Received 09.05.2020 ▪ Accepted 01.06.2020 ▪ Published online 01.07.2020

Morphofunctional changes in testes of rats born to mothers with simulated fetoplacental insufficiency and its correction

N. Yu. Seliukova1,2, Yu. B. Laryanovska2, I. V. Volokhov1,2, D. V. Morozenko2, R. V. Dotsenko2, A. O. Zemlianskyi2, K. V. Misiura1

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1SI «V. Danilevsky Institute for Endocrine Pathology Problems of NAMS of Ukraine»,
10 Alchevskikh str., Kharkiv, 61002, Ukraine

2National University of Pharmacy,
53 Pushkinskaya str., Kharkiv, 61002, Ukraine

Nowadays, it is almost unknown how fetoplacental insufficiency of mothers affects the formation of the reproductive system in male offspring during puberty. Therefore, the aim of this work was to study the histological structure of the testes of male offspring born to mothers of different ages with fetoplacental insufficiency and to evaluate the effectiveness of a new pharmaceutical composition for the correction of pathological conditions of pregnancy. The experiment involved healthy mature female Wistar rats in young (3–4 months) and mature (8–10 months) reproductive age. Eight groups with 7 pregnant females in each one were formed: groups 1 and 2 — intact animals of young and mature reproductive age, respectively; groups 3 and 4 — females with experimental fetoplacental insufficiency of young and mature reproductive age; groups 5 and 6 — young and mature animals with experimental fetoplacental insufficiency and addition to food depending on the weight of animals from 11 to 19 days of pregnancy pharmaceutical composition. Groups 7 and 8 — young and mature animals with experimental fetoplacental insufficiency with addition a comparison drug Dipyridamole to the food. Modeling of fetoplacental insufficiency was performed by daily subcutaneous injection to females from the 12th to the 18th day of pregnancy 50% oil solution of carbon tetrachloride at a dose of 2 ml/kg body weight. Offspring were decontaminated on the 50th day of life (puberty) by rapid decapitation. Samples of male testicles were fixed in 10% formalin solution, performed on alcohols of increasing strength, poured into paraffin. Sections were made from the blocks, which were stained with hematoxylin and eosin. Qualitative assessment of histostructure was performed on sections of the body in rats. Summing up the results of histological analysis and morphometric parameters characterizing the condition of the testicles of rats, we can draw the following conclusions. In the offspring born to reproductively young females with fetoplacental insufficiency, inhibition of the rate of germ cell differentiation was found, while in the offspring born to reproductively mature females with fetoplacental insufficiency, the negative effects of this effect were leveled and the rate of spermatogenesis increased. When the pharmaceutical composition was administered to both young and mature pregnant females on the background of fetoplacental insufficiency, it activated the processes of proliferation and differentiation of spermatogenic epithelium in their offspring, which was reflected in the appearance of mature sperm in the seminal tubules. The comparison drug Dipyridamole, administered according to the same regimen to both young and mature pregnant females with fetoplacental insufficiency, also helped the 50-day-old offspring of these females to restore the rate of spermatogenesis at the level of the pharmaceutical composition.

Key words: fetoplacental insufficiency, male offspring, mother’s age, pharmacological correction

  1. Bekmukhambetov Y, Mamyrbayev A, Dzharkenov T, Kravtsova N, Utesheva Z, Tusupkaliev A, Ryzhkova S, Darzhanova K, Bekzhanova M. Metabolic and immunologic aspects of fetoplacental insufficiency. Am. J. Reprod. Immunol. 2016; 76 (4): 299–306.
  2. Botting KJ, McMillen IC, Forbes H, Nyengaard JR, Morrison JL. Chronic hypoxemia in late gestation decreases cardiomyocyte number but does not change expression of hypoxia-responsive genes. J. Am. Heart. Assoc. 2014; 3 (4): e000531.
  3. Burren CP, Caswell R, Castle B, Welch CR, Hilliard TN, Smithson SF, Ellard S. TRPV6 compound heterozygous variants result in impaired placental calcium transport and severe undermineralization and dysplasia of the fetal skeleton. Am. J. Med. Genet. A. 2018; 176 (9): 1950–1955.
  4. Burton GJ, Fowden AL, Thornburg KL. Placental origins of chronic disease. Physiol. Rev. 2016; 96 (4): 1509–1565.
  5. European Convention for the protection of vertebrate animals used for research or other scientific purposes. The Verkhovna Rada of Ukraine. 18.03.1986. Available at: (in Ukrainian)
  6. Guarner-Lans V, Ramírez-Higuera A, Rubio-Ruiz ME, Castrejón-Téllez V, Soto ME, Pérez-Torres I. Early programming of adult systemic essential hypertension. Int. J. Mol. Sci. 2020; 21 (4): 1203.
  7. Kryvetsky VV, Moskalenko RА, Karpenko LІ, Zakorko IMS. Features of morphofunctional study of the testis’ endocrine component in experimental conditions. J. Clin. Exp. Med. Res. 2013; 1 (2): 149–153. Available at: (in Ukrainian)
  8. Kupriyanova LS. Pathomorphological features of the structure of the ovaries of fetuses from mothers whose pregnancy proceeded against the background of placental dysfunction. Zaporozhye Med. J. 2014; 5 (86): 78–81. (in Russian)
  9. Luyckx VA, Brenner BM. Birth weight, malnutrition and kidney-associated outcomes — a global concern. Nat. Rev. Nephrol. 2015; 11 (3): 135–149.
  10. Merkulov GA. Course of pathohistological technique. Leningrad, Medicine, 1969: 424 p. (in Russian)
  11. Regulations on the Ethics Committee (Bioethics). Order no. 1287 dated 19.11.2012. Available at: (in Ukrainian)
  12. Rodríguez-Rodríguez P, Ramiro-Cortijo D, Reyes-Hernández CG, López de Pablo AL, González MC, Arribas SM. Implication of oxidative stress in fetal programming of cardiovascular disease. Front. Physiol. 2018; 9: 602.
  13. Savelyeva GM, Fedorova MV, Klimenko PA, Sichinava LG. Placental insufficiency. Moscow, Medicine, 1991: 272 p. (in Russian)
  14. Shallie PD, Naicker T. The placenta as a window to the brain: A review on the role of placental markers in prenatal programming of neurodevelopment. Int. J. Dev. Neurosci. 2019; 73 (1): 41–49.
  15. Simmons RA. Developmental origins of diabetes: The role of oxidative stress. Best. Pract. Res. Clin. Endocrinol. Metab. 2012; 26 (5): 701–708.
  16. Yakovleva LV, Zaichenko GV, Tsypkun AG, Laryanovska YB., Butenko IG, Deeva TV, Kudina OV, Pavlenko NY. Preclinical study of drugs intended for the treatment of placental dysfunction. Methodical recommendations. Kyiv, DFC of the Ministry of Health of Ukraine, 2009: 59 p. (in Ukrainian)
  17. Yalovchuk AV. Long-term results of nervous system disorders in infants born to mothers with complicated pregnancy. Bukovynian Medical Bulletin. 2006;10 (2): 83–86. (in Ukrainian)




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