title: Reduced intrafollicular androstenedione and estradiol levels in early-treated prenatally androgenized female rhesus monkeys receiving follicle-stimulating hormone therapy for in vitro fertilization.
abstract: Five early-treated and four late-treated prenatally androgenized and five normal female rhesus monkeys were studied to determine whether prenatal testosterone propionate exposure beginning Gestational Days 40-44 (early-treated) or 100-115 (late-treated) affects follicular steroidogenesis during recombinant human FSH (rhFSH) treatment. All monkeys underwent rhFSH injections, without human chorionic gonadotropin administration, followed by oocyte retrieval. Serum FSH, LH, estradiol (E2), progesterone (P), 17alpha-hydroxyprogesterone (17 OHP), androstenedione (A4), testosterone, and dihydrotestosterone were measured basally during rhFSH therapy and at oocyte retrieval. Follicle fluid (FF) sex steroids, oocyte fertilization, and embryo development were analyzed. Circulating FSH, E2, 17 OHP, A4, and dihydrotestosterone levels increased similarly in all females. Serum LH levels decreased from basal levels in normal and late-treated prenatally androgenized females but were unchanged in early-treated prenatally androgenized females. Serum P levels at oocyte retrieval were comparable with those before FSH treatment in all females. All prenatally androgenized females showed reduced FF levels of A4 and E2 but not P or dihydrotestosterone. Intrafollicular T concentrations also were significantly lower in late-treated compared with early-treated prenatally androgenized females or normal females. In early-treated prenatally androgenized females, but not the other female groups, intrafollicular A4 and E2 levels were reduced in follicles containing oocytes that failed fertilization or produced zygotes with cleavage arrest before or at the five- to eight-cell embryo stage. Therefore, in monkeys receiving rhFSH therapy alone without human chorionic gonadotropin administration, early prenatal androgenization reduced FF concentrations of E2 and A4 in association with abnormal oocyte development, without having an effect on P, testosterone, or dihydrotestosterone concentrations.
authors.affiliation: Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota 55905, USA. ddumesic@mayo.edu
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Dumesic
authors.forename: R Dee
authors.initials: RD
authors.lastname: Schramm
authors.forename: Ian M
authors.initials: IM
authors.lastname: Bird
authors.forename: Eric
authors.initials: E
authors.lastname: Peterson
authors.forename: Ann Marie
authors.initials: AM
authors.lastname: Paprocki
authors.forename: Rao
authors.initials: R
authors.lastname: Zhou
authors.forename: David H
authors.initials: DH
authors.lastname: Abbott
mesh_terms: D000728:Androgens / Q000494:pharmacology; D000735:Androstenedione / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004958:Estradiol / Q000378:metabolism*; D005260:Female; D005307:Fertilization in Vitro / Q000379:methods*; D005640:Follicle Stimulating Hormone / Q000097:blood / Q000627:therapeutic use*; D006728:Hormones / Q000097:blood; D007328:Insulin / Q000097:blood; D008253:Macaca mulatta; D008297:Male; D009865:Oocytes / Q000187:drug effects / Q000502:physiology; D006080:Ovarian Follicle / Q000187:drug effects / Q000378:metabolism*; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D000728:Androgens; D001786:Blood Glucose; D006728:Hormones; D007328:Insulin; D011994:Recombinant Proteins; D000735:Androstenedione; D004958:Estradiol; D005640:Follicle Stimulating Hormone