TY - JOUR

T1 - Нарушения гормонального статуса и процесса овуляции у инфантильных самок крыс с синдромом поликистозных яичников, индуцированным дегидроэпиандростероном

AU - Деркач, К. В.

AU - Печальнова, Алена Сергеевна

AU - Морина, И.Ю.

AU - Федорчук, Ирина

AU - ЗОРИНА, И.И.

AU - Нагорнюк, Кристина Яновна

AU - Романова, И.В.

AU - Шпаков, Александр Олегович

PY - 2026/4/10

Y1 - 2026/4/10

N2 - BACKGROUND: Rodent models of polycystic ovary syndrome, including those induced by dehydroepiandrosterone, are widely used to study the pathogenesis of this disorder; however, ovarian steroidogenesis and ovulation markers in this model remain insufficiently characterized. There are no data on the ability of luteinizing hormone receptor agonists to stimulate ovulation in rats with this model of polycystic ovary syndrome, which is important for assisted reproductive technologies. AIM: This study aimed to investigate ovarian steroidogenesis, ovulation markers, and ovarian morphology in infantile female rats with dehydroepiandrosterone-induced polycystic ovary syndrome, and to assess the effects of the allosteric agonist TP03, 5-amino-N-tert-butyl-2-(methylsulfanyl)-4-(3-(nicotinamido)phenyl)thieno[2,3-d]pyrimidine-6-carbox-amide, on these parameters. METHODS: Female Wistar rats, starting at 23–26 days of age, were treated with dehydroepiandrosterone for 6 weeks (6 mg/100 g/day, subcutaneously). The following parameters were assessed: body and ovarian weight, serum levels of testosterone, progesterone, and estradiol (enzyme-linked immunosorbent assay), ovarian gene expression (reversetranscription polymerase chain reaction), and ovarian morphology (number of tertiary and preovulatory follicles, corpora lutea, and follicular cysts) by microscopy. Rats with polycystic ovary syndrome were stimulated with an ovulation-inducing drug at a dose of 15 IU/rat, followed by TP03 at a dose of 25 mg/kg 48 h later; the studied parameters were evaluated 16 h later. RESULTS: In dehydroepiandrosterone-induced rats, ovarian weight, the number of tertiary follicles and corpora lutea of previous cycles, progesterone levels, and the expression of genes responsible for steroidogenesis (Star, Cyp11a1, Cyp17a1) and ovulation (Adamts-1, Vegf-a) were decreased, whereas testosterone levels were increased and follicular cysts were detected in the ovaries, consistent with the pathogenesis of polycystic ovary syndrome. Treatment with ovulation-inducing drugs increased ovarian weight, progesterone levels, and Cyp17a1 gene expression, and stimulated ovulation, leading to the formation of corpora lutea. Luteinized unruptured follicles were also detected in the ovaries; this finding was associated with decreased expression of the ADAMTS-1 metalloproteinase and VEGF-A genes involved in follicular rupture. CONCLUSION: Treatment of infantile rats with dehydroepiandrosterone-induced polycystic ovary syndrome using TP03 induces ovulation; however, along with normal corpora lutea, luteinized unruptured follicles are formed as a result of decreased expression of genes involved in follicular rupture.

AB - BACKGROUND: Rodent models of polycystic ovary syndrome, including those induced by dehydroepiandrosterone, are widely used to study the pathogenesis of this disorder; however, ovarian steroidogenesis and ovulation markers in this model remain insufficiently characterized. There are no data on the ability of luteinizing hormone receptor agonists to stimulate ovulation in rats with this model of polycystic ovary syndrome, which is important for assisted reproductive technologies. AIM: This study aimed to investigate ovarian steroidogenesis, ovulation markers, and ovarian morphology in infantile female rats with dehydroepiandrosterone-induced polycystic ovary syndrome, and to assess the effects of the allosteric agonist TP03, 5-amino-N-tert-butyl-2-(methylsulfanyl)-4-(3-(nicotinamido)phenyl)thieno[2,3-d]pyrimidine-6-carbox-amide, on these parameters. METHODS: Female Wistar rats, starting at 23–26 days of age, were treated with dehydroepiandrosterone for 6 weeks (6 mg/100 g/day, subcutaneously). The following parameters were assessed: body and ovarian weight, serum levels of testosterone, progesterone, and estradiol (enzyme-linked immunosorbent assay), ovarian gene expression (reversetranscription polymerase chain reaction), and ovarian morphology (number of tertiary and preovulatory follicles, corpora lutea, and follicular cysts) by microscopy. Rats with polycystic ovary syndrome were stimulated with an ovulation-inducing drug at a dose of 15 IU/rat, followed by TP03 at a dose of 25 mg/kg 48 h later; the studied parameters were evaluated 16 h later. RESULTS: In dehydroepiandrosterone-induced rats, ovarian weight, the number of tertiary follicles and corpora lutea of previous cycles, progesterone levels, and the expression of genes responsible for steroidogenesis (Star, Cyp11a1, Cyp17a1) and ovulation (Adamts-1, Vegf-a) were decreased, whereas testosterone levels were increased and follicular cysts were detected in the ovaries, consistent with the pathogenesis of polycystic ovary syndrome. Treatment with ovulation-inducing drugs increased ovarian weight, progesterone levels, and Cyp17a1 gene expression, and stimulated ovulation, leading to the formation of corpora lutea. Luteinized unruptured follicles were also detected in the ovaries; this finding was associated with decreased expression of the ADAMTS-1 metalloproteinase and VEGF-A genes involved in follicular rupture. CONCLUSION: Treatment of infantile rats with dehydroepiandrosterone-induced polycystic ovary syndrome using TP03 induces ovulation; however, along with normal corpora lutea, luteinized unruptured follicles are formed as a result of decreased expression of genes involved in follicular rupture.

KW - allosteric agonist

KW - corpus luteum

KW - dehydroepiandrosterone

KW - luteinized unruptured follicle

KW - ovarian steroidogenesis

KW - ovulation

KW - polycystic ovary syndrome

KW - progesterone

KW - rats

UR - https://elibrary.ru/LSOFFW

UR - https://www.mendeley.com/catalogue/fb8b5a2a-a730-3fc9-a4e0-e5721d38bc87/

U2 - 10.17816/rcf694205

DO - 10.17816/rcf694205

M3 - статья

VL - 24

SP - 65

EP - 79

JO - Reviews on Clinical Pharmacology and Drug Therapy

JF - Reviews on Clinical Pharmacology and Drug Therapy

SN - 1683-4100

IS - 1

ER -