Reproductive physiology Flashcards
Distinguish between biological sex, sexual reproduction and sexual intercourse
Biological sex: depends on chromosomes and which gametes are produced
Sexual reproduction: produces offspring that are genetically different from the parents
Sexual intercourse: procreative activity to allow for sexual reproduction and bonding
What is the urethra an opening for in males
Ejaculatory duct and urine from the bladder
Urogenital system
Summarise human male anatomy
§ Testis – contain seminiferous tubules (to produce sperm) and Leydig cells which produce testosterone.
§ Epididymis – one within each scrotal sac. Sperm are stored in these and at ejaculation, sperm pass through the vas deferens (contractile) and are mixed with fluid from the seminal vesicles. The fluid then leaves the duct and passes into the urethra to mix with prostate secretions.
What is the key aim of the male reproductive system
The human male reproductive system is (if compared to the female system) relatively simple. The two main functions are the provision of androgens (primarily testosterone) to initiate and sustain the necessary male phenotype, and the production of mature sperm.
Summarise the regulatory hormones in the male reproductive system
Gonadotrophin releasing hormone (GnRH) Hypothalamus Luteinising hormone (LH) Anterior pituitary Follicle stimulating hormone (FSH) Anterior pituitary Testosterone (T) Testis
Describe the male HPG axis
GnRH released in pulses each hour from hypothalamus
GnRH causes pulsatile LH/FSH release from the APG
LH stimulates Leydig cells (only cells to express LH receptors) to produce testosterone
FSH stimulates Sertoli cells to support spermatogenesis, also requires testosterone
Describe the role of the Sertoli cells and Leydig cells in the male reproductive system
Sertoli cells: form the seminiferous tubules, containing FSH/androgen receptors; act as primary control of spermatogenesis - in response to FSH will produce INHIBIN and androgen binding protein to support spermatogenesis (carries the testosterone in the seminiferous fluid)
Leydig cells: lie outside tubules, with LH receptors, responding by stimulation by producing testosterone - assists spermatogenesis
When are the germ cells activated in males
During puberty
Not all cells enter the cyclic development phase, some germ cells return to their quiescent state until they are stimulated to develop.
Outline the process of spermatogenesis
Spermatogonia outside of seminiferous tubules divide by mitosis, with one cell remaining a spermatogonia and the other forming a 1o spermatocyte (2n)
The 1o spermatocytes then undergo meiotic division to produce haploid 2o spermatocytes, containing either 22X or 22Y chromosomes. At this stage, they pass between the Sertoli cells forming the seminiferous tubules.
The 2o spermatocytes (n) undergo meiosis 2 to produce four spermatids (n) which enter luminal compartments for nutrition - Sertoli cell secretions give spermatids their rudimentary tails.
Spermatids differentiate to spermatozoa in spermiogenesis
Spermatozoa travel to epididymis for flagella development and mitochondrial gain
What is the role of the different meiotic divisions in spermatogenesis
The 1o spermatocyte (2n) undergoes meiosis 1 to produce two 2o spermatocytes (n)
The 2o spermatocytes (n) undergo meiosis 2 to produce four spermatids (n) which enter luminal compartments for nutrition
Summarise male reproductive function
Starts at puberty
Functions continually
Normally continues throughout the rest of life
Sperm quantity and quality generally decreases with increasing age
LH stimulates testosterone production
FSH and testosterone sustain Sertoli cell function
Sertoli cells support spermatogenesis
Generally, why is sperm quality quite low
200m sperm/day, starts at puberty.
So it’s a really rapid process, and therefore error prone
Only 4% of the sperm sample will be able to fertilise the egg
But this is still a high number of viable sperm, giving the shear quantity of sperm in the ejaculate.
Summarise the female reproductive system
Starts at puberty
Functions cyclically
Normally operates until ~45 years of age
Egg quality generally decreases with increasing age
FSH stimulates (some) development of ovarian follicles & 17β-estradiol synthesis
LH stimulates progesterone production
The steroids regulate uterine endometrium
What is the key consequence of egg quality decreasing with increasing age
Held in meiotic arrest until stimulated.
More chance of abnormalities in fetus.
Describe the role of the ovaries
The ovary Parallel functions to the testes, in that they produces the gametes (oocytes) and the steroids needed for female reproductive function (progesterone and estrogens).
Describe the role of the Fallopian tube and uterus
The Fallopian tube (oviduct) through which the oocyte reaches the uterus. Provides an appropriate environment to sustain either an oocyte or a conceptus (fertilised oocyte).
