Female Fertility and Environmental Pollution

Abstract

A realistic picture of our world shows that it is heavily polluted everywhere. Coastal regions and oceans are polluted by farm fertilizer, manure runoff, sewage and industrial discharges, and large isles of waste plastic are floating around, impacting sea life. Terrestrial ecosystems are contaminated by heavy metals and organic chemicals that can be taken up by and accumulate in crop plants, and water tables are heavily contaminated by untreated industrial discharges. As deadly particulates can drift far, poor air quality has become a significant global problem and one that is not exclusive to major industrialized cities. The consequences are a dramatic impairment of our ecosystem and biodiversity and increases in degenerative or man-made diseases. In this respect, it has been demonstrated that environmental pollution impairs fertility in all mammalian species. The worst consequences are observed for females since the number of germ cells present in the ovary is fixed during fetal life, and the cells are not renewable. This means that any pollutant affecting hormonal homeostasis and/or the reproductive apparatus inevitably harms reproductive performance. This decline will have important social and economic consequences that can no longer be overlooked.

Keywords: endocrine disruptors; environmental pollution; female reproduction; heavy metals; hormones; ovary.

Figure 1

Ovarian follicle development and hypothalamic/pituitary/ovarian axis. (A) Schematic representation of mammalian follicle development from primordial stage to corpus luteum formation. The ovulated oocyte is arrested at metaphase II (MII) until fertilization. (B) GnRH (Gonadotropin releasing Hormone) stimulates FSH and LH release. When gonadotropins bind specific receptors present on ovarian somatic cells, they stimulate estrogen and progesterone production, which exert negative feedback on gonadotropin release.

Figure 2

Two cell, two-gonadotropin theory. Ovarian steroids are synthesized from cholesterol (CH) via the cooperation of theca and granulosa cells. In theca cells, LH and its receptor (LHR) stimulate androgen synthesis via Gαs-mediated increases in cAMP that, in turn, activates PKA. This kinase can increase steroidogenic acute regulatory protein (StAR) expression and activity in collaboration with the orphan nuclear receptor Steroidogenic factor-1 (SF-1) an), which acts as a global regulator of steroidogenesis. StAR moves cholesterol (Ch) into the mitochondria (mit), where it is converted to progesterone (Pr) and then androstenedione (Andr). In granulosa cells, FSH and FSHR stimulate the activity of 17βhydroxysteroid dehydrogenase (17βHSD) and aromatase, which produce estron (E1) and estradiol (E2) from Andr and T (testosterone).

Figure 3

Schematic representation of cellular effects of various reactive oxygen species (ROS) levels. While low levels stimulate cell recovery/survival, high levels alter epigenetic mechanisms and induce degenerative processes or apoptosis via activation of p53 and pro-apoptotic genes. HIF (Hypoxia inducible factor) and NfKB (nuclear factor kappa light-chain-enhancer of activated B cells) are both involved in inflammation response, MAPK and PI3K/AKT (phosphatidylinositol 3-kinases/protein kinase B). are major regulators of cell cycle and survival and JNK (c-Jun N-terminal kinase) and P38 are key mediators of oxidative stress often associated with apoptosis and increased caspase activity.