Lecture 1 Oestrous Cycle 23_24 PDF

BVSc – Year 1 VETS10022 Reproductive Physiology 1. The Oestrous Cycle Nadia Cerminara School of Physiology, Pharmacology and Neuroscience [email protected] Recommended reading Veterinary reproduction and obstetrics Chapter 1 David E Noakes(Editor) Timothy J Parkinson(Editor) Gary C W England...

BVSc – Year 1 VETS10022 Reproductive Physiology 1. The Oestrous Cycle Nadia Cerminara School of Physiology, Pharmacology and Neuroscience [email protected] Recommended reading Veterinary reproduction and obstetrics Chapter 1 David E Noakes(Editor) Timothy J Parkinson(Editor) Gary C W England(Editor) eBook 2019 Tenth edition https://bris.on.worldcat.org/oclc/1077474208. Cunningham's Textbook of Veterinary Physiology Chapters 35-37 Bradley G. Klein (Edtior) eBook 2019 Sixth edition https://www.vlebooks.com/Product/Index/1210707?page=0&startBoo kmarkId=-1 2 Signposting to other teaching CBL – Section A with attitude, Routine fertility visit, & Wanted students for lambing Other lectures – Comparative Reproduction, Reproduction in cats & dogs, Reproduction in rabbits & rodents, Reproduction in cattle, Cyclical changes in the endometrium, & male reproduction lectures Lab/Practicals – Lambing, Anatomy Intended Learning Outcomes By the end of this lecture you should be able to: Define the terms ovarian cycle, ovum, ovulation, corpus luteum, and luteinisation Briefly explain the female reproductive endocrine axis Use the ovarian cycle of the cow to generally explain the phases of the oestrous cycle Briefly explain follicular development and follicular waves in relation to the oestrous cycle Overview Female Reproductive System Ovary Oviduct (= uterine tube = Fallopian tube) Uterine horn Body of uterus Cervix Vagina Vestibule Vulva Functions of female reproductive system Gametogenic - to produce ova Endocrine - to produce the hormones oestrogen and progesterone To prepare the reproductive tract for copulation, fertilisation, pregnancy, and parturition 5 Intended Learning Outcomes By the end of this lecture you should be able to: Define the terms ovarian cycle, ovum, ovulation, corpus luteum, and luteinisation Briefly explain the female reproductive endocrine axis Use the ovarian cycle of the cow to generally explain the phases of the oestrous cycle Briefly explain follicular development and follicular waves in relation to the oestrous cycle Some terminology Oestrus (Estrus): behavioural changes associated with sexual receptivity – “heat “ Oestrous (Estrous) cycle: cyclical nature of ovarian activity that facilitates female animals to go from a period of reproductive receptivity (oestrus) to nonreceptivity for the establishment of pregnancy following mating Ovum (pl. ova): mature oocyte (ready to fertilize). Ovulation: The release of the ovum from the follicle (with surrounding follicular cells) into the abdominal cavity Ovarian cycle: Interval between two successive ovulations. Includes follicle maturation and rupture (ovulation), then luteinisation and regression of the corpus luteum followed by recommencement of the cycle, unless pregnancy intervenes Corpus luteum: a mass of remaining follicular cells formed in the ovary at the site of a ruptured ovarian follicle following ovulation. Produces progesterone and oestrogens. Luteinisation: the process of the remaining follicular cells becoming Corpus Luteum after the ovulation follicle Corpus luteum Intended Learning Outcomes By the end of this lecture you should be able to: Define the terms ovarian cycle, ovum, ovulation, corpus luteum, and luteinisation Briefly explain the female reproductive endocrine axis Use the ovarian cycle of the cow to generally explain the phases of the oestrous cycle Briefly explain follicular development and follicular waves in relation to the oestrous cycle Female reproductive endocrine axis hypothalamus Gonadotropin-releasing hormone (GnRH) anterior lobe of pituitary gland Follicle-stimulating hormone (FSH) Lutenising hormone (LH) Oestrogen Follicle Progesterone Ovary Corpus Luteum Oestrogen