Pregnancy, Menstrual Cycle and Reproduction Flashcards
How is foetal sex determined by the Y chromosome?
SRY gene codes for TDF or SRY-protein which switches on testicular development. The Sertoli cells of the testes produce Mullerian-inhibiting substance, which prevents Mullerian duct development.
Where is testosterone produced?
Leydig cells
What is the effect of testosterone (Development)
Causes Wolffian duct to differentiate into the epididymis, vas deferens, ejaculatory ducts and seminal vesicles.
What is the next step in male sex development (post-W. duct differentiation)?
Externally under the influence of dihydrotestosterone (DHT) produced from testosterone in target tissue, the penis forms and the tissue near it fuses to form the scrotum.
The testes descend into the scrotum (stimulated by testosterone)
How is foetal sex determined by the XX chromosomes?
Absence of Y chromosome = absence of SRY gene = the female will not have testes and will not secrete MIF or testosterone.
Absence of MIF = Mullerian system does not degenerate and a vagina and female external genitalia develop
Summary of differentiation until 6 weeks
Primitive gonads are identical
Summary of differentiation after 6 weeks
- If Y chromosomes are present and thus SRY gene: testes form and Mullerian development is inhibitied
- If Y chromosome is absent: ovaries form and Mullerian development occurs
Where do both the male and female gonads derive embryologically?
the urogenital ridge
Until when are primordial gonads undifferentiated?
6 weeks
In the genetic male, the testes begin to develop during the –th week?
7th week
What are germ cells? Where do they develop?
- Cells that develop into sperm and ova
- Originate from the yolk sac of the hind gut
- Specialised cells which develop into gametes
Anomalies of primary sex development
- Gonadal dysgeneses
- Intersex - 4XY disorders of sex differentiation
- Intersex - 4XX disorders of sex differentiation
- Androgen insensitivity testosterone syndrome
Gonadal dysgeneses CAUSE
- Non-disjunction
- Sex chromosome deletion
Hypothalamic-pituitary-gonadal axis
- Normally, gonadotrophin releasing hormone (GnRH) secreting neuroendocrine cells of the hypothalamus fire a brief burst of action potentials approximately every 90 minutes, secreting GnRH at this time
- The GnRH travels to the anterior pituitary via the hypothalamal-hypophyseal portal vessels and triggers the release of both LH and FSH
- FSH primary acts on the Sertoli cells to stimulate the secretion of paracrine agents required to initiate spermatogenesis
- LH acts primarily on the Leydig cells to stimulate testosterone secretion. Testosterone acts locally by diffusing from the interstitial spaces into the seminiferous tubules and then enters the Sertoli cells where it is able to facilitate spermatogenesis
Hypothalamic-pituitary-gonadal axis - NEGATIVE FEEDBACK
- Testosterone inhibits LH secretion in 2 ways:
- Acts on the hypothalamus to decrease the amplitude of GnRH resulting in a decrease in its secretion
- Acts directly on the anterior pituitary gland to decrease LH response to GnRH
- Sertoli cells release INHIBIN which acts on the anterior pituitary to inhibit the release of FSH`
Hormonal control of puberty - before puberty
- Low pulsatility amplitude of GnRH and GHRH (growth hormone releasing hormone) secretion from hypothalamus
- Low levels of pituitary FSH, LH and gonadal sex steroids
Hormonal control of puberty - at pubertal age
- The trigger is not clearly understood
- Increased amplitude of GnRH and GHRH
- Increased levels of FSH, LH and sex steroids
- Increased levels of growth hormone
Normal puberty
- Centrally driven
- Depends on intact Hypothalamus-Pituitary-Gonadal axis
- Influenced by nutrition, leptin and insulin, socio-cultural, genetic and exercise factors
- Trigger is not well understood
Causes of precocious puberty
- Gonadotrophin dependent
- Gonadotrophin independent
- Other variants
Gonadotrophin dependent (precocious puberty) reasons
- Intracranial lesions
- Infections
- Encephalitis
- Gn secreting tumours
- Hypothyroidism
Gonadotrophin independent (precocious puberty) reasons
- CAH
- Sex hormone secreting tumours
- E2 ingestion
Other variants (precocious puberty) reasons
Premature thelarche or adrenarche
Treatment of premature adrenarche
androgen receptor blockage
Causes of delayed puberty
General
- Constitutional delay (most cases) - Malabsorption (coeliac disease, inflammatory bowel disease) - Chronic disease or underweight
Gonadal failure
- Turner’s syndrome autoimmune syndrome
Gonadotrophin deficiency
- Kallman's syndrome - Hypothalamic/pituitary lesions
What covers the testes anteriorly?