The uterus, in which the conceptus normally implants and is supported throughout pregnancy.
Describe the changes in the female HPO cycle throughout the menstrual cycle
Folicular phase- mainly Oestradiol released from the ovary- this has negative feedback on the axis
Midycle- mainly Oestradiol released from the ovary- this now has positive feedback on the axis- generates the rapid peak of LH and FSH needed for ovulation.
Luteal phase- mainly progesterone released from the ovaries- negative feedback on the axis
Summarise female sex hormone production
Ovum surrounded by granulosum cells, then by thecal cells with LH receptors, to allow LH to simulate steroidogenesis to androgen stage (lack aromatase)
Androgens diffuse into granulosa cells containing FSH receptors (only tissue in body that expresses) and aromatase, and when FSH binds, aromatase activated to convert androgens to oestradiol
When corpus luteum stage, androgens produced and transformed to oestradiol and progesterone
What are the gonadotrophin-independent stages of egg development
Primordial follicle pool
Primary follicles
Preantral follicle
What are the gonadotrophin-dependent stages of egg development
small antral follicle
large antral follicle
preovulatory follicle.
All, except the preovulatory follicle can undergo atresia.
Differentiate between the granulosa cells and the thecae cells
The thecal cells of the developing follicles are responsible for the production of estrogens, and the granulosa-luteal cells produce estrogens and progesterone during the second half of the ovarian cycle.
§ Thecal cells – oestrogen and androgens – LH.
§ Granulosa cells – androgens à oestradiol (produce progesterone in the second-half of the cycle) – FSH. Progestogens – maintain endometrium. Oestrogens – stimulate proliferation of the endometrium.
Describe the length of the human menstrual cycle
The human menstrual cycle lasts approximately 28 days, but this varies substantially between human females, and also in individuals. Most sources suggest a normal range between 21 – 35 days in adult females, but in younger teenagers (i.e shortly after menarche), the length may be up to 45 days. At the other end of the reproductive spectrum, when a woman is approaching the menopause, her menstrual cycle is likely to become irregular in length; shorter or longer, or perhaps skip a month or two before resuming.
What does the menstrual cycle consist of
§ Composed of the endometrial & ovarian cycles.
o Endometrial – menstrual, repair and proliferative, secretory phases.
o Ovarian – follicular, luteal phase.
Describe the follicular phase (first 14 days) of the ovarian cycle
Early Follicular Phase: Day 1 (start of bleeding) - Day 5; 5-10 eggs start to enlarge and grow, competing with each other to grow, so only one (Graafian) follicle will become dominant; FSH produced by APG causes follicles to grow and produce oestradiol
Early-Mid Follicular Phase: follicles growing release oestradiol (begins to negatively feedback on LH/FSH to decrease levels; autocrine feedback loop arises, where more oestrogen production stimulates increased granulosa cell growth, in turn leading to more oestrogen
Mid Follicular Phase: oestrogen and inhibin reduces FSH to LH to very low levels, so all follicles regress except the Graafian follicle
Late Follicular Phase: Oestrogen reaches high level and when bypasses threshold, causes a positive feedback loop on GnRH/LH secretion to cause an LH surge and ovulation
Summarise the menstrual phase (first 5 days) of the endometrial cycle
day 1 of cycle; shed blood (20-80mls) and endometrial lining (functional zone)
remaining basal endometrium very thin
Describe the repair and proliferative phase of the endometrial cycle (next 9 days)
Dependent on the follicular phase off the ovarian cycle:
thecae and granulosa cells stimulate 17B-oestradiol function
This stimulates endometrial cell proliferation, increasing its thickness 2-3 fold, number and length of glands and length of arteries.
Describe the luteal phase of the ovarian cycle
Luteal phase: corpus luteum produces progesterone (men should NOT produce) to prepare the endometrium for implantation
If no fertilisation then progesterone, oestrogen and inhibin have a direct negative feedback on the APG to reduce LH/FSH production, and indirectly on GnRH
Thus causing progesterone and Oestradiol to fall- leading to shedding of the endometrial lining.
