Cell-free nucleic acids and melatonin levels in human follicular fluid predict embryo quality in patients undergoing in-vitro fertilization treatment

Khan, Haroon Latif; Bhatti, Shahzad; Khan, Yahya; Abbas, Sana; Munir, Zaid; Sherwani, Ismail Abdur Rahman Khan; Suhail, Samina; Hassan, Zahira; Aydin, Hikmet Hakan

doi:10.1016/j.jogoh.2019.08.007

Cited by 15 publications

(8 citation statements)

References 23 publications

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“…Similar results were reported in pigs, where high amounts of cfDNA in FF were related to poor-quality oocyte development, cell death, and GCs apoptosis [16]. Other studies in humans have also confirmed these findings, showing low amounts of cfDNA in the FF of women with high embryonic development [18,49,[51][52][53][54]. It is important to emphasize that both pig and human studies were performed using different follicle sizes and oocyte development stages compared to our study, which suggests that cfDNA may be a more reliable parameter because it presents the same behavior at different stages of development [49,54].…”

Section: Plos Onesupporting

confidence: 83%

“…Some components such as Glycine, L-glutamate, L-alanine, glucose, pyruvate, estradiol, and progesterone have been identified as indicators of oocyte quality [11][12][13]. Recently, several studies have demonstrated the presence of cell-free DNA (cfDNA) and specific microRNAs (miRNAs) in FF [14][15][16][17][18][19]. In addition to FF, CC and follicular cells are also part of the follicular environment and communicate directly or indirectly with oocytes.…”

Section: Introductionmentioning

confidence: 99%

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Biochemical profiling of the follicular environment to predict oocyte competence in cattle

Kussano,

Franco,

Dode

2024

PLoS ONE

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To identify markers of oocyte competence, we compared the biochemical characteristics of fluid and cells from follicles containing oocytes with different capacities to form an embryo. Follicles (5–6 mm) were dissected, and follicular fluid (FF), granulosa cells (GC), cumulus cells (CC) from immature and mature cumulus-oocyte-complexes (COC) were individually collected. The oocytes were matured, fertilized, and cultured individually until day 8 (D8) of development. On D8, the samples were grouped according to embryo production into those that gave rise to blastocysts (EMB) and those that did not reach the blastocyst stage (NEMB). In CCs from immature and mature COCs and GCs, expression of CASP3, SERPINE2, VCAN, LUM, FSHR, EGFR, PGR, and GHR genes was quantified. Cell-free DNA (cfDNA), progesterone, and estradiol concentrations in the FF were determined. Data were analyzed by Mann–Whitney U test (GraphPad Prism 9). GHR was highly expressed in immature CCs from the EMB group, whereas CASP3 was highly expressed in mature CCs from the NEMB group (P<0.05). During maturation, the expression of CASP3 and GHR genes increased only in the NEMB group. ART2 cfDNA was highly detected in FF of the NEMB compared to the EMB group. Progesterone concentration was similar between the groups, whereas estradiol concentration was higher (P<0.05) in the EMB than in the NEMB group. It was concluded that a higher level of GHR transcripts in immature CCs, lower CASP3 expression in CCs from matured COCs, lower levels of ART2, and higher estradiol concentrations in FF may indicate oocytes with greater potential for development.

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Section: Plos Onesupporting

confidence: 83%

Section: Introductionmentioning

confidence: 99%

Biochemical profiling of the follicular environment to predict oocyte competence in cattle

Kussano,

Franco,

Dode

2024

PLoS ONE

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“…Other organs such as the ovary can produce melatonin, which plays a crucial role in oocyte maturation . Inspired by this, we examined melatonin expression and found it present in oviduct fluid at a concentration similar to that in follicular fluid . Our results indicate that melatonin can rectify the abnormal levels of 5‐mC, potentially in a DNMT1‐related manner; downregulation of DNMT1, ROS, and 5‐mC levels and increase in blastocyst rate by melatonin; and the attenuation of these effects by luzindole.…”

Section: Discussionmentioning

confidence: 84%

Extracellular vesicles and melatonin benefit embryonic develop by regulating reactive oxygen species and 5‐methylcytosine

Luo

et al. 2020

Journal of Pineal Research

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Embryo culture conditions are crucial as they can affect embryo quality and even offspring. Oviductal extracellular vesicles (EVs) long been considered a major factor influencing interactions between the oviduct and embryos, and thus its absence is associated with inferior embryonic development in in vitro culture. Herein, we demonstrated that melatonin is present in oviduct fluids and oviduct fluid‐derived EVs. Addition of either EVs (1.87 × 1011 particles/mL) or melatonin (340 ng/mL) led to a significant downregulation of reactive oxygen species (ROS) and 5‐methylcytosine (5‐mC), as well as an increase in the blastocyst rate of embryos, which was inhibited by the addition of luzindole—a melatonin receptor agonist. A combination of EVs (1.87 × 1010 particles/mL) and melatonin (at 34.3 pg/mL) led to the same results as well as a significant decrease in the apoptosis index and increase in the inner cell mass (ICM)/trophectoderm (TE) index. These results suggest that an EV‐melatonin treatment benefits embryonic development. Our findings provide insights into the role of EVs and melatonin during cell communication and provide new evidence of the communication between embryos and maternal oviduct.

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“…In addition, melatonin has been shown to preserve mouse spermatogenesis and reduce levels of free radicals, protecting sperm from oxidative damage [35,36]. Moreover, melatonin levels may influence the in vitro fertilization outcomes since its levels positively correlate with antral follicle count [77] and could therefore predict embryo quality [78]. However, some data suggest that an excess of melatonin leads to infertility [79].…”

Section: Melatoninmentioning

confidence: 99%

Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Infertility

Sciarra

Franceschini

Campolo

et al. 2020

IJMS

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Infertility represents a growing health problem in industrialized countries. Thus, a greater understanding of the molecular networks involved in this disease could be critical for the development of new therapies. A recent finding revealed that circadian rhythmicity disruption is one of the main causes of poor reproductive outcome. The circadian clock system beats circadian rhythms and modulates several physiological functions such as the sleep-wake cycle, body temperature, heart rate, and hormones secretion, all of which enable the body to function in response to a 24 h cycle. This intricated machinery is driven by specific genes, called “clock genes” that fine-tune body homeostasis. Stress of modern lifestyle can determine changes in hormone secretion, favoring the onset of infertility-related conditions that might reflect disfunctions within the hypothalamic–pituitary–gonadal axis. Consequently, the loss of rhythmicity in the suprachiasmatic nuclei might affect pulsatile sexual hormones release. Herein, we provide an overview of the recent findings, in both animal models and humans, about how fertility is influenced by circadian rhythm. In addition, we explore the complex interaction among hormones, fertility and the circadian clock. A deeper analysis of these interactions might lead to novel insights that could ameliorate the therapeutic management of infertility and related disorders.

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Cell-free nucleic acids and melatonin levels in human follicular fluid predict embryo quality in patients undergoing in-vitro fertilization treatment

Cited by 15 publications

References 23 publications

Biochemical profiling of the follicular environment to predict oocyte competence in cattle

Biochemical profiling of the follicular environment to predict oocyte competence in cattle

Extracellular vesicles and melatonin benefit embryonic develop by regulating reactive oxygen species and 5‐methylcytosine

Disruption of Circadian Rhythms: A Crucial Factor in the Etiology of Infertility

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