From time to time, we post a few topics we’d like to cover and take a poll from our audience on our community tab. And you know what: the control of the menstrual cycle won by a landslide. We know it shows up on some tests but we don’t think that’s the only reason it won: it’s also – fascinating – a process that, like many biology topics, has so much complexity behind it with different hormones regulating it – and involves a variety of structures. Our goal is that by the end of this video, you’ll agree. Before we start, let’s intro some terms. The menstrual cycle is a cycle of changes that involve reproductive hormones and female reproductive structures. It has an average length of 28 days but that can vary. Ultimately, the changes that occur in this cycle prepare the female reproductive system for potential pregnancy. We want you to know we’ve observed some sources isolate “menstrual cycle” to the events that happen in the uterine cycle – that is, specific changes involving the uterus - while other sources will use the term “menstrual cycle” as more of an encompassing term that includes the uterine cycle and also the ovarian cycle (which is focused on changes in the ovaries). Ultimately, it’s important to understand that there are changes happening that impact the ovary – which you can refer to as the ovarian cycle – and there are changes that involve the uterus – which you can refer to as the uterine cycle – and those changes correlate and impact each other and they’re both happening together. Concurrently. And it is the two of them that are the focus of this video. First let’s intro some major structures involved. In our endocrine system video when we mentioned the female reproductive system, we showed the ovaries. Not technically connected to the ovaries – but very close - are fallopian tubes. And they lead to the uterus. A little function review: an ovary releases an egg. There are two ovaries but generally only one of the ovaries will release one egg each month. The egg travels through the fallopian tube. If sperm is present, the egg can get fertilized in the fallopian tube and the egg already starts some cell divisions on its way to implant in the lining of the uterus where it can continue to develop. If the egg is not fertilized in the fallopian tube, it starts breaking down and cannot get implanted in the uterus. So that was some basic structure. Let's now ~circle~ (ha) through this diagram of the ovarian cycle and uterine cycle phases. You'll see the uterine cycle is the outer ring and then the ovarian cycle is the inner ring; all of this is using an average 28 day cycle. This diagram emphasizes that both cycles are happening concurrently. We’re going to refer to this circle diagram when explaining events happening in both the uterine cycle and ovarian cycle. The ovarian cycle includes 2 main phases: follicular phase and luteal phase. The uterine cycle includes 3 main phases: menstrual flow, proliferative phase, and secretory phase. So let’s walk through each of these phases now. So let’s start with the first phase of the uterine cycle: the menstrual flow phase. On day one of our circle diagram, the uterine lining is shedding. This uterine lining will shed for a few days, and while the average is 5 days, this can vary. This is referred to as menses or having a period – that’s why it’s in the menstrual flow phase. At the same time - because remember these cycles happen concurrently - the ovarian cycle which you can see on our circle diagram is in the first of its two phases: the follicular phase. During this phase, follicles are starting to grow in the ovaries. Each follicle contains an egg cell. The follicle is like a little egg house that will continue to grow throughout this phase. Let’s return to the uterus as we look at the next uterine cycle phase: the proliferative phase. Around day 5 or 6 or 7 - again remember the days are approximate- the uterine lining - or endometrium if you want to use a fancier term - starts to regrow. This is a big deal because eventually it will need to be rich with blood vessels so that it could have the ability to nourish a blastocyst someday – a blastocyst is a fertilized egg that has done several divisions. Meanwhile, around this time in the ovarian cycle, we’re STILL in the follicular phase. But around day 5, the follicles have been growing more, and as they do, they will eventually start to approach the surface of the ovaries. Around day 14– a major event happens in the ovarian cycle. Ovulation! Generally, the most mature and dominant follicle which is bulging at the surface of one of the ovaries will break open – rupture- and out comes an egg. The egg will leave the ovary and travel the fallopian tube where it can be fertilized by a sperm cell. The other follicles – had all degenerated at some point in this follicular phase; the egg each of them had is lost. Forever. Keep in mind though there are a lot more eggs available for the next cycle. When ovulation is over, the ovarian cycle will enter the luteal phase. And that ruptured follicle that we mentioned - well guess what, it's actually still around. It is now a structure called the corpus luteum, still in the ovary. Its work is not done; soon it will be secreting hormones that help that lining of the uterus build up and prepare for possible implantation. Let’s look at the uterine cycle now - it also will enter a new phase after ovulation: it’s the secretory phase. All this endometrial tissue – this uterine lining – is continuing to build up and prepare for potential implantation of a blastocyst. If no blastocyst implants in the uterus, ultimately, the corpus luteum will break down and the endometrium will start to degenerate. Day 1 of a new cycle will be when bleeding occurs again. Ok so that was a broad overview. But what about the control of all of this? The regulation? We’re going to first introduce the hormones and glands that regulate those cycles and then walk through the cycle again and explain how those hormones regulate each phase. So to introduce the glands and hormones: you’ve got the gland called the hypothalamus. The hypothalamus releases GnRH or gonadotropin-releasing hormone. The main function of GnRH? GnRH stimulates another gland known as the anterior pituitary. The anterior pituitary is a gland that releases FSH – follicle stimulating hormone – and LH – luteinizing hormone. For females, FSH has a major role in stimulating follicles so it helps them grow. The other hormone, LH, also helps out with this but it’s also critical in starting ovulation which releases the egg, and it also helps the ovaries with their work of making hormones. Finally, the ovaries themselves are glands that secrete hormones. Progesterone and estradiol (which is a form of estrogen) are two ovarian hormones that will have major roles in the menstrual cycle which we’ll get to very soon. So, remember the major events we mentioned that were happening in an average 28 day cycle? Now, we’ll talk about the regulation of them and we’ll use the circle chart all over again. Back to day one, uterine cycle: we’re in the menstrual flow phase. After the corpus luteum broke down, estradiol and progesterone levels dropped, and this hormone drop can lead to blood vessels in the uterine lining to constrict, which cuts off circulation to the uterine lining and contributes to the breakdown of the uterine lining. This results in bleeding or menses. Now, meanwhile, let’s consider the ovarian cycle. Follicular phase, early on in the follicular phase. The hypothalamus will be secreting GnRH which stimulates the anterior pituitary to release FSH and LH, though in low amounts. Small follicles have FSH receptors. FSH will stimulate the growth of the follicles. As these follicles grow, they begin to release estradiol. Low levels of estradiol will result in negative feedback on the hypothalamus and anterior pituitary, which inhibits the secretion of GnRH and keeps levels of LH and FSH relatively low. Let’s move to the next uterine cycle phase: the proliferative phase. Remember in this phase, the lining – the endometrium - is stimulated to grow thanks largely to that increasing estradiol. Back to the ovarian cycle - still in the follicular phase , though later in the follicular phase- the low FSH levels prevented most follicles from making it to this point - but there will be a mature follicle that is dominant and making more and more estradiol. Now it gets tricky here so hang with me - while you remember LOW levels of estradiol inhibiting the hypothalamus and anterior pituitary ultimately leading to low secretion of GnRH, FSH, and LH, high levels of estradiol actually stimulate these glands resulting in more GnRH secretion through positive feedback. So when that estradiol reaches a certain high level, GnRH secretion will go up and as expected with that, the anterior pituitary will start cranking out more FSH and LH. LH starts to really increase! This rapid increase is known as a LH surge. The LH surge will trigger ovulation to happen roughly a day or so later. Recall that ovulation is when there is a bursting of that mature, dominant follicle, releasing the egg. The ovarian cycle moves to the luteal phase after ovulation. LH is involved in stimulating that follicle that had burst to become the corpus luteum. Now we had mentioned the corpus luteum has a job helping the uterine lining build up as it prepares for potential pregnancy. And it does, as the corpus luteum produces estradiol and progesterone, which are important for the next uterine cycle phase. That next phase of the uterine cycle is the secretory phase where both estradiol and progesterone – especially progesterone - are responsible for helping to build up and maintain the uterine lining. In addition, that estradiol and progesterone – the combination of the two - will inhibit the hypothalamus and anterior pituitary through negative feedback which ultimately means less GnRH, FSH, and LH will be secreted. That’s important because there could, after all, be a potential pregnancy and so more follicles do not need to be developed right now. Now if there is no implantation of a blastocyst in the uterus? Let’s look at the end of the ovarian cycle in the luteal phase, where the corpus luteum breaks down. If it breaks down, it’s not going to be making all the estradiol and progesterone. Those hormone levels drop significantly which will stop the building of the uterine lining - that endometrium. What does that lead to? Surprise! It’s back to day one and the menstrual flow phase of the uterine cycle and the endometrium begins to shed. With the drop of both estradiol and progesterone, that negative feedback is gradually lifted, so now the hypothalamus can resume GnRH secretion as the cycle starts anew. Just a little helpful note if you do a rewatch of this hormonal control part of the video: you can catch negative and positive feedback examples: we had a negative feedback example in the early to mid follicular phase and in the luteal phase after ovulation. We mentioned positive feedback happening in the late follicular phase. If you want more examples of negative or positive feedback mechanisms in this process - because there are more - or more details to explore like how the dominant follicle is selected - check out our further reading in our description. And one more helpful note is to see the big picture: a general chart showing general hormone levels throughout this example 28 day period. Here are the general levels of the pituitary hormones – FSH and LH. And here are the general levels of ovarian hormones we mentioned - estradiol and progesterone. If just focusing on major events here: we can see the low levels of these hormones at day 1 and then you can see estradiol rise – it’s being made by the follicles – when the estradiol reaches a certain level, it results in FSH and LH rising. When estradiol peaks, it leads to an LH surge – that LH surge triggers ovulation roughly a day or so later. Then after ovulation, that ruptured follicle becomes the corpus luteum, and the corpus luteum will soon start to secrete estradiol and progesterone– if no implantation of a blastocyst in the uterus happens – that corpus luteum will ultimately break down. The hormone levels plummet. We could start again. So, now one question you might have. What if a blastocyst did implant? Would all this still start over? No, because if pregnancy occurred, that uterine lining would need to be maintained and NOT shed – it’s important for the developing embryo – and the body also would not release more eggs at the same time when there is already a pregnancy. Instead, the blastocyst will start releasing hCG. hCG is a major hormone that many pregnancy tests will use to detect a pregnancy. hCG will be involved in stimulating the corpus luteum to remain active and that is important because the progesterone that the corpus luteum secretes is especially critical for maintaining that uterine lining. Eventually, the placenta will take over with secreting hormones and the corpus luteum will no longer be needed. Exciting. And definitely a topic for another video. Well, that’s it for the Amoeba Sisters, and we remind you to stay curious.