Summarise the endometrial cycle
Endometrial cycle: lining of uterus with superficial and deeper stromal layer; proliferative phase followed by secretory phase
Proliferative phase: endometrium grows before ovulation
Secretory phase: follows ovulation - stimulated by oestrogen and progesterone to cause thickening and secretion of glycogen and polysaccharides
Ischaemic phase: broken down as progesterone falls - leading to shedding
Menstrual phase: bleeding as shed lining
Describe the secretory phase of the endometrial cycle
Next 13 days after ovulation
P and E2 released from the corpus luteum - production of nutrients and other factors
P- epithelial glands widen, endometrium thickens, increased coiling of spinal arteries.
Differentiate between the terminology used in the endometrial cycle and the ovarian cycle
Note the terminology used: a focus on endometrial or uterine function will employ proliferative and secretory, as these describe endometrial function; for an ovarian emphasis, the terms would be follicular and luteal, as these summarise the state of the dominant ovarian follicle in the cycle.
Describe the hormones that dominant in the different phases of the ovarian cycle
§ Oestrogen dominates the proliferative or follicular phase.
§ Progesterone dominates the secretory or luteal phase.
Describe the changes in length of the uterus lining during the menstrual cycle
§ Thinnest – 2-4mm.
§ Thickest – 7-16mm.
What happens to the basal body temperature at ovulation
Note that the basal body temperature rises slightly (about 0.5°C) around the time of ovulation.
Maintained while progesterone stays high
Outline folliculogenesis in the ovum
- Oogonia 44+XX (diploid).
a. Mitotic division. - Primary oocytes 44+XX (diploid).
a. 1st meiotic division. - Secondary oocyte (+polar body) 22+X, 22+X (haploid).
a. 2nd meiotic division. - Ovum (+ polar body) 22+X, 22+X (haploid).
When are the first and meiotic divisions completed
Note – 1st meiotic division is linked to the LH surge, meiosis 2 follows immediately after this BUT pauses in metaphase 2 (as shown). Note – the second polar body is generated after the 2nd meiotic division which occurs in the fertilised cell.
Originally the primary oocytes were held in the prophase stage
Describe the halting of the meiotic phases during follicular development
§ During meiosis, both the 1st and 2nd divisions are paused during follicular development.
o Meiosis 1 starts during embryonic development, but halts at diplotene stage of prophase 1 (primary follicle) which is arrested until puberty (meiosis then resumes and 2nd follicles develop).
o 2nd follicles then undergo a second arrest.
How long does it take for the primordial follicle to develop into a secondary (mature) oocyte
§ Time taken for primordial follicle à secondary oocyte is MORE than one month.
o The human ovary contains multiple follicles at ALL stages of development with one dominant (Graafian) follicle at any one time.
o The ovaries alternate the release as well (so each one releases one follicle each ~56 days).- get non-identical twins when two follicles released at the same time
Summarise oogenesis
Ovulation = release of mature oocyte (egg) from the ovary
Oocyte is 2n at this stage, in meiotic arrest (metaphase II)
Enters the Fallopian tube
Needs to be fertilised within 24 hours, as it degenerates after this
How many follicles do the ovaries contain
Contain ~6 million primordial follicles at ~20 weeks of development.
By delivery of the infant, this has fallen to ~1 million per ovary.
About 400 follicles will be ovulated during the reproductive life-time.
How much sperm is produced in the testes per day
Produce about 100 million sperm per day, from puberty onwards.
From an evolutionary perspective, describe the importance of sexual reproduction
From an evolutionary perspective, the most important role of sex is to ensure that fertilisation of a mature oocyte by a mature sperm takes place, this being the necessary first step in continuing the human race.
Our understanding of these topics is now much more complex, with many more nuanced and important aspects, which will also be considered in this topic.
The term ‘sex’ and its related definitions is pertinent to three different aspects of relevance to sexual reproduction.
What are the key features of sexual intercourse
Required for sexual reproduction Sexual activity Sexual pleasure Human bonding Given that sexual intercourse is (normally) required for human reproduction, this is an important part of this topic. The ‘normally’ is included to acknowledge that during the last 30 years, the development of Assisted Reproduction or In Vitro Fertilisation, and linked technologies, there are complex topics which are linked to reproduction
Describe the key features of biological sex
Identifies gender
Result of chromosomes
Production of gametes
The production of gametes, and the process of fertilisation, are essential precursors to human pregnancy. Gametogenesis has been considered earlier in this chapter, so the focus here will be on fertilisation.
What may be the most important sexual organ in humans
It has been suggested (often) that the most important sexual organ in humans is the brain.
Describe the brain pathways involved in sexual intercourse
§ Meso-limbic DA system – reward & pleasure pathways.
