Concentrations of sex steroids in fluid from human antral follicles are dynamic and characterize transition from follicular recruitment to dominance
To study the dynamic changes of the human intrafollicular concentrations of all sex steroid hormones throughout the natural menstrual cycle using liquid chromatography-tandem mass spectrometry. Observational Study. Follicular fluid (FF; n = 50) and granulosa cells (n = 25) were collected from antral...
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| Published in: | Fertility and sterility |
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| Language: | English |
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14.08.2025
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| Abstract | To study the dynamic changes of the human intrafollicular concentrations of all sex steroid hormones throughout the natural menstrual cycle using liquid chromatography-tandem mass spectrometry.
Observational Study.
Follicular fluid (FF; n = 50) and granulosa cells (n = 25) were collected from antral (2-10 mm in diameter) and Graafian follicles (>10-18 mm) in 34 patients undergoing ovarian tissue cryopreservation for fertility preservation from 2014 to 2023. FF from preovulatory (n = 16) and ovulatory (n = 50) follicles was donated by 50 women undergoing ovarian stimulation for fertility treatment. Preovulatory samples were aspirated before induction of final maturation of follicles, and ovulatory samples were collected during oocyte retrieval, 36 hours post trigger.
Fifty patients underwent in vitro fertilization/intracytoplasmic sperm injection, and 34 underwent fertility preservation.
Concentrations of sex steroids and gene expression of key steroidogenic enzymes in human follicles throughout the menstrual cycle.
Sex steroid levels were low in small follicles (2-4 mm) and increased with follicular diameter. In the early to midfollicular phase, levels of 17OH-progesterone (700-900 nM), androstenedione (2,000 nM), and testosterone (340 nM) were elevated. In preovulatory follicles, 17OH-progesterone peaked at 5,300 nM, whereas androstenedione and testosterone declined to <100 nM. This decline coincided with increased CYP19A1 expression, resulting in a 17β-estradiol peak (∼8,000 nM) before ovulation. Progesterone remained <100 nM until surging to 20,000 nM at ovulation. Upregulation of HSD3B2 and CYP19A1 suggested a metabolic shift from the Δ5 pathway (favoring 17β-estradiol production) to the Δ4 pathway (favoring progesterone synthesis), corresponding with ovulation.
This is the first study to comprehensively map intrafollicular concentrations of all major sex steroids in FF, alongside gene expression of key enzymes in granulosa cells, across the follicular phase of the menstrual cycle using liquid chromatography-tandem mass spectrometry. These findings enhance our understanding of hormonal regulation and the timing mechanisms that govern human follicle development and ovarian function. |
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| AbstractList | To study the dynamic changes of the human intrafollicular concentrations of all sex steroid hormones throughout the natural menstrual cycle using liquid chromatography-tandem mass spectrometry.
Observational Study.
Follicular fluid (FF; n = 50) and granulosa cells (n = 25) were collected from antral (2-10 mm in diameter) and Graafian follicles (>10-18 mm) in 34 patients undergoing ovarian tissue cryopreservation for fertility preservation from 2014 to 2023. FF from preovulatory (n = 16) and ovulatory (n = 50) follicles was donated by 50 women undergoing ovarian stimulation for fertility treatment. Preovulatory samples were aspirated before induction of final maturation of follicles, and ovulatory samples were collected during oocyte retrieval, 36 hours post trigger.
Fifty patients underwent in vitro fertilization/intracytoplasmic sperm injection, and 34 underwent fertility preservation.
Concentrations of sex steroids and gene expression of key steroidogenic enzymes in human follicles throughout the menstrual cycle.
Sex steroid levels were low in small follicles (2-4 mm) and increased with follicular diameter. In the early to midfollicular phase, levels of 17OH-progesterone (700-900 nM), androstenedione (2,000 nM), and testosterone (340 nM) were elevated. In preovulatory follicles, 17OH-progesterone peaked at 5,300 nM, whereas androstenedione and testosterone declined to <100 nM. This decline coincided with increased CYP19A1 expression, resulting in a 17β-estradiol peak (∼8,000 nM) before ovulation. Progesterone remained <100 nM until surging to 20,000 nM at ovulation. Upregulation of HSD3B2 and CYP19A1 suggested a metabolic shift from the Δ5 pathway (favoring 17β-estradiol production) to the Δ4 pathway (favoring progesterone synthesis), corresponding with ovulation.
