Terence (Reproductive endocrinology) Flashcards
Genetic sex
Sex chromosomes determine genetic sex i.e. genetic females are XX and genetic males are XY.
One sex chromosome is inherited from your mother and one from your father.
Males inherit the Y from their father and X from mother.
Sexual differentiation occurs early in embryogenesis and is dictated by the presence or absence of the Y chromosome which encodes the sex determining Y gene (SRY).
The SRY gene encodes a transcription factor that activates a testis-forming pathway at about week 7 of development.
In the absence of a Y chromosome the embryo will develop into a female.
Sexual differentiation in the embryo
The early embryo has two systems of ducts (25-30 days post conception).
- Wolffian ducts- capable of developing into the male reproductive tracts
- Mullerian ducts- capable of developing into the female reproductive tracts
In the early stages both genders have these ducts and then it develops into either male or female tracts.
SRY induces the expression of
- Anti-Mullerian hormone (AMH)
- Testosterone
- Dihydrotestosterone (DHT) produced from testosterone by the enzyme 5 alpha reductase
These hormones cause degeneration of Mullerial duct and are critical in sexual differentiation in the embryo and subsequent sexual development.
Oogenesis
- Oogenesis occurs in the ovaries and begins in foetal life (in-utero) development. - primordial germ cells or oogonia undergo numerous mitotic divisions
- 7 months after conception the oogonia stop dividing and a third differentiate into primary oocytes.
- These primary oocytes start the first phase of meiosis by replicating their DNA (in-utero). However, meiotic division is not completed and these cells are said to be in meiotic arrest (stop until puberty).
- At puberty those primary oocytes destined for ovulation (20-25 per month) complete the first meiotic division. This results in the production of 2 daughter cells each with 23 chromosomes. However, only one cell retains all the cytoplasm and is called the secondary oocyte and the other is non-functional and called the polar body.
- The second meiotic division occurs after ovulation (in the fallopian tube) and is completed after fertilisation. (Produces a second polar body and an ovum).
Key terms
- Corpus luteum
- Menopause
- Endometrium
- Oestradiol
- Menstruation
- Corpus luteum- A yellow mass of cells that forms in an ovarian follicle during the luteal phase of the menstrual cycle in mammals; it secretes steroid hormones
- Menopause- The ending of menstruation
- Endometrium- The mucous membrane that lines the uterus in mammals and in which fertilised eggs are implanted
- Oestradiol- A potent oestrogenic hormone produces in the ovaries of all vertebrates
- Menstruation- the periodic discharging of the menses, the flow of blood and cells from the lining of the uterus in females of humans and other primates
Hormonal regulation of the female reproductive system
The average onset of puberty in females is age 11 and onset is signalled by high pulses of Gonadotropin Releasing Hormone (GnRH).
GnRH stimulates the release from the anterior pituitary gland of:
- Follicle stimulating hormone (FSH)
- Luteinising Hormone (LH)
FSH and LH promotes:
- follicular development in the ovaries
- the production of the sex hormones oestrogen and progesterone
- initiates the menstrual cycle
- ovulation
The menstrual cycle
The menstrual cycle is the monthly cycle of release of the oocyte and the preparation of the uterine (endometrial) lining of the uterus for pregnancy which is then shed (menstruation) if fertilisation does not take place.
Occurs from puberty to menopause.
Takes 21-35 days from first day of bleeding to last day before next bleed.
There are three phases based on follicular histology:
- Follicular phase- a follicle is a small structure in the very that contains one immature egg/oocyte. In this phase a follicle grows and develops into a mature follicle (fluid filled sac containing the oocyte)
- Ovulatory phase- the release of the oocyte from the ovary (lasts 1-3 days)
- Luteal phase- beginning after ovulation with the development of the corpus luteum from the follicle (13-14 days)
These phases are regulated by hormones.
The follicular phase
Involves menstruation, maturing follicle and the mature follicle.
Hypothalamus releases GnRH which acts on the anterior pituitary leading to a release of FSH and LH. These act on the follicle which produce low levels of oestrodiol which in turn inhibits secretion of GnRH.
Increase in FSH and LH stimulates follicular growth.
10-25 primary follicles containing an oocyte develop each month in response to an increase in FSH. The drop in FSH due to increase in estradiol results in only one follicle surviving.
LH and FSH act on different cells in the follicle to stimulate the production of oestradiol and promote follicle development and maturation.
LH acts on theca cells (synthesise testosterone).
FSH acts on granulosa cells (synthesise oestradiol from testosterone).
The ovulatory phase
LH and FSH stimulate maturation of one of the growing follicles.
Hypothalamus releases GnRH which acts on the anterior pituitary leading to a release of FSH and LH. These act on the follicle and the follicle produces high levels of estradiol. In high concentration oestradiol is stimulatory on the release of GnRH causing a rise in LH and FSH (resulting in ovulation about a day later) and also causes the endometrium to thicken.