Sac-like extension of the peritoneum → tunica vaginalis
Name of white fibrous capsule?
Tunica albugenia
Septa divide the testes into compartments containing — — where sperm are produced
seminiferous tubules
What do seminiferous tubules drain into?
- A network called RETE TESTIS
- The sperm then travel through efferent ductules which leave the rete testis and pierce the tunica albuginea and empty into a single duct within the epididymis
- The epididymis leads to a vas deference (a large thick walled tube lined with smooth muscle)
Which cells promote sperm cell development?
Sertoli cells
What forms the blood-testis barrier
tight junctions between sertoli cells separating sperm from immune system
Heat exchange of Pampiniform Plexus
- Spermatogenesis cannot take place at 37 degrees but needs to take place at a temperature that is lower (35)
- A special temperature regulation is done by heat exchange that happens by the pampiform plexus where venous blood carries away heat
Spermatogenesis
- Spermatogonia produce 2 kinds of daughter cells
- Type A remain outside blood-testis barrier and produce more daughter cells until death
- Type B differentiate into primary spermatocytes and these cells must pass through the blood-testis barrier to move inward toward lumen. Meiosis I produces 2 secondary spermatocytes and Meiosis II produce 4 spermatids.
What is spermiogenesis?
the transformation of spermatids into spermatozoa (where a tail is sprouted and cytoplasm is discarded)
Which two structures secrete most of the fluid in which ejaculated sperm is suspended?
- prostate gland
- seminal vesicles
Chemical substances secrete by main two secretory structures (male)
- The prostate and seminal vesicle secretions contain a large number of different chemical substances
- Buffers for protecting sperm against the acidic vaginal secretions and residual urine in the male urethra
- Chemicals (particularly from SV) increase sperm motility e.g. fructose to provide energy
- Prostaglandins - to stimulate female peristaltic contractions
What percentage of the expelled fluid is from which structure?
- 60% seminal vesicle fluid
- 30% prostatic
- 10% sperm and trace of bulbourethral fluid
Normal sperm count
50-120 million mL
How do bulbourethral glands contribute?
small volume of lubricating mucoid secretions
Summary of path of sperm to outside:
8
- Seminiferous tubules
- Rete testis
- Efferent ducts
- Epididymis
- Vas Deferens
- Ejaculatory ducts
- Urethra
- Penile urethra
Spermatic ducts
Efferent ductules
Epididymis
Ductus vas deferens
Ejaculatory duct
Efferent ductules
12 small ciliated ducts collecting sperm from the rete testes and transporting it to the epididymis
Epididymis
- 6 m long coiled duct adhering to the posterior of testis
- Site of sperm maturation and storage
- fertile for 40-60 days
Ductus vas deferens
muscular tube 45cm long passing up from scrotum through the inguinal canal to posterior surface of bladder
Ejaculatory duct
2cm duct formed from ductus deferens and seminal vesicle and passing through prostate to empty into urethra
2 main phases of menstrual cycle
Follicular phase: Day 1-13
Luteal phase: Day 14-28
Different types of follicles
Primordial Primary Preantral Early antral Mature
Primordial follicles
Consist of one primary oocyte surrounded by a single layer of granulosa cells which secrete oestrogen, small amounts of progesterone (just before ovulation) and inhibin.
