Female Reproductive Endocrinology II Flashcards by Joel Glotfelty

In the selected follicle, fully differentiate into androgen producing cells, producing androstenedione and testosterone

Theca cells

How well did you know this?

Not at all

Perfectly

Also, GC cells in the selected follicle begin to express high levels of

CYP19 (P450 aramotase) and 17B-HSD

How well did you know this?

Not at all

Perfectly

The enzymes that convert androgens into E2

CYP19 (P450 aramotase) and 17B-HSD

How well did you know this?

Not at all

Perfectly

During the advanced phase of antral follicle growth, a developmental switch occurs; whereby we see an increase in the production of

How well did you know this?

Not at all

Perfectly

This transient elevation in serum E2 exerts a positive feedback effect on the production and release of

FSH and LH from the pituitary

How well did you know this?

Not at all

Perfectly

Rising FSH during the late follicular phase induces the expression of

LH receptors within the GC of the selected follicle

How well did you know this?

Not at all

Perfectly

Therefore, the selected follicle can now respond to

FSH and LH

How well did you know this?

Not at all

Perfectly

The rise in FSH and LH during the late follicular phase of the cycle supports further growth and differentiation of

Previously recruited younger follicles

How well did you know this?

Not at all

Perfectly

The rise in FSH and LH during the late follicular phase of the cycle supports a robust increase in

Steroidogenesis by the selected follicle

How well did you know this?

Not at all

Perfectly

The rise in FSH and LH during the late follicular phase of the cycle supports initial luteinization of the

Selected follicle

How well did you know this?

Not at all

Perfectly

Inhibin B secretion drops just prior to mid-cycle; this releases its feedback inhibition on the pituitary peptide

Activin

How well did you know this?

Not at all

Perfectly

Activin is expressed within gonadotropes, and activin stimulates

FSH secretion

How well did you know this?

Not at all

Perfectly

The feedback dynamics between the selected follicle and the hypothalamus pituitary lead to the

Preovulatory gonadotropin surge

How well did you know this?

Not at all

Perfectly

The combination of preovulatory levels of E2, rising progesterone, and an increase in inhibin A production by the (luteinizing) GC within the preovulatory follicle, and ultimately the corpus luteum, disrupts the patterns of

GnRH pulsatility

How well did you know this?

Not at all

Perfectly

This results in negative feedback at the level of the hypothalamus on the secretion of both

FSH (E2 dependent) and LH (P4 dependent)

How well did you know this?

Not at all

Perfectly

Note that the hypothalamus expresses

-mediate negative feedback on gonadotropin secretion

Estrogen receptor-alpha (ERa) and progesterone receptor

How well did you know this?

Not at all

Perfectly

This results in a profound decline in gonadotropin secretion upon ovulation, and this continues through the

Luteal phase

How well did you know this?

Not at all

Perfectly

During the luteal phase, we see a negative feedback on LH secretion via chronic stimulation by

Progesterone

How well did you know this?

Not at all

Perfectly

It is this cyclical nature of E2, progesterone, and gonadotropin secretion, with inhibins and activin, that controls

Female Cyclicity

How well did you know this?

Not at all

Perfectly

In antral follicles, theca cells are stimulated by LH to produce

Androstenedione and (some) testosterone

How well did you know this?

Not at all

Perfectly

GC cells are then stimulated by FSH to

Aromatize these androgens

How well did you know this?

Not at all

Perfectly

A product of GC within preantral and small antral follicles, and thus represents the number of follicles which reach somewhat advanced stages of development

AMH

How well did you know this?

Not at all

Perfectly

Therefore, AMH is a marker of healthy growing follicles and this correlates with

Fertility

How well did you know this?

Not at all

Perfectly

Following this peak in a woman’s mid-20s, AMH declines to undetectable levels around age

40-45 years

How well did you know this?

Not at all

Perfectly

What this all means is that the depletion of the ovarian follicular reserve, and serum AMH levels are

Indicates the greatest number of healthy growing follicles and hence, maximum fertility

Peak AMH

The decline in fertility which begins in a woman’s early 30s is reflected by the precipitous decline in

AMH

In a woman less than 38 years old with normal follicular status, serum AMH levels should be between

2.0-6.8 ng/mL

Dependent upon the gonadotropin surge, and LH is a main player

Ovulation

Can be considered the"ovulation gonadotropin"

LH and FSH stimulate the terminal differentiation of GC; whereby GC switch from almost the exclusive production of E2 to the production of

E2 and progesterone (luteinization)

This change in steroidogenesis begins immediately prior to ovulation with the expression of LH receptors within the

GC of the dominant follicle q

A thermogenic hormone; this accounts for the biphasic 0.5 ˚F rise in basal body temperature that occurs upon ovulation and during the luteal phase

Progesterone

LH also stimulates the production of

Prostaglandins

Collectively, the aforementioned molecules dissociate some of the intercellular connections that join

Increases in the follicular vasculature are also involved; these angiogenic effects appear to be mediated by

Prostaglandins, cytokines, and growth factors

The oocyte is ovulated with an attached surrounding layer of GC called the

Cumulus GC

Thus, the ovulated complex is referred to as the

Oocyte-cumulus complex

Upon ovulation, changes in cAMP signaling in the GC and oocyte signal the oocyte to complete the

First meiotic division

This can be identified microscopically by the extrusion of the first

Polar body into the ooplasm

A haploid product of meiosis I that contains one set of 23 paired chromosomes; this structure fragments and disappears

1st polar body

The oocyte-cumulus complex is extruded into the region of the fimbrae of the

Oviduct (Fallopian tube)

The remnant of what was the preovulatory follicle is just the

GC and theca cells

The remnant of what was the preovulatory follicle is stimulated by LH to terminally differentiate into the

