preprints.org > biology and life sciences > cell and developmental biology > doi: 10.20944/preprints202310.0843.v1

Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 12 October 2023 / Approved: 12 October 2023 / Online: 13 October 2023 (04:30:41 CEST)

It is known that exposure to heavy metals such as lead (Pb) and cadmium (Cd) has several adverse effects, particularly on the human reproductive system. Pb and Cd have been associated with infertility in both men and women. In pregnant women, they have been associated with spontaneous abortion, preterm birth, and impairment of the development of the fetus. Since these heavy metals come from both natural and anthropogenic activities and their harmful effects have been observed even at levels of exposure, their exposure remains a public health issue, especially for the reproductive system. Given this, the present study aimed to investigate the potential reproductive effects of Pb and Cd levels in the follicular fluid (FF) of infertile women and no-smokers exposed to heavy metals for professional reasons or living in rural areas near landfills and waste disposal areas, to correlate the intrafollicular presence of these metals with possible alterations in the ultrastructure of human cumulus-oocyte complexes (COCs), probably responsible of infertility. Blood and FF metals were measured using atomic absorption spectrometry. COCs corresponding to each FF analyzed were subjected to ultrastructural analyses by transmission electron microscopy. We demonstrated for the first time that intrafollicular levels of Pb (0.66 µg/dL to 0.85 µg/dL) and Cd (0.26 µg/L - 0.41 µg/L) could be associated with morphological alterations of both the oocyte and CCs ultrastructure. Since blood Cd levels (0.54 µg/L - 1.87 µg/L) were above the current reference values established by the guidelines of the Agency for Toxic Substances and Disease Registry (ATSDR) and the Environmental Protection Agency (EPA), whereas blood Pb levels (1.28 µg/dL - 3.98 µg/dL) were below the ATSDR reference values we believe that these alterations could be due especially to Cd, even if we cannot exclude a possible additional effect of Pb. Our results highlighted that oocytes were affected in maturation and quality, whereas CCs showed scarcely active steroidogenic elements. Regressing CCs, with cytoplasmic alterations, were also numerous. According to Cd's endocrine-disrupting activity, the poor steroidogenic activity of CCs might correlate with delayed oocyte cytoplasmic maturation. So, we conclude that levels of heavy metals in the blood and the FF might negatively affect fertilization, embryo development, and pregnancy, compromising oocyte competence to fertilization both directly and indirectly, impairing CC steroidogenic activity, and inducing CC apoptosis.

heavy metals; lead; cadmium; oocyte; cumulus cells; human; electron micros

Biology and Life Sciences, Cell and Developmental Biology

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