This is the first study to comprehensively map intrafollicular concentrations of all major sex steroids in FF, alongside gene expression of key enzymes in granulosa cells, across the follicular phase of the menstrual cycle using liquid chromatography-tandem mass spectrometry. These findings enhance our understanding of hormonal regulation and the timing mechanisms that govern human follicle development and ovarian function. To study the dynamic changes of the human intrafollicular concentrations of all sex steroid hormones throughout the natural menstrual cycle using LC-MS/MS.OBJECTIVETo study the dynamic changes of the human intrafollicular concentrations of all sex steroid hormones throughout the natural menstrual cycle using LC-MS/MS.Observational Study.DESIGNObservational Study.Follicular fluid (FF; n = 50) and granulosa cells (n = 25) were collected from antral (2-10 mm in diameter) and Graafian follicles (>10-18 mm) in 34 patients undergoing ovarian tissue cryopreservation for fertility preservation from 2014-2023. FF from preovulatory (n = 16) and ovulatory (n = 50) follicles was donated by 50 women undergoing ovarian stimulation for fertility treatment. Preovulatory samples were aspirated prior to induction of final maturation of follicles, and ovulatory samples were collected during oocyte retrieval, 36 hours post trigger.SUBJECTSFollicular fluid (FF; n = 50) and granulosa cells (n = 25) were collected from antral (2-10 mm in diameter) and Graafian follicles (>10-18 mm) in 34 patients undergoing ovarian tissue cryopreservation for fertility preservation from 2014-2023. FF from preovulatory (n = 16) and ovulatory (n = 50) follicles was donated by 50 women undergoing ovarian stimulation for fertility treatment. Preovulatory samples were aspirated prior to induction of final maturation of follicles, and ovulatory samples were collected during oocyte retrieval, 36 hours post trigger.Fifty patients underwent IVF/ICSI and 34 underwent fertility preservation.EXPOSUREFifty patients underwent IVF/ICSI and 34 underwent fertility preservation.Concentrations of sex steroids and gene expression of key steroidogenic enzymes in human follicles throughout the menstrual cycle.MAIN OUTCOME MEASURE(S)Concentrations of sex steroids and gene expression of key steroidogenic enzymes in human follicles throughout the menstrual cycle.Sex steroid levels were low in small follicles (2-4 mm) and increased with follicular diameter. In the early to mid-follicular phase, levels of 17OH-progesterone (700-900 nM), androstenedione (2,000 nM), and testosterone (340 nM) were elevated. In preovulatory follicles, 17OH-progesterone peaked at 5,300 nM, while androstenedione and testosterone declined to below 100 nM. This decline coincided with increased CYP19A1 expression (p < 0.05), resulting in a 17β-estradiol peak (∼8,000 nM) prior to ovulation. Progesterone remained below 100 nM until surging to 20,000 nM at ovulation. Upregulation of HSD3B2 and CYP19A1 (p < 0.05) suggested a metabolic shift from the Δ5 pathway (favoring 17β-estradiol production) to the Δ4 pathway (favoring progesterone synthesis), corresponding with ovulation.RESULTSSex steroid levels were low in small follicles (2-4 mm) and increased with follicular diameter. In the early to mid-follicular phase, levels of 17OH-progesterone (700-900 nM), androstenedione (2,000 nM), and testosterone (340 nM) were elevated. In preovulatory follicles, 17OH-progesterone peaked at 5,300 nM, while androstenedione and testosterone declined to below 100 nM. This decline coincided with increased CYP19A1 expression (p < 0.05), resulting in a 17β-estradiol peak (∼8,000 nM) prior to ovulation. Progesterone remained below 100 nM until surging to 20,000 nM at ovulation. Upregulation of HSD3B2 and CYP19A1 (p < 0.05) suggested a metabolic shift from the Δ5 pathway (favoring 17β-estradiol production) to the Δ4 pathway (favoring progesterone synthesis), corresponding with ovulation.This is the first study to comprehensively map intrafollicular concentrations of all major sex steroids in FF, alongside gene expression of key enzymes in granulosa cells, across the follicular phase of the menstrual cycle using LC-MS/MS. These findings enhance our understanding of hormonal regulation and the timing mechanisms that govern human follicle development and ovarian function.CONCLUSIONThis is the first study to comprehensively map intrafollicular concentrations of all major sex steroids in FF, alongside gene expression of key enzymes in granulosa cells, across the follicular phase of the menstrual cycle using LC-MS/MS. These findings enhance our understanding of hormonal regulation and the timing mechanisms that govern human follicle development and ovarian function. |
| Author | Zheng, Mengxue Mamsen, Linn Salto Hay-Schmidt, Anders Styrishave, Bjarne Andersen, Claus Yding Johannsen, Malene Louise |
| Author_xml | – sequence: 1 givenname: Malene Louise surname: Johannsen fullname: Johannsen, Malene Louise email: malene.louise.johannsen@regionh.dk organization: Laboratory of Reproductive Biology, Department of Gynecology, Fertility and Obstetrics, Copenhagen University Hospital, Copenhagen, Denmark; Toxicology and Drug Metabolism Group, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. Electronic address: malene.louise.johannsen@regionh.dk – sequence: 2 givenname: Linn Salto surname: Mamsen fullname: Mamsen, Linn Salto organization: Laboratory of Reproductive Biology, Department of Gynecology, Fertility and Obstetrics, Copenhagen University Hospital, Copenhagen, Denmark – sequence: 3 givenname: Mengxue surname: Zheng fullname: Zheng, Mengxue organization: Laboratory of Reproductive Biology, Department of Gynecology, Fertility and Obstetrics, Copenhagen University Hospital, Copenhagen, Denmark – sequence: 4 givenname: Bjarne surname: Styrishave fullname: Styrishave, Bjarne organization: Toxicology and Drug Metabolism Group, Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – sequence: 5 givenname: Anders surname: Hay-Schmidt fullname: Hay-Schmidt, Anders organization: Department of Odontology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark – sequence: 6 givenname: Claus Yding surname: Andersen fullname: Andersen, Claus Yding organization: The Fertility Clinic, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark; Faculty of Health and Medical Sciences, Department of Clinical Medicine, University of Copenhagen, Copenhagen, Denmark; Department of Urology, Copenhagen University Hospital, Herlev and Gentofte Hospital, Herlev, Denmark |
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| Keywords | LC-MS/MS folliculogenesis sex steroids antral follicles Human reproduction |
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