Embryology LC 2: Ovulation to Implantation PDF

COURSE OUTLINE II. MENSTRUAL CYCLE I. HPO AXIS Menstrual Cycle (Endometrial ovarian cycle) II. MENSTRUAL CYCLE ○ In each menstrual cycle, distinct events III. ENDOMETRI...

COURSE OUTLINE II. MENSTRUAL CYCLE I. HPO AXIS Menstrual Cycle (Endometrial ovarian cycle) II. MENSTRUAL CYCLE ○ In each menstrual cycle, distinct events III. ENDOMETRIAL CYCLE occur in the ovaries and the endometrium. ○ Menstrual phase ○ Composed of two interrelated cycles: ○ Proliferative phase i. Endometrial cycle (proliferative ○ Menstrual cycle and secretory phase) - changes IV. PROLIFERATIVE PHASE in uterus lining (endometrium) OVERVIEW ii. Ovarian Cycle (follicular and luteal phase) - events in the V. OVARIAN CYCLE ovaries ○ Follicular phase ○ Luteal phase VI. ULTRASOUND FINDINGS AND III. ENDOMETRIAL CYCLE EARLY PREGNANCY VII. FERTILITY AND HORMONE Menstrual Phase PRODUCTION ○ On the first day of menstruation (menstrual VIII. FERTILIZATION phase), the endometrium (lining of the IX. ZYGOTE uterus) sheds, causing it to thin from day 1 ○ Definition to day 3. The endometrium then ○ Transition to Blastocysts regenerates under the influence of estrogen produced by the ovaries. ○ Oocyte transport X. IMPLANTATION Proliferative Phase ○ Requirements ○ During a normal menstrual cycle, the ○ Chronological process follicular phase corresponds to the proliferative phase of the endometrium, during which the endometrial lining thickens in preparation for possible I. HPO AXIS implantation. The estrogen secreted by the growing follicles stimulates the thickening and regeneration of the endometrial lining. This process requires angiogenesis to ensure that, if ovulation and fertilization occur, the embryo can successfully implant into a well-vascularized area of the endometrium. Menstrual Cycle ○ A typical menstrual cycle ranges from 28 to 35 days, with variations in some cases (some books say until 40 days). Figure 1. Female Hypothalamus-Pituitary Axis ○ The cycle starts on the first day of menstruation (the first day of bleeding) and Hypothalamic-Pituitary-Ovarian Axis (HPO Axis) ends the day before the next menstruation ○ The HPO axis regulates the normal begins. The first day of menstruation is menstrual cycle. used to calculate the last menstrual period ○ Process: (LMP) and is the reference point for - Hypothalamus produces determining the age of the pregnancy if gonadotropin-releasing hormone conception occurs. (GnRH), which sends a signal to the anterior pituitary to secrete the gonadotropins, namely the IV. PROLIFERATIVE PHASE OVERVIEW follicle stimulating hormone (FSH) and luteinizing hormone (LH). - Gonadotropins, FSH and LH, are In the first half of the cycle, the proliferative phase responsible of signaling some occurs in both cycles simultaneously: mechanisms in the ovary. They 1. Ovarian Cycle: Follicles are recruited, and stimulate the ovaries to regulate one mature follicle prepares to ovulate sequence of events, such as (release an egg). follicle development, ovulation, 2. Endometrial Cycle: The endometrial lining and hormone production. thickens under the influence of estrogen to - FSH is secreted first followed by provide a suitable environment for LH. implantation if fertilization occurs. BATCH 2028 1E EMBRYOLOGY LC 2: OVULATION TO IMPLANTATION Dr. LICNACHAN M.M. 09/02/24 leading to a drop in hormone V. OVARIAN CYCLE levels, aka hormonal withdrawal, and ovarian steroids. Follicular Phase Hormonal withdrawal causes the ○ In the ovarian cycle, the first stop is the endometrial lining to shed, follicular phase, where multiple follicles are leading to menstruation. This recruited. One dominant follicle, known as shedding is necessary to refresh the Graafian follicle, matures and will the lining for a new cycle, in release the oocyte during ovulation. preparation for possible future GnRH from the hypothalamus implantation. triggers the release of FSH from ○ If fertilization does occur [with the anterior pituitary. FSH pregnancy]: stimulates the recruitment and The corpus luteum continues to growth of ovarian follicles. secrete progesterone and The dominant follicle matures into human chorionic gonadotropin the Graafian follicle, which (hCG) to maintain the produces estrogen. Estrogen endometrial lining, until the levels rise, stimulating the placenta takes over hormone thickening of the endometrium. production. Around mid-cycle, estrogen Clinical correlation: The presence provides positive feedback to of hCG in the urine is detected in the hypothalamus, leading to a pregnancy tests. surge of LH, which triggers ○ Angiogenesis and Implantation ovulation. Adequate angiogenesis The LH surge causes the mature (formation of new blood vessels) Graafian follicle to rupture, is crucial for a successful releasing the oocyte (egg) in a implantation. Poor angiogenesis process called ovulation. Whats can lead to miscarriage or causes the follicle to rupture? The abortion. high concentration of LH increases collagenase activity VI. ULTRASOUND FINDINGS resulting in digestion