In this retrospective and consecutive cohort study, our aim was to determine whether maternal blood sugar levels during pregnancy were associated with the risk of newborn congenital urogenital abnormalities, such as testicular hydrocele and cryptorchidism. We found that maternal hyperglycemia during pregnancy may induce testicular abnormalities in infants. However, whether the diagnosis of GDM could contribute to the development of the urogenital system in infants requires further investigation.
Up to the present time, a large number of studies have noticed the association between diabetes mellitus (DM) and male reproductive function, such as infertility. Many researchers also suggested that DM may participate in a novel pathophysiological mechanism of some earlier degenerative changes within the testis and epididymis, erectile and ejaculatory dysfunction, and a reduction in semen volume, sperm counts, sperm motility and altered sperm morphology 12 13. A recent study conducted by Tian et al. demonstrated that the male infertility mechanism caused by diabetes is due to the effects of oxidative stress and autophagy on the function of testes via the PI3K/Akt/mTOR signaling pathway 14. However,limited data has described the influence of hyperglycemia itself on the development of male reproductive organs. Therefore, this present clinical study provided a comprehensive analysis of the association between hyperglycemia and testicular abnormality.
Our studies also demonstrated that women with abnormal blood sugar levels during pregnancy tended to give birth to infants with lower birth weight and height. The birth weight is one of the best parameters in evaluation indexes. An infant with a birth weight of 2500g or less is called low birth weight, and when lower than expected for its gestational age, is called small for gestational age(SGA) 15. The SGA infants had less nutrition in the maternal uterus, leading to a higher risk of incomplete urinary system development16 17. If fetuses developed in an adverse intrauterine environment, they would receive fewer nutrients, and the probability of infants born with a below-average weight would rise 18. This cohort study suggested that testicular hydrocele and cryptorchidism were associated with lower birth weight, implying a possible mechanism that abnormal maternal blood sugar levels could lead to higher risks of malformations of the urogenital by impacting the birth weight of the fetus. This result suggested that abnormal maternal blood sugar levels might cause the fetus to grow in a harmful environment, but the relevant pathology requires further investigation.
During pregnancy, the level of blood sugar increases physiologically 19. However, it is unclear how the abnormal maternal blood sugar levels result in congenital urogenital malformations, especially testicular hydrocele and cryptorchidism. When the concentrations of the glucose surpass the limit, the risk of newborns having testicular hydrocele and cryptorchidism would raise significantly 20. However, there are no specific indicators to predict fetal malformations caused by hyperglycemia. In our study, we investigated the risk of testicular hydrocele and cryptorchidism in the offspring of women with pregnancy hyperglycemia, and we found that higher OGTT1H and OGTT2H were associated with a higher risk of testicular hydrocele. Additionally, increased OGTT0H level was related to a higher risk of cryptorchidism, which reveals a possible direction to prevent congenital testicular abnormalities.
There are some limitations in this study, for example, whether pregnant women took measures was not recorded. In addition, in some pharmacological studies, some idiosyncratic reactions were found in animal models but not in humans 21. we do not have known the molecular mechanisms and factors responsible for the high incidence of congenital testicular malformation which need to be further discussed.The positive rate of GDM and other diseases with hyperglycemia is low worldwide, and the rate of fetal malformation caused by related diseases, such as GDM, is often underestimated 22. Early fetal malformations can lead to spontaneous abortions before they are detected. Therefore, it is of great significance to investigate how the maternal blood sugar level plays a pathological role in the testicular development in infants. One more impediment of this examination was its single-focus plan: the investigation was done in a tertiary maternal and kid wellbeing emergency clinic.
At present, hydrocele and congenital cryptorchidism are two of the most common abnormalities in male genitalia 23. However, the relevance of maternal hyperglycemia during pregnancy and infant congenital urogenital abnormalities is unclear 5. In order to improve outcomes for current pregnancy and the future health of infants, it is of great significance to study the specific predictive indexes of fetal malformation and the influence of blood glucose at different moments during fetal development 24 25. According to this study, we can utilize the prenatal measurement of the maternal blood sugar level during pregnancy to evaluate the intrauterine environment, decreasing the possibility of fetal malformations. In addition, screening and diagnosing fetal malformations in the early phase is greatly beneficial for mothers with abnormal blood glucose, such as gestational and pre-gestational diabetic mothers 26.