37. Physiology of Follicular Development Flashcards

1
Q

During the development of the ovarian follicle, first meiotic arrest occurs at _________ and is associated with elevated levels of ________

Large antral follicles gain meiotic competence and stay in arrest until ____ surge (can stay in this stage 50 years!)

A

Prophase I; cAMP

LH

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2
Q

Meiosis I finishes before ovulation, at which time the first ______ is extruded. The second is extruded after resumption of meiosis II only after fertilization

A

Polar body

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3
Q

The second meiotic arrest during follicular development occurs during ________ and is associated with elevated levels of _________. If fertilization occurs, meiosis II resumes and there is rapid degradation of _____ as well as extrusion of a 2nd polar body

A

Metaphase II; MAPK proteins; MAPK

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4
Q

The adult ovary can be divided into an inner medulla and outer cortex. Differentiate these two components

A

Inner medulla is highly vascular, contains nerves, interstitial cells, and lymphatics

Outer cortex consists of densely cellular stroma; ovarian follicles reside within the stroma at different points of their development

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5
Q

3 phases of ovarian follicle cycle

A

Follicular phase
Ovulatory phase
Luteal phase

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6
Q

During the follicular phase, the ______ ____ is the functional unit of the ovary

A

Ovarian follicle

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7
Q

During the follicular phase, the ovarian follicle is the functional unit of the ovary; it performs ______ and _____ functions

A

Gametogenic; endocrine

[pre-menopausal cycling woman contains follicular structures at many different stages]

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8
Q

The primordial follicle is surrounded by a single layer of _______ cells; it releases ______ factors but no steroid hormones at this stage. It represents the ovarian reserve, of which most will undergo ________

A

Pregranulosa; paracrine; atresia

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9
Q

_______ follicles develop prior to the formation of the fluid-filled antral follicles

A

Pre-antral

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10
Q

The primary follicle as it transitions to the preantral follicle consists of a central ______ oocyte, a single layer of granulosa cells which take on a _____ shape, the size of the follicle increases due to growth of the oocyte, and there is early production of secreted glycoproteins

A

Primary; cuboidal

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11
Q

At what part of the follicular phase does the zona pellucida begin to develop?

A

Preantral follicle — early production of secreted glycoproteins ZP1, ZP2, and ZP3

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12
Q

As the preantral follicle grows, it is associated with a secondary follicle, which consists of a primary oocyte surrounded by 3-6 layers of ______ ______ cells.

The secondary follicle secretes paracrine factors which induce local stromal cells to differentiate into ____ cells

A

Cuboidal granulosa

Thecal

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13
Q

As the secondary follicle secretes paracrine factors to induce differentiation of stromal cells —> thecal cells, these can further be differentiated based on the inner glandular and highly vascular ________, and the fibrous capsule-like ______

A

Theca interna; theca externa

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14
Q

Progression of the primary follicle to the secondary follicle requires increased vascularization — how does this occur?

A

The follicle migrates from the outer cortex to the inner cortex, closer to the ovarian vasculature

The follicles release angiogenic factors that induce development of 1-2 arterioles, generating a vascular wreath around the follicle

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15
Q

The increased vascularization that occurs with progression to the secondary follicle also involves development of the _____ ____, which provides binding sites for sperm during fertilization

A

Zona pellucida

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16
Q

The oocyte itself is avascular, but recieves its nutrition from ____ cells

A

Granulosa

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17
Q

As preantral follicles grow and progress through secondary follicle stage, contact between the granulosa and oocyte is maintained. Cytoplasmic processes eventually penetrate the ZP and form ____ ____ at the oocyte surface, structures which also form between adjacent granulosa cells for intercellular communication

A

Gap junctions

18
Q

T/F: The preantral secondary follicle has minimal endocrine function

A

True

19
Q

The preantral secondary follicle has minimal endocrine function. Granulosa cells express ______ receptors (although growth at this point is not dependent on this hormone). Granulosa cells do not produce ovarian hormones at this point. Thecal cells are analogous to testicular Leydig cells. They express _____ receptors and their major product is ________, but at this point production is minimal or absent

A

FSH; LH; androstendione

20
Q

In the preantral to antral transition, proliferation of granulosa cells continues, leading to the continued increase in follicular size. _____ ______ from granulosa cell secretions begins to appear between.

A

Follicular fluid

21
Q

In the preantral to antral transition, proliferation of granulosa cells continues, leading to the continued increase in follicular size. Follicular fluid from granulosa cell secretions begins to appear between. Fluid drops eventually coalesce to form a singular _____ _____, marking the beginning of the _____ phase

A

Follicular antrum; antral

22
Q

The increase of follicular size that occurs with the beginning of the antral phase is dependent on what 3 factors?