Inhibin Progesterone Regulation of FSH/LH by GnRH GnRH is produced in the hypothalamus by two groups of neuroendocrine cells: Pulsatile centre (tonic) Surge centre The pulsatile centre is responsible for the lowlevel, basal secretion of GnRH in both males and females. The surge centre is responsible for the surge of FSH and LH in response to high levels of oestrogen Pulsatile and surge modes of GnRH release Pulsatile Surge Oestrogen decreases GnRH pulse amplitude Progesterone decreases GnRH pulse frequency Intended Learning Outcomes By the end of this lecture you should be able to: Define the terms ovarian cycle, ovum, ovulation, corpus luteum, and luteinisation Briefly explain the female reproductive endocrine axis Use the ovarian cycle of the cow to generally explain the phases of the oestrous cycle Briefly explain follicular development and follicular waves in relation to the oestrous cycle Introduction to the oestrous cycle In the non-pregnant female, the reproductive tract has two main functions: 1. Preparation for ovulation 2. Preparation for pregnancy These two functions are mutually incompatible and therefore exerted in distinct phases The switching between the two phases results in repetitive reproductive cycles Types of Oestrous Cycles Monoestrous - Single oestrous cycle during the year - E.g. bitch (female dog, wolf, fox, otter) (depending on breeds) Seasonal - oestrus events occur during a specific period of time - Interrupted by a period of acyclicity (anoestrus) - E.g. sheep, goat, deer, cats, horses - Polyoestrous Successive oestrous cycles throughout the year Non-seasonal - Uninterrupted - E.g. cow, sow (guinea pig etc) 14 Oestrous Cycle Oestrous cycle can be divided into Proestrus Follicular = for ovulation Oestrus phase Metoestrus Luteal = for phase Dioestrus pregnancy First day of the oestrous phase is often considered the first day of the oestrous cycle Time interval between the period of oestrus/estrus is the length of the oestrous cycle Oestrous phases are arbitrary & sometimes difficult to distinguish in cow Cow, horse: average 21 days Sheep: average 17 days etc 15 Proestrus Phases of the oestrus cycle Without conception, the Corpus Luteum (CL) regresses & progesterone declines Rapid follicular growth, oestrogen increases Vascularity of the female reproductive tract increases Endometrial glands begin to grow Estrus LH surge Sexual receptivity Ovulation Metestrus CL starts to develop, progesterone levels increase Oestrogen is low Diestrus Sexually inactive Lasts until giving birth if pregnant; CL regresses at end if not pregnant Progesterone high Reproductive organs under dominant influence of progesterone Intended Learning Outcomes By the end of this lecture you should be able to: Define the terms ovarian cycle, ovum, ovulation, corpus luteum, and luteinisation Briefly explain the female reproductive endocrine axis Use the ovarian cycle of the cow to generally explain the phases of the oestrous cycle Briefly explain follicular development and follicular waves in relation to the oestrous cycle Oogenesis Changes in bovine oocyte number across the lifespan 210 206 210 162 86 86 90 60 119 120 132 Number (1000's) 132 117 121 Decrease from puberty to 17 years of age 150 130 156 120 90 60 25 12 yr 3 22 8 yr 30 30 Age (yr) Age (wk or yr) 18 17 yr 5 yr 1.5 yr 1 yr 31 wk 26 wk 19 wk 13 wk 10 wk 1.5 yr 0 0 5 wk Female mammals are born with a finite number of primary oocytes 150 1 wk Starts before a female is born, pauses during juvenile period, resumes during puberty, and ends at fertilization Number (1000's) Oogenesis - production of female gametes (ova) Constant from birth to puberty 180 180 Mitosis Meiosis - I Birth Meiosis - II Mitosis –diploid (2n) chromosome number is kept. Meiosis –reduction in the diploid (2n) chromosome count to a haploid (1n) chromosome count. Early in embryogenesis, oogonia proliferate by mitosis and migrate into the ovary Meiosis starts at an embryonic stage Meiotic arrest before the first meiotic cell division => wait until puberty and the follicle