Primary follicles
- The oocyte increases in size and become separated from the inner granulosa cells but the zona pellucida (secreted by the surrounding follicular cells).
- The zona pellucida contains glycoproteins that play an important role in the binding of a sperm cell to the surface of the egg after ovulation.
- The inner layer of granulosa cells stay in contact with the oocyte via cytoplasmic processes that transverse the zona pellucida and form gap junctions through which nutrients and chemical messengers are passed to it.
Preantral follicle
- Through the mitosis of the granulosa cells the follicle grows larger
- Connective-tissue cells surrounding the granulosa cells differentiate and from layers of cells known as the THECA which function together with the granulosa cells in the synthesis of oestrogen.
Early antral follicle
- The primary oocyte reaches full size
- The ANTRUM (fluid filled space) begins to form in the midst of the granulosa cells as a result of the fluid they secrete)
Mature follicle
- At the beginning of each menstrual cycle around 10-25 of these preantral and early antral follicles being to develop into larger antral follicles
- Around 1 week into the cycle, a further selection process occurs whereby only one of the larger antral follicles - the dominant follicle - continues to develop
- The non-dominant follicles undergo atresia (a degenerative process)
- The dominant follicle enlarges as a result of the increase in fluid
- As the time for ovulation approaches the primary oocyte emerges from its meiotic arrest due to the surge in LH and completes its first meiotic division to become a secondary oocyte
- The mature follicle (graafian follicle) becomes so large that it balloons out on the surface of the ovary
When does ovulation occur?
When the thin walls of the follicle and ovary rupture at the site where they are joined because of enzymatic digestion the secondary oocyte is carried out of the ovary and onto the ovarian surface by the antral fluid - this occurs on DAY 14
Luteal phase - Day 14-28
- After the mature/graafian follicle discharges its antral fluid and egg, it collapses and undergoes rapid transformation
- The granulosa cells enlarge greatly and a gland-like structure called the CORPUS LUTEUM is formed, and secretes oestrogen, progesterone and inhibin
- If the discharged egg in the fallopian tube does not get fertilised by fusing with a sperm cell, the corpus luteum reaches its maximum development with in 10 days and then rapidly degenerates via apoptosis which triggers MENSTRUATION and the beginning of a new cycle.
Site of synthesis of ovarian hormones
Oestrogen
- Oestrogen is synthesised and released into the blood during the follicular phase mainly by GRANULOSA cells - After ovulation, oestrogen is synthesised and released by the CORPUS LUTEUM
Progesterone
- Progesterone is synthesised and released in very small amounts by the GRANULOSA and THECA cells just before ovulation
Major hormones in menstrual cycle
GnRH FSH LH Oestrogen Progesterone
Sequence of menstrual cycle depends on the levels of
GnRH
When does FSH increase, and then decrease?
Increases in the early part of the follicular phase and then steadily decreases throughout the remainder of the cycle except for a small mid-cycle peak.
Why does FSH secretion increase as one cycle ends and another begins?
This is due to decreased progesterone, oestrogen and inhibin and thus no negative feedback on the hypothalamus and anterior pituitary.
Elevated FSH secretion means that the enlargement of preantral and early antral follicles is stimulated.
FSH acts on – cells in the first week to …
FSH acts on the granulosa cells in the first week (because they have FSH receptors but no LH receptors at this point in the cycle) to stimulate their multiplication, and production of oestrogen. Oestrogen works with FSH (and growth factors) to stimulate the proliferation of granulosa cells
FSH is involved with the degradation of …
FSH is also involved with the degradation of non-dominant follicles; since there is not enough FSH to prevent size decrease and thus atresia
FSH induces – receptors on …
FSH induces LH receptors on dominant maturing follicles
When the dominant follicle starts to secrete more oestrogen, what is the effect on FSH?
When the dominant follicle starts to secrete more oestrogen it causes levels of FSH to decrease because oestrogen exerts a negative feedback mechanism on the secretion of gonadotrophins from AP + hypothalamus.