Follicular Phase Of The Menstrual Cycle

Question 1

D. Follicular Phase of the Menstrual Cycle

Question 2

The follicular phase is the term given to the first approximately 14 days of the menstrual cycle. It is

Question 3

composed of both an endocrine-independent and an endocrine-dependent development of ovarian

Question 4

follicles.

Question 5

Follicle activation: Every day a group of approximately 50 oocytes begin to grow in the ovary (Eldar-

Question 6

Geva et al.

Answer 6

2000). Mechanisms involved in determining the selection of oocytes and oocyte

Question 7

stimulation within the primary follicles have been the focus of many studies in recent years and a

Question 8

picture

Answer 8

albeit incomplete

Question 9

above). Evidence from animal models has brought to light complex

Answer 9

intra-ovarian control mechanisms

Question 10

that involve members of the TGFB super family

Answer 10

in particular BMP15 and GDF9 subfamilies

Question 11

ligand

Answer 11

leukemia inhibitory factor (LIF)

Question 12

2006). Deletion or disruption of the BMP15 gene results in impaired early foliculogenesis

Answer 12

making it a

Question 13

good candidate in the search for signals that trigger the initial growth of primordial follicles. However

Question 14

primordial follicle activation is likely dependent upon the activities of several inhibitory and stimulatory

Question 15

molecules

Answer 15

some of which are only now being identified.

Question 16

The selection of the follicles for activation appears to be random and is not hormonally

Question 17

stimulated.

Question 18

These waves of follicles grow for over 10 months after which most undergo atresia.

Question 19

Follicles

Question 20

AECRUITMENT-SELECTION

Question 21

Gonadotropins

Question 22

Ovarian Factors

Question 23

Dominant

Question 24

Follicle

Question 25

atresia

Question 26

DAY OF MENSTRUAL CYCLE

Question 27

Figure 16. Dominant follicle selection

Question 28

14

Question 30

A small group of 5-10 developing follicles per ovary are rescued from atresia once a month by the

Question 31

increasing systemic concentrations of FSH that are present during the early follicular phase (cyclic

Question 32

recruitment

Answer 32

Peters & McNatty

Question 33

follicles is therefore purely due to good fortune; that is

Answer 33

their development happens to coincide with an

Question 34

appropriate hormonal milieu.

Question 35

An antral follicle count (AFC) using ultrasound early in the menstrual cycle can be used as a means

Question 36

of assessing ovarian reserve and an indication of the likelihood of obtaining sufficient growing

Question 37

follicles in an IVF treatment cycle after ovarian stimulation.

Question 38

Estrogen and progesterone concentrations are low during the early stages of the follicular phase

Question 39

(Figure 13) leading to a subtle but continuous increase in FSH and LH (removal of steroid negative

Question 40

feedback).

Question 41

Increasing systemic concentrations of FSH stimulate antrum formation in the rescued follicles and

Question 42

also stimulate GC division (hyperplasia) resulting in an exponential growth in GC numbers.

Question 43

FSH and LH also stimulate the steroid synthetic pathways of the GC to produce estrogen (see

Question 44

above). Since GC numbers increase exponentially

Answer 44

the estrogen concentration also increases

Question 45

in an exponential fashion until peak systemic concentrations (-200-300 pg/mL) occur just

Question 46

prior to ovulation.

Question 47

The rising concentrations of estradiol have three important influences on the early menstrual cycle.

Question 48

> Endometrial cell preparation: Estradiol simulates the proliferation of endometrial cells and

Question 49

prepares the intracellular mechanisms of the endometrial cells for the subsequent actions of

Question 50

progesterone later in the menstrual cycle.

Question 51

> Dominant follicle selection: Of the 5 to 10 follicles per ovary that were initially recruited by FSH

Question 52

for development

Answer 52

only one or two will develop into a preovulatory state (Figure 16). The elevated

Question 53

levels of estrogen prior to ovulation cause a decrease in FSH levels in response to negative

Question 54

feedback (Figures 14 & 15). Ovarian inhibin may also participate in suppressing FSH pituitary

Question 55

output and closing the FSH window.’ Decreased FSH Ilevels may partially be responsible for

Question 56

selection of the dominant preovulatory follicle by the production of a more androgenic

Question 57

microenvironment within follicles adjacent to the growing dominant follicle. Furthermore

Answer 57

the GC

Question 58

of the dominant growing folicle secrete a variety of peptides that may inhibit development of the

Question 59

adjacent follicles via an autocrine/paracrine mechanism. Antimüllerian hormone produced by the

Question 60

GC is also believed to play a role in dominant follicle selection. The mechanism(s) of dominate

Question 61

follicle selection have been well studied and while a definitive mechanism(s) is/are not entirely

Question 62

clear a favored current theory proposes follicle dominance arises by selective follicular

Question 63

sensitization leading to enhanced FSH responsiveness and ability to continue development in an

Question 64

environment with low FSH levels.

Question 65

> Induction of the LH surge: High estradiol concentrations towards the end of the follicular phase

Question 66

induce the LH surge that stimulates the ovulatory response and the resumption of meiosis by the

Question 67

oOcyte (see above). As part of the ovulatory response

Answer 67

the LH surge luteinizes the GC to form the

Question 68

corpus luteum and converts the steroidogenic pathway from a predominately estrogen-producing

Question 69

system to a predominately progesterone-producing system.