of collagen fibers surrounding the follicle. Ovulation (oocyte breaks free and floats our of the ovary) lasts about 24 hours, during which fertilization can occur—meaning a female can only become pregnant within this 24-hour window. If fertilization doesn’t occur, the egg will die, therefore, no pregnancy. ○ Clinical correlation: some women experience stabbing pain during ovulation, called mittelschmerz. Luteal Phase ○ After ovulation, the luteal phase Figure 2. Transvaginal Ultrasound of Intrauterine Pregnancy commence. After ovulation, the remnants of the follicle from which the mature egg was released transform into the corpus Ultrasound Findings and Early Pregnancy luteum through a process called ○ A transvaginal ultrasound shows the luteinization. [LH - role in corpus luteum uterus with a gestational sac and a yolk maintenance] sac, indicating an intrauterine pregnancy. Hormone secretion: The However, if there is no heartbeat yet, it granulosa cells surrounding the may be early in the pregnancy. oocyte secrete estrogen, while ○ A corpus luteum cyst may also be the theca cells secrete observed in such event. This cyst is crucial progesterone. in early pregnancy because it produces ○ If fertilization does not occur [without progesterone and hCG to support the preganancy]: pregnancy. The corpus luteum will Why is this important? At this degenerate, regress, or undergo early stage, the placenta has not apoptosis 9-11 days after yet developed fully to take over ovulation. hormone production. Therefore, This results in decreased levels of the corpus luteum is responsible progesterone and estrogen, for maintaining progesterone BATCH 2028 1E EMBRYOLOGY LC 2: OVULATION TO IMPLANTATION Dr. LICNACHAN M.M. 09/02/24 levels to sustain the pregnancy egg. The fallopian tube is narrow and has until the placenta is established. these fimbriae to help collect the egg released from the ovary. ○ Site of Fertilization: Fertilization typically VII. FERTILITY AND HORMONE occurs in the ampulla of the fallopian tube. PRODUCTION Once the egg is captured by the fimbriae, sperm that were deposited during 1. Primary Oocyte: The initial stage of the intercourse travel through the tube to meet egg. the egg. The sperm waits for the egg, and 2. Secondary Oocyte: The next stage, which out of the millions of sperm, only one will develops into the mature Graafian follicle. successfully penetrate and fertilize the 3. Mature Graafian Follicle: Releases the mature egg. egg during ovulation. Sperm can survive for up to 72 4. Post-Ovulation: The remnants of the hours in the female reproductive Graafian follicle form the corpus luteum, tract. Fertilization must occur which secretes progesterone to help within 24 hours of ovulation for a maintain the pregnancy if fertilization chance at conception. If the egg occurs. is not fertilized within this time frame, it will disintegrate. For optimal chances of VIII. FERTILIZATION conception, it is important to have sexual intercourse around the time of ovulation. Frequent Process by which male and female gametes fuse intercourse is not always ○ Normally occurs in the oviduct necessary; instead, focusing on ○ Must take place within few hours, and no timing can be more effective. more than a day after ovulation ○ Spermatozoa must be preset at the time of oocyte arrival Figure 4. Phases of Fertilization [Phase 1 to 3] Phases of Fertilization Figure 3. Effect of Capacitation. i. Penetration of the corona radiata ii. Pentration of zona pellucida Spermatozoa undergoes: iii. Fusion of the oocyte and sperm cell i. Capacitation: period of conditioning in the membranes female reproductive tract that in the human lasts approximately 7 hours Occurs in the fallopian tube Glyocportien coat and seminal plasma proteins are removed from the plasma membrane that overlies the acrosomal region og the spermtozoa ii. Acrosome reaction: this reaction culminate in the release of enzymes needed to penetrate the zona pellucida, including acrosin- and trypsin-like substances Zona pellucida: thick glycoprotein layer surrounding the oocyte membrane Figure 5. Fertilization. After a sperm cell comes in contact with the outer layers of an egg cell, the acrosome, which is a prominence at the anterior tip of the spermatozoa, undergoes a series of Fertilization → highly complex process well-defined structural changes that opens a path for the sperm ○ After ovulation, the fimbriae (finger-like nucleus. projections) of the fallopian tube catch the BATCH 2028 1E EMBRYOLOGY LC 2: OVULATION TO IMPLANTATION Dr. LICNACHAN M.M. 09/02/24 In-depth Process of Fertilization transformed into the decidua during ○ Initial Contact: Hundreds of sperm travel pregnancy. The transport of the zygote is towards the egg, initially breaking through facilitated by the cilia lining the fallopian the corona radiata, which is the outer layer tubes, which help to move the zygote into of cells surrounding the egg. the uterus for implantation in the decidua. ○ When sperm contact the zona pellucida (the glycoprotein layer surrounding the