The present and future state of hormonal treatment for male infertility.
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Although male factors contribute to over half of all cases of infertility, most infertile men are described as 'idiopathic oligo/asthenozoospermic' rather than diagnosed precisely; hence, specific medical treatment is not possible. One uncommon but treatable cause of male infertility is gonadotrophin deficiency in which gonadotrophin replacement therapy is highly effective at inducing spermatogenesis and fertility. Hormonal therapy is a logical approach for empirical drug therapy given the fundamental role of hormonal regulation in spermatogenesis. However, treatment with GnRH analogues, gonadotrophins, androgens, anti-estrogens, aromatase inhibitors, growth hormone- and prolactin-suppressing drugs is ineffective in unselected infertile men. Prolonged high-dose glucocorticoid therapy for sperm autoimmunity may improve pregnancy rates modestly, but the risks are generally unacceptable compared with IVF or ICSI. For these reasons, modern reproductive technologies, notably ICSI/IVF, have become the de-facto standard empirical treatment of male infertility, despite involving significant though infrequent risks to the fetus and mother. There remains a potential for hormonal methods to improve sperm quality or ultrastructure in subgroups of infertile men more responsive to hormonal manipulation or using novel protein or gene-targeted therapies or biochemical approaches based on post-hormonal receptor mechanisms that stimulate spermatogenesis. How such novel hormonal methods will develop in conjunction with improved ICSI/IVF or cloning technologies, and the potential role of adjunctive hormonal therapy remains to be clarified. (+info)
Infertility in 5,10-methylenetetrahydrofolate reductase (MTHFR)-deficient male mice is partially alleviated by lifetime dietary betaine supplementation.
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Metabolism of folate is essential for proper cellular function. Within the folate pathway, methylenetetrahydrofolate reductase (MTHFR) reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a methyl donor for remethylation of homocysteine to methionine, the precursor of S-adenosylmethionine. S-adenosylmethionine is the methyl donor for numerous cellular reactions. In adult male mice, MTHFR levels are highest in the testis; this finding, in conjunction with recent clinical evidence, suggest an important role for MTHFR in spermatogenesis. Indeed, we show here that severe MTHFR deficiency in male mice results in abnormal spermatogenesis and infertility. Maternal oral administration of betaine, an alternative methyl donor, throughout pregnancy and nursing, resulted in improved testicular histology in Mthfr-/- offspring at Postnatal Day 6, but not at 8 mo of age. However, when betaine supplementation was maintained postweaning, testicular histology improved, and sperm numbers and fertility increased significantly. We postulate that the adverse effects of MTHFR deficiency on spermatogenesis, may, in part, be mediated by alterations in the transmethylation pathway and suggest that betaine supplementation may provide a means to bypass MTHFR deficiency and its adverse effects on spermatogenesis by maintaining normal methylation levels within male germ cells. (+info)
Caenorhabditis elegans prom-1 is required for meiotic prophase progression and homologous chromosome pairing.
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A novel gene, prom-1, was isolated in a screen for Caenorhabditis elegans mutants with increased apoptosis in the germline. prom-1 encodes an F-box protein with limited homology to the putative human tumor suppressor FBXO47. Mutations in the prom-1 locus cause a strong reduction in bivalent formation, which results in increased embryonic lethality and a Him phenotype. Furthermore, retarded and asynchronous nuclear reorganization as well as reduced homologous synapsis occur during meiotic prophase. Accumulation of recombination protein RAD-51 in meiotic nuclei suggests disturbed repair of double-stranded DNA breaks. Nuclei in prom-1 mutant gonads timely complete mitotic proliferation and premeiotic replication, but they undergo prolonged delay upon meiotic entry. We, therefore, propose that prom-1 regulates the timely progression through meiotic prophase I and that in its absence the recognition of homologous chromosomes is strongly impaired. (+info)
Electrochemical sensors, MTT and immunofluorescence assays for monitoring the proliferation effects of cissus populnea extracts on Sertoli cells.
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Use of human chorionic gonadotropin in a male Pacific walrus (Odobenus rosmarus divergens) to induce rut and achieve a pregnancy in a nulliparous female.
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Walrus in US zoos have a very low reproductive rate of 11 births in 80 years, and little is known about Pacific walrus (Odobenus rosmarus divergens) reproductive biology. To address this, we initiated a program in which detailed biological data were recorded on captive walrus. As part of a 7-year study, 1 male and 1 female 16-year-old captive Pacific walrus were carefully monitored with weekly serum hormone analysis, daily glans penis smears for spermatozoa, and abdominal ultrasound for pregnancy. The female ovulated once annually from late December through mid-January and then exhibited 9 months of sustained elevated progesterone. This nonconceptive estrous cycle profile is consistent with reports from wild walrus females. In contrast, the male's seasonal rut routinely occurred in late February through May with a serum testosterone peak in March. This profile differed from the reported adult male cycle in wild walrus of November through March. During the period of the female's ovulation, the male had nadir testosterone levels and was consistently azoospermic. Likewise, during the male's spermatogenic rut in the spring, the female was anovulatory with elevated progesterone. On this basis, the male was treated for 14 weeks with human chorionic gonadotropin (hCG) in an attempt to increase testosterone levels in synchrony with the female's annual ovulation. The treatment successfully induced rut characterized by sustained elevated serum testosterone levels and production of spermatozoa. The male and female successfully bred, and the female became pregnant. Upon discontinuation of hCG treatment, the male resumed baseline testosterone levels. We theorize that the lack of synchronization of rut and ovulatory cycles is a primary reason for reproductive failure in these captive walrus. (+info)
Insulin rescues impaired spermatogenesis via the hypothalamic-pituitary-gonadal axis in Akita diabetic mice and restores male fertility.
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Mucuna pruriens and its major constituent L-DOPA recover spermatogenic loss by combating ROS, loss of mitochondrial membrane potential and apoptosis.
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