Mini-puberty

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Mini-puberty is a transient hormonal activation of the hypothalamic-pituitary-gonadal (HPG) axis that occurs in infants shortly after birth. This period is characterized by a surge in the secretion of gonadotropins (LH and FSH) and sex steroids (testosterone in males and estradiol in females), similar to but less intense than the hormonal changes that occur in puberty during adolescence. Mini-puberty plays a crucial role in the early development of the reproductive system and the establishment of secondary sexual characteristics.

Contents

Physiology

Hypothalamic-pituitary-gonadal axis activation

Mini-puberty begins within the first few days or weeks of life and typically lasts until 6–12 months of age. [1] The HPG axis is temporarily reactivated, resulting in increased secretion of gonadotropin-releasing hormone (GnRH) from the hypothalamus. GnRH stimulates the pituitary gland to release luteinizing hormone (LH) and follicle-stimulating hormone (FSH), which in turn stimulate the gonads (testes in males and ovaries in females) to produce sex steroids.

Hormonal changes

Clinical significance

Developmental role

Mini-puberty is crucial for several developmental processes, including:

Diagnostic marker

Mini-puberty can serve as a valuable diagnostic window for identifying congenital abnormalities of the HPG axis or gonads. [4] [5] Conditions such as congenital hypogonadotropic hypogonadism and certain forms of intersex can be diagnosed during this period by evaluating hormone levels and gonadal response.

Potential disorders

Disruptions in the mini-puberty process can lead to various clinical conditions, including:

Environmental influences

Environmental factors, such as exposure to Endocrine Disrupting Chemicals (EDCs), have been shown to impact mini-puberty. [1] [8] [9] EDCs are widespread in daily life and can be found in products such as pesticides and personal care items. Bisphenol A (BPA) [10] and many phthalates [11] are known to interfere with the earlier HPG axis activation during pregnancy for boys, affecting testosterone levels during mini-puberty, anogenital distance (AGD), and testicular descent.

More recently, BPA and phthalate exposure during mini-puberty have been shown to interfere with HPG axis activation and testosterone levels during that same time frame, suggesting that mini-puberty is a particularly vulnerable window for EDC exposure. [12] Such disruptions may lead to long-term consequences, including delayed or precocious puberty, reproductive health issues, and increased risk of conditions like polycystic ovary syndrome (PCOS), [13] breast cancer [14] and prostate cancer.

In a small study, it was shown that "PCDD/Fs and PCBs measured in breast milk collected within the first 3 weeks following birth were more strongly associated with sexually dimorphic outcomes than exposures measured in maternal blood collected between weeks 28 and 43" of pregnancy, [9] adding evidence that EDC exposure during mini-puberty may interfere with endocrine and neurological development.

Research and future directions

Although the phenomenon has been known for over 40 years, [2] research into mini-puberty continues to uncover its broader implications for long-term health and development. The potential impact of environmental factors and endocrine disruptors on mini-puberty is an area of active investigation. At the same time, researchers also investigate if mini-puberty may be a window to treat certain disorders, e.g. treating micropenis using gonadotropin (testosterone) injections. [15]