egg), they trigger the acrosome reaction. This reaction releases digestive enzymes from the sperm's acrosome (a cap-like structure) that break down the zona pellucida, allowing the sperm to reach the oocyte's plasma membrane. ○ One sperm successfully penetrates the zona pellucida and makes contact with the oocyte's plasma membrane. The sperm’s plasma membrane then fuses with the oocyte’s plasma membrane, allowing the sperm to release its nucleus into the cytoplasm of the oocyte. ○ Once a sperm has penetrated the zona pellucida and fused with the oocyte, the oocyte undergoes changes to prevent other sperm from entering. The sperm's Figure 6. Zygote cleavage and blastocyst formation. The morula genetic material combines with that of the period begins at the 12- to 16-cell stage and ends when the oocyte, forming a zygote. This marks the blastocyst forms, which occurs when there are 50 to 60 blas- tomeres present. The polar bodies, shown in the 2-cell stage, are successful fertilization of the egg. small nonfunctional cells that degenerate. Main results of fertilization: Transition to Blastocyst 1. Restoration of the diploud number of ○ As the developing embryo (zygote) chromosomes approaches the decidua, it forms a a. Half from father and half from structure called the blastocyst. The mother blastocyst is a cell that has been 2. Determination of chromosomal sex differentiated 58 times, hence, containing a. An X-carrying sperm produces a 58 cells. It has 5 embryo producing cells female (XX), and a Y-carrying called inner cell mass, and remaining 53 sperm produces a male (XY) cells called trophectoderm. embryo Inner Cell Mass: These cells will b. Hence, males determine the sex develop into the embryo and form of the child, as females naturally the three germ layers (endoderm, have two X chromosomes (XX). mesoderm, and ectoderm), which The sex of the child depends on will eventually become the fetus. whether the male contributes an Outer Cells (Trophectoderm): X or Y chromosome during These cells will form the fertilization. trophoblast, which will develop 3. Initiation of cleavage into the placenta. a. Series of mitotic divisions ○ The blastocyst implants into the decidua, which is the endometrium transformed IX. ZYGOTE during pregnancy to support the developing embryo. A zygote is a diploid cell with 46 chromosomes Oocyte transport occurs via: resulting from the fusion of sperm and egg. It i. Sweeping movements of the fimbriae undergoes cleavage and at this stage, ir produces blastomeres. ii. Peristaltic muscular contractions of the ○ Stages of Development: fallopian tube 4-Cell Stage: blastomere iii. Cilia in the tubal mucosa 16-Cell Stage: morula Blastocyt: After the morula, the cells undergo further division and X. IMPLANTATION differentiation. A fluid-filled cavity called the blastocoel forms, and Requirements for Implantation: the structure becomes the ○ The blastocyst must release cytokines blastocyst. (interleukin-1 alpha, interleukin-1 beta), ○ As the zygote divides, it moves towards and human chorionic gonadotropin the uterus, where the endometrium has (hCG). BATCH 2028 1E EMBRYOLOGY LC 2: OVULATION TO IMPLANTATION Dr. LICNACHAN M.M. 09/02/24 ○ The receptive endometrium (now called the decidua) responds by producing hormones: i. Leukemia inhibitory factor (LIF) ii. Follistatin iii. Colony-stimulating factor 1 (CSF-1) - immunomodulatory actions and proangiogenic actions required for implantation ○ These hormones inhibit proliferation and promote differentiation in the endometrial epithelium and stroma, making the uterine environment receptive to implantation. ○ In simple terms, for implantation to occur, the blastocyst releases interleukins. The endometrium, which is referred to as the decidua during pregnancy, needs certain hormones to help support this process. ○ After fertilization, the embryo travels to the uterus for implantation. The most common site for implantation is the endometrium (also known as the decidua) in the uterus. If implantation does not occur in the uterus, it may result in an ectopic pregnancy, where the embryo implants outside the uterine cavity. ○ Blasocyts implants into the uterine wall 6 or 7 days after fertilization. Figure 7. Three important processes involved during implantation. Chronological Process of Implantation: 1. Apposition: Initial contact between the blastocyst and the uterine wall. 2. Adherence: Increased physical contact between the blastocyst and the uterine epithelium. 3. Invasion: Penetration and invasion of the syncytiotrophoblast and cytotrophoblast into the endometrium, reaching the inner third of the myometrium and uterine vasculature. ○ Syncytiotrophoblast: This is a type of trophoblast derived from the outer layer of the blastocyst (trophectoderm). It plays a crucial role in forming the placenta. References: Sadler, T. W. (2011). Langman’s Medical Embryology. LWW. Cunningham, F. G., Leveno, K. J., Dashe, J. S., Hoffman, B. L., Spong, C. Y., & Casey, B. M. (2022). Williams Obstetrics 26e. McGraw Hill Professional. BATCH 2028 1E