Lifetime changes of the oocyte pool: Contributing factors with a focus on ovulatory inflammation

Abstract

In mammalian species, females are born with a number of oocytes exceeding what they release via ovulation. In humans, an average girl is born with over a thousand times more oocytes than she will ovulate in her lifetime. The reason for having such an excessive number of oocytes in a neonatal female ovary is currently unknown. However, it is well established that the oocyte number decreases throughout the entire lifetime until the ovary loses them all. In this review, data published in the past 80 years were used to assess the current knowledge regarding the changing number of oocytes in humans and mice, as well as the reported factors that contribute to the decline of oocyte numbers. Briefly, a collective estimation indicates that an average girl is born with approximately 600,000 oocytes, which is 2,000 times more than the number of oocytes that she will ovulate in her lifetime. The oocyte number begins to decrease immediately after birth and is reduced to half of the initial number by puberty and almost zero by age 50 years. Multiple factors that are either intrinsic or extrinsic to the ovary contribute to the decline of the oocyte number. The inflammation caused by the ovulatory luteinizing hormone surge is discussed as a potential contributing factor to the decline of the oocyte pool during the reproductive lifespan.

Keywords: Atretic follicle; Folliculogenesis; Germ cells; Inflammation; Oocytes; Reproductive health.

Figure 1.

Lifetime changes in the oocyte pool in humans and mice. (A) The graph depicts the cumulative human data from the seven most relevant and reliable published articles that claim that oocyte counting was done in non-pathological ovaries. (B) This is a replica of the human oocyte pool, but only representing the age groups of 30–55 years. (C) The graph contains cumulative data collected from the 10 most relevant and reliable published articles. The reliability of published data was judged by an outlier test. The numbers in the parentheses are the numbers of articles used to calculate the average oocyte numbers in each age group. The gray area represents mean±standard error of the mean. Data analysis and graph-plotting were conducted using GraphPad Prism 5 (GraphPad Inc., La Jolla, CA, USA).

Figure 2.

Contributing factors to the decline of the oocyte pool. Internal factors leading to the decline of the oocyte pool include oocyte attrition, follicular atresia, and meiotic errors. External factors, such as environmental toxicants and medical treatments, can either trigger internal factors or directly cause the reduction of the oocyte pool.

Figure 3.

Ovulatory inflammation and the oocyte pool. The luteinizing hormone (LH) surge stimulates theca and mural granulosa cells (GCs) to produce prostaglandin E2 (PGE2) and interleukin 1 beta (IL-1β), which then trigger them and resident immune cells to produce inflammatory cytokines. These cytokines increase pro-inflammatory immune cells in the ovary by facilitating their infiltration into the ovarian tissue from the circulating bloodstream, causing localized inflammatory situation in the ovary. As a result, germ cells and follicles may get damaged directly by the proinflammatory cells or indirectly via reactive oxygen species (ROS) produced by the immune cells or ovarian cells. The repeated ovulatory inflammation itself and physical tearing of the ovarian surface epithelium (OSE) result in both the loss of germ cells and neoplastic transformation. NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cells; GR, glucocorticoid receptor; PGR, progesterone recepto; NFKBIA, NF-κB inhibitor alpha.