A

Increase in antral size
Volume of follicular fluid
Proliferation of granulosa cells

23
Q

During the beginning of the antral phase, the oocyte becomes suspended in fluid surrounded by a dense mass of granulosa cells called the _____ ____

A

Cumulus oophorus

24
Q

The _____ phase is associated with a 100-fold increase in granulosa cells of 2 different populations: _____ and ______

A

Antral; mural; cumulus

25
Q

Differentiate the mural granulosa cells from the cumulus cells (cumulus oophorus/corona radiata) that can be differentiated during the antral phase

A

Mural granulosa = outer wall of follicle; become highly steroidogenic

Cumulus cells = maintain gap and adhesion junctions with oocyte. Released during ovulation with oocyte

26
Q

Growth during the antral phase becomes responsive to ________

Theca interna is responsive to ____

Granulosa cells are responsive to ____

A

Gonadotropins

LH

FSH

27
Q

What do the theca interna cells do in response to LH binding its receptors in the antral stage?

A

Synthesize androgens from acetate and cholesterol — androstenedione is major steroid product

28
Q

What do the granulosa cells do in response to FSH binding its receptors in the antral stage?

A

Convert androgens from thecal cells to estrogen via aromatization

Induces expression of LH receptors late in follicular phase

29
Q

The oocyte grows rapidly in the early stages of antral follicles, but growth slows in larger follicles. At the antral stage, the oocyte becomes competent to complete meiosis I at ovulation, but will maintain meiotic arrest until the midcycle ____ surge. Meiotic arrest is achieved by maintenance of elevated _____ levels in the mature oocyte

A

LH; cAMP

30
Q

Several large antral follicles are recruited to begin development each monthly cycle; there is selection of 1 dominant follicle early in the _____ phase, largely dependent on the follicles’ sensitivity to _____

A

Follicular; FSH

31
Q

Mural granulosa cells produce low levels of _____ and ________, causing decline in FSH levels. The largest follicle with the most FSH receptors becomes the dominant follicle, and the others will undergo _____, which is the apoptosis of oocytes and associated _____ cells

A

Estrogen; inhibin B; atresia; granulosa

32
Q

Midcycle, the dominant follicle becomes a large preovulatory follicle known as the _______ follicle

A

Graafian

33
Q

The _________ period is defined as the time from onset of LH surge to ovulation, only lasting about 32-36 hours. During this time structural changes are occuring in preparation of ovulation

There are also changes in steroidogenic function of the theca and mural granulosa cells; this prepares the cells for ________ process, formation of the ______, and increased production of _______

A

Periovulatory

Luteinization; corpus luteum; progesterone

34
Q

Follicular development can be induced as a treatment for sub- or infertility via Assisted Reproductive Procedures. What are 2 examples of this?

A

Clomiphene citrate

GnRH agonists or antagonists followed by FSH treatment

35
Q

Follicular development can be induced as a treatment for sub- or infertility via Assisted Reproductive Procedures. What is the MOA of clomiphene citrate?

A

Selective estrogen receptor modulator — inerferes with estrogen negative feedback leading to increased FSH availability

This increases antral follicle dev’t, multiple oocytes can be ovulated, and ovulation is triggered with LH or hCG to time process correctly

[this is the process of artificial insemination; 2-3 follicles will develop if successful]

36
Q

Follicular development can be induced as a treatment for sub- or infertility via Assisted Reproductive Procedures. What is the MOA of GnRH agonists or antagonists followed by FSH tx?

A

This prevents LH surge; extra FSH leads to development of multiple follicles. hCG trigger mimics LH surge to time egg collection

[this is the process of IVF; 15-16 follicles will develop if successful]

37
Q

The LH surge induces differentiation (luteinization) of granulosa to _____ _____ cells

A

Granulosa lutein

38
Q

At the time of LH surge, the thecal and mural granulosa cells express LH receptors. This induces a shift in steroidogenic activity. There is a transient inhibition of _____ expression, resulting in a rapid decline that reduces positive feedback on ____ secretion

A

Aromatase; LH

39
Q

Increased vascularization of granulosa during luteinization leads to increased cholesterol availability for _____ production

A

Progesterone

40
Q

The LH surge induces what structural changes in the follicle?

A

Release of cytokines and hydrolytic enzymes from theca and granulosa —> breakdown of follicle wall, tunica albuginea, surface epithelium

Cumulus-oocyte complex detaches (free floating in antrum)

Basal lamina of mural granulosa degraded — angiogenic factors released, increased blood supply to folicle/corpus luteum

LH surge induces oocte to progress to metaphase II

41
Q

During ovulation and luteinization, increased size of follicle and position in cortex causes a bulge on the ovarian surface. The bulging ____ wall becomes thin and avascular. CT breaks down and ruptures, causing follicular fluid, _____, and surrounding _______ cells to flow out to peritoneal cavity.

_____ then sweep the cumulus mass into oviductal ostium.

A

Stigma; oocyte; cumulus

Fimbria