development is driven by Gdf9 and BMP15. Knockouts of these genes result in the failure of primordial follicles to develop into primary follicles.  These are normally found within the [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]] itself.

*Oocyte surrounded by a single layer of follicular cuboidal cells.

*Oocyte surrounded by a single layer of follicular cuboidal cells.

* The primary follicle will develop into a secondary follicle.

* The primary follicle will develop into a secondary follicle.

** Granulosa cells proliferate into multiple layers and at the end of this the [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]] is fully grown.  

** Granulosa cells proliferate into multiple layers and at the end of this the [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]] is fully grown.  

* Events that characterize this transition are:

* Events that characterize this transition are:

**Thecal layer becomes organised into the Theca Interna and the Theca Externa

**Thecal layer becomes organised into the Theca Interna and the Theca Externa

[[Image:Secondary Follicle.jpg|thumb|right|150px|Histological Section of the Ovary showing Characteristics of the Secondary Follicle- Courtesy of J.Bredl, Copyright RVC 2008]]

[[Image:Secondary Follicle.jpg|thumb|right|150px|Histological Section of the Ovary showing Characteristics of the Secondary Follicle- Courtesy of J.Bredl, Copyright RVC 2008]]

*The [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]] has developed a thick translucent glycoprotein layer called the Zona Pellucida.

*The [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]] has developed a thick translucent glycoprotein layer called the Zona Pellucida.

*[[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|Oocyte]] surrounded by two or more layers of follicular cuboidal cells. These cells differentiate into the inner Granulosa cells and outer Theca cells.

*[[The_Ovary_-_Oogenesis_- Anatomy & Physiology|Oocyte]] surrounded by two or more layers of follicular cuboidal cells. These cells differentiate into the inner Granulosa cells and outer Theca cells.

* Connective tissue cells surrounding the granulosa cells differentiate to form the layers of theca cells which produce androgens.

* Connective tissue cells surrounding the granulosa cells differentiate to form the layers of theca cells which produce androgens.

* Theca cells produce Androstienedione which is converted to [[Ovaries_Endocrine_Function_-_Anatomy_%26_Physiology|17β-Oestrodiol ]](E2) by the Granulosa cell enzyme Aromatase.

* Theca cells produce Androstienedione which is converted to [[Ovaries_Endocrine_Function_- Anatomy & Physiology|17β-Oestrodiol ]](E2) by the Granulosa cell enzyme Aromatase.

*Granulosa cells become responsive to Follicle Stimulating Hormone (FSH) and start producing [[Ovaries_Endocrine_Function_-_Anatomy_%26_Physiology|17β-Oestrodiol]] and small amounts of Inhibin and Progesterone.

*Granulosa cells become responsive to Follicle Stimulating Hormone (FSH) and start producing [[Ovaries_Endocrine_Function_- Anatomy & Physiology|17β-Oestrodiol]] and small amounts of Inhibin and Progesterone.

* Despite the presence of the zona pellucida, the inner granulosa cells are able to communicate with the [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]] through gap junctions.

* Despite the presence of the zona pellucida, the inner granulosa cells are able to communicate with the [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]] through gap junctions.

* Following formation of the theca cells, the primary [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]] reaches full size.

* Following formation of the theca cells, the primary [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]] reaches full size.

* Granulosa cells secrete fluid, resulting in the formation of a fluid filled space known as the antrum.

* Granulosa cells secrete fluid, resulting in the formation of a fluid filled space known as the antrum.

*The folliclular Antrum enlarges due to the Granulosa cells becoming receptive to LH.

*The folliclular Antrum enlarges due to the Granulosa cells becoming receptive to LH.

*All of the other follicles undergo degeneration.

*All of the other follicles undergo degeneration.

*Ovulation of the Dominant follicle's [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|Oocyte]] occurs in response to an LH surge.

*Ovulation of the Dominant follicle's [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|Oocyte]] occurs in response to an LH surge.

[[Image:Atretic Follicle.jpg|thumb|right|150px|Histological Section of the Ovary showing Characteristics of the Atretic Follicle - Courtesy of J.Bredl, Copyright RVC 2008]]

[[Image:Atretic Follicle.jpg|thumb|right|150px|Histological Section of the Ovary showing Characteristics of the Atretic Follicle - Courtesy of J.Bredl, Copyright RVC 2008]]

* Atresia is the the fate of most of the ovarian follicles as only a small number are [[The_Ovary_-_Ovulation_-_Anatomy_%26_Physiology|ovulated]].  

* Atresia is the the fate of most of the ovarian follicles as only a small number are [[The_Ovary_-_Ovulation_- Anatomy & Physiology|ovulated]].  

