## 5 Studies on the Effects of _M. oleifera_ Leaf Extracts on Male Reproductive Function
### Diabetes Mellitus  
It is estimated that about 382 million people globally are living with diabetes mellitus [102]. Diabetes mellitus can result in various medical complications; however, the most common complication is male fertility [103]. Studies have shown that 51% of diabetic males show signs of infertility, which indicates that diabetes mellitus leads to alterations in male reproductive function [102; 103].  
The serum levels of insulin and glucose in diabetic males affect the maturation of sperm cells on the acrosome and plasma membrane [102], which subsequently affects sperm viability, motility and morphology [104]. Insulin and glucose levels also play essential roles in the sugar movement in sperm cells, which indirectly control motility during capacitation and fertilisation [103].  
Glucose is a crucial requirement in spermatogenesis and acrosome reaction and is diffused into the mammalian testicular cells via a concentration gradient utilising specific enzyme transporter known as glucose transporters (GLUTs). The family of these glucose transporters comprises 14 members, categorised into groups of three based on similarities of their sequences. Therefore, reduced insulin levels result in the inactivity of GLUT2 function, which results in low glucose levels and subsequent low energy, thereby reducing the rate of spermatogenesis and motility [105]. Furthermore, _M. oleifera_ leaf extracts in male animal models exposed to diabetic conditions show its ameliorative effects on the male reproductive system.  
_M. oleifera_ leaf extracts on male albino Swiss mice exposed to diabetic conditions for 21 days increased sperm count and motility [89]. Diabetes mellitus can affect spermatogenesis by indirectly affecting the epithelium of the seminiferous tubules and reducing FSH [7]. Reduced FSH result in poor activation of Sertoli cells, which leads to impaired spermatogenesis [103]. In some cases of diabetes mellitus (T2 DM), there is inhibition of the HPG-axis, which leads to low production of FSH and LH in response to GnRH, as well as reduced testosterone levels as a result of diminishing Leydig cells of the testis [7]. Fortunately, _M. oleifera_ has an androgenic effect on the male reproductive system in vitro [22]. _M. oleifera_ leaf extract on male Wistar rats induced with diabetes increased LH, FSH and testosterone levels, which were reduced by the damaging effects of diabetes mellitus [88].  
Oxidative stress is regarded as the leading cause of reproductive deficiency in patients with diabetes mellitus [106]. Diabetes mellitus induces oxidative stress through elevated levels of ROS, lipid peroxidation [102] and reduced total antioxidant capacity (TAC) in the seminal fluid [107]. This increases the DNA fragmentation of sperms, alteration in ATP synthesis of the mitochondria and decreases sperm motility [102]. _M. oleifera_ leaf extract reduced lipid peroxidation and increased the capacity of the antioxidant defensive system by increasing SOD, CAT, GSH and ascorbic acid in the testes of diabetes mellitus-induced rats. This indicates that _M. Oleifera_ may ameliorate the effects of diabetes on male fertility through the enhancement of the antioxidant defence system of the testis [88].  
Hyperglycaemic conditions have also been correlated with decreased germ cell population, epithelial cell clusters, reduced stereocilia and lipid vacuolisation in the testes [88]. A reduced seminal vesicle weight, mass and weight of the testis, number of Leydig cells, diameter of the seminiferous tubules and height of the germinal epithelium in hyperglycemia conditions were also shown in another study [102]. _M. Oleifera_ showed ameliorative effects on the testicular histology of diabetic rats by increasing the mean number of spermatagonia in the seminiferous tubules and increasing the population of the round (normal) spermatids. _M. Oleifera_ also increased the diameter of the seminiferous tubules, the nuclear diameter of the Leydig cells [88] and the weight of the epididymis [89].