§ Nigro-striatal tract – control of movements.
§ Neuro-endocrine pathways – regulating fertility and parenting.
Activation of pleasure pathways therefore encourages intercourse, thus continuation of the human race. These brain functions complement those discussed earlier in this chapter, in which the role of the brain in controlling the production of gametes (hypothalamic-pituitary-gonadal axes) was considered.
Summarise the penile erection pathways
Penile erection pathways:
o Sexy thoughts in brain OR tactile stimulus to penis.
§ Brain – limbic system.
o Spinal cord – efferent to penis, afferent back.
§ Pudendal nerve.
What are the 3 efferent pathways involved in penile erection
PSNS fibres in the pelvic nerve
sympathetic fibres in the hypogastric nerve
efferent somatic fibres in the pudendal nerve
Describe how erection is achieved
Initiated by: increased parasympathetic activity to smooth muscle of pudendal artery
Increases the activity of Nitric Oxide Synthase (NOS), and hence nitric oxide (NO)- due to release of ACh and vasoactive intestinal peptide (VIP)
NO increases production of cyclic GMP which induces dilatation of arterial smooth muscle.
counteracts sympathetic-maintained myogenic tone
increases blood flow in corpus cavernosum
which compresses the dorsal vein, restricting the outflow of blood
The urethra is protected from increased pressure by surrounding corpus spongiosum (less turgid)
How is detumescence achieved
Cyclic GMP is normally de-activated by a phosphodiesterase enzyme, and this will reverse the changes leading to penile erection. Viagra inhibits the phosphodiesterase, thus potentiating the effects of cyclic GMP.
Describe the erection of the clitoris
The female equivalent of the penis is the clitoris
The clitoris, like the penis, increases in size as a result of an increased blood flow into the tissue
The mechanism is the same (i.e. release of NO)
Summarise the main processes of fertilisation
Deposition of sperm within female system following sexual intercourse.
Sperm are deposited near cervix
Cervical mucus is normally hostile to sperm
This forms a physical barrier to sperm
Cervical mucus changes at mid-cycle
This change permits sperm to enter uterus
Passage of sperm through uterus
Passage of sperm into Fallopian tube
Swim from there to Fallopian tube ampulla
~30 µm/sec average speed; 2 mm/min; 12 cm/hour
Survival of the fittest (a few days)
Capacitation – takes time within uterus
Capacitation is essential preparation before the sperm meet the oocyte
Meeting of egg with sperm
Fusion of egg and one sperm (within 24 hours post ovulation)
Acrosome reaction: penetration of Zona Pellucida (& Coronal cells)
Calcium flux- rapid depolarisation of egg plasma membrane.
Resumption of meiosis, release of 2nd polar body
Alignment of maternal and paternal chromosomes to generate zygote.
Change in Zona Pellucida to prevent additional sperm fusing with zygote.
Initiation of mitotic (cleavage) divisions in embryo.
Describe the formation of the male pronucleus in the zygote
By this stage, Meiosis II in the maternal chromosomes is completed, leading to the formation of polar body II, and the female pronucleus. The head of the sperm is undergoing decondensation, with the previously tightly packed paternal chromosomes forming a much looser structure. Both pronuclei are haploid at this stage of fertilisation.
Describe what happens after formation of the paternal and maternal pronuclei
Both pronuclei are now visible; note that by this stage duplication of the DNA in both pronuclei has been duplicated, making 2n chromosomes of maternal and of paternal origin. The next stage is development is a mitotic division, giving 2 daughter cells, which must have the same chromosomal complement, so duplication is required at this stage. Maternal and paternal chromosomes mix for the first time, as the metaphase plate of the first cleavage division is formed.
Separation of the male (blue) and female (red) chromatids can be seen; each cell should receive one paternal copy and one maternal copy of each chromosome, so the 2 cells shown in (F) have an identical chromosomal complement.
What is important to remember about the egg nucleus
In addition, it is in error in suggesting that there is an ‘egg nucleus’ – that should be an egg (oocyte for preference) pronucleus; also the ‘nuclei’ do not ‘fuse’.
Summarise the events that happen after fertilisation
Meosis of maternal chromosomes resumes, forming female pronucleus (23 chromatids), and 2nd polar body.
Sperm chromosomes decondense to form male pronucleus (23 chromatids).
Chromatids in both pronuclei are duplicated
They align on the mitotic spindle, and are separated into 2 identical ‘daughter’ cells (1st cleavage division of the embryo).