See also

References

  1. 1 2 3 4 5 6 7 8 Lucaccioni, Laura; Trevisani, Viola; Boncompagni, Alessandra; Marrozzini, Lucia; Berardi, Alberto; Iughetti, Lorenzo (2021-01-18). "Minipuberty: Looking Back to Understand Moving Forward". Frontiers in Pediatrics. 8. doi: 10.3389/fped.2020.612235 . ISSN   2296-2360. PMC   7848193 . PMID   33537266.
  2. 1 2 3 4 5 6 Becker, Marianne; Hesse, Volker (2020-06-29). "Minipuberty: Why Does it Happen?" . Hormone Research in Paediatrics. 93 (2): 76–84. doi:10.1159/000508329. ISSN   1663-2818. PMID   32599600.
  3. Nordenström, Anna (2022-08-01). "Potential impact of mini-puberty on fertility" . Annales d'Endocrinologie. 83 (4): 250–253. doi:10.1016/j.ando.2022.06.002. ISSN   0003-4266. PMID   35728696.
  4. Grumbach, Melvin M. (May 2005). "A Window of Opportunity: The Diagnosis of Gonadotropin Deficiency in the Male Infant 1" . The Journal of Clinical Endocrinology & Metabolism. 90 (5): 3122–3127. doi:10.1210/jc.2004-2465. ISSN   0021-972X. PMID   15728198.
  5. Quinton, Richard; Mamoojee, Yaasir; Jayasena, Channa N.; Young, Jacques; Howard, Sasha; Dunkel, Leo; Cheetham, Tim; Smith, Neil; Dwyer, Andrew A. (February 2017). "Society for Endocrinology UK guidance on the evaluation of suspected disorders of sexual development: emphasizing the opportunity to predict adolescent pubertal failure through a neonatal diagnosis of absent minipuberty" . Clinical Endocrinology. 86 (2): 305–306. doi:10.1111/cen.13257. hdl: 10044/1/45453 . ISSN   0300-0664. PMID   27749014.
  6. Rohayem, Julia; Alexander, Emma C; Heger, Sabine; Nordenström, Anna; Howard, Sasha R (2024-03-04). "Mini-Puberty, Physiological and Disordered: Consequences, and Potential for Therapeutic Replacement". Endocrine Reviews. 45 (4): 460–492. doi:10.1210/endrev/bnae003. ISSN   0163-769X. PMC   11244267 . PMID   38436980.
  7. Dwyer, Andrew A. (January 2020). "Minipuberty: A Primer for Pediatric Nurses" . Journal of Pediatric Nursing. 50: 138–139. doi:10.1016/j.pedn.2019.10.012. ISSN   0882-5963. PMID   31874718.
  8. Ünüvar, Tolga; Büyükgebiz, Atilla (2012-04-15). "Fetal and Neonatal Endocrine Disruptors" (PDF). Journal of Clinical Research in Pediatric Endocrinology. 4 (2): 51–60. doi:10.4274/Jcrpe.569. PMC   3386773 . PMID   22672860.
  9. 1 2 Winneke, Gerhard; Ranft, Ulrich; Wittsiepe, Jürgen; Kasper-Sonnenberg, Monika; Fürst, Peter; Krämer, Ursula; Seitner, Gabriele; Wilhelm, Michael (March 2014). "Behavioral Sexual Dimorphism in School-Age Children and Early Developmental Exposure to Dioxins and PCBs: A Follow-Up Study of the Duisburg Cohort". Environmental Health Perspectives. 122 (3): 292–298. doi:10.1289/ehp.1306533. ISSN   0091-6765. PMC   3948031 . PMID   24273228.
  10. Sun, Xiaowei; Li, Dekun; Liang, Hong; Miao, Maohua; Song, Xiuxia; Wang, Ziliang; Zhou, Zhijun; Yuan, Wei (December 2018). "Maternal exposure to bisphenol A and anogenital distance throughout infancy: A longitudinal study from Shanghai, China". Environment International. 121 (Pt 1): 269–275. Bibcode:2018EnInt.121..269S. doi: 10.1016/j.envint.2018.08.055 . PMID   30223203.
  11. Muerköster, Anna-Patricia; Frederiksen, Hanne; Juul, Anders; Andersson, Anna-Maria; Jensen, Richard Christian; Glintborg, Dorte; Kyhl, Henriette Boye; Andersen, Marianne Skovsager; Timmermann, Clara Amalie Gade; Jensen, Tina Kold (November 2020). "Maternal phthalate exposure associated with decreased testosterone/LH ratio in male offspring during mini-puberty. Odense Child Cohort". Environment International. 144: 106025. Bibcode:2020EnInt.14406025M. doi:10.1016/j.envint.2020.106025. PMID   32798799.
  12. Lærkeholm Müller, Matilde; Busch, Alexander Siegfried; Ljubicic, Marie Lindhardt; Upners, Emmie N.; Fischer, Margit B.; Hagen, Casper P.; Albrethsen, Jakob; Frederiksen, Hanne; Juul, Anders; Andersson, Anna-Maria (2023-05-01). "Urinary concentration of phthalates and bisphenol A during minipuberty is associated with reproductive hormone concentrations in infant boys". International Journal of Hygiene and Environmental Health. 250: 114166. Bibcode:2023IJHEH.25014166L. doi: 10.1016/j.ijheh.2023.114166 . ISSN   1438-4639. PMID   37058994.
  13. Palioura, Eleni; Diamanti-Kandarakis, Evanthia (December 2015). "Polycystic ovary syndrome (PCOS) and endocrine disrupting chemicals (EDCs)" . Reviews in Endocrine and Metabolic Disorders. 16 (4): 365–371. doi:10.1007/s11154-016-9326-7. ISSN   1389-9155. PMID   26825073.
  14. Burks, Hope; Pashos, Nicholas; Martin, Elizabeth; Mclachlan, John; Bunnell, Bruce; Burow, Matthew (December 2017). "Endocrine disruptors and the tumor microenvironment: A new paradigm in breast cancer biology" . Molecular and Cellular Endocrinology. 457: 13–19. doi:10.1016/j.mce.2016.12.010. PMID   28012841.
  15. Avril, Tristan; Hennocq, Quentin; Lambert, Anne-Sophie; Leger, Juliane; Simon, Dominique; Martinerie, Laetitia; Bouvattier, Claire (2023-04-01). "Gonadotropin administration to mimic mini-puberty in hypogonadotropic males: pump or injections?". Endocrine Connections. 12 (4). doi:10.1530/EC-22-0252. ISSN   2049-3614. PMC   10083662 . PMID   36724045.