Novel RHOXF1 mutation causes male infertility by inducing severe oligoasthenozoospermia

Oligoasthenozoospermia (OAT) is a common cause of male infertility, with most OAT patients resulting from genetic defects. In this study, we recruited a severe OAT patient and his family for genetic analysis, identifying a heterozygous RHOXF1 mutation (c.412 G>A p.Glu138Lys) in the patient and his brother, inherited from their mother who carried a heterozygous RHOXF1 mutation. The RHOXF1 mutation (c.412 G>A p.Glu138Lys) resulted in reduced testosterone secretion, elevated luteinizing hormone (LH) levels, disrupted sex hormone secretion, and inability to produce sperm. We reported for the first time that the RHOXF1 gene mutation (c.412 G>A p.Glu138Lys) caused severe OAT in human males. Our study not only contributes to expanding the spectrum of genetic defects associated with severe OAT but also facilitates accurate genetic screening and clinical diagnosis.