The luteal phase
LH stimulates growth of a corpus luteum from a follicular tissue left behind after ovulation. Hypothalamus releases GnRH which acts on the anterior pituitary leading to a release of FSH and LH. These act on the corpus luteum. The corpus luteum secretes estradiol and progesterone that block GnRH production by the hypothalamus and LH and FSH production by the anterior pituitary.
The oestrogen and progesterone secreted by the corpus luteum stimulates the growth of the endometrial lining of the uterus in order to prepare it for pregnancy. It also releases inhibin which inhibits production of FSH.
Corpus luteum needs FSH to survive. If the egg is not fertilised the corpus luteum degenerates/dies , levels of oestrogen and progesterone decrease and a new cycle begins.
The contraceptive pill/implant
The combined oral contraceptive pill (COCP) includes an oestrogen and progestogen (synthetic form of progesterone).
Prevents ovulation by suppressing the release of gonadotropins from anterior pituitary (LH and FSH).
Taken by mouth eery day and inhibits female fertility.
First approved in the US in 1960.
There are also progesterone only pills (POPS).
Implants e.g. Nexplanon release progesterone.
Key points of menstrual cycle
GnRH secreted by the hypothalamus triggers the release of FSH and LH from the pituitary. In females, this signals the ovaries to produce oestradiol and progesterone.
FSH stimulates the growth and maturation of follicles on the ovaries, which house and nourish the developing eggs. The follicle releases inhibin which inhibits the production of FSH.
Progesterone stimulates the growth of the endometrial lining of the uterus in order to prepare it for pregnancy. A strong surge of LH at around day 14 of the cycle triggers ovulation of an egg from the most mature follicle.
After ovulation, the ruptured follicle becomes a corpus luteum, which secrets progesterone to either regrow the uterine lining or to support the pregnancy is it occurs.
The menopause is primarily due to the depletion of the finite pool of follicle, but also reduced sensitivity to FSH and LH. This leads to the cessation of the menstrual cycle resulting in an excess of LH and FSH and a deficiency in oestrogen and progesterone.
Fertilisation
The binding of the sperm to the zona pellucida triggers a reaction in the sperm called the acrosomal reaction where acrosomal enzymes are released.
The acrosomal enzymes digest a path through the zona pellucida.
There first sperm to penetrate the zona pellucida triggers a reaction that prevents the entry of additional sperm by hardening of the zona pellucida.
The sperm DNA now enters the oocyte. The now fertilised egg is called a zygote (formed by the union of two gametes).
Early development, implantation and placentation
Zygote undergoes a number of mitotic divisions resulting in a 16-32 cell conceptus and each cell is totipotent (capable of giving rise to any cell).
After 3 or 4 days conceptus reaches the uterus.
Totipotency lost and conceptus differentiates and develops into a blastocyst.
Progesterone has prepared the lining of the uterus for implantation and the blastocyst embeds into the wall of the uterus.
About 10 to 12 days after fertilisation, the blastocyst develops into an embryo. It remains an embryo until about 9 weeks after implantation, when it becomes a foetus.
Trophoblasts form outer layer of a blastocyst.
Trophoblasts provide nutrients to the developing embryo during the first 3 months.
Trophoblasts release human chorionic gonadotropin (hCG) which ensures survival of the croups luteum.
Corpus luteum produces progesterone/oestradiol for the first 3 months ensuring maintenance of pregnancy. (At 3 months the placenta takes over and if there is a break in the time between the corpus luteum producing the hormones and the placenta taking over the woman will miscarry. Lots of miscarriages happen at this point).
Conceptus- term for everything derived from the zygote.
Totipotent- the cell has the capacity to develop into a complete organisation.
Identical twins (monozygotic twins)- arise from cleavage and separation of the conceptus.
Fraternal twins (dizygotic twins) result from the release and fertilisation of 2 eggs. (Can happen if female has higher levels of FSH so more than 1 egg can survive, family genetic predisposition of twins).
The pregnancy test
Human Chorionic Gonadotropin (hCG) can be detected in urine or blood after implantation, which occurs 6-12 days after fertilisation.
Most pregnancy tests detect the presence of hCG in the blood or urine.
Hormones and the maintenance of pregnancy
At around 3 months trophoblasts differentiate into the placenta and stop making hCG and start to produce progesterone/oestradiol. The placenta takes over the role of the corpus luteum which degenerates due to a fall in hCG.
The switch from the corpus luteum making progesterone and oestradiol to the placenta is critical in maintaining pregnancy. The failure to switch is a common cause of miscarriage. There can’t be any time gap in this switch.
Progesterone/oestrogen is essential for maintenance of pregnancy and in preparation of uterus for parturition- the action of giving birth.
Oxytocin is produced in the hypothalamus and stored in the posterior pituitary gland and is released in large amounts after distension of the cervix and uterus during labour.