is recruited to develop First meiotic cell division occur just before ovulation (i.e., ovulated ovum is a secondary oocyte) Sperm entry triggers second meiosis From puberty In embryo Oogenesis Mature egg *Dog/wolf/fox ovulate primary oocyte Sperm entry Follicular Development Also known as folliculogenesis Development of follicles (oocytes and their supporting cells). Follicle is a small pocket-like sac located inside the ovary, responsible for the monthly growth, maturation, and release of an egg. Cells in the ovary (follicular cells = granulosa cells) surround the ovum Occurs after puberty Follicle also stimulates the production of sex hormones Granulosa cells Oocyte Primary follicle Cumulus oophorus Oocyte Oocyte Secondary follicle Graafian follicle 20 Histology and imaging of the ovary Various stages of follicles are seen in the ovary at any given time The preovulatory (mature) follicle is detectable by ultrasound because of the large cavity Thus, you can estimate the stage of the cycle by imaging analysis In DR, e.g. Corpus Luteum is seen only in some of the specimens. Follicular Development antrum ‘Primordial follicle’ = primary oocyte with enlarged cytoplasm, with a flat one-celllayer of follicular (granulosa) cells The dormant status Follicular (granulosa) cells Theca interna ‘Primary follicle’ = chosen to re-commence growth Follicular cells become cuboid and proliferate into multiple layers Theca externa D ‘Secondary follicle’ = with antrum (a cavity) with fluid from follicular cells One follicle = One ovum + surrounding follicular (granulosa) cells Follicular cells secrete oestrogens and inhibin Theca cells secrete androgens E. ‘Preovulatory follicle’ Also known as a ‘Graafian’ or ‘Tertiary’ follicle Among several, one of secondary follicles is chosen to mature for ovulation How do changes in the ovary relate to the oestrous cycle? Oestrogen dominance Proestrus Follicles develop Progesterone dominance Diestrus Oestrus Metestrus Ovulation Follicular Follicular cells become CL CL secretes progesterone Luteal Proestrus CL degrades and becomes CA Next follicles develop CL= Corpus Luteum CA= Corpus Albicans Follicles may develop during the luteal phase as well, but they don’t fully mature (requiring LH surge) Follicular waves Small groups of follicles continuously grow and mature in synchrony called a follicular wave During a wave, a group of follicles initially grow together followed by a selection of one or a few follicles A follicular wave consists of 3 phases: Recruitment, Selection, Dominance Even if selected and become dominant, they don’t fully mature for ovulation unless LH surge occurs (anovulatory waves vs ovulatory wave) Mature Dominant Selected Recruited Non-selected follicles undergo atresia Different species have a different number of waves per oestrous cycle: Horse 1-2 Cow 2-3 Sheep 3 or more Humans 1 anovulatory waves Ovulatory wave Follicular waves Mature Anovulatory waves Ovulatory wave Dominant Selected Recruited anovulatory waves Ovulatory wave Synchronous growth and maturation of small groups of follicles = follicular wave Discovered with use of high-resolution ultrasound During a wave, a group of follicles initially grow together followed by a selection of one or a few follicles A follicular wave consists of 3 phases: Recruitment, Selection, Dominance Even if selected and become dominant, they don’t fully mature for ovulation unless LH surge occurs (anovulatory waves vs ovulatory wave) Non-selected follicles undergo atresia Species variation – cattle 2-3/cycle, horses 1-2, sheep 3>, pigs and humans 1 Number of ovulated ova The number of matured follicles in a ovulatory wave varies by species Mature Monovular species (only one follicle usually ovulates) – horse, cow, human Dominant Polyovular species (multiple follicles ovulate) – sheep, pig, dog, cats Recruited Selected anovulatory waves Ovulatory wave Intended Learning Outcomes By the end of this lecture you should be able to: Define the terms ovarian cycle, ovum, ovulation, corpus luteum, and luteinisation