* It may occur at any stage of follicular development from primary to tertiary follicle.

* It may occur at any stage of follicular development from primary to tertiary follicle.

* Atretic follicles are characterized by:

* Atretic follicles are characterized by:

* At the beginning of each cycle, a few primary follicles begin to develop into antral follicles.

* At the beginning of each cycle, a few primary follicles begin to develop into antral follicles.

* What causes the selection of particular follicles is unknown, but it is thought to be due to the paracrine action of growth factors such as EGF and IGFs.

* What causes the selection of particular follicles is unknown, but it is thought to be due to the paracrine action of growth factors such as EGF and IGFs.

* Major enlargement of the follicle is not due to the [[The_Ovary_-_Oogenesis_-_Anatomy_%26_Physiology|oocyte]] increasing in size, but down to the gain in follicular fluid secreted by the granulosa cells.

* Major enlargement of the follicle is not due to the [[The_Ovary_-_Oogenesis_- Anatomy & Physiology|oocyte]] increasing in size, but down to the gain in follicular fluid secreted by the granulosa cells.

* A further selection process occurs whereby a single follicle (the dominant follicle) is selected for continued development.

* A further selection process occurs whereby a single follicle (the dominant follicle) is selected for continued development.

* What causes this single follicle to be chosen is unknown.

* What causes this single follicle to be chosen is unknown.

* The dominant follicle enlarges, mainly as a result of its expanding antrum.

* The dominant follicle enlarges, mainly as a result of its expanding antrum.

* Growth of the dominant follicle is dependent on LH as the granulosa cells acquire LH receptors.

* Growth of the dominant follicle is dependent on LH as the granulosa cells acquire LH receptors.

* [[The_Ovary_-_Ovulation_-_Anatomy_%26_Physiology|Ovulation]] occurs in response to a dramatic increase in LH levels.

* [[The_Ovary_-_Ovulation_- Anatomy & Physiology|Ovulation]] occurs in response to a dramatic increase in LH levels.

* The role of FSH is superceeded by LH in the dominant follicle.

* The role of FSH is superceeded by LH in the dominant follicle.

* Initially, FSH acts on granulosa cells to induce synthesis of oestrogens.

* Initially, FSH acts on granulosa cells to induce synthesis of oestrogens.

* Oestrogen has a paracrine action within the ovary to induce the proliferation of granulosa cells.

* Oestrogen has a paracrine action within the ovary to induce the proliferation of granulosa cells.

* During early-mid follicular phase of the [[Female_Reproductive_Tract_-Oestrous_Cycle_-_Anatomy_%26_Physiology|oestrous cycle]], plasma oestrogen exerts a negative feedback inhibition on gonadotrophin secretion.  

* During early-mid follicular phase of the [[Female_Reproductive_Tract_-Oestrous_Cycle_- Anatomy & Physiology|oestrous cycle]], plasma oestrogen exerts a negative feedback inhibition on gonadotrophin secretion.  

* As a result of this, FSH levels begin to fall.

* As a result of this, FSH levels begin to fall.

* The inhibiting effect of oestrogen only occurs whilst plasma oestrogen is below a certain threshold value.

* The inhibiting effect of oestrogen only occurs whilst plasma oestrogen is below a certain threshold value.

* During later stages of the follicular phase of the [[Female_Reproductive_Tract_-Oestrous_Cycle_-_Anatomy_%26_Physiology|oestrous cycle]], one follicle willl become dominant and it becomes the major producer of oestrogen.

* During later stages of the follicular phase of the [[Female_Reproductive_Tract_-Oestrous_Cycle_- Anatomy & Physiology|oestrous cycle]], one follicle willl become dominant and it becomes the major producer of oestrogen.

* Under the influence of oestrogen, granulosa cells which were previously unresponsive to LH, acquire LH-receptors and become responsive to LH.

* Under the influence of oestrogen, granulosa cells which were previously unresponsive to LH, acquire LH-receptors and become responsive to LH.

* The plasma concentration of oestrogen starts to rise.

* The plasma concentration of oestrogen starts to rise.

* When plasma concentrations rise above the threshold value, it acts to enhance gonadotrophin secretion by positive feedback.

* When plasma concentrations rise above the threshold value, it acts to enhance gonadotrophin secretion by positive feedback.

* The high level of oestrogen causes the LH surge that leads to [[The_Ovary_-_Ovulation_-_Anatomy_%26_Physiology|ovulation]].

* The high level of oestrogen causes the LH surge that leads to [[The_Ovary_-_Ovulation_- Anatomy & Physiology|ovulation]].

[[Category:Reproductive System]]

[[Category:Reproductive System]]