Corpus Luteum

In general, in response to LH, luteal cells produce

E2 and progesterone

Indicates that ovulation has occurred

Luteal progesterone

A woman who has ovulated can predict a meager rise in basal body temperature through the

Mid-luteal phase of her cycle

Targets the uterus, and has a quiescing effect on the myometrium (uterine muscle)

Progesterone

The corpus luteum also produces

Inhibin A

Like inhibin B during the early-mid follicular phase, inhibin A exerts negative feedback on

Gonadotropin secretion

In the event of fertilization, elevated progesterone is absolutely required for

Implantation

Has proliferative and angiogenic effects within the endometrium -also required for implantation

If pregnancy does not occur, LH levels decline, and without LH, the corpus luteum undergoes

Degeneration (luteolysis)

Mediated by prostaglandins and other factors

Luteolysis

The fertile endometrium undergoes cycles of

Proliferation, differentiation, and tissue breakdown

The endometrium has which two main layers?

1. ) Functional upper layer | 2. ) Deep basal layer

During the proliferative (i.e. follicular) phase of the cycle, the endometrium is stimulated by

Within the functional endometrium, E2 induces the expression of

ERa, progesterone receptors (PR), and growth factors

This enables regeneration (due to shedding from the previous cycle) and proliferation of the

Endometrium

Recall that the secretory (i.e. luteal) phase of the cycle begins following

Ovulation

During the early secretory phase, the endometrium is targeted by

E2 and progesterone

Results in the development of a rich blood supply that supports the endocrine and paracrine mechanisms required for implantation of the blastocyst

E2 and Progesterone's effects on the endometrium in early secretory phase

With rising progesterone levels during the mid secretory phase, we see a down-regulation of

PR and ERa

During the mid-phase, also causes changes in gene expression within the endometrium that induce decidualization -prepares endometrium for implantation

Progesterone

Consider that optimal conditions for implantation exist for approximately

6-10 days post LH surge

During the late secretory phase, the uterus is essentially a refractory tissue; it briefly assumes the properties of a

Pregnant Uterus

Should implantation occur, a complex cascade of events is initiated through interactions between the embryo and the decidua which maintain the

Pregnant Uterus

Results from the precipitous drop in progesterone and E2 that occurs during the late\ luteal phase

Menstruation

The processes which enable the endometrial breakdown in fact begin due to progesterone-stimulated changes in gene expression during the

Early secretory phase

Primes the endometrium to shed

Progesterone

In the absence of progesterone and E2 support, the upper 2/3 of the functional layer sheds off, the uterus again assumes the

Steroid-responsive phenotype

Diagnosed as the inability of a couple to conceive after one year of unprotected intercourse

Infertility

Indicates that a woman has never conceived

Primary infertility

Type of infertility where a woman has conceived previously

Secondary infertility

The incidence of diagnosed female infertility is approximately

13%

The absence of menses by age 13 without normal growth or secondary sexual development; or no menses by age 15 with normal growth and secondary sexual development

Primary amenorrhea

Having had one or more consecutive cycles with the absence of 3 consecutive cycles for 6 consecutive months

Secondary Amenorrhea

Defects in the mechanisms leading to ovulation and/or the luteal phase are classified as

Functional causes of infertility

Pelvic and cervical anomalies are classified as

Structural causes of infertility

The basic premise for treating infertility is to support enhanced follicular growth so that several preovulatory follicles develop for

Retrieval or Ovulation

The basic idea is to exogenously manipulate the hormonal regulation of the

Menstrual Cycle

First,neuroendocrine function is controlled by the use of either a

GnRH agonist or antagonist

A so-called selective estrogen receptor modulator (ER antagonist within the hypothalamus) which releases GnRH from feedback inhibition by E2

Clomiphene

Therefore, the short term effect of Clomiphene is that of a

GnRH antagonist

Can be given on days 3-5 of the cycle for 5 days, and this results in spikes of GnRH secretion

Clomiphene

These GnRH spikes subsequently drive FSH secretion leading to enhanced follicular growth and the formation of several

Preovulatory follicles

These follicles functionally differentiate as would occur naturally, and thus produce

E2 and inhibins

In the event of a GnRH suppression protocol, a GnRH pulsatility is disrupted using either an antagonist (e.g., clomiphene) or agonist such as

Leuprolide

Recall that the chronic loss of GnRH pulsatility, as occurs with GnRH antagonists or agonists, attenuates

FSH secretion

This causes the down-regulation of the

Pituitary drive

Once down-regulation has been established (as determined by a serum E2 < 50 pg/ml), we administer

Recombinant FSH (rFSH)

After a few days of rFSH treatment, follicle growth is assessed by

Transvaginal ultrasound

So long as ≥ 3 follicles with a diameter of ≥ 17 mm are detected, the processes leading to ovulation are induced by giving

hCG

Oocytes are aspirated from the large follicles guided by transvaginal ultrasound at around

36 hours post hCG

Keep in mind that with the development of several preovulatory follicles, and the exposure of these follicles to a hefty dose of LH (i.e. hCG), comes the normal pattern of increased

E2 secretion, luteinization (P4 secretion), and endometrial priming

Under normal circumstances, fertilization occurs within the

Oviduct

The oocyte can be fertilized up to approximately

24 hours post ovulation

During the fertilization process, a single sperm burrows through the outer cumulus GC and binds to the

Zona pellucida of the oocyte

The cortical reaction within the oocyte occurs as follows: sperm binding stimulates its incorporation into the ooplasm, and this is followed by which three things?

1. ) Oocyte membrane hyperpolarization 2. ) Increased intracellular [Ca2+] 3. ) Cortical granule hardening

These cellular changes prevent additional sperm-oocyte interactions, known as

Polyspermia

Female Reproductive Endocrinology II Flashcards

(100 cards)