Briefly explain the female reproductive endocrine axis Use the ovarian cycle of the cow to generally explain the phases of the oestrous cycle Briefly explain follicular development and follicular waves in relation to the oestrous cycle Hormonal regulation of oestrous cycle Follicular phase (early, proestrus) Follicular cells proliferate CL from previous cycle regresses Increasing oestrogens Negative feedback to hypothalamus anovulatory wave Proestrus Vascularity of the female reproductive tract increases Endometrial glands begin to grow Hormonal regulation of oestrous cycle Follicular phase (late, estrus) Follicular cells proliferate anovulatory wave More follicular cells proliferate High oestrogen No progesterone Positive feedback High FSH, LH surge ovulation Estrus Sexual receptivity Allows male to mount Reproductive organs under dominant influence of oestrogen Hormonal regulation of oestrous cycle Follicular phase (end of estrus) Follicular cells proliferate Increasing estrogens Increasing FSH,LH Peak of FSH/LH ovulation Negative feedback High estrogen Rapid decrease of FSH/LH End of follicular phase Hormonal regulation of oestrous cycle Luteal phase (metoestrus & dioestrous) Peak of FSH/LH High estrogen Rapid decrease of FSH/LH end of estrus Follicular cells that remained after ovulation undergo luteinisation Corpus luteum is formed secretes Progesterone FSH increases, triggering growth of follicles Reproductive organs under dominant influence of progesterone CL regresses at the end of this period if female is not pregnant Proestrus phase Ovarian changes Hormone changes Growth of follicles. Large follicles: Follicles begin ↑Oest. → ↓FSH producing oestrogen. ↑Inhibin → ↓FSH Corpus luteum (CL) from previous cycle regresses. CL regressing: ↓Prog. → ↑GnRH → ↑LH Key for next few slides: Oest = oestradiol Prog = progesterone CL = corpus luteum Uterine changes Blood flow begins to increase. Endometrial glands begin to proliferate. Endometrium (the uterine epithelium) begins to hypertrophy. Sanguineous vaginal discharge in bitches. Behavioural changes Heat signs appear (heat induced by oestrogens). Can also think of Proestrus as late Dioestrus Oestrus phase Ovarian changes Final follicle maturation Maximum production of oestrogens Hormone changes Uterine changes Pre-ovulatory follicle ↑↑Oest. → ↑↑GnRH →↑↑ LH (LH surge) → Ovulation No CL therefore no prog. Behavioural changes Endometrium and Standing heat endometrial glands (female allows continue to grow mating) Increase in blood flow causes oedema and hyperaemia Uterine contractility increases Oestradiol-induced release of LH is responsible for ovulation. Can also think of Metoestrus as early Dioestrus Metoestrus Ovarian changes Formation of corpus luteum Corpus luteum begins to produce progesterone Hormone changes Corpus Luteum ↑Prog. → ↓GnRH → ↓LH Small follicles present ↓Inhibin and ↓Oest. Growth of follicular wave ↑FSH (anovulatory wave because ↑Prog. therefore no LH surge) Uterine changes Behavioural changes Uterine glands No heat (female become coiled does not allow and have high mounting). secretory Progesterone activity. suppresses heat. Sanguineous Except in the bitch vaginal discharge that shows heat for in cows. some time after oestrus (as dogs ovulate immature oocytes that need to mature in the oviduct) Dioestrus Ovarian changes Corpus luteum reaches full maturation Corpus luteum produces highest levels of progesterone. Hormone changes Active CL ↑Prog. → ↓GnRH → ↓LH Follicular growth (ovulatory wave) ↑FSH At late dioestrus CL → ↑Oxytocin → PGF2α (from uterus) → Luteolysis Uterine changes Uterine glands and epithelium reach maximal growth and then begin to involute. Glandular secretion reaches a peak and then begins to decrease. Vascularisation decreases. Uterine contractility subsides. Behavioural changes No heat Summary Types of oestrous cycles Stages of the ovarian cycles oestrous cycles follicular/luteal phases Follicular waves Hormonal regulation of oestrous cycle via the secretion of gonadotropins LH and FSH (and inhibin) 37