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. 2021 Apr 14:9:647002.
doi: 10.3389/fcell.2021.647002. eCollection 2021.

Nitrite and Nitrate Levels in Follicular Fluid From Human Oocyte Donors Are Related to Ovarian Response and Embryo Quality

Florentin-Daniel Staicu  1   2 , Analuce Canha-Gouveia  1   2 , Cristina Soriano-Úbeda  1   2   3 , Juan Carlos Martínez-Soto  2   4 , Evdochia Adoamnei  2   5 , Jorge E Chavarro  6   7   8 , Carmen Matás  1   2
Affiliations

Nitrite and Nitrate Levels in Follicular Fluid From Human Oocyte Donors Are Related to Ovarian Response and Embryo Quality

Florentin-Daniel Staicu et al. Front Cell Dev Biol. .

Abstract

Nitric oxide, a key regulatory molecule in the follicular fluid, has been suggested as a possible biomarker to predict ovarian response in stimulated cycles and the potential of the retrieved oocytes for developing high-quality embryos. Nevertheless, a consensus on whether or not nitric oxide can help in this context has not been reached. We simultaneously measured the oxidation products of nitric oxide, nitrite, and nitrate, via high-performance liquid chromatography (HPLC)-UV in follicular fluid samples from 72 oocyte donors. We found no associations of follicular fluid nitrite, nitrate, total nitric oxide, or nitrate/nitrite ratio with total or metaphase II (MII) oocyte yield. However, nitrite and nitrate levels were related to the yield of MII oocytes when this outcome was expressed as a proportion of all oocytes retrieved. The adjusted MII proportion in the lowest and highest nitrite levels were 68% (58-77%) and 79% (70-85%), respectively (p, linear trend = 0.02), whereas the adjusted MII proportion in extreme tertiles of nitrate levels were 79% (70-85%) and 68% (57-77%) (p, linear trend = 0.03). In addition, nitrate levels showed a suggestive inverse correlation with embryos with maximum or high potential of implantation (p = 0.07). These results suggest that the follicular fluid concentrations of nitrite and nitrate may be a useful tool in predicting how healthy oocyte donors respond to superovulation and the implantation potential of the embryos produced from their oocytes.

Keywords: embryo; follicular fluid; nitrate; nitric oxide; nitrite; oocyte.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Morphological classification of blastocysts in day 5 of in vitro development according to the criteria established by the Spanish Association for the Study of the Biology of Reproduction (ASEBIR) based on the morphological evaluation of the inner cell mass (ICM) and trophectoderm (TE) (Hurtado de Mendoza et al., 2015; Cuevas Saiz et al., 2018). The implantation potential of blastocysts according to this classification is established as follows: grade (A), maximum; grade (B), high; grade (C), medium; grade (D), low (see Table 1). Scale bar represents 25 μm.
FIGURE 2
FIGURE 2
High-performance liquid chromatography (HPLC)-UV chromatogram. The peak located at 10.2 min was identified as nitrite (NO2), while the peak at 31.6 min was identified as nitrate (NO3). The peak areas of each compound in the standard solutions were used for the calculation of the calibration curve, from which the concentrations in follicular fluid samples (e.g., samples 1 and 2) were obtained.
FIGURE 3
FIGURE 3
Distribution of grade A and B embryos (maximum and high potential of implantation, respectively) at day 5 of development according to the NO3 levels in the follicular fluid of healthy women undergoing ovarian stimulation as part of their participation in an oocyte donation program (n = 75).
See this image and copyright information in PMC

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