Physiology of Term Maturation

The mechanism controlling the duration of the follicular cycle determines the term maturation of the oocyte. 

Understanding what controls the duration of the follicular phase is important not only because it is central to reproduction, but also because this is the only time when it could be controlled by a physician.

Just like a fetus in the womb does not have control over the time of uterine contractions of delivery, the oocyte has no control over the duration of the follicular phase. Instead, it is determined by the lifespan of the follicle. To better understand the life-cycle of the ovarian follicle it is useful to look at its more simple cousin, the hair follicle.

Both types of follicles are comparable histologically and in other key features:

  • Predictable duration of the lifecycle
  • Begin at a similar depth below the epithelium
  • Require growth/differentiation factors (GDF), Bone morphogenetic proteins (BMP), and transforming growth factor-beta (TGF-beta – SMAD)
  • Maximum size is determined by surrounding tissues
  • Have a distinctive “ripe to rupture” stage
  • The terminal phase of development involves prostaglandins
  • Respond to NSAID

An inflamed hair follicle (a pustule), progresses through several distinct phases. First, it is just a small bump, then it will fill with fluid, then a black spot will appear, and at some point, it will reach its maximum size, and then it will rupture (“ovulate”). The life cycle, from the bump to rupture, has a predictable duration, which is determined by the ability of local tissue to accommodate the follicle’s expansion. Once the maximum size is reached, the follicle begins to disintegrate without any additional forces required.  

Unlike the hair follicle, the expansion of the ovarian follicle is driven by FSH and LH. However, the limitations of expansion by the local environment still apply: once the follicle reaches a certain size, the inflammation sets in (that is why the basal temperature rises), and at about 25 mm it begins to disintegrate spontaneously in a manner similar to the pustule – independent of the reproductive hormones. According to the new ovulation paradigm, this spontaneous disintegration of the ovarian follicle results in LH-independent rise of the progesterone, which triggers gonadotropins surge that signals the end of the follicular phase. If this happens at about 16 days after the start of the follicular phase, the oocyte will ovulate fully competent – term. If it happens earlier, the oocyte will also ovulate, but this ovulation may end up pre-term.

To summarize, the ability of an oocyte to reach term maturation is determined by the duration of the follicular phase, which in its own turn is determined by properties of the ovarian cortex, inflammation, level of FSH and LH, and the activity of mural granulosa within the follicle, which is responsible for the production of a fluid, which causes